AVAHO

This transcript has been edited for clarity.

Hello. It’s Mark Kris reporting back after attending the New York Lung Cancer Foundation Summit here in New York. A large amount of discussion went on, but as usual, I was most interested in the perioperative space.

In previous videos, I’ve talked about this ongoing discussion of whether you should operate and give adjuvant therapy or give neoadjuvant therapy, and I’ve addressed that already. One thing I want to bring up – and as we move off of that argument, which frankly doesn’t have an answer today, with neoadjuvant therapy, having all the data to support it – is what are the patterns of recurrence now that we have more successful systemic therapies, both targeted therapies and checkpoint inhibitors?

I was taught early on by my surgical mentors that the issue here was systemic control. While they could do very successful surgery to get high levels of local control, they could not control systemic disease. Sadly, the tools we had early on with chemotherapy were just not good enough. Suddenly, we have better tools to control systemic spread. In the past, the vast majority of occurrences were systemic; they’re now local.

What I think we need to do as a group of practitioners trying to deal with the problems getting in the way of curing our patients is look at what the issue is now. Frankly, the big issue now, as systemic therapy has controlled metastatic disease, is recurrence in the chest.

We give adjuvant osimertinib. Please remember what the numbers are. In the osimertinib arm, of the 11 recurrences reported in the European Society for Medical Oncology presentation a few years back, nine of them were in the chest or mediastinal nodes. In the arm that got no osimertinib afterward, there were 46 recurrences, and 32 of those 46 recurrences were in the chest, either the lung or mediastinal nodes. Therefore, 74% of the recurrences are suddenly in the chest. What’s the issue here?

The issue is we need to find strategies to give better disease control in the chest, as we have made inroads in controlling systemic disease with the targeted therapies in the endothelial growth factor receptor space, and very likely the checkpoint inhibitors, too, as that data kind of filters out. We need to think about how better to get local control.

I think rather than continue to get into this argument of neoadjuvant vs adjuvant, we should move to what’s really hurting our patients. Again, the data I quoted you was from the ADAURA trial, which was adjuvant therapy, and I’m sure the neoadjuvant is going to show the same thing. It’s better systemic therapy but now, more trouble in the chest.

How are we going to deal with that? I’d like to throw out one strategy, and that is to rethink the role of radiation in these patients. Again, if the problem is local in the chest, lung, and lymph nodes, we have to think about local therapy. Yes, we’re not recommending it routinely for everybody, but now that we have better systemic control, we need to rethink our options. The obvious one to rethink is about giving radiotherapy.

We should also use what we learned in the earlier trials, which is that there is harm in giving excessive radiation to the heart. If you avoid the heart, you avoid the harm. We have better planning strategies for stereotactic body radiotherapy and more traditional radiation, and of course, we have proton therapy as well.

As we continue to struggle with the idea of that patient with stage II or III disease, whether to give adjuvant vs neoadjuvant therapy, please remember to consider their risk in 2024. Their risk for first recurrence is in the chest.

What are we going to do to better control disease in the chest? We have a challenge. I’m sure we can meet it if we put our heads together.

Dr. Kris is professor of medicine at Weill Cornell Medical College, and attending physician, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York. He disclosed ties with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer, and PUMA.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hello. It’s Mark Kris reporting back after attending the New York Lung Cancer Foundation Summit here in New York. A large amount of discussion went on, but as usual, I was most interested in the perioperative space.

In previous videos, I’ve talked about this ongoing discussion of whether you should operate and give adjuvant therapy or give neoadjuvant therapy, and I’ve addressed that already. One thing I want to bring up – and as we move off of that argument, which frankly doesn’t have an answer today, with neoadjuvant therapy, having all the data to support it – is what are the patterns of recurrence now that we have more successful systemic therapies, both targeted therapies and checkpoint inhibitors?

I was taught early on by my surgical mentors that the issue here was systemic control. While they could do very successful surgery to get high levels of local control, they could not control systemic disease. Sadly, the tools we had early on with chemotherapy were just not good enough. Suddenly, we have better tools to control systemic spread. In the past, the vast majority of occurrences were systemic; they’re now local.

What I think we need to do as a group of practitioners trying to deal with the problems getting in the way of curing our patients is look at what the issue is now. Frankly, the big issue now, as systemic therapy has controlled metastatic disease, is recurrence in the chest.

We give adjuvant osimertinib. Please remember what the numbers are. In the osimertinib arm, of the 11 recurrences reported in the European Society for Medical Oncology presentation a few years back, nine of them were in the chest or mediastinal nodes. In the arm that got no osimertinib afterward, there were 46 recurrences, and 32 of those 46 recurrences were in the chest, either the lung or mediastinal nodes. Therefore, 74% of the recurrences are suddenly in the chest. What’s the issue here?

The issue is we need to find strategies to give better disease control in the chest, as we have made inroads in controlling systemic disease with the targeted therapies in the endothelial growth factor receptor space, and very likely the checkpoint inhibitors, too, as that data kind of filters out. We need to think about how better to get local control.

I think rather than continue to get into this argument of neoadjuvant vs adjuvant, we should move to what’s really hurting our patients. Again, the data I quoted you was from the ADAURA trial, which was adjuvant therapy, and I’m sure the neoadjuvant is going to show the same thing. It’s better systemic therapy but now, more trouble in the chest.

How are we going to deal with that? I’d like to throw out one strategy, and that is to rethink the role of radiation in these patients. Again, if the problem is local in the chest, lung, and lymph nodes, we have to think about local therapy. Yes, we’re not recommending it routinely for everybody, but now that we have better systemic control, we need to rethink our options. The obvious one to rethink is about giving radiotherapy.

We should also use what we learned in the earlier trials, which is that there is harm in giving excessive radiation to the heart. If you avoid the heart, you avoid the harm. We have better planning strategies for stereotactic body radiotherapy and more traditional radiation, and of course, we have proton therapy as well.

As we continue to struggle with the idea of that patient with stage II or III disease, whether to give adjuvant vs neoadjuvant therapy, please remember to consider their risk in 2024. Their risk for first recurrence is in the chest.

What are we going to do to better control disease in the chest? We have a challenge. I’m sure we can meet it if we put our heads together.

Dr. Kris is professor of medicine at Weill Cornell Medical College, and attending physician, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York. He disclosed ties with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer, and PUMA.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hello. It’s Mark Kris reporting back after attending the New York Lung Cancer Foundation Summit here in New York. A large amount of discussion went on, but as usual, I was most interested in the perioperative space.

In previous videos, I’ve talked about this ongoing discussion of whether you should operate and give adjuvant therapy or give neoadjuvant therapy, and I’ve addressed that already. One thing I want to bring up – and as we move off of that argument, which frankly doesn’t have an answer today, with neoadjuvant therapy, having all the data to support it – is what are the patterns of recurrence now that we have more successful systemic therapies, both targeted therapies and checkpoint inhibitors?

I was taught early on by my surgical mentors that the issue here was systemic control. While they could do very successful surgery to get high levels of local control, they could not control systemic disease. Sadly, the tools we had early on with chemotherapy were just not good enough. Suddenly, we have better tools to control systemic spread. In the past, the vast majority of occurrences were systemic; they’re now local.

What I think we need to do as a group of practitioners trying to deal with the problems getting in the way of curing our patients is look at what the issue is now. Frankly, the big issue now, as systemic therapy has controlled metastatic disease, is recurrence in the chest.

We give adjuvant osimertinib. Please remember what the numbers are. In the osimertinib arm, of the 11 recurrences reported in the European Society for Medical Oncology presentation a few years back, nine of them were in the chest or mediastinal nodes. In the arm that got no osimertinib afterward, there were 46 recurrences, and 32 of those 46 recurrences were in the chest, either the lung or mediastinal nodes. Therefore, 74% of the recurrences are suddenly in the chest. What’s the issue here?

The issue is we need to find strategies to give better disease control in the chest, as we have made inroads in controlling systemic disease with the targeted therapies in the endothelial growth factor receptor space, and very likely the checkpoint inhibitors, too, as that data kind of filters out. We need to think about how better to get local control.

I think rather than continue to get into this argument of neoadjuvant vs adjuvant, we should move to what’s really hurting our patients. Again, the data I quoted you was from the ADAURA trial, which was adjuvant therapy, and I’m sure the neoadjuvant is going to show the same thing. It’s better systemic therapy but now, more trouble in the chest.

How are we going to deal with that? I’d like to throw out one strategy, and that is to rethink the role of radiation in these patients. Again, if the problem is local in the chest, lung, and lymph nodes, we have to think about local therapy. Yes, we’re not recommending it routinely for everybody, but now that we have better systemic control, we need to rethink our options. The obvious one to rethink is about giving radiotherapy.

We should also use what we learned in the earlier trials, which is that there is harm in giving excessive radiation to the heart. If you avoid the heart, you avoid the harm. We have better planning strategies for stereotactic body radiotherapy and more traditional radiation, and of course, we have proton therapy as well.

As we continue to struggle with the idea of that patient with stage II or III disease, whether to give adjuvant vs neoadjuvant therapy, please remember to consider their risk in 2024. Their risk for first recurrence is in the chest.

What are we going to do to better control disease in the chest? We have a challenge. I’m sure we can meet it if we put our heads together.

Dr. Kris is professor of medicine at Weill Cornell Medical College, and attending physician, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York. He disclosed ties with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer, and PUMA.

A version of this article appeared on Medscape.com.

New and evolving research in locally advanced rectal cancer suggests that selective use of treatments in some patients can achieve outcomes similar to those of standard regimens, according to the chair of the Department of Radiation Oncology at Duke University School of Medicine, Durham, North Carolina.

Total neoadjuvant therapy (TNT) is the standard treatment that involves systemic chemotherapy and radiation therapy before surgery for patients with locally advanced rectal cancer, Christopher G. Willett, MD, explained, in an interview. However, recent clinical trials support several strategies for “deintensification” of TNT for patients with locally advanced rectal cancer, he said.

Some patients may not require surgery or radiation therapy, or they may not require any treatment modalities including radiation therapy, chemotherapy, and surgery, Dr. Willett continued.

However, “these patients require close surveillance post treatment to identify any recurrence that may require salvage treatment,” he added.

During a presentation at the 2024 National Comprehensive Cancer Network Annual Conference, Dr. Willett primarily discussed the following three strategies for deintensifying overall therapy for locally advanced rectal cancer:

• Selective surgical omission for patients with rectal cancer having a complete clinical response after TNT with close surveillance following treatment.
• Selective omission of radiation therapy for patients with surgery such as sphincter-sparing surgery.
• Selective omission of all treatment modalities (radiation therapy, chemotherapy and surgery). 

Does Watch and Wait Work?

Selective surgical omission, also known as a “watch and wait” or nonoperative management (NOM), involves treating patients with chemotherapy or a combination of chemo and radiation therapy but without surgery, Dr. Willett said during his presentation at the meeting.

Data from the OPRA trial published in the Journal of Clinical Oncology showed that 36% of patients who started on NOM developed tumor regrowth, most of which occurred in the first 2-3 years. Five-year disease-free survival rates were similar in patients who had total mesorectal excision (TME) upfront and those who had salvage TME procedures after tumor regrowth (61% and 62%, respectively). An update to the OPRA trial showed that the clinical outcomes persisted, and the results suggest no significant differences in disease-free survival between upfront surgery vs. watch and wait, Dr. Willett said.
 

Does Selective Omission of Radiotherapy Work?

Selective omission of radiotherapy is another option for reducing the overall treatment burden in patients with locally advanced rectal cancer, Dr. Willett. For these patients, who are at relatively low risk for recurrence, radiation along with surgery may not be needed.

Data from the FOWARC trial, published in the Journal of Clinical Oncology in 2016 and 2019, included 495 patients from 15 centers in China. In the randomized trial, the researchers found no significant difference in the primary outcome of disease-free survival between patients assigned in a 1:1:1 ratio to three arms:

• FOLFOX chemotherapy alone (a combination of chemotherapy drugs including folinic acid, fluorouracil, and oxaliplatin).
• FOLFOX plus chemoradiation.
• FU (fluorouracil)/LV (leucovorin calcium) plus chemoradiation.

Although the data were ultimately inconclusive because of potential staging bias, the findings were “promising for recommending radiation omission in these patients,” Dr. Willett said.

The larger PROSPECT study published in The New England Journal of Medicine in 2023 was similarly encouraging, he said. In this trial, 1194 patients with locally advanced rectal cancer were randomized to FOLFOX or chemoradiation prior to sphincter-sparing surgery. The two groups showed similar 5-year estimated overall survival, complete resection (R0), and pathological complete response.

“These further data support the idea that we don’t need radiotherapy anymore,” Dr. Willett said.

PROSPECT was “a very well-done trial” that also showed important patient reported outcomes, he said. At 12 months after surgery, patients in the chemoradiation group had higher scores on fatigue and neuropathy measures, but less than 15% were severe. Sexual function scores for men and women were worse in the chemoradiation group, although overall health-related quality-of-life scores were not significantly different between the groups, he noted.
 

Does Dropping Everything But Immunotherapy Work?

Research is very preliminary, but a small study of 12 patients with mismatch repair-deficit (MMRd) locally advanced rectal cancer published in The New England Journal of Medicine “lends optimism” to a personalized treatment approach via a programmed death 1 (PD-1) blockade, Dr. Willett said. The “small, but impressive numbers” showed that all 12 patients treated with dostarlimab only (an anti-PD-1 monoclonal antibody) had durable disease control at a follow-up of 6-24 months.

This option is feasible for patients with MMRd locally advanced rectal cancer, Dr. Willett said in an interview. “Patients treated with only dostarlimab (a PD-1 inhibitor) had excellent outcomes and did not require radiation therapy, chemotherapy, and surgery. This is potentially a new paradigm of treatment for MMRd rectal cancer.”

What are the Clinical Implications and Next Steps?

Patients should be carefully evaluated and selected for treatment approaches by experienced multidisciplinary teams with vigilant posttreatment surveillance, including history and physical exam, endoscopy, computed tomography (CT) of the chest, and abdomen and pelvic magnetic resonance imaging (MRI), Dr. Willett said in the interview.

Data on the treatment of patients with MMRd rectal cancer using dostarlimab and other immune checkpoint inhibitors are preliminary; more patients and further follow-up are required, he said. This treatment is applicable to only 5%-10% of patients with rectal cancer, he continued.

“There is a need for biomarkers such as circulating tumor DNA to further aid in selection and monitoring of patients with rectal cancer,” Dr. Willett said.

Other preliminary research is examining circulating tumor DNA analysis to guide adjuvant treatment for patients with resected stage II colon cancer, he noted in his presentation. Currently, ctDNA-driven therapy is not recommended by the NCCN, but more research is needed to determine whether this strategy might be applied to decision-making in rectal cancer patients, especially with watch and wait/nonoperative strategies, he said.
 

What Are the Takeaways for Deintensifying Treatment of Rectal Cancer?

The global continuum of rectal cancer clinical trials has provided significant evidence that, for select patients, the deintensification of treatment strategies may result in the avoidance of radiation and even avoidance of surgery, which can profoundly improve long-term quality of life, Al B. Benson III, MD, said in an interview.

“A critical takeaway message for clinicians who are determining which individual patient might benefit from a less intensive regimen to treat locally advanced rectal cancer is to first have a multidisciplinary consensus which should encompass review of a rectal MRI, pathology, chest and abdominal imaging, colonoscopy, as well as the patient’s clinical status including comorbidities,” said Dr. Benson, who served as chair of the NCCN Guidelines Panel for Colon/Rectal/Anal Cancers and Small Intestine Adenocarcinoma.

“The location of the rectal tumor (distal versus proximal) and clinical TNM stage also will inform the discussion as to which of the potential total neoadjuvant therapy regimens would be most optimal to reduce the risk of local recurrence and maintain long-term quality of life for the individual patient,” explained Dr. Benson, professor of medicine at Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago.

The effectiveness of less intense treatment for rectal cancer remains a work in progress, Dr. Benson said in an interview. “There is much we still do not know, such as the optimal selection of patients and the durability of this approach over time.”

Patients who undergo watch and wait require intensive follow-up, including sigmoidoscopy, digital rectal exam, and rectal MRI, to detect any evidence of local recurrence that would warrant further intervention, including possible radiation and surgery, he said. A highly skilled multidisciplinary team is a must for individuals who are potential candidates for a less intense treatment regimen, he emphasized.  

The treatment of locally advanced rectal cancer continues to evolve, but there is no question that TNT has transformed patient outcomes, including the ability to deintensify treatment for select patients, Dr. Benson said. 

However, many research gaps remain, Dr. Benson said in an interview. “For the MSI/dMMR patient who has achieved a complete response from immunotherapy we will need more long-term data to determine the durability of a complete clinical response and long-term avoidance of other interventions including radiation, chemotherapy and surgery.

“The wait and watch strategy for the much more common MSS patient also will require much longer follow-up to determine which patients are destined to recur and which are not,” he added.

“The introduction of monitoring with ctDNA determination over time offers an opportunity to streamline surveillance of patients who have completed combination therapy and for those undergoing watch and wait; however, much more information is required to determine which of the various ctDNA assays are most optimal, and the frequency and duration of ctDNA determination that will lend this approach as a standard of care,” Dr. Benson said.

Dr. Willett and Dr. Benson had no financial conflicts to disclose.

New and evolving research in locally advanced rectal cancer suggests that selective use of treatments in some patients can achieve outcomes similar to those of standard regimens, according to the chair of the Department of Radiation Oncology at Duke University School of Medicine, Durham, North Carolina.

Total neoadjuvant therapy (TNT) is the standard treatment that involves systemic chemotherapy and radiation therapy before surgery for patients with locally advanced rectal cancer, Christopher G. Willett, MD, explained, in an interview. However, recent clinical trials support several strategies for “deintensification” of TNT for patients with locally advanced rectal cancer, he said.

Some patients may not require surgery or radiation therapy, or they may not require any treatment modalities including radiation therapy, chemotherapy, and surgery, Dr. Willett continued.

However, “these patients require close surveillance post treatment to identify any recurrence that may require salvage treatment,” he added.

During a presentation at the 2024 National Comprehensive Cancer Network Annual Conference, Dr. Willett primarily discussed the following three strategies for deintensifying overall therapy for locally advanced rectal cancer:

• Selective surgical omission for patients with rectal cancer having a complete clinical response after TNT with close surveillance following treatment.
• Selective omission of radiation therapy for patients with surgery such as sphincter-sparing surgery.
• Selective omission of all treatment modalities (radiation therapy, chemotherapy and surgery). 

Does Watch and Wait Work?

Selective surgical omission, also known as a “watch and wait” or nonoperative management (NOM), involves treating patients with chemotherapy or a combination of chemo and radiation therapy but without surgery, Dr. Willett said during his presentation at the meeting.

Data from the OPRA trial published in the Journal of Clinical Oncology showed that 36% of patients who started on NOM developed tumor regrowth, most of which occurred in the first 2-3 years. Five-year disease-free survival rates were similar in patients who had total mesorectal excision (TME) upfront and those who had salvage TME procedures after tumor regrowth (61% and 62%, respectively). An update to the OPRA trial showed that the clinical outcomes persisted, and the results suggest no significant differences in disease-free survival between upfront surgery vs. watch and wait, Dr. Willett said.
 

Does Selective Omission of Radiotherapy Work?

Selective omission of radiotherapy is another option for reducing the overall treatment burden in patients with locally advanced rectal cancer, Dr. Willett. For these patients, who are at relatively low risk for recurrence, radiation along with surgery may not be needed.

Data from the FOWARC trial, published in the Journal of Clinical Oncology in 2016 and 2019, included 495 patients from 15 centers in China. In the randomized trial, the researchers found no significant difference in the primary outcome of disease-free survival between patients assigned in a 1:1:1 ratio to three arms:

• FOLFOX chemotherapy alone (a combination of chemotherapy drugs including folinic acid, fluorouracil, and oxaliplatin).
• FOLFOX plus chemoradiation.
• FU (fluorouracil)/LV (leucovorin calcium) plus chemoradiation.

Although the data were ultimately inconclusive because of potential staging bias, the findings were “promising for recommending radiation omission in these patients,” Dr. Willett said.

The larger PROSPECT study published in The New England Journal of Medicine in 2023 was similarly encouraging, he said. In this trial, 1194 patients with locally advanced rectal cancer were randomized to FOLFOX or chemoradiation prior to sphincter-sparing surgery. The two groups showed similar 5-year estimated overall survival, complete resection (R0), and pathological complete response.

“These further data support the idea that we don’t need radiotherapy anymore,” Dr. Willett said.

PROSPECT was “a very well-done trial” that also showed important patient reported outcomes, he said. At 12 months after surgery, patients in the chemoradiation group had higher scores on fatigue and neuropathy measures, but less than 15% were severe. Sexual function scores for men and women were worse in the chemoradiation group, although overall health-related quality-of-life scores were not significantly different between the groups, he noted.
 

Does Dropping Everything But Immunotherapy Work?

Research is very preliminary, but a small study of 12 patients with mismatch repair-deficit (MMRd) locally advanced rectal cancer published in The New England Journal of Medicine “lends optimism” to a personalized treatment approach via a programmed death 1 (PD-1) blockade, Dr. Willett said. The “small, but impressive numbers” showed that all 12 patients treated with dostarlimab only (an anti-PD-1 monoclonal antibody) had durable disease control at a follow-up of 6-24 months.

This option is feasible for patients with MMRd locally advanced rectal cancer, Dr. Willett said in an interview. “Patients treated with only dostarlimab (a PD-1 inhibitor) had excellent outcomes and did not require radiation therapy, chemotherapy, and surgery. This is potentially a new paradigm of treatment for MMRd rectal cancer.”

What are the Clinical Implications and Next Steps?

Patients should be carefully evaluated and selected for treatment approaches by experienced multidisciplinary teams with vigilant posttreatment surveillance, including history and physical exam, endoscopy, computed tomography (CT) of the chest, and abdomen and pelvic magnetic resonance imaging (MRI), Dr. Willett said in the interview.

Data on the treatment of patients with MMRd rectal cancer using dostarlimab and other immune checkpoint inhibitors are preliminary; more patients and further follow-up are required, he said. This treatment is applicable to only 5%-10% of patients with rectal cancer, he continued.

“There is a need for biomarkers such as circulating tumor DNA to further aid in selection and monitoring of patients with rectal cancer,” Dr. Willett said.

Other preliminary research is examining circulating tumor DNA analysis to guide adjuvant treatment for patients with resected stage II colon cancer, he noted in his presentation. Currently, ctDNA-driven therapy is not recommended by the NCCN, but more research is needed to determine whether this strategy might be applied to decision-making in rectal cancer patients, especially with watch and wait/nonoperative strategies, he said.
 

What Are the Takeaways for Deintensifying Treatment of Rectal Cancer?

The global continuum of rectal cancer clinical trials has provided significant evidence that, for select patients, the deintensification of treatment strategies may result in the avoidance of radiation and even avoidance of surgery, which can profoundly improve long-term quality of life, Al B. Benson III, MD, said in an interview.

“A critical takeaway message for clinicians who are determining which individual patient might benefit from a less intensive regimen to treat locally advanced rectal cancer is to first have a multidisciplinary consensus which should encompass review of a rectal MRI, pathology, chest and abdominal imaging, colonoscopy, as well as the patient’s clinical status including comorbidities,” said Dr. Benson, who served as chair of the NCCN Guidelines Panel for Colon/Rectal/Anal Cancers and Small Intestine Adenocarcinoma.

“The location of the rectal tumor (distal versus proximal) and clinical TNM stage also will inform the discussion as to which of the potential total neoadjuvant therapy regimens would be most optimal to reduce the risk of local recurrence and maintain long-term quality of life for the individual patient,” explained Dr. Benson, professor of medicine at Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago.

The effectiveness of less intense treatment for rectal cancer remains a work in progress, Dr. Benson said in an interview. “There is much we still do not know, such as the optimal selection of patients and the durability of this approach over time.”

Patients who undergo watch and wait require intensive follow-up, including sigmoidoscopy, digital rectal exam, and rectal MRI, to detect any evidence of local recurrence that would warrant further intervention, including possible radiation and surgery, he said. A highly skilled multidisciplinary team is a must for individuals who are potential candidates for a less intense treatment regimen, he emphasized.  

The treatment of locally advanced rectal cancer continues to evolve, but there is no question that TNT has transformed patient outcomes, including the ability to deintensify treatment for select patients, Dr. Benson said. 

However, many research gaps remain, Dr. Benson said in an interview. “For the MSI/dMMR patient who has achieved a complete response from immunotherapy we will need more long-term data to determine the durability of a complete clinical response and long-term avoidance of other interventions including radiation, chemotherapy and surgery.

“The wait and watch strategy for the much more common MSS patient also will require much longer follow-up to determine which patients are destined to recur and which are not,” he added.

“The introduction of monitoring with ctDNA determination over time offers an opportunity to streamline surveillance of patients who have completed combination therapy and for those undergoing watch and wait; however, much more information is required to determine which of the various ctDNA assays are most optimal, and the frequency and duration of ctDNA determination that will lend this approach as a standard of care,” Dr. Benson said.

Dr. Willett and Dr. Benson had no financial conflicts to disclose.

New and evolving research in locally advanced rectal cancer suggests that selective use of treatments in some patients can achieve outcomes similar to those of standard regimens, according to the chair of the Department of Radiation Oncology at Duke University School of Medicine, Durham, North Carolina.

Total neoadjuvant therapy (TNT) is the standard treatment that involves systemic chemotherapy and radiation therapy before surgery for patients with locally advanced rectal cancer, Christopher G. Willett, MD, explained, in an interview. However, recent clinical trials support several strategies for “deintensification” of TNT for patients with locally advanced rectal cancer, he said.

Some patients may not require surgery or radiation therapy, or they may not require any treatment modalities including radiation therapy, chemotherapy, and surgery, Dr. Willett continued.

However, “these patients require close surveillance post treatment to identify any recurrence that may require salvage treatment,” he added.

During a presentation at the 2024 National Comprehensive Cancer Network Annual Conference, Dr. Willett primarily discussed the following three strategies for deintensifying overall therapy for locally advanced rectal cancer:

• Selective surgical omission for patients with rectal cancer having a complete clinical response after TNT with close surveillance following treatment.
• Selective omission of radiation therapy for patients with surgery such as sphincter-sparing surgery.
• Selective omission of all treatment modalities (radiation therapy, chemotherapy and surgery). 

Does Watch and Wait Work?

Selective surgical omission, also known as a “watch and wait” or nonoperative management (NOM), involves treating patients with chemotherapy or a combination of chemo and radiation therapy but without surgery, Dr. Willett said during his presentation at the meeting.

Data from the OPRA trial published in the Journal of Clinical Oncology showed that 36% of patients who started on NOM developed tumor regrowth, most of which occurred in the first 2-3 years. Five-year disease-free survival rates were similar in patients who had total mesorectal excision (TME) upfront and those who had salvage TME procedures after tumor regrowth (61% and 62%, respectively). An update to the OPRA trial showed that the clinical outcomes persisted, and the results suggest no significant differences in disease-free survival between upfront surgery vs. watch and wait, Dr. Willett said.
 

Does Selective Omission of Radiotherapy Work?

Selective omission of radiotherapy is another option for reducing the overall treatment burden in patients with locally advanced rectal cancer, Dr. Willett. For these patients, who are at relatively low risk for recurrence, radiation along with surgery may not be needed.

Data from the FOWARC trial, published in the Journal of Clinical Oncology in 2016 and 2019, included 495 patients from 15 centers in China. In the randomized trial, the researchers found no significant difference in the primary outcome of disease-free survival between patients assigned in a 1:1:1 ratio to three arms:

• FOLFOX chemotherapy alone (a combination of chemotherapy drugs including folinic acid, fluorouracil, and oxaliplatin).
• FOLFOX plus chemoradiation.
• FU (fluorouracil)/LV (leucovorin calcium) plus chemoradiation.

Although the data were ultimately inconclusive because of potential staging bias, the findings were “promising for recommending radiation omission in these patients,” Dr. Willett said.

The larger PROSPECT study published in The New England Journal of Medicine in 2023 was similarly encouraging, he said. In this trial, 1194 patients with locally advanced rectal cancer were randomized to FOLFOX or chemoradiation prior to sphincter-sparing surgery. The two groups showed similar 5-year estimated overall survival, complete resection (R0), and pathological complete response.

“These further data support the idea that we don’t need radiotherapy anymore,” Dr. Willett said.

PROSPECT was “a very well-done trial” that also showed important patient reported outcomes, he said. At 12 months after surgery, patients in the chemoradiation group had higher scores on fatigue and neuropathy measures, but less than 15% were severe. Sexual function scores for men and women were worse in the chemoradiation group, although overall health-related quality-of-life scores were not significantly different between the groups, he noted.
 

Does Dropping Everything But Immunotherapy Work?

Research is very preliminary, but a small study of 12 patients with mismatch repair-deficit (MMRd) locally advanced rectal cancer published in The New England Journal of Medicine “lends optimism” to a personalized treatment approach via a programmed death 1 (PD-1) blockade, Dr. Willett said. The “small, but impressive numbers” showed that all 12 patients treated with dostarlimab only (an anti-PD-1 monoclonal antibody) had durable disease control at a follow-up of 6-24 months.

This option is feasible for patients with MMRd locally advanced rectal cancer, Dr. Willett said in an interview. “Patients treated with only dostarlimab (a PD-1 inhibitor) had excellent outcomes and did not require radiation therapy, chemotherapy, and surgery. This is potentially a new paradigm of treatment for MMRd rectal cancer.”

What are the Clinical Implications and Next Steps?

Patients should be carefully evaluated and selected for treatment approaches by experienced multidisciplinary teams with vigilant posttreatment surveillance, including history and physical exam, endoscopy, computed tomography (CT) of the chest, and abdomen and pelvic magnetic resonance imaging (MRI), Dr. Willett said in the interview.

Data on the treatment of patients with MMRd rectal cancer using dostarlimab and other immune checkpoint inhibitors are preliminary; more patients and further follow-up are required, he said. This treatment is applicable to only 5%-10% of patients with rectal cancer, he continued.

“There is a need for biomarkers such as circulating tumor DNA to further aid in selection and monitoring of patients with rectal cancer,” Dr. Willett said.

Other preliminary research is examining circulating tumor DNA analysis to guide adjuvant treatment for patients with resected stage II colon cancer, he noted in his presentation. Currently, ctDNA-driven therapy is not recommended by the NCCN, but more research is needed to determine whether this strategy might be applied to decision-making in rectal cancer patients, especially with watch and wait/nonoperative strategies, he said.
 

What Are the Takeaways for Deintensifying Treatment of Rectal Cancer?

The global continuum of rectal cancer clinical trials has provided significant evidence that, for select patients, the deintensification of treatment strategies may result in the avoidance of radiation and even avoidance of surgery, which can profoundly improve long-term quality of life, Al B. Benson III, MD, said in an interview.

“A critical takeaway message for clinicians who are determining which individual patient might benefit from a less intensive regimen to treat locally advanced rectal cancer is to first have a multidisciplinary consensus which should encompass review of a rectal MRI, pathology, chest and abdominal imaging, colonoscopy, as well as the patient’s clinical status including comorbidities,” said Dr. Benson, who served as chair of the NCCN Guidelines Panel for Colon/Rectal/Anal Cancers and Small Intestine Adenocarcinoma.

“The location of the rectal tumor (distal versus proximal) and clinical TNM stage also will inform the discussion as to which of the potential total neoadjuvant therapy regimens would be most optimal to reduce the risk of local recurrence and maintain long-term quality of life for the individual patient,” explained Dr. Benson, professor of medicine at Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago.

The effectiveness of less intense treatment for rectal cancer remains a work in progress, Dr. Benson said in an interview. “There is much we still do not know, such as the optimal selection of patients and the durability of this approach over time.”

Patients who undergo watch and wait require intensive follow-up, including sigmoidoscopy, digital rectal exam, and rectal MRI, to detect any evidence of local recurrence that would warrant further intervention, including possible radiation and surgery, he said. A highly skilled multidisciplinary team is a must for individuals who are potential candidates for a less intense treatment regimen, he emphasized.  

The treatment of locally advanced rectal cancer continues to evolve, but there is no question that TNT has transformed patient outcomes, including the ability to deintensify treatment for select patients, Dr. Benson said. 

However, many research gaps remain, Dr. Benson said in an interview. “For the MSI/dMMR patient who has achieved a complete response from immunotherapy we will need more long-term data to determine the durability of a complete clinical response and long-term avoidance of other interventions including radiation, chemotherapy and surgery.

“The wait and watch strategy for the much more common MSS patient also will require much longer follow-up to determine which patients are destined to recur and which are not,” he added.

“The introduction of monitoring with ctDNA determination over time offers an opportunity to streamline surveillance of patients who have completed combination therapy and for those undergoing watch and wait; however, much more information is required to determine which of the various ctDNA assays are most optimal, and the frequency and duration of ctDNA determination that will lend this approach as a standard of care,” Dr. Benson said.

Dr. Willett and Dr. Benson had no financial conflicts to disclose.

The US Food and Drug Administration (FDA) has approved the first-in-class interleukin (IL)-15 superagonist nogapendekin alfa inbakicept-pmln (Anktiva), plus bacillus Calmette-Guérin (BCG), for the treatment of certain non–muscle-invasive bladder cancers that fail to respond to BCG alone.

Specifically, the agent is approved to treat patients with BCG-unresponsive non–muscle-invasive bladder cancer carcinoma in situ with or without Ta or T1 papillary disease. 

The FDA declined an initial approval for the combination in May 2023 because of deficiencies the agency observed during its prelicense inspection of third-party manufacturing organizations. In October 2023, ImmunityBio resubmitted the Biologics License Application, which was accepted.

The new therapy represents addresses “an unmet need” in this high-risk bladder cancer population, the company stated in a press release announcing the initial study findings. Typically, patients with intermediate or high-risk disease undergo bladder tumor resection followed by treatment with BCG, but the cancer recurs in up to 50% of patients, including those who experience a complete response, explained ImmunityBio, which acquired Altor BioScience. 

Approval was based on findings from the single arm, phase 2/3 open-label QUILT-3.032 study, which included 77 patients with BCG-unresponsive, high-risk disease following transurethral resection. All had Eastern Cooperative Oncology Group performance status of 0-2. 

Patients received nogapendekin alfa inbakicept-pmln induction via intravesical instillation with BCG followed by maintenance therapy for up to 37 months. 

According to the FDA’s press release, 62% of patients had a complete response, defined as a negative cystoscopy and urine cytology; 58% of those with a complete response had a duration of response lasting at least 12 months and 40% had a duration of response lasting 24 months or longer.

The safety of the combination was evaluated in a cohort of 88 patients. Serious adverse reactions occurred in 16% of patients. The most common treatment-emergent adverse effects included dysuria, pollakiuria, and hematuria, which are associated with intravesical BCG; 86% of these events were grade 1 or 2. Overall, 7% of patients discontinued the combination owing to adverse reactions.

The recommended dose is 400 mcg administered intravesically with BCG once a week for 6 weeks as induction therapy, with an option for a second induction course if patients don’t achieve a complete response at 3 months. The recommended maintenance therapy dose is 400 mcg with BCG once a week for 3 weeks at months 4, 7, 10, 13, and 19. Patients who achieve a complete response at 25 months and beyond may receive maintenance instillations with BCG once a week for 3 weeks at months 25, 31, and 37. The maximum treatment duration is 37 months.

The FDA recommends discontinuing treatment if disease persists after second induction or owing to disease recurrence, progression, or unacceptable toxicity. 
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the first-in-class interleukin (IL)-15 superagonist nogapendekin alfa inbakicept-pmln (Anktiva), plus bacillus Calmette-Guérin (BCG), for the treatment of certain non–muscle-invasive bladder cancers that fail to respond to BCG alone.

Specifically, the agent is approved to treat patients with BCG-unresponsive non–muscle-invasive bladder cancer carcinoma in situ with or without Ta or T1 papillary disease. 

The FDA declined an initial approval for the combination in May 2023 because of deficiencies the agency observed during its prelicense inspection of third-party manufacturing organizations. In October 2023, ImmunityBio resubmitted the Biologics License Application, which was accepted.

The new therapy represents addresses “an unmet need” in this high-risk bladder cancer population, the company stated in a press release announcing the initial study findings. Typically, patients with intermediate or high-risk disease undergo bladder tumor resection followed by treatment with BCG, but the cancer recurs in up to 50% of patients, including those who experience a complete response, explained ImmunityBio, which acquired Altor BioScience. 

Approval was based on findings from the single arm, phase 2/3 open-label QUILT-3.032 study, which included 77 patients with BCG-unresponsive, high-risk disease following transurethral resection. All had Eastern Cooperative Oncology Group performance status of 0-2. 

Patients received nogapendekin alfa inbakicept-pmln induction via intravesical instillation with BCG followed by maintenance therapy for up to 37 months. 

According to the FDA’s press release, 62% of patients had a complete response, defined as a negative cystoscopy and urine cytology; 58% of those with a complete response had a duration of response lasting at least 12 months and 40% had a duration of response lasting 24 months or longer.

The safety of the combination was evaluated in a cohort of 88 patients. Serious adverse reactions occurred in 16% of patients. The most common treatment-emergent adverse effects included dysuria, pollakiuria, and hematuria, which are associated with intravesical BCG; 86% of these events were grade 1 or 2. Overall, 7% of patients discontinued the combination owing to adverse reactions.

The recommended dose is 400 mcg administered intravesically with BCG once a week for 6 weeks as induction therapy, with an option for a second induction course if patients don’t achieve a complete response at 3 months. The recommended maintenance therapy dose is 400 mcg with BCG once a week for 3 weeks at months 4, 7, 10, 13, and 19. Patients who achieve a complete response at 25 months and beyond may receive maintenance instillations with BCG once a week for 3 weeks at months 25, 31, and 37. The maximum treatment duration is 37 months.

The FDA recommends discontinuing treatment if disease persists after second induction or owing to disease recurrence, progression, or unacceptable toxicity. 
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the first-in-class interleukin (IL)-15 superagonist nogapendekin alfa inbakicept-pmln (Anktiva), plus bacillus Calmette-Guérin (BCG), for the treatment of certain non–muscle-invasive bladder cancers that fail to respond to BCG alone.

Specifically, the agent is approved to treat patients with BCG-unresponsive non–muscle-invasive bladder cancer carcinoma in situ with or without Ta or T1 papillary disease. 

The FDA declined an initial approval for the combination in May 2023 because of deficiencies the agency observed during its prelicense inspection of third-party manufacturing organizations. In October 2023, ImmunityBio resubmitted the Biologics License Application, which was accepted.

The new therapy represents addresses “an unmet need” in this high-risk bladder cancer population, the company stated in a press release announcing the initial study findings. Typically, patients with intermediate or high-risk disease undergo bladder tumor resection followed by treatment with BCG, but the cancer recurs in up to 50% of patients, including those who experience a complete response, explained ImmunityBio, which acquired Altor BioScience. 

Approval was based on findings from the single arm, phase 2/3 open-label QUILT-3.032 study, which included 77 patients with BCG-unresponsive, high-risk disease following transurethral resection. All had Eastern Cooperative Oncology Group performance status of 0-2. 

Patients received nogapendekin alfa inbakicept-pmln induction via intravesical instillation with BCG followed by maintenance therapy for up to 37 months. 

According to the FDA’s press release, 62% of patients had a complete response, defined as a negative cystoscopy and urine cytology; 58% of those with a complete response had a duration of response lasting at least 12 months and 40% had a duration of response lasting 24 months or longer.

The safety of the combination was evaluated in a cohort of 88 patients. Serious adverse reactions occurred in 16% of patients. The most common treatment-emergent adverse effects included dysuria, pollakiuria, and hematuria, which are associated with intravesical BCG; 86% of these events were grade 1 or 2. Overall, 7% of patients discontinued the combination owing to adverse reactions.

The recommended dose is 400 mcg administered intravesically with BCG once a week for 6 weeks as induction therapy, with an option for a second induction course if patients don’t achieve a complete response at 3 months. The recommended maintenance therapy dose is 400 mcg with BCG once a week for 3 weeks at months 4, 7, 10, 13, and 19. Patients who achieve a complete response at 25 months and beyond may receive maintenance instillations with BCG once a week for 3 weeks at months 25, 31, and 37. The maximum treatment duration is 37 months.

The FDA recommends discontinuing treatment if disease persists after second induction or owing to disease recurrence, progression, or unacceptable toxicity. 
 

A version of this article appeared on Medscape.com.

TOPLINE:

A new three-phase screening protocol that incorporates a PSA test, a four-kallikrein panel, and an MRI scan appears to improve the prostate cancer detection rate among men invited to participate in a single screening compared with those not invited, according to preliminary findings from the Finnish ProScreen randomized clinical trial.

METHODOLOGY:

• Prostate-specific antigen (PSA) screening is currently recommended for men in the United States starting at age 55. However, the test is controversial, in large part because it often detects prostate cancer that is not clinically relevant and may lead to overtreatment of men with low-grade disease.
• The current ProScreen trial assessed a screening intervention that aims to reduce unnecessary diagnoses of prostate cancer but still catch relevant cancers and reduce prostate cancer mortality.
• The researchers randomized 60,745 eligible men aged 50-63 years to be invited to a three-phase screening intervention (n = 15,201) or to be part of a control group that was not invited to screen (n = 45,544).
• The screening group who agreed to participate (n = 7744) first underwent a PSA test. Those with a PSA of ≥ 3.0 ng/mL then underwent a four-kallikrein panel to identify high-grade prostate cancer. Those with a kallikrein panel risk score of 7.5% or higher underwent an MRI of the prostate gland.
• Targeted biopsies were performed in those with abnormal prostate gland findings on MRI. Most patients with a negative MRI were not recommended for systematic biopsy unless they had a PSA density of ≥ 0.15 ng/mL.

TAKEAWAY:

• Among the 7744 invited men who agreed to the three-phase screening protocol (51%), ultimately 209 (2.7% of all screened participants) had a targeted transrectal prostate biopsy. Overall, 136 of the biopsies (65%) detected cancer — 32 low-grade and 128 high-grade prostate cancers, for cumulative incidence rates of 0.41% and 1.65%, respectively.
• Over a 3.2-year median follow-up among the 7457 invited men who refused screening, seven low-grade and 44 high-grade prostate cancers were detected (cumulative incidence rates, 0.1% and 0.6%, respectively).
• Among the entire invited screening group, 39 low-grade (cumulative incidence, 0.26%) and 172 high-grade prostate cancers (cumulative incidence, 1.13%) were detected.
• Among men in the control group, 65 low-grade prostate cancers were ultimately identified and 282 high-grade. The risk difference between the invited screening group and control group was 0.11% for low-grade disease and 0.51% for high-grade disease. Compared with the control group, the intervention led to the detection of one additional low-grade prostate cancer per 909 men invited to screen and one additional high-grade prostate cancer per 196 men invited.

IN PRACTICE:

The three-phase screening approach used in this study detected additional cancers, compared with a control group not invited for screening, but “these results are descriptive and should be interpreted provisionally pending results from the trial on the primary outcomes of prostate cancer mortality,” the investigators said.

SOURCE:

This study was conducted by the ProScreen Trial Investigators, including first author Anssi Auvinen, MD, PhD, of Tampere University, Tampere, Finland, and was published online in JAMAalongside an accompanying editorial.

LIMITATIONS:

Absolute differences between the two randomized groups in this study were small and had unclear clinical importance. Prior screening was reported by several participants and may have reduced cancer detection. The results are based on a single invitation for screening, meaning some high-grade cancers were likely missed; subsequent screening invitations may identify missed cancers. No data were available on cancers missed at screening, and interval cancer incidence is needed to assess sensitivity of the screening protocol used in the study.

DISCLOSURES:

The ProScreen trial is funded by grants from the Academy of Finland, the Finnish Cancer Foundation, the Jane and Aatos Erkko Foundation, the Finland State Research Funding, Helsinki University Hospital, the Sigrid Jusélius Foundation, and the Päivikki and Sakari Sohlberg Foundation. Dr. Auvinen reported having no disclosures. Multiple co-authors reported associations outside the submitted work. The full list of author disclosures is included with the full text of the article.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A new three-phase screening protocol that incorporates a PSA test, a four-kallikrein panel, and an MRI scan appears to improve the prostate cancer detection rate among men invited to participate in a single screening compared with those not invited, according to preliminary findings from the Finnish ProScreen randomized clinical trial.

METHODOLOGY:

• Prostate-specific antigen (PSA) screening is currently recommended for men in the United States starting at age 55. However, the test is controversial, in large part because it often detects prostate cancer that is not clinically relevant and may lead to overtreatment of men with low-grade disease.
• The current ProScreen trial assessed a screening intervention that aims to reduce unnecessary diagnoses of prostate cancer but still catch relevant cancers and reduce prostate cancer mortality.
• The researchers randomized 60,745 eligible men aged 50-63 years to be invited to a three-phase screening intervention (n = 15,201) or to be part of a control group that was not invited to screen (n = 45,544).
• The screening group who agreed to participate (n = 7744) first underwent a PSA test. Those with a PSA of ≥ 3.0 ng/mL then underwent a four-kallikrein panel to identify high-grade prostate cancer. Those with a kallikrein panel risk score of 7.5% or higher underwent an MRI of the prostate gland.
• Targeted biopsies were performed in those with abnormal prostate gland findings on MRI. Most patients with a negative MRI were not recommended for systematic biopsy unless they had a PSA density of ≥ 0.15 ng/mL.

TAKEAWAY:

• Among the 7744 invited men who agreed to the three-phase screening protocol (51%), ultimately 209 (2.7% of all screened participants) had a targeted transrectal prostate biopsy. Overall, 136 of the biopsies (65%) detected cancer — 32 low-grade and 128 high-grade prostate cancers, for cumulative incidence rates of 0.41% and 1.65%, respectively.
• Over a 3.2-year median follow-up among the 7457 invited men who refused screening, seven low-grade and 44 high-grade prostate cancers were detected (cumulative incidence rates, 0.1% and 0.6%, respectively).
• Among the entire invited screening group, 39 low-grade (cumulative incidence, 0.26%) and 172 high-grade prostate cancers (cumulative incidence, 1.13%) were detected.
• Among men in the control group, 65 low-grade prostate cancers were ultimately identified and 282 high-grade. The risk difference between the invited screening group and control group was 0.11% for low-grade disease and 0.51% for high-grade disease. Compared with the control group, the intervention led to the detection of one additional low-grade prostate cancer per 909 men invited to screen and one additional high-grade prostate cancer per 196 men invited.

IN PRACTICE:

The three-phase screening approach used in this study detected additional cancers, compared with a control group not invited for screening, but “these results are descriptive and should be interpreted provisionally pending results from the trial on the primary outcomes of prostate cancer mortality,” the investigators said.

SOURCE:

This study was conducted by the ProScreen Trial Investigators, including first author Anssi Auvinen, MD, PhD, of Tampere University, Tampere, Finland, and was published online in JAMAalongside an accompanying editorial.

LIMITATIONS:

Absolute differences between the two randomized groups in this study were small and had unclear clinical importance. Prior screening was reported by several participants and may have reduced cancer detection. The results are based on a single invitation for screening, meaning some high-grade cancers were likely missed; subsequent screening invitations may identify missed cancers. No data were available on cancers missed at screening, and interval cancer incidence is needed to assess sensitivity of the screening protocol used in the study.

DISCLOSURES:

The ProScreen trial is funded by grants from the Academy of Finland, the Finnish Cancer Foundation, the Jane and Aatos Erkko Foundation, the Finland State Research Funding, Helsinki University Hospital, the Sigrid Jusélius Foundation, and the Päivikki and Sakari Sohlberg Foundation. Dr. Auvinen reported having no disclosures. Multiple co-authors reported associations outside the submitted work. The full list of author disclosures is included with the full text of the article.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A new three-phase screening protocol that incorporates a PSA test, a four-kallikrein panel, and an MRI scan appears to improve the prostate cancer detection rate among men invited to participate in a single screening compared with those not invited, according to preliminary findings from the Finnish ProScreen randomized clinical trial.

METHODOLOGY:

• Prostate-specific antigen (PSA) screening is currently recommended for men in the United States starting at age 55. However, the test is controversial, in large part because it often detects prostate cancer that is not clinically relevant and may lead to overtreatment of men with low-grade disease.
• The current ProScreen trial assessed a screening intervention that aims to reduce unnecessary diagnoses of prostate cancer but still catch relevant cancers and reduce prostate cancer mortality.
• The researchers randomized 60,745 eligible men aged 50-63 years to be invited to a three-phase screening intervention (n = 15,201) or to be part of a control group that was not invited to screen (n = 45,544).
• The screening group who agreed to participate (n = 7744) first underwent a PSA test. Those with a PSA of ≥ 3.0 ng/mL then underwent a four-kallikrein panel to identify high-grade prostate cancer. Those with a kallikrein panel risk score of 7.5% or higher underwent an MRI of the prostate gland.
• Targeted biopsies were performed in those with abnormal prostate gland findings on MRI. Most patients with a negative MRI were not recommended for systematic biopsy unless they had a PSA density of ≥ 0.15 ng/mL.

TAKEAWAY:

• Among the 7744 invited men who agreed to the three-phase screening protocol (51%), ultimately 209 (2.7% of all screened participants) had a targeted transrectal prostate biopsy. Overall, 136 of the biopsies (65%) detected cancer — 32 low-grade and 128 high-grade prostate cancers, for cumulative incidence rates of 0.41% and 1.65%, respectively.
• Over a 3.2-year median follow-up among the 7457 invited men who refused screening, seven low-grade and 44 high-grade prostate cancers were detected (cumulative incidence rates, 0.1% and 0.6%, respectively).
• Among the entire invited screening group, 39 low-grade (cumulative incidence, 0.26%) and 172 high-grade prostate cancers (cumulative incidence, 1.13%) were detected.
• Among men in the control group, 65 low-grade prostate cancers were ultimately identified and 282 high-grade. The risk difference between the invited screening group and control group was 0.11% for low-grade disease and 0.51% for high-grade disease. Compared with the control group, the intervention led to the detection of one additional low-grade prostate cancer per 909 men invited to screen and one additional high-grade prostate cancer per 196 men invited.

IN PRACTICE:

The three-phase screening approach used in this study detected additional cancers, compared with a control group not invited for screening, but “these results are descriptive and should be interpreted provisionally pending results from the trial on the primary outcomes of prostate cancer mortality,” the investigators said.

SOURCE:

This study was conducted by the ProScreen Trial Investigators, including first author Anssi Auvinen, MD, PhD, of Tampere University, Tampere, Finland, and was published online in JAMAalongside an accompanying editorial.

LIMITATIONS:

Absolute differences between the two randomized groups in this study were small and had unclear clinical importance. Prior screening was reported by several participants and may have reduced cancer detection. The results are based on a single invitation for screening, meaning some high-grade cancers were likely missed; subsequent screening invitations may identify missed cancers. No data were available on cancers missed at screening, and interval cancer incidence is needed to assess sensitivity of the screening protocol used in the study.

DISCLOSURES:

The ProScreen trial is funded by grants from the Academy of Finland, the Finnish Cancer Foundation, the Jane and Aatos Erkko Foundation, the Finland State Research Funding, Helsinki University Hospital, the Sigrid Jusélius Foundation, and the Päivikki and Sakari Sohlberg Foundation. Dr. Auvinen reported having no disclosures. Multiple co-authors reported associations outside the submitted work. The full list of author disclosures is included with the full text of the article.
 

A version of this article appeared on Medscape.com.

There have been many attempts to use immunotherapy to improve outcomes in pancreatic cancer, but they haven’t worked out.

The trials, however, have focused on adding immune checkpoint inhibitors to chemotherapy in metastatic disease, leaving open the question of whether immunotherapy might have a role in the neoadjuvant setting before surgery.

In the first study to test the hypothesis, Zev A. Wainberg, MD, a gastrointestinal medical oncologist at the University of California Los Angeles, reported promising results at the American Association for Cancer Research annual meeting.

The small, single arm pilot study included 28 patients with borderline resectable pancreatic cancer, meaning that tumors had some degree of vascular involvement. About 20% of pancreatic tumors are borderline resectable, Dr. Wainberg said.

Patients received 480 mg of nivolumab intravenously every 4 weeks plus mFOLFIRINOX chemotherapy (oxaliplatin, irinotecan, leucovorin, and 5-fluorouracil) on days 1 and 15 of the 28-day cycle.

Patients who downstaged to resectable disease after three cycles went on to surgery; if not, treatment continued for another 3 months. The median number of cycles was 5.5, and almost all patients completed at least 3.

Overall, 19 of the 22 patients who proceeded to surgery (86%) had a pathologic response to neoadjuvant treatment with nivolumab: 2 complete responses, 2 near-complete responses, and 15 partial responses.

Among patients receiving surgery, 21 had R0 resections, meaning negative surgical margins with no tumor left behind. This is key because R0 resections predict longer survival, and “every effort should be made to achieve” this outcome, Dr. Wainberg said. The remaining patient had an R1 resection.

Median progression-free survival was 21.9 months among all patients and 27.3 months among the 22 patients who had resections.

Median overall survival was 34.6 months across the entire group and 44 months among those who had surgery. Overall, 82% of patients were alive at 12 months, and 77% were alive at 18 months.

The study outcomes, especially among the surgery cohort, stand in contrast to those observed in patients who receive the current standard neoadjuvant regimen for borderline resectable pancreatic cancer, mFOLFIRINOX alone, with studies finding a median overall survival of 29.8 months.

Adding nivolumab to neoadjuvant treatment also did not increase side effects. More than half of patients had grade 3 or worse adverse events, but they were all related to mFOLFIRINOX. There were no significant surgical complications, including no grade 2 or higher fistulas.

“We are very pleased” with the outcomes, Dr. Wainberg said. “We need to be studying [immune checkpoint inhibitors] earlier on in both borderline and locally advanced disease. Pancreatic cancer needs all the help it can get to engage immunity.”

Moderator Alice Ho, MD, a radiation oncologist at Duke University in Durham, North Carolina, called the R0 resection rate “stunning” in a “field that very much needs improvements and advancements.”

Dr. Ho also noted that the trial raises “a lot of interesting questions.”

For instance, why exactly is the addition of nivolumab seemingly improving outcomes?

The combination neoadjuvant therapy appeared to increase tertiary lymphoid structures, plasma cells, and CD4+ T cells — all indications that immunotherapy is having a positive impact — but the treatment also seemed to upregulate pathways for adenosine, an immunosuppressant associated with worse responses to checkpoint blockade.

A larger study is already in the works. In addition to a PD-1 blocker and mFOLFIRINOX, patients will receive a CD73 inhibitor to block adenosine production, Dr. Wainberg said.

Bristol Myers Squibb (BMS) provided the nivolumab used in the study. Dr. Wainberg is a consultant for and reported research funding from BMS and other companies. Dr. Ho had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

There have been many attempts to use immunotherapy to improve outcomes in pancreatic cancer, but they haven’t worked out.

The trials, however, have focused on adding immune checkpoint inhibitors to chemotherapy in metastatic disease, leaving open the question of whether immunotherapy might have a role in the neoadjuvant setting before surgery.

In the first study to test the hypothesis, Zev A. Wainberg, MD, a gastrointestinal medical oncologist at the University of California Los Angeles, reported promising results at the American Association for Cancer Research annual meeting.

The small, single arm pilot study included 28 patients with borderline resectable pancreatic cancer, meaning that tumors had some degree of vascular involvement. About 20% of pancreatic tumors are borderline resectable, Dr. Wainberg said.

Patients received 480 mg of nivolumab intravenously every 4 weeks plus mFOLFIRINOX chemotherapy (oxaliplatin, irinotecan, leucovorin, and 5-fluorouracil) on days 1 and 15 of the 28-day cycle.

Patients who downstaged to resectable disease after three cycles went on to surgery; if not, treatment continued for another 3 months. The median number of cycles was 5.5, and almost all patients completed at least 3.

Overall, 19 of the 22 patients who proceeded to surgery (86%) had a pathologic response to neoadjuvant treatment with nivolumab: 2 complete responses, 2 near-complete responses, and 15 partial responses.

Among patients receiving surgery, 21 had R0 resections, meaning negative surgical margins with no tumor left behind. This is key because R0 resections predict longer survival, and “every effort should be made to achieve” this outcome, Dr. Wainberg said. The remaining patient had an R1 resection.

Median progression-free survival was 21.9 months among all patients and 27.3 months among the 22 patients who had resections.

Median overall survival was 34.6 months across the entire group and 44 months among those who had surgery. Overall, 82% of patients were alive at 12 months, and 77% were alive at 18 months.

The study outcomes, especially among the surgery cohort, stand in contrast to those observed in patients who receive the current standard neoadjuvant regimen for borderline resectable pancreatic cancer, mFOLFIRINOX alone, with studies finding a median overall survival of 29.8 months.

Adding nivolumab to neoadjuvant treatment also did not increase side effects. More than half of patients had grade 3 or worse adverse events, but they were all related to mFOLFIRINOX. There were no significant surgical complications, including no grade 2 or higher fistulas.

“We are very pleased” with the outcomes, Dr. Wainberg said. “We need to be studying [immune checkpoint inhibitors] earlier on in both borderline and locally advanced disease. Pancreatic cancer needs all the help it can get to engage immunity.”

Moderator Alice Ho, MD, a radiation oncologist at Duke University in Durham, North Carolina, called the R0 resection rate “stunning” in a “field that very much needs improvements and advancements.”

Dr. Ho also noted that the trial raises “a lot of interesting questions.”

For instance, why exactly is the addition of nivolumab seemingly improving outcomes?

The combination neoadjuvant therapy appeared to increase tertiary lymphoid structures, plasma cells, and CD4+ T cells — all indications that immunotherapy is having a positive impact — but the treatment also seemed to upregulate pathways for adenosine, an immunosuppressant associated with worse responses to checkpoint blockade.

A larger study is already in the works. In addition to a PD-1 blocker and mFOLFIRINOX, patients will receive a CD73 inhibitor to block adenosine production, Dr. Wainberg said.

Bristol Myers Squibb (BMS) provided the nivolumab used in the study. Dr. Wainberg is a consultant for and reported research funding from BMS and other companies. Dr. Ho had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

There have been many attempts to use immunotherapy to improve outcomes in pancreatic cancer, but they haven’t worked out.

The trials, however, have focused on adding immune checkpoint inhibitors to chemotherapy in metastatic disease, leaving open the question of whether immunotherapy might have a role in the neoadjuvant setting before surgery.

In the first study to test the hypothesis, Zev A. Wainberg, MD, a gastrointestinal medical oncologist at the University of California Los Angeles, reported promising results at the American Association for Cancer Research annual meeting.

The small, single arm pilot study included 28 patients with borderline resectable pancreatic cancer, meaning that tumors had some degree of vascular involvement. About 20% of pancreatic tumors are borderline resectable, Dr. Wainberg said.

Patients received 480 mg of nivolumab intravenously every 4 weeks plus mFOLFIRINOX chemotherapy (oxaliplatin, irinotecan, leucovorin, and 5-fluorouracil) on days 1 and 15 of the 28-day cycle.

Patients who downstaged to resectable disease after three cycles went on to surgery; if not, treatment continued for another 3 months. The median number of cycles was 5.5, and almost all patients completed at least 3.

Overall, 19 of the 22 patients who proceeded to surgery (86%) had a pathologic response to neoadjuvant treatment with nivolumab: 2 complete responses, 2 near-complete responses, and 15 partial responses.

Among patients receiving surgery, 21 had R0 resections, meaning negative surgical margins with no tumor left behind. This is key because R0 resections predict longer survival, and “every effort should be made to achieve” this outcome, Dr. Wainberg said. The remaining patient had an R1 resection.

Median progression-free survival was 21.9 months among all patients and 27.3 months among the 22 patients who had resections.

Median overall survival was 34.6 months across the entire group and 44 months among those who had surgery. Overall, 82% of patients were alive at 12 months, and 77% were alive at 18 months.

The study outcomes, especially among the surgery cohort, stand in contrast to those observed in patients who receive the current standard neoadjuvant regimen for borderline resectable pancreatic cancer, mFOLFIRINOX alone, with studies finding a median overall survival of 29.8 months.

Adding nivolumab to neoadjuvant treatment also did not increase side effects. More than half of patients had grade 3 or worse adverse events, but they were all related to mFOLFIRINOX. There were no significant surgical complications, including no grade 2 or higher fistulas.

“We are very pleased” with the outcomes, Dr. Wainberg said. “We need to be studying [immune checkpoint inhibitors] earlier on in both borderline and locally advanced disease. Pancreatic cancer needs all the help it can get to engage immunity.”

Moderator Alice Ho, MD, a radiation oncologist at Duke University in Durham, North Carolina, called the R0 resection rate “stunning” in a “field that very much needs improvements and advancements.”

Dr. Ho also noted that the trial raises “a lot of interesting questions.”

For instance, why exactly is the addition of nivolumab seemingly improving outcomes?

The combination neoadjuvant therapy appeared to increase tertiary lymphoid structures, plasma cells, and CD4+ T cells — all indications that immunotherapy is having a positive impact — but the treatment also seemed to upregulate pathways for adenosine, an immunosuppressant associated with worse responses to checkpoint blockade.

A larger study is already in the works. In addition to a PD-1 blocker and mFOLFIRINOX, patients will receive a CD73 inhibitor to block adenosine production, Dr. Wainberg said.

Bristol Myers Squibb (BMS) provided the nivolumab used in the study. Dr. Wainberg is a consultant for and reported research funding from BMS and other companies. Dr. Ho had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

The latest research supports immune checkpoint inhibitor therapy for clear cell and non–clear cell renal cell carcinoma, but patient selection is key to optimize outcomes, according to a medical oncologist from the Dana-Farber Cancer Institute, Boston.

Michael Serzan, MD, who works in the Lank Center for Genitourinary Oncology at the institute, stated this at the 2024 National Comprehensive Cancer Network Annual Conference, during a presentation.

A systematic review and meta-analysis published in 2022 in European Urology Open Science summarized six randomized controlled trials with a total of 5121 adult patients. In the review, the researchers found that immune checkpoint inhibitors plus vascular endothelial growth factor tyrosine kinase inhibitors (VEGF TKI) were associated with consistent improvements across all risk groups for metastatic renal cell carcinoma.

Additional newer research supports the use of immunotherapy combinations or other immunotherapy plus tyrosine kinase inhibitors as first-line or adjuvant treatments for renal cell carcinoma, Dr. Serzan said during an interview. However, more genomic and histology-directed therapies are needed, he noted.
 

Tips for Evaluating Risk When Treating Renal Cell Carcinoma?

For patients with localized clear cell renal cell carcinoma who have undergone partial or radical nephrectomy, there are several models that estimate the risk of recurrence based on pathologic tumor stage, grade, histology, invasion, and the extent of necrosis, Dr. Serzan said. These models can help guide selection of patients who may be at high risk of recurrence and, therefore, may benefit from adjuvant therapy.

For patients with metastatic clear cell renal cell carcinoma, the IMDC and MSKCC prognostic models stratify patients to favorable, intermediate, and poor risk groups based on clinical and lab factors. The IMDC risk stratification model is used as a prognostic model to stratify patients diagnosed with metastatic kidney cancer, Dr. Serzan said.
 

What Research Supports Treatments for Clear Cell and Non–Clear Cell Renal Cell Carcinoma?

The US Food and Drug Administration (FDA) approved pembrolizumab in 2021 for the adjuvant treatment of renal cell carcinoma (RCC) in patients with intermediate-risk or high-risk of recurrence after nephrectomy or after nephrectomy and resection of metastatic lesions.

Pembrolizumab is the first adjuvant therapy shown to significantly improve overall survival in these patients, Dr. Serzan said. In the KEYNOTE-564 study, published in 2024 in the Journal of Clinical Oncology, pembrolizumab demonstrated an improvement in disease free survival as well as overall survival when compared with placebo.

Several similar studies of adjuvant immune checkpoint inhibitors for renal cell carcinoma involving atezolizumab vs. placebo, nivolumab plus ipilimumab vs. placebo, and nivolumab vs. observation have not shown significant benefits in terms of disease-free survival, Dr. Serzan noted.

The current NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer (Version: 3.2024), which were updated this year, support the use of adjuvant pembrolizumab for patients with stage II, III, or IV clear cell renal cell carcinoma after partial or radical nephrectomy, he said.

Looking ahead, biomarkers are needed to understand the risk of recurrence, and which patients benefit from adjuvant pembrolizumab, Dr. Serzan added.
 

Where Do VEGF-TKIs Fit In?

VEGF is a treatment target for renal cancer, and angiogenesis inhibition with VEGF TKIs continues to be a subject for study, Dr. Serzan said. In the CABOSUN study, published in the Journal of Clinical Oncology in 2017, patients were randomized to cabozantinib or sunitinib. Progression-free survival was significantly greater in the cabozantinib group, but overall survival was similar between the groups.

In another randomized trial, the CheckMate 214 study, patients received either sunitinib or a combination of nivolumab plus ipilimumab in four doses given every 3 weeks, followed by nivolumab alone every 2 weeks, and these patients were stratified by risk, Dr. Serzan noted.

The median progression-free survival was 12.4 months in the combination group vs. 8.5 months in the sunitinib group for patients at intermediate or poor risk of recurrence. The median progression-free survival was significantly greater in sunitinib patients with favorable risk vs. combination patients with favorable risk (28.9 months vs. 12.4 months).

Overall survival was higher for all patients with combination therapy vs. sunitinib regardless of risk stratification.

Dr. Serzan reviewed the pros of VEGF/PD1 (programmed death-ligand 1) combinations as including a high response rate (generally 52%-72%) and a low rate of primary progressive disease (5%-12%), as well as favorable progression-free and overall survival and low rates of immune-related adverse events.

However, cons of this treatment include lack of data on treatment-free survival as well as the decrease in progression-free survival and overall survival hazard ratios over time and potential chronic VEGF/TKI toxicities, he said.
 

What Treatments Are Recommended for Metastatic Clear Cell Renal Cell Carcinoma Now?

Clear cell renal cell carcinoma (ccRCC) is the most prevalent histological subtype of kidney cancer, accounting for 70%-75% of cases, and these patients are prone to metastasis, recurrence, and resistance to radiotherapy and chemotherapy, according to authors of a recent review published in Frontiers in Oncology.

Dr. Serzan shared his preferred protocol for treatment-naive metastatic ccRCC patients, based on the NCCN guidelines for Kidney Cancer (Version: 3.2024) that had been updated in 2024.

For those with sarcomatoid features, he favors the use of nivolumab/ipilimumab combination, while those without sarcomatoid features, if highly symptomatic, may be treated with any of several combinations: nivolumab/ipilimumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.

For asymptomatic patients without sarcomatoid features, treatment depends on eligibility for immune checkpoint inhibitors or ipilimumab, Dr. Serzan said. His first choice for those eligible is nivolumab/ipilimumab; those not eligible for ipilimumab could receive nivolumab, pembrolizumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.

For patients not eligible for ICIs because of uncontrolled autoimmune disease, or high-dose glucocorticoids, Dr. Serzan recommended treatment with cabozantinib, lenvatinib/everolimus, pazopanib, or sunitinib.
 

What are Some Takeaway Points About Immunotherapy and Renal Cell Carcinoma?

“Immunotherapy has revolutionized treatment for renal cell carcinoma, with significant increases in overall survival, and a small but consistent cure fraction that was unimaginable 10 years ago,” Eric Jonasch, MD, of The University of Texas MD Anderson Cancer Center and vice-chair of the NCCN Guidelines Panel for Kidney Cancer, said in an interview.

However, challenges to implementing new treatments in clinical practice are ongoing, he said. The major challenges facing clinicians, patients, and their families include the cost of therapy, logistics of treatment administration, and managing toxicities, Dr. Jonasch said.  

Patient selection is key to optimize outcomes with immunotherapy, and shared decision-making is essential to ensure that choice of therapy matches patient expectations and needs — and to maintain clear and open channels of communication while patients are on therapy, Dr. Jonasch said. “In my clinic, we empower patients to take treatment breaks to manage side effects, thereby optimizing quality of life while maintaining treatment efficacy,” he said.

Although significant progress has been made in managing renal cell carcinoma, more research is needed to increase the proportion of patients cured, said Dr. Jonasch. “A clearer understanding of the determinants of response and resistance, which will be driven by information rich clinical trials, will help move us in that direction,” he said.

Dr. Serzan had no financial conflicts to disclose. Dr. Jonasch disclosed research support from AbbVie, Arrowhead, Aveo, BMS, Corvus, Merck, NiKang, ProfoundBio, and Telix, as well as honoraria from Aveo, Eisai, Exelixis, GlaxoSmithKline, Ipsen, Merck, Novartis, NiKang, and Takeda.

The latest research supports immune checkpoint inhibitor therapy for clear cell and non–clear cell renal cell carcinoma, but patient selection is key to optimize outcomes, according to a medical oncologist from the Dana-Farber Cancer Institute, Boston.

Michael Serzan, MD, who works in the Lank Center for Genitourinary Oncology at the institute, stated this at the 2024 National Comprehensive Cancer Network Annual Conference, during a presentation.

A systematic review and meta-analysis published in 2022 in European Urology Open Science summarized six randomized controlled trials with a total of 5121 adult patients. In the review, the researchers found that immune checkpoint inhibitors plus vascular endothelial growth factor tyrosine kinase inhibitors (VEGF TKI) were associated with consistent improvements across all risk groups for metastatic renal cell carcinoma.

Additional newer research supports the use of immunotherapy combinations or other immunotherapy plus tyrosine kinase inhibitors as first-line or adjuvant treatments for renal cell carcinoma, Dr. Serzan said during an interview. However, more genomic and histology-directed therapies are needed, he noted.
 

Tips for Evaluating Risk When Treating Renal Cell Carcinoma?

For patients with localized clear cell renal cell carcinoma who have undergone partial or radical nephrectomy, there are several models that estimate the risk of recurrence based on pathologic tumor stage, grade, histology, invasion, and the extent of necrosis, Dr. Serzan said. These models can help guide selection of patients who may be at high risk of recurrence and, therefore, may benefit from adjuvant therapy.

For patients with metastatic clear cell renal cell carcinoma, the IMDC and MSKCC prognostic models stratify patients to favorable, intermediate, and poor risk groups based on clinical and lab factors. The IMDC risk stratification model is used as a prognostic model to stratify patients diagnosed with metastatic kidney cancer, Dr. Serzan said.
 

What Research Supports Treatments for Clear Cell and Non–Clear Cell Renal Cell Carcinoma?

The US Food and Drug Administration (FDA) approved pembrolizumab in 2021 for the adjuvant treatment of renal cell carcinoma (RCC) in patients with intermediate-risk or high-risk of recurrence after nephrectomy or after nephrectomy and resection of metastatic lesions.

Pembrolizumab is the first adjuvant therapy shown to significantly improve overall survival in these patients, Dr. Serzan said. In the KEYNOTE-564 study, published in 2024 in the Journal of Clinical Oncology, pembrolizumab demonstrated an improvement in disease free survival as well as overall survival when compared with placebo.

Several similar studies of adjuvant immune checkpoint inhibitors for renal cell carcinoma involving atezolizumab vs. placebo, nivolumab plus ipilimumab vs. placebo, and nivolumab vs. observation have not shown significant benefits in terms of disease-free survival, Dr. Serzan noted.

The current NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer (Version: 3.2024), which were updated this year, support the use of adjuvant pembrolizumab for patients with stage II, III, or IV clear cell renal cell carcinoma after partial or radical nephrectomy, he said.

Looking ahead, biomarkers are needed to understand the risk of recurrence, and which patients benefit from adjuvant pembrolizumab, Dr. Serzan added.
 

Where Do VEGF-TKIs Fit In?

VEGF is a treatment target for renal cancer, and angiogenesis inhibition with VEGF TKIs continues to be a subject for study, Dr. Serzan said. In the CABOSUN study, published in the Journal of Clinical Oncology in 2017, patients were randomized to cabozantinib or sunitinib. Progression-free survival was significantly greater in the cabozantinib group, but overall survival was similar between the groups.

In another randomized trial, the CheckMate 214 study, patients received either sunitinib or a combination of nivolumab plus ipilimumab in four doses given every 3 weeks, followed by nivolumab alone every 2 weeks, and these patients were stratified by risk, Dr. Serzan noted.

The median progression-free survival was 12.4 months in the combination group vs. 8.5 months in the sunitinib group for patients at intermediate or poor risk of recurrence. The median progression-free survival was significantly greater in sunitinib patients with favorable risk vs. combination patients with favorable risk (28.9 months vs. 12.4 months).

Overall survival was higher for all patients with combination therapy vs. sunitinib regardless of risk stratification.

Dr. Serzan reviewed the pros of VEGF/PD1 (programmed death-ligand 1) combinations as including a high response rate (generally 52%-72%) and a low rate of primary progressive disease (5%-12%), as well as favorable progression-free and overall survival and low rates of immune-related adverse events.

However, cons of this treatment include lack of data on treatment-free survival as well as the decrease in progression-free survival and overall survival hazard ratios over time and potential chronic VEGF/TKI toxicities, he said.
 

What Treatments Are Recommended for Metastatic Clear Cell Renal Cell Carcinoma Now?

Clear cell renal cell carcinoma (ccRCC) is the most prevalent histological subtype of kidney cancer, accounting for 70%-75% of cases, and these patients are prone to metastasis, recurrence, and resistance to radiotherapy and chemotherapy, according to authors of a recent review published in Frontiers in Oncology.

Dr. Serzan shared his preferred protocol for treatment-naive metastatic ccRCC patients, based on the NCCN guidelines for Kidney Cancer (Version: 3.2024) that had been updated in 2024.

For those with sarcomatoid features, he favors the use of nivolumab/ipilimumab combination, while those without sarcomatoid features, if highly symptomatic, may be treated with any of several combinations: nivolumab/ipilimumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.

For asymptomatic patients without sarcomatoid features, treatment depends on eligibility for immune checkpoint inhibitors or ipilimumab, Dr. Serzan said. His first choice for those eligible is nivolumab/ipilimumab; those not eligible for ipilimumab could receive nivolumab, pembrolizumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.

For patients not eligible for ICIs because of uncontrolled autoimmune disease, or high-dose glucocorticoids, Dr. Serzan recommended treatment with cabozantinib, lenvatinib/everolimus, pazopanib, or sunitinib.
 

What are Some Takeaway Points About Immunotherapy and Renal Cell Carcinoma?

“Immunotherapy has revolutionized treatment for renal cell carcinoma, with significant increases in overall survival, and a small but consistent cure fraction that was unimaginable 10 years ago,” Eric Jonasch, MD, of The University of Texas MD Anderson Cancer Center and vice-chair of the NCCN Guidelines Panel for Kidney Cancer, said in an interview.

However, challenges to implementing new treatments in clinical practice are ongoing, he said. The major challenges facing clinicians, patients, and their families include the cost of therapy, logistics of treatment administration, and managing toxicities, Dr. Jonasch said.  

Patient selection is key to optimize outcomes with immunotherapy, and shared decision-making is essential to ensure that choice of therapy matches patient expectations and needs — and to maintain clear and open channels of communication while patients are on therapy, Dr. Jonasch said. “In my clinic, we empower patients to take treatment breaks to manage side effects, thereby optimizing quality of life while maintaining treatment efficacy,” he said.

Although significant progress has been made in managing renal cell carcinoma, more research is needed to increase the proportion of patients cured, said Dr. Jonasch. “A clearer understanding of the determinants of response and resistance, which will be driven by information rich clinical trials, will help move us in that direction,” he said.

Dr. Serzan had no financial conflicts to disclose. Dr. Jonasch disclosed research support from AbbVie, Arrowhead, Aveo, BMS, Corvus, Merck, NiKang, ProfoundBio, and Telix, as well as honoraria from Aveo, Eisai, Exelixis, GlaxoSmithKline, Ipsen, Merck, Novartis, NiKang, and Takeda.

The latest research supports immune checkpoint inhibitor therapy for clear cell and non–clear cell renal cell carcinoma, but patient selection is key to optimize outcomes, according to a medical oncologist from the Dana-Farber Cancer Institute, Boston.

Michael Serzan, MD, who works in the Lank Center for Genitourinary Oncology at the institute, stated this at the 2024 National Comprehensive Cancer Network Annual Conference, during a presentation.

A systematic review and meta-analysis published in 2022 in European Urology Open Science summarized six randomized controlled trials with a total of 5121 adult patients. In the review, the researchers found that immune checkpoint inhibitors plus vascular endothelial growth factor tyrosine kinase inhibitors (VEGF TKI) were associated with consistent improvements across all risk groups for metastatic renal cell carcinoma.

Additional newer research supports the use of immunotherapy combinations or other immunotherapy plus tyrosine kinase inhibitors as first-line or adjuvant treatments for renal cell carcinoma, Dr. Serzan said during an interview. However, more genomic and histology-directed therapies are needed, he noted.
 

Tips for Evaluating Risk When Treating Renal Cell Carcinoma?

For patients with localized clear cell renal cell carcinoma who have undergone partial or radical nephrectomy, there are several models that estimate the risk of recurrence based on pathologic tumor stage, grade, histology, invasion, and the extent of necrosis, Dr. Serzan said. These models can help guide selection of patients who may be at high risk of recurrence and, therefore, may benefit from adjuvant therapy.

For patients with metastatic clear cell renal cell carcinoma, the IMDC and MSKCC prognostic models stratify patients to favorable, intermediate, and poor risk groups based on clinical and lab factors. The IMDC risk stratification model is used as a prognostic model to stratify patients diagnosed with metastatic kidney cancer, Dr. Serzan said.
 

What Research Supports Treatments for Clear Cell and Non–Clear Cell Renal Cell Carcinoma?

The US Food and Drug Administration (FDA) approved pembrolizumab in 2021 for the adjuvant treatment of renal cell carcinoma (RCC) in patients with intermediate-risk or high-risk of recurrence after nephrectomy or after nephrectomy and resection of metastatic lesions.

Pembrolizumab is the first adjuvant therapy shown to significantly improve overall survival in these patients, Dr. Serzan said. In the KEYNOTE-564 study, published in 2024 in the Journal of Clinical Oncology, pembrolizumab demonstrated an improvement in disease free survival as well as overall survival when compared with placebo.

Several similar studies of adjuvant immune checkpoint inhibitors for renal cell carcinoma involving atezolizumab vs. placebo, nivolumab plus ipilimumab vs. placebo, and nivolumab vs. observation have not shown significant benefits in terms of disease-free survival, Dr. Serzan noted.

The current NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer (Version: 3.2024), which were updated this year, support the use of adjuvant pembrolizumab for patients with stage II, III, or IV clear cell renal cell carcinoma after partial or radical nephrectomy, he said.

Looking ahead, biomarkers are needed to understand the risk of recurrence, and which patients benefit from adjuvant pembrolizumab, Dr. Serzan added.
 

Where Do VEGF-TKIs Fit In?

VEGF is a treatment target for renal cancer, and angiogenesis inhibition with VEGF TKIs continues to be a subject for study, Dr. Serzan said. In the CABOSUN study, published in the Journal of Clinical Oncology in 2017, patients were randomized to cabozantinib or sunitinib. Progression-free survival was significantly greater in the cabozantinib group, but overall survival was similar between the groups.

In another randomized trial, the CheckMate 214 study, patients received either sunitinib or a combination of nivolumab plus ipilimumab in four doses given every 3 weeks, followed by nivolumab alone every 2 weeks, and these patients were stratified by risk, Dr. Serzan noted.

The median progression-free survival was 12.4 months in the combination group vs. 8.5 months in the sunitinib group for patients at intermediate or poor risk of recurrence. The median progression-free survival was significantly greater in sunitinib patients with favorable risk vs. combination patients with favorable risk (28.9 months vs. 12.4 months).

Overall survival was higher for all patients with combination therapy vs. sunitinib regardless of risk stratification.

Dr. Serzan reviewed the pros of VEGF/PD1 (programmed death-ligand 1) combinations as including a high response rate (generally 52%-72%) and a low rate of primary progressive disease (5%-12%), as well as favorable progression-free and overall survival and low rates of immune-related adverse events.

However, cons of this treatment include lack of data on treatment-free survival as well as the decrease in progression-free survival and overall survival hazard ratios over time and potential chronic VEGF/TKI toxicities, he said.
 

What Treatments Are Recommended for Metastatic Clear Cell Renal Cell Carcinoma Now?

Clear cell renal cell carcinoma (ccRCC) is the most prevalent histological subtype of kidney cancer, accounting for 70%-75% of cases, and these patients are prone to metastasis, recurrence, and resistance to radiotherapy and chemotherapy, according to authors of a recent review published in Frontiers in Oncology.

Dr. Serzan shared his preferred protocol for treatment-naive metastatic ccRCC patients, based on the NCCN guidelines for Kidney Cancer (Version: 3.2024) that had been updated in 2024.

For those with sarcomatoid features, he favors the use of nivolumab/ipilimumab combination, while those without sarcomatoid features, if highly symptomatic, may be treated with any of several combinations: nivolumab/ipilimumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.

For asymptomatic patients without sarcomatoid features, treatment depends on eligibility for immune checkpoint inhibitors or ipilimumab, Dr. Serzan said. His first choice for those eligible is nivolumab/ipilimumab; those not eligible for ipilimumab could receive nivolumab, pembrolizumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.

For patients not eligible for ICIs because of uncontrolled autoimmune disease, or high-dose glucocorticoids, Dr. Serzan recommended treatment with cabozantinib, lenvatinib/everolimus, pazopanib, or sunitinib.
 

What are Some Takeaway Points About Immunotherapy and Renal Cell Carcinoma?

“Immunotherapy has revolutionized treatment for renal cell carcinoma, with significant increases in overall survival, and a small but consistent cure fraction that was unimaginable 10 years ago,” Eric Jonasch, MD, of The University of Texas MD Anderson Cancer Center and vice-chair of the NCCN Guidelines Panel for Kidney Cancer, said in an interview.

However, challenges to implementing new treatments in clinical practice are ongoing, he said. The major challenges facing clinicians, patients, and their families include the cost of therapy, logistics of treatment administration, and managing toxicities, Dr. Jonasch said.  

Patient selection is key to optimize outcomes with immunotherapy, and shared decision-making is essential to ensure that choice of therapy matches patient expectations and needs — and to maintain clear and open channels of communication while patients are on therapy, Dr. Jonasch said. “In my clinic, we empower patients to take treatment breaks to manage side effects, thereby optimizing quality of life while maintaining treatment efficacy,” he said.

Although significant progress has been made in managing renal cell carcinoma, more research is needed to increase the proportion of patients cured, said Dr. Jonasch. “A clearer understanding of the determinants of response and resistance, which will be driven by information rich clinical trials, will help move us in that direction,” he said.

Dr. Serzan had no financial conflicts to disclose. Dr. Jonasch disclosed research support from AbbVie, Arrowhead, Aveo, BMS, Corvus, Merck, NiKang, ProfoundBio, and Telix, as well as honoraria from Aveo, Eisai, Exelixis, GlaxoSmithKline, Ipsen, Merck, Novartis, NiKang, and Takeda.

Men with low-risk prostate cancer who go on active surveillance rather than treatment are best followed-up for more than 15 years — and perhaps indefinitely — according one of the longest studies to date to look at the issue. 

Previous studies have shown that active surveillance continued for 15 years is appropriate to identify men who progress and need treatment, but now data out to 25 years “suggest that meticulous follow-up is needed over a longer time if the chance for cure is not to be missed,” said Emmeli Palmstedt, PhD, a research student in the Department of Urology at the Sahlgrenska Academy at the University of Gothenburg, Sweden. “These data are crucial, given the long current life expectancy” of men in otherwise good health. 

Dr. Palmstedt presented the findings at the 2024 annual meeting of the European Association of Urology.

At many centers, active surveillance is a standard of care for men with low-risk prostate cancer based on a benefit-to-risk ratio that favors delayed intervention, according to Palmstedt. Several studies, including the Göteburg-1 active surveillance trial initiated at her institution, have supported follow-up for 15 years. A new set of data from Göteborg now extends to 25 years.
 

Long-Life Expectancy Justifies Extended Surveillance

The prospective Göteborg study began enrolling men with very low- or low-risk (78%) or intermediate-risk (22%) prostate cancer in 1995. In the active surveillance program, prostate-specific antigen (PSA) was measured routinely with biopsies ordered for PSA levels ≥ 2.5 ng/mL. 

In an analysis published in 2016 when 202 (43%) of 474 patients managed with active surveillance had discontinued surveillance to start treatment, the median follow-up period was 8 years. The rate of mortality associated with prostate cancer at 15 years was estimated to be 0% for men in the very low-risk group, 4% for men in the low-risk group, and 10% for those with intermediate-risk tumors. The estimates for failure-free survival at 15 years were 88%, 77%, and 40% for the very low-, low-, and intermediate-risk groups, respectively.

In the most recent follow-up, when the median age in the Göteburg-1 study was 80 years (the median age at diagnosis was 66 years), the median follow-up period was 15.1 years with a range of up to 28.1 years. In this analysis, which focused on patients with low-risk prostate cancer at baseline, discontinuations from active surveillance had climbed to 47%. Most of these men discontinued to initiate treatment, but 79 (16%) had failed acute surveillance, meaning their progression was not caught in time for curative-intent treatment, and 2% had died from prostate cancer.
 

Treatment-Free Survival Falls to 31% 

The rate of treatment-free survival, which was estimated to be 65% in the 15-year analysis published in 2016, had declined to 31%. The rate of failure-free survival was 59%, and prostate cancer-specific survival was 92%, according to the researchers. 

While Dr. Palmstedt did not separate out her data for very low- and low-risk patients, she noted that deaths from prostate cancer among all low-risk patients climbed fourfold (8% vs 2%) since the 2016 figures were published. The proportion of men no longer failure-free climbed from 10% to more than 40%. 

“These are non-negligible numbers,” said Dr. Palmstedt, who added that overall survival fell from 69% at 15 years to 37% at 25 years.

Although some men between the 15-year and 25-year timepoints were switched to watchful waiting, these data have not yet been analyzed.

The low rate of deaths from prostate cancer over the extended period is reassuring, Dr. Palmstedt said, but the main message from the new study is that active surveillance permits curative-intent treatment to be offered even after late follow-up. She emphasized that patients without progression by 15 years cannot be considered “safe.”

Based on these data, “men with a long remaining life expectancy should be informed that active surveillance is still viable after 15 years,” Dr. Palmstedt said.
 

Active Surveillance Now More Common

Over the past decade, the proportion of men with prostate cancer managed with active surveillance has been rising steadily, according to Matthew R. Cooperberg, MD, MPH, professor of urology at the University of California, San Francisco. In a study published last year in JAMA Network Open, Dr. Cooperberg and his colleagues reported that rates of active surveillance rose from 26.5% in 2014 to 59.6% in 2021. However, given the value of the approach for avoiding overtreatment of men with low-risk prostate cancers, even that increase is not enough, he said.

“The window of opportunity for cure is typically very wide,” Dr. Cooperberg said. Although many men “will never need treatment ... long-term surveillance is definitely important” for those that do, he said. The data from trials like Göteborg-1 support the principle that this strategy still preserves the option of treatment when it is needed. 

“Treatment for cure at age 70 is generally far preferable to treatment at 55, and surveillance should absolutely be preferred treatment for the vast majority of men with low-grade disease at diagnosis,” he explained.

Dr. Palmstedt reported no potential conflicts of interest. Dr. Cooperberg reported financial relationships with Astellas, AstraZeneca, Bayer, Dendreon, Exact Sciences, Janssen, Merck, Pfizer, and Verana Health. 
 

A version of this article appeared on Medscape.com.

Men with low-risk prostate cancer who go on active surveillance rather than treatment are best followed-up for more than 15 years — and perhaps indefinitely — according one of the longest studies to date to look at the issue. 

Previous studies have shown that active surveillance continued for 15 years is appropriate to identify men who progress and need treatment, but now data out to 25 years “suggest that meticulous follow-up is needed over a longer time if the chance for cure is not to be missed,” said Emmeli Palmstedt, PhD, a research student in the Department of Urology at the Sahlgrenska Academy at the University of Gothenburg, Sweden. “These data are crucial, given the long current life expectancy” of men in otherwise good health. 

Dr. Palmstedt presented the findings at the 2024 annual meeting of the European Association of Urology.

At many centers, active surveillance is a standard of care for men with low-risk prostate cancer based on a benefit-to-risk ratio that favors delayed intervention, according to Palmstedt. Several studies, including the Göteburg-1 active surveillance trial initiated at her institution, have supported follow-up for 15 years. A new set of data from Göteborg now extends to 25 years.
 

Long-Life Expectancy Justifies Extended Surveillance

The prospective Göteborg study began enrolling men with very low- or low-risk (78%) or intermediate-risk (22%) prostate cancer in 1995. In the active surveillance program, prostate-specific antigen (PSA) was measured routinely with biopsies ordered for PSA levels ≥ 2.5 ng/mL. 

In an analysis published in 2016 when 202 (43%) of 474 patients managed with active surveillance had discontinued surveillance to start treatment, the median follow-up period was 8 years. The rate of mortality associated with prostate cancer at 15 years was estimated to be 0% for men in the very low-risk group, 4% for men in the low-risk group, and 10% for those with intermediate-risk tumors. The estimates for failure-free survival at 15 years were 88%, 77%, and 40% for the very low-, low-, and intermediate-risk groups, respectively.

In the most recent follow-up, when the median age in the Göteburg-1 study was 80 years (the median age at diagnosis was 66 years), the median follow-up period was 15.1 years with a range of up to 28.1 years. In this analysis, which focused on patients with low-risk prostate cancer at baseline, discontinuations from active surveillance had climbed to 47%. Most of these men discontinued to initiate treatment, but 79 (16%) had failed acute surveillance, meaning their progression was not caught in time for curative-intent treatment, and 2% had died from prostate cancer.
 

Treatment-Free Survival Falls to 31% 

The rate of treatment-free survival, which was estimated to be 65% in the 15-year analysis published in 2016, had declined to 31%. The rate of failure-free survival was 59%, and prostate cancer-specific survival was 92%, according to the researchers. 

While Dr. Palmstedt did not separate out her data for very low- and low-risk patients, she noted that deaths from prostate cancer among all low-risk patients climbed fourfold (8% vs 2%) since the 2016 figures were published. The proportion of men no longer failure-free climbed from 10% to more than 40%. 

“These are non-negligible numbers,” said Dr. Palmstedt, who added that overall survival fell from 69% at 15 years to 37% at 25 years.

Although some men between the 15-year and 25-year timepoints were switched to watchful waiting, these data have not yet been analyzed.

The low rate of deaths from prostate cancer over the extended period is reassuring, Dr. Palmstedt said, but the main message from the new study is that active surveillance permits curative-intent treatment to be offered even after late follow-up. She emphasized that patients without progression by 15 years cannot be considered “safe.”

Based on these data, “men with a long remaining life expectancy should be informed that active surveillance is still viable after 15 years,” Dr. Palmstedt said.
 

Active Surveillance Now More Common

Over the past decade, the proportion of men with prostate cancer managed with active surveillance has been rising steadily, according to Matthew R. Cooperberg, MD, MPH, professor of urology at the University of California, San Francisco. In a study published last year in JAMA Network Open, Dr. Cooperberg and his colleagues reported that rates of active surveillance rose from 26.5% in 2014 to 59.6% in 2021. However, given the value of the approach for avoiding overtreatment of men with low-risk prostate cancers, even that increase is not enough, he said.

“The window of opportunity for cure is typically very wide,” Dr. Cooperberg said. Although many men “will never need treatment ... long-term surveillance is definitely important” for those that do, he said. The data from trials like Göteborg-1 support the principle that this strategy still preserves the option of treatment when it is needed. 

“Treatment for cure at age 70 is generally far preferable to treatment at 55, and surveillance should absolutely be preferred treatment for the vast majority of men with low-grade disease at diagnosis,” he explained.

Dr. Palmstedt reported no potential conflicts of interest. Dr. Cooperberg reported financial relationships with Astellas, AstraZeneca, Bayer, Dendreon, Exact Sciences, Janssen, Merck, Pfizer, and Verana Health. 
 

A version of this article appeared on Medscape.com.

Men with low-risk prostate cancer who go on active surveillance rather than treatment are best followed-up for more than 15 years — and perhaps indefinitely — according one of the longest studies to date to look at the issue. 

Previous studies have shown that active surveillance continued for 15 years is appropriate to identify men who progress and need treatment, but now data out to 25 years “suggest that meticulous follow-up is needed over a longer time if the chance for cure is not to be missed,” said Emmeli Palmstedt, PhD, a research student in the Department of Urology at the Sahlgrenska Academy at the University of Gothenburg, Sweden. “These data are crucial, given the long current life expectancy” of men in otherwise good health. 

Dr. Palmstedt presented the findings at the 2024 annual meeting of the European Association of Urology.

At many centers, active surveillance is a standard of care for men with low-risk prostate cancer based on a benefit-to-risk ratio that favors delayed intervention, according to Palmstedt. Several studies, including the Göteburg-1 active surveillance trial initiated at her institution, have supported follow-up for 15 years. A new set of data from Göteborg now extends to 25 years.
 

Long-Life Expectancy Justifies Extended Surveillance

The prospective Göteborg study began enrolling men with very low- or low-risk (78%) or intermediate-risk (22%) prostate cancer in 1995. In the active surveillance program, prostate-specific antigen (PSA) was measured routinely with biopsies ordered for PSA levels ≥ 2.5 ng/mL. 

In an analysis published in 2016 when 202 (43%) of 474 patients managed with active surveillance had discontinued surveillance to start treatment, the median follow-up period was 8 years. The rate of mortality associated with prostate cancer at 15 years was estimated to be 0% for men in the very low-risk group, 4% for men in the low-risk group, and 10% for those with intermediate-risk tumors. The estimates for failure-free survival at 15 years were 88%, 77%, and 40% for the very low-, low-, and intermediate-risk groups, respectively.

In the most recent follow-up, when the median age in the Göteburg-1 study was 80 years (the median age at diagnosis was 66 years), the median follow-up period was 15.1 years with a range of up to 28.1 years. In this analysis, which focused on patients with low-risk prostate cancer at baseline, discontinuations from active surveillance had climbed to 47%. Most of these men discontinued to initiate treatment, but 79 (16%) had failed acute surveillance, meaning their progression was not caught in time for curative-intent treatment, and 2% had died from prostate cancer.
 

Treatment-Free Survival Falls to 31% 

The rate of treatment-free survival, which was estimated to be 65% in the 15-year analysis published in 2016, had declined to 31%. The rate of failure-free survival was 59%, and prostate cancer-specific survival was 92%, according to the researchers. 

While Dr. Palmstedt did not separate out her data for very low- and low-risk patients, she noted that deaths from prostate cancer among all low-risk patients climbed fourfold (8% vs 2%) since the 2016 figures were published. The proportion of men no longer failure-free climbed from 10% to more than 40%. 

“These are non-negligible numbers,” said Dr. Palmstedt, who added that overall survival fell from 69% at 15 years to 37% at 25 years.

Although some men between the 15-year and 25-year timepoints were switched to watchful waiting, these data have not yet been analyzed.

The low rate of deaths from prostate cancer over the extended period is reassuring, Dr. Palmstedt said, but the main message from the new study is that active surveillance permits curative-intent treatment to be offered even after late follow-up. She emphasized that patients without progression by 15 years cannot be considered “safe.”

Based on these data, “men with a long remaining life expectancy should be informed that active surveillance is still viable after 15 years,” Dr. Palmstedt said.
 

Active Surveillance Now More Common

Over the past decade, the proportion of men with prostate cancer managed with active surveillance has been rising steadily, according to Matthew R. Cooperberg, MD, MPH, professor of urology at the University of California, San Francisco. In a study published last year in JAMA Network Open, Dr. Cooperberg and his colleagues reported that rates of active surveillance rose from 26.5% in 2014 to 59.6% in 2021. However, given the value of the approach for avoiding overtreatment of men with low-risk prostate cancers, even that increase is not enough, he said.

“The window of opportunity for cure is typically very wide,” Dr. Cooperberg said. Although many men “will never need treatment ... long-term surveillance is definitely important” for those that do, he said. The data from trials like Göteborg-1 support the principle that this strategy still preserves the option of treatment when it is needed. 

“Treatment for cure at age 70 is generally far preferable to treatment at 55, and surveillance should absolutely be preferred treatment for the vast majority of men with low-grade disease at diagnosis,” he explained.

Dr. Palmstedt reported no potential conflicts of interest. Dr. Cooperberg reported financial relationships with Astellas, AstraZeneca, Bayer, Dendreon, Exact Sciences, Janssen, Merck, Pfizer, and Verana Health. 
 

A version of this article appeared on Medscape.com.

A study conducted in the United States showed that many individuals undergo lung cancer screening despite having a higher likelihood of experiencing harm rather than benefit. Why does this happen? Could it also occur in Italy?

Reasons in Favor

The authors of the study, which was published in Annals of Family Medicine interviewed 40 former military personnel with a significant history of smoking. Though the patients presented with various comorbidities and had a limited life expectancy, the Veterans Health Administration had offered them lung cancer screening.

Of the 40 respondents, 26 had accepted the screening test. When asked why they had done so, they responded, “to take care of my health and achieve my life goals,” “because screening is an opportunity to identify potential issues,” “because it was recommended by a doctor I trust,” and “because I don’t want to regret not accepting it.” Strangely, when deciding about lung cancer screening, the respondents did not consider their poor health or life expectancy.
 

Potential Harms 

The screening was also welcomed because low-dose computed tomography (LDCT) is a noninvasive test. However, many participants were unaware that the screening needed to be repeated annually and that further imaging or other types of tests could follow LDCT, such as biopsies and bronchoscopies.

Many did not recall discussing with the doctor the potential harms of screening, including overdiagnosis, stress due to false positives, and complications and risks associated with investigations and treatments. Informed about this, several patients stated that they would not necessarily undergo further tests or antitumor treatments, especially if intensive or invasive.

The authors of the article emphasized the importance of shared decision-making with patients who have a marginal expected benefit from screening. But is it correct to offer screening under these conditions? Guidelines advise against screening individuals with limited life expectancy and multiple comorbidities because the risk-benefit ratio is not favorable.
 

Screening in Italy

Italy has no organized public program for lung screening. However, in 2022, the Rete Italiana Screening Polmonare (RISP) program for early lung cancer diagnosis was launched. Supported by European funds, it is coordinated by the National Cancer Institute (INT) in Milan and aims to recruit 10,000 high-risk candidates for free screening at 18 hospitals across Italy.

Optimizing participant selection is important in any screening, but in a program like RISP, it is essential, said Alessandro Pardolesi, MD, a thoracic surgeon at INT. “Subjects with multiple comorbidities would create a limit to the study, because there would be too many confounding factors. By maintaining correct inclusion criteria, we can build a reproducible model to demonstrate that screening has a clear social and economic impact. Only after proving its effectiveness can we consider extending it to patients with pre-existing issues or who are very elderly,” he said. The RISP project is limited to participants aged 55-75 years. Participants must be smokers or have quit smoking no more than 15 years ago, with an average consumption of 20 cigarettes per day for 30 years.

Participant selection for the RISP program is also dictated by the costs to be incurred. “If something emerges from the CT scan, whether oncologic or not, it needs to be investigated, triggering mechanisms that consume time, space, and resources,” said Dr. Pardolesi. The economic aspect is crucial for determining the effectiveness of screening. “We need to demonstrate that in addition to increasing the patient’s life expectancy, healthcare costs are reduced. By anticipating the diagnosis, the intervention is less expensive, the patient is discharged in three days, and there’s no need for therapy, so there’s a saving. This is important, given the increasingly evident economic problems of the Italian public health system,” said Dr. Pardolesi.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

A study conducted in the United States showed that many individuals undergo lung cancer screening despite having a higher likelihood of experiencing harm rather than benefit. Why does this happen? Could it also occur in Italy?

Reasons in Favor

The authors of the study, which was published in Annals of Family Medicine interviewed 40 former military personnel with a significant history of smoking. Though the patients presented with various comorbidities and had a limited life expectancy, the Veterans Health Administration had offered them lung cancer screening.

Of the 40 respondents, 26 had accepted the screening test. When asked why they had done so, they responded, “to take care of my health and achieve my life goals,” “because screening is an opportunity to identify potential issues,” “because it was recommended by a doctor I trust,” and “because I don’t want to regret not accepting it.” Strangely, when deciding about lung cancer screening, the respondents did not consider their poor health or life expectancy.
 

Potential Harms 

The screening was also welcomed because low-dose computed tomography (LDCT) is a noninvasive test. However, many participants were unaware that the screening needed to be repeated annually and that further imaging or other types of tests could follow LDCT, such as biopsies and bronchoscopies.

Many did not recall discussing with the doctor the potential harms of screening, including overdiagnosis, stress due to false positives, and complications and risks associated with investigations and treatments. Informed about this, several patients stated that they would not necessarily undergo further tests or antitumor treatments, especially if intensive or invasive.

The authors of the article emphasized the importance of shared decision-making with patients who have a marginal expected benefit from screening. But is it correct to offer screening under these conditions? Guidelines advise against screening individuals with limited life expectancy and multiple comorbidities because the risk-benefit ratio is not favorable.
 

Screening in Italy

Italy has no organized public program for lung screening. However, in 2022, the Rete Italiana Screening Polmonare (RISP) program for early lung cancer diagnosis was launched. Supported by European funds, it is coordinated by the National Cancer Institute (INT) in Milan and aims to recruit 10,000 high-risk candidates for free screening at 18 hospitals across Italy.

Optimizing participant selection is important in any screening, but in a program like RISP, it is essential, said Alessandro Pardolesi, MD, a thoracic surgeon at INT. “Subjects with multiple comorbidities would create a limit to the study, because there would be too many confounding factors. By maintaining correct inclusion criteria, we can build a reproducible model to demonstrate that screening has a clear social and economic impact. Only after proving its effectiveness can we consider extending it to patients with pre-existing issues or who are very elderly,” he said. The RISP project is limited to participants aged 55-75 years. Participants must be smokers or have quit smoking no more than 15 years ago, with an average consumption of 20 cigarettes per day for 30 years.

Participant selection for the RISP program is also dictated by the costs to be incurred. “If something emerges from the CT scan, whether oncologic or not, it needs to be investigated, triggering mechanisms that consume time, space, and resources,” said Dr. Pardolesi. The economic aspect is crucial for determining the effectiveness of screening. “We need to demonstrate that in addition to increasing the patient’s life expectancy, healthcare costs are reduced. By anticipating the diagnosis, the intervention is less expensive, the patient is discharged in three days, and there’s no need for therapy, so there’s a saving. This is important, given the increasingly evident economic problems of the Italian public health system,” said Dr. Pardolesi.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

A study conducted in the United States showed that many individuals undergo lung cancer screening despite having a higher likelihood of experiencing harm rather than benefit. Why does this happen? Could it also occur in Italy?

Reasons in Favor

The authors of the study, which was published in Annals of Family Medicine interviewed 40 former military personnel with a significant history of smoking. Though the patients presented with various comorbidities and had a limited life expectancy, the Veterans Health Administration had offered them lung cancer screening.

Of the 40 respondents, 26 had accepted the screening test. When asked why they had done so, they responded, “to take care of my health and achieve my life goals,” “because screening is an opportunity to identify potential issues,” “because it was recommended by a doctor I trust,” and “because I don’t want to regret not accepting it.” Strangely, when deciding about lung cancer screening, the respondents did not consider their poor health or life expectancy.
 

Potential Harms 

The screening was also welcomed because low-dose computed tomography (LDCT) is a noninvasive test. However, many participants were unaware that the screening needed to be repeated annually and that further imaging or other types of tests could follow LDCT, such as biopsies and bronchoscopies.

Many did not recall discussing with the doctor the potential harms of screening, including overdiagnosis, stress due to false positives, and complications and risks associated with investigations and treatments. Informed about this, several patients stated that they would not necessarily undergo further tests or antitumor treatments, especially if intensive or invasive.

The authors of the article emphasized the importance of shared decision-making with patients who have a marginal expected benefit from screening. But is it correct to offer screening under these conditions? Guidelines advise against screening individuals with limited life expectancy and multiple comorbidities because the risk-benefit ratio is not favorable.
 

Screening in Italy

Italy has no organized public program for lung screening. However, in 2022, the Rete Italiana Screening Polmonare (RISP) program for early lung cancer diagnosis was launched. Supported by European funds, it is coordinated by the National Cancer Institute (INT) in Milan and aims to recruit 10,000 high-risk candidates for free screening at 18 hospitals across Italy.

Optimizing participant selection is important in any screening, but in a program like RISP, it is essential, said Alessandro Pardolesi, MD, a thoracic surgeon at INT. “Subjects with multiple comorbidities would create a limit to the study, because there would be too many confounding factors. By maintaining correct inclusion criteria, we can build a reproducible model to demonstrate that screening has a clear social and economic impact. Only after proving its effectiveness can we consider extending it to patients with pre-existing issues or who are very elderly,” he said. The RISP project is limited to participants aged 55-75 years. Participants must be smokers or have quit smoking no more than 15 years ago, with an average consumption of 20 cigarettes per day for 30 years.

Participant selection for the RISP program is also dictated by the costs to be incurred. “If something emerges from the CT scan, whether oncologic or not, it needs to be investigated, triggering mechanisms that consume time, space, and resources,” said Dr. Pardolesi. The economic aspect is crucial for determining the effectiveness of screening. “We need to demonstrate that in addition to increasing the patient’s life expectancy, healthcare costs are reduced. By anticipating the diagnosis, the intervention is less expensive, the patient is discharged in three days, and there’s no need for therapy, so there’s a saving. This is important, given the increasingly evident economic problems of the Italian public health system,” said Dr. Pardolesi.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

More women today are surviving breast cancer if it’s caught early, largely because of better screening and more effective and targeted treatments.

However, not everyone has benefited equitably from this progress. Critical gaps in breast cancer outcomes and survival remain for women in racial and ethnic minority groups.

Black women for instance, have a 41% higher death rate from breast cancer compared with White patients. They also have a greater incidence of aggressive disease like triple-negative breast cancer. Native American and Hispanic women, meanwhile, are more likely to be diagnosed with breast cancer at an earlier age than White women and experience more aggressive breast cancers.

In 2023, Farhad Islami, MD, PhD, and his team published an updated analysis of racial/ethnic and socioeconomic disparities in cancer trends based on data from 2014 to 2020. The analysis found that Black women in particular, were the least likely to have an early-stage diagnosis of breast cancer. Localized‐stage breast cancer was diagnosed in 57% of Black women versus 68% of White women.

American Cancer Society

“Despite substantial progress in cancer prevention, early detection, and treatments, the burden of cancer remains greater among populations that have been historically marginalized, including people of color, people with lower socioeconomic status, and people living in nonmetropolitan areas,” said Dr. Islami, who is senior scientific director of cancer disparity research in the Surveillance & Health Equity Science Department at the American Cancer Society.

The reasons behind outcomes disparities in breast cancer are complex, making solutions challenging, say experts researching racial differences in cancer outcomes.

While social determinants of health (SDH) seem to be drivers of higher breast cancer mortality in Black women, biological differences between Black and White women are also linked to poorer outcomes in Black women with breast cancer, new studies suggest. Among the findings of this research is that breast cancer tests may be contributing to the disparities and misguiding care for some patients of color.
 

SDH and Screening Rates Differences By Race

A range of factors contribute to racial and ethnic disparities in breast cancer outcomes, said Pamela Ganschow, MD, an associate professor in the Department of Internal Medicine at the University of Illinois Cancer Center in Chicago and part of the university’s Cancer Prevention and Control research program. These include socioeconomic status, access to timely and high-quality care across the cancer control continuum, cultural beliefs, differences in genetic makeup and tumor biology, as well as system biases, such as implicit biases and systemic racism, Dr. Ganschow said.

Dr. Islami adds that gaps in access to cancer prevention, early detection, and treatment are largely rooted in fundamental inequities in social determinants of health (SDH), such as whether a patient has safe housing, transportation, education, job opportunities, income, access to nutritious foods, and language and literacy skills, among others.

Dr. Islami’s analysis, for example, shows that people of color are generally more likely to have lower educational attainment and to experience poverty, food insecurity, and housing insecurity compared with White people. Among people aged 18-64 years, the age-adjusted proportion of individuals with no health insurance in 2021 was also higher among Black (13.7%), American Indian/Alaskan Native (18.7%), and Hispanic (28.7%) patients than among White (7.8%) or Asian (5.9%) people, according to the report.

Competing needs can also get in the way of prioritizing cancer screenings, especially for patients in lower socio-economic populations, Dr. Ganschow said.

University of Illinois Cancer Center

Biological Differences, Bad Testing Recommendations May Contribute to Poor Outcomes

Differences in biology may be one overlooked internal driver of lower breast cancer survival in Black women.

Researchers at Sanford Burnham Prebys in La Jolla, California, recently analyzed the breast cells of White and Black women, finding significant molecular differences that may be contributing to higher breast cancer mortality rates in Black women.

Investigators analyzed both healthy tissue and tumor tissue from 185 Black women and compared the samples to that of White women. They discovered differences among Black and White women in the way their DNA repair genes are expressed, both in healthy breast tissue and in tumors positive for estrogen receptor breast cancer. Molecular differences were also present in the cellular signals that control how fast cells, including cancer cells, grow.

DNA repair is part of normal cellular function and helps cells recover from damage that can occur during DNA replication or in response to external factors, such as stress.

“One of the first lines of defense, to prevent the cell from becoming a tumor are DNA damage repair pathways,” said Svasti Haricharan, PhD, a coauthor of the study and an assistant professor at Sanford Burnham Prebys. “We know there are many different DNA damage repair pathways that respond to different types of DNA damage. What we didn’t know was that, even in our normal cells, based on your race and ethnicity, you have different levels of DNA repair proteins.”

Sanford Burnham Prebys

University of Illinois Cancer Center

How Neighborhood Impacts Breast Cancer, Death Rates

Living in a disadvantaged neighborhood also lowers breast cancer survival, according to new research. A disadvantaged neighborhood is generally defined as a location associated with higher concentrations of poverty, higher rates of unemployment, and less access to health care, quality housing, food, and community resources, according to the Centers for Disease Control and Prevention.

Authors of a study published in JAMA Network Open on April 18 identified 350,824 patients with breast cancer. Of these, 41,519 (11.8%) were Hispanic, 39,631 (11.3%) were non-Hispanic Black, and 234,698 (66.9%) were non-Hispanic White. Investigators divided the patients into five groups representing the lowest to highest neighborhood socioeconomic indices using the Yost Index. (The Yost Index is used by the National Cancer Institute for cancer surveillance and is based on variables such as household income, home value, median rent, percentage below 150% of the poverty line, education, and unemployment.)

Of the Black and Hispanic patients in the study, the highest proportions of both demographics lived in the most disadvantaged neighborhoods. (16,141 Black patients [30.9%]) and 10,168 Hispanic patients [19.5%]). Although 45% of White patients also fell into that same category, the highest proportion of White patients in the study lived in the most advantaged neighborhoods (66,529 patients [76.2%]).

Findings showed patients in the most disadvantaged neighborhoods had the highest proportion of triple-negative breast cancer. Patients in this group also had the lowest proportion of patients who completed surgery and radiation, and the highest proportion of patients who received chemotherapy, compared with all other neighborhood groups. The most advantaged neighborhoods group had higher proportions of localized-stage cancer, a higher proportion of patients who underwent surgery and radiation, and the lowest proportion of patients receiving chemotherapy treatment.

Patients in the most disadvantaged neighborhoods also had the highest risk of mortality (hazard ratio [HR,] 1.53; 95% CI, 1.48-1.59; P less than .001) compared with patients living in the most advantaged neighborhoods. Non-Hispanic Black patients in particular, had the highest risk of mortality, compared with non-Hispanic White patients (HR, 1.16; 95% CI, 1.13-1.20; P less than .001).

Authors wrote that the findings suggest neighborhood disadvantage is independently associated with shorter survival in patients with breast cancer, even after controlling for individual-level factors, tumor characteristics, and treatment.

“To address these residual disparities associated with neighborhood disadvantage, research must focus on which components of the built environment influence outcomes,” the authors said.

Another recent study also found correlations among where breast cancer patients lived and how they fared with the disease.

Jasmine M. Miller-Kleinhenz, PhD, an assistant professor at University of Mississippi Medical Center in Jackson, studied how historical redlining impacts breast cancer development and outcomes in her research published in JAMA Network Open, earlier this year. Redlining refers to the practice of denying people access to credit because of where they live. Historically, mortgage lenders widely redlined neighborhoods with predominantly Black residents. The 1968 Fair Housing Act outlawed racially motivated redlining, but consequences from historical redlining still exist.

University of Mississippi Medical Center

Hope for Improved Outcomes, Higher Survival Rates

Investigators hope the findings of all of this new research lead to better, more targeted treatments and, in turn, improved outcomes.

Dr. Haricharan is optimistic about the improvement of breast cancer outcomes as more is learned about the biology of Black patients and other non-White patients.

There is a growing effort to include more data from minoritized populations in breast cancer research studies, Dr. Haricharan said, and she foresees associated changes to clinical protocols in the future. Her own team is working on creating larger data sets that are more representative of non-White patients to further analyze the differences found in their prior study.

“I think there’s this understanding that, until we have data sets that are more representative, we really are catering to [only one] population in terms of our diagnostic and therapeutic technological advances,” she said.

The American Cancer Society meanwhile, is launching a new initiative in May that aims to collect more health data from Black women to ultimately develop more effective cancer interventions. VOICES of Black Women will focus on collecting and studying health data from Black women through online surveys. The society’s goal is to enroll at least 100,000 Black women in the United States between ages 25 and 55.

Dr. Miller-Kleinhenz called the initiative “an important step to starting to research and answer some of these lingering questions about why there continue to be breast cancer disparities.”

More women today are surviving breast cancer if it’s caught early, largely because of better screening and more effective and targeted treatments.

However, not everyone has benefited equitably from this progress. Critical gaps in breast cancer outcomes and survival remain for women in racial and ethnic minority groups.

Black women for instance, have a 41% higher death rate from breast cancer compared with White patients. They also have a greater incidence of aggressive disease like triple-negative breast cancer. Native American and Hispanic women, meanwhile, are more likely to be diagnosed with breast cancer at an earlier age than White women and experience more aggressive breast cancers.

In 2023, Farhad Islami, MD, PhD, and his team published an updated analysis of racial/ethnic and socioeconomic disparities in cancer trends based on data from 2014 to 2020. The analysis found that Black women in particular, were the least likely to have an early-stage diagnosis of breast cancer. Localized‐stage breast cancer was diagnosed in 57% of Black women versus 68% of White women.

American Cancer Society

“Despite substantial progress in cancer prevention, early detection, and treatments, the burden of cancer remains greater among populations that have been historically marginalized, including people of color, people with lower socioeconomic status, and people living in nonmetropolitan areas,” said Dr. Islami, who is senior scientific director of cancer disparity research in the Surveillance & Health Equity Science Department at the American Cancer Society.

The reasons behind outcomes disparities in breast cancer are complex, making solutions challenging, say experts researching racial differences in cancer outcomes.

While social determinants of health (SDH) seem to be drivers of higher breast cancer mortality in Black women, biological differences between Black and White women are also linked to poorer outcomes in Black women with breast cancer, new studies suggest. Among the findings of this research is that breast cancer tests may be contributing to the disparities and misguiding care for some patients of color.
 

SDH and Screening Rates Differences By Race

A range of factors contribute to racial and ethnic disparities in breast cancer outcomes, said Pamela Ganschow, MD, an associate professor in the Department of Internal Medicine at the University of Illinois Cancer Center in Chicago and part of the university’s Cancer Prevention and Control research program. These include socioeconomic status, access to timely and high-quality care across the cancer control continuum, cultural beliefs, differences in genetic makeup and tumor biology, as well as system biases, such as implicit biases and systemic racism, Dr. Ganschow said.

Dr. Islami adds that gaps in access to cancer prevention, early detection, and treatment are largely rooted in fundamental inequities in social determinants of health (SDH), such as whether a patient has safe housing, transportation, education, job opportunities, income, access to nutritious foods, and language and literacy skills, among others.

Dr. Islami’s analysis, for example, shows that people of color are generally more likely to have lower educational attainment and to experience poverty, food insecurity, and housing insecurity compared with White people. Among people aged 18-64 years, the age-adjusted proportion of individuals with no health insurance in 2021 was also higher among Black (13.7%), American Indian/Alaskan Native (18.7%), and Hispanic (28.7%) patients than among White (7.8%) or Asian (5.9%) people, according to the report.

Competing needs can also get in the way of prioritizing cancer screenings, especially for patients in lower socio-economic populations, Dr. Ganschow said.

University of Illinois Cancer Center

Biological Differences, Bad Testing Recommendations May Contribute to Poor Outcomes

Differences in biology may be one overlooked internal driver of lower breast cancer survival in Black women.

Researchers at Sanford Burnham Prebys in La Jolla, California, recently analyzed the breast cells of White and Black women, finding significant molecular differences that may be contributing to higher breast cancer mortality rates in Black women.

Investigators analyzed both healthy tissue and tumor tissue from 185 Black women and compared the samples to that of White women. They discovered differences among Black and White women in the way their DNA repair genes are expressed, both in healthy breast tissue and in tumors positive for estrogen receptor breast cancer. Molecular differences were also present in the cellular signals that control how fast cells, including cancer cells, grow.

DNA repair is part of normal cellular function and helps cells recover from damage that can occur during DNA replication or in response to external factors, such as stress.

“One of the first lines of defense, to prevent the cell from becoming a tumor are DNA damage repair pathways,” said Svasti Haricharan, PhD, a coauthor of the study and an assistant professor at Sanford Burnham Prebys. “We know there are many different DNA damage repair pathways that respond to different types of DNA damage. What we didn’t know was that, even in our normal cells, based on your race and ethnicity, you have different levels of DNA repair proteins.”

Sanford Burnham Prebys

University of Illinois Cancer Center

How Neighborhood Impacts Breast Cancer, Death Rates

Living in a disadvantaged neighborhood also lowers breast cancer survival, according to new research. A disadvantaged neighborhood is generally defined as a location associated with higher concentrations of poverty, higher rates of unemployment, and less access to health care, quality housing, food, and community resources, according to the Centers for Disease Control and Prevention.

Authors of a study published in JAMA Network Open on April 18 identified 350,824 patients with breast cancer. Of these, 41,519 (11.8%) were Hispanic, 39,631 (11.3%) were non-Hispanic Black, and 234,698 (66.9%) were non-Hispanic White. Investigators divided the patients into five groups representing the lowest to highest neighborhood socioeconomic indices using the Yost Index. (The Yost Index is used by the National Cancer Institute for cancer surveillance and is based on variables such as household income, home value, median rent, percentage below 150% of the poverty line, education, and unemployment.)

Of the Black and Hispanic patients in the study, the highest proportions of both demographics lived in the most disadvantaged neighborhoods. (16,141 Black patients [30.9%]) and 10,168 Hispanic patients [19.5%]). Although 45% of White patients also fell into that same category, the highest proportion of White patients in the study lived in the most advantaged neighborhoods (66,529 patients [76.2%]).

Findings showed patients in the most disadvantaged neighborhoods had the highest proportion of triple-negative breast cancer. Patients in this group also had the lowest proportion of patients who completed surgery and radiation, and the highest proportion of patients who received chemotherapy, compared with all other neighborhood groups. The most advantaged neighborhoods group had higher proportions of localized-stage cancer, a higher proportion of patients who underwent surgery and radiation, and the lowest proportion of patients receiving chemotherapy treatment.

Patients in the most disadvantaged neighborhoods also had the highest risk of mortality (hazard ratio [HR,] 1.53; 95% CI, 1.48-1.59; P less than .001) compared with patients living in the most advantaged neighborhoods. Non-Hispanic Black patients in particular, had the highest risk of mortality, compared with non-Hispanic White patients (HR, 1.16; 95% CI, 1.13-1.20; P less than .001).

Authors wrote that the findings suggest neighborhood disadvantage is independently associated with shorter survival in patients with breast cancer, even after controlling for individual-level factors, tumor characteristics, and treatment.

“To address these residual disparities associated with neighborhood disadvantage, research must focus on which components of the built environment influence outcomes,” the authors said.

Another recent study also found correlations among where breast cancer patients lived and how they fared with the disease.

Jasmine M. Miller-Kleinhenz, PhD, an assistant professor at University of Mississippi Medical Center in Jackson, studied how historical redlining impacts breast cancer development and outcomes in her research published in JAMA Network Open, earlier this year. Redlining refers to the practice of denying people access to credit because of where they live. Historically, mortgage lenders widely redlined neighborhoods with predominantly Black residents. The 1968 Fair Housing Act outlawed racially motivated redlining, but consequences from historical redlining still exist.

University of Mississippi Medical Center

Hope for Improved Outcomes, Higher Survival Rates

Investigators hope the findings of all of this new research lead to better, more targeted treatments and, in turn, improved outcomes.

Dr. Haricharan is optimistic about the improvement of breast cancer outcomes as more is learned about the biology of Black patients and other non-White patients.

There is a growing effort to include more data from minoritized populations in breast cancer research studies, Dr. Haricharan said, and she foresees associated changes to clinical protocols in the future. Her own team is working on creating larger data sets that are more representative of non-White patients to further analyze the differences found in their prior study.

“I think there’s this understanding that, until we have data sets that are more representative, we really are catering to [only one] population in terms of our diagnostic and therapeutic technological advances,” she said.

The American Cancer Society meanwhile, is launching a new initiative in May that aims to collect more health data from Black women to ultimately develop more effective cancer interventions. VOICES of Black Women will focus on collecting and studying health data from Black women through online surveys. The society’s goal is to enroll at least 100,000 Black women in the United States between ages 25 and 55.

Dr. Miller-Kleinhenz called the initiative “an important step to starting to research and answer some of these lingering questions about why there continue to be breast cancer disparities.”

More women today are surviving breast cancer if it’s caught early, largely because of better screening and more effective and targeted treatments.

However, not everyone has benefited equitably from this progress. Critical gaps in breast cancer outcomes and survival remain for women in racial and ethnic minority groups.

Black women for instance, have a 41% higher death rate from breast cancer compared with White patients. They also have a greater incidence of aggressive disease like triple-negative breast cancer. Native American and Hispanic women, meanwhile, are more likely to be diagnosed with breast cancer at an earlier age than White women and experience more aggressive breast cancers.

In 2023, Farhad Islami, MD, PhD, and his team published an updated analysis of racial/ethnic and socioeconomic disparities in cancer trends based on data from 2014 to 2020. The analysis found that Black women in particular, were the least likely to have an early-stage diagnosis of breast cancer. Localized‐stage breast cancer was diagnosed in 57% of Black women versus 68% of White women.

American Cancer Society

“Despite substantial progress in cancer prevention, early detection, and treatments, the burden of cancer remains greater among populations that have been historically marginalized, including people of color, people with lower socioeconomic status, and people living in nonmetropolitan areas,” said Dr. Islami, who is senior scientific director of cancer disparity research in the Surveillance & Health Equity Science Department at the American Cancer Society.

The reasons behind outcomes disparities in breast cancer are complex, making solutions challenging, say experts researching racial differences in cancer outcomes.

While social determinants of health (SDH) seem to be drivers of higher breast cancer mortality in Black women, biological differences between Black and White women are also linked to poorer outcomes in Black women with breast cancer, new studies suggest. Among the findings of this research is that breast cancer tests may be contributing to the disparities and misguiding care for some patients of color.
 

SDH and Screening Rates Differences By Race

A range of factors contribute to racial and ethnic disparities in breast cancer outcomes, said Pamela Ganschow, MD, an associate professor in the Department of Internal Medicine at the University of Illinois Cancer Center in Chicago and part of the university’s Cancer Prevention and Control research program. These include socioeconomic status, access to timely and high-quality care across the cancer control continuum, cultural beliefs, differences in genetic makeup and tumor biology, as well as system biases, such as implicit biases and systemic racism, Dr. Ganschow said.

Dr. Islami adds that gaps in access to cancer prevention, early detection, and treatment are largely rooted in fundamental inequities in social determinants of health (SDH), such as whether a patient has safe housing, transportation, education, job opportunities, income, access to nutritious foods, and language and literacy skills, among others.

Dr. Islami’s analysis, for example, shows that people of color are generally more likely to have lower educational attainment and to experience poverty, food insecurity, and housing insecurity compared with White people. Among people aged 18-64 years, the age-adjusted proportion of individuals with no health insurance in 2021 was also higher among Black (13.7%), American Indian/Alaskan Native (18.7%), and Hispanic (28.7%) patients than among White (7.8%) or Asian (5.9%) people, according to the report.

Competing needs can also get in the way of prioritizing cancer screenings, especially for patients in lower socio-economic populations, Dr. Ganschow said.

University of Illinois Cancer Center

Biological Differences, Bad Testing Recommendations May Contribute to Poor Outcomes

Differences in biology may be one overlooked internal driver of lower breast cancer survival in Black women.

Researchers at Sanford Burnham Prebys in La Jolla, California, recently analyzed the breast cells of White and Black women, finding significant molecular differences that may be contributing to higher breast cancer mortality rates in Black women.

Investigators analyzed both healthy tissue and tumor tissue from 185 Black women and compared the samples to that of White women. They discovered differences among Black and White women in the way their DNA repair genes are expressed, both in healthy breast tissue and in tumors positive for estrogen receptor breast cancer. Molecular differences were also present in the cellular signals that control how fast cells, including cancer cells, grow.

DNA repair is part of normal cellular function and helps cells recover from damage that can occur during DNA replication or in response to external factors, such as stress.

“One of the first lines of defense, to prevent the cell from becoming a tumor are DNA damage repair pathways,” said Svasti Haricharan, PhD, a coauthor of the study and an assistant professor at Sanford Burnham Prebys. “We know there are many different DNA damage repair pathways that respond to different types of DNA damage. What we didn’t know was that, even in our normal cells, based on your race and ethnicity, you have different levels of DNA repair proteins.”

Sanford Burnham Prebys

University of Illinois Cancer Center

How Neighborhood Impacts Breast Cancer, Death Rates

Living in a disadvantaged neighborhood also lowers breast cancer survival, according to new research. A disadvantaged neighborhood is generally defined as a location associated with higher concentrations of poverty, higher rates of unemployment, and less access to health care, quality housing, food, and community resources, according to the Centers for Disease Control and Prevention.

Authors of a study published in JAMA Network Open on April 18 identified 350,824 patients with breast cancer. Of these, 41,519 (11.8%) were Hispanic, 39,631 (11.3%) were non-Hispanic Black, and 234,698 (66.9%) were non-Hispanic White. Investigators divided the patients into five groups representing the lowest to highest neighborhood socioeconomic indices using the Yost Index. (The Yost Index is used by the National Cancer Institute for cancer surveillance and is based on variables such as household income, home value, median rent, percentage below 150% of the poverty line, education, and unemployment.)

Of the Black and Hispanic patients in the study, the highest proportions of both demographics lived in the most disadvantaged neighborhoods. (16,141 Black patients [30.9%]) and 10,168 Hispanic patients [19.5%]). Although 45% of White patients also fell into that same category, the highest proportion of White patients in the study lived in the most advantaged neighborhoods (66,529 patients [76.2%]).

Findings showed patients in the most disadvantaged neighborhoods had the highest proportion of triple-negative breast cancer. Patients in this group also had the lowest proportion of patients who completed surgery and radiation, and the highest proportion of patients who received chemotherapy, compared with all other neighborhood groups. The most advantaged neighborhoods group had higher proportions of localized-stage cancer, a higher proportion of patients who underwent surgery and radiation, and the lowest proportion of patients receiving chemotherapy treatment.

Patients in the most disadvantaged neighborhoods also had the highest risk of mortality (hazard ratio [HR,] 1.53; 95% CI, 1.48-1.59; P less than .001) compared with patients living in the most advantaged neighborhoods. Non-Hispanic Black patients in particular, had the highest risk of mortality, compared with non-Hispanic White patients (HR, 1.16; 95% CI, 1.13-1.20; P less than .001).

Authors wrote that the findings suggest neighborhood disadvantage is independently associated with shorter survival in patients with breast cancer, even after controlling for individual-level factors, tumor characteristics, and treatment.

“To address these residual disparities associated with neighborhood disadvantage, research must focus on which components of the built environment influence outcomes,” the authors said.

Another recent study also found correlations among where breast cancer patients lived and how they fared with the disease.

Jasmine M. Miller-Kleinhenz, PhD, an assistant professor at University of Mississippi Medical Center in Jackson, studied how historical redlining impacts breast cancer development and outcomes in her research published in JAMA Network Open, earlier this year. Redlining refers to the practice of denying people access to credit because of where they live. Historically, mortgage lenders widely redlined neighborhoods with predominantly Black residents. The 1968 Fair Housing Act outlawed racially motivated redlining, but consequences from historical redlining still exist.

University of Mississippi Medical Center

Hope for Improved Outcomes, Higher Survival Rates

Investigators hope the findings of all of this new research lead to better, more targeted treatments and, in turn, improved outcomes.

Dr. Haricharan is optimistic about the improvement of breast cancer outcomes as more is learned about the biology of Black patients and other non-White patients.

There is a growing effort to include more data from minoritized populations in breast cancer research studies, Dr. Haricharan said, and she foresees associated changes to clinical protocols in the future. Her own team is working on creating larger data sets that are more representative of non-White patients to further analyze the differences found in their prior study.

“I think there’s this understanding that, until we have data sets that are more representative, we really are catering to [only one] population in terms of our diagnostic and therapeutic technological advances,” she said.

The American Cancer Society meanwhile, is launching a new initiative in May that aims to collect more health data from Black women to ultimately develop more effective cancer interventions. VOICES of Black Women will focus on collecting and studying health data from Black women through online surveys. The society’s goal is to enroll at least 100,000 Black women in the United States between ages 25 and 55.

Dr. Miller-Kleinhenz called the initiative “an important step to starting to research and answer some of these lingering questions about why there continue to be breast cancer disparities.”

Gut microbiota signatures associated with KRAS mutations in patients with colorectal cancer (CRC) have been identified by researchers.

Their findings suggest that the gut microbes may serve as noninvasive biomarkers to help identify subtypes of CRC and guide personalized treatment recommendations.

“Our new work contributes to the growing body of evidence highlighting the significance of microbiota-driven mechanisms in cancer pathogenesis,” lead investigator Weizhong Tang, MD, with Guangxi Medical University Cancer Hospital in Nanning, China, said in a statement. 

The research was recently published online in Microbiology Spectrum. 

The onset and growth of CRC has been linked both to imbalances in the gut microbiome and to mutations in the KRAS gene — about 40% of people with CRC have a KRAS mutation. Yet, the interplay between gut dysbiosis and KRAS mutations in CRC remains unclear. 

To investigate further, Dr. Tang and colleagues used 16s rRNA sequencing to analyze stool samples from 94 patients with CRC, including 24 with KRAS-mutated CRC and 70 with KRAS wild-type (nonmutated) CRC. 

The researchers identified 26 distinct types of gut microbiota with statistically significant differences in abundance between the KRAS mutant and KRAS wild-type CRC patients.

At the genus level, Fusobacterium, Clostridium, and Shewanella were all abundant in the KRAS mutant group. 

Fusobacterium is a Gram-negative microbe found in the gastrointestinal tract and the oral cavity. Recent studies have established a strong link between Fusobacterium and CRC development. Other work found elevated levels of Fusobacterium nucleatum were not only closely associated with KRAS mutation but also correlated with chemoresistance in CRC.

Clostridium produces metabolites in the large intestine, which are known to cause DNA damage and trigger inflammatory responses, thereby increasing the risk of CRC development. 

Similarly, Shewanella has been proven to be a contributor to CRC development.

The researchers say it’s “plausible” to consider all three as potential noninvasive biomarkers for identifying KRAS mutation in CRC patients.

In contrast, Bifidobacterium and Akkermansia were abundant in the KRAS wild-type group. 

Bifidobacterium is a probiotic with antitumor activity and Akkermansia is a Gram-negative anaerobic bacterium abundant in the gut and currently recognized as a potential probiotic. 

The researchers speculated that CRC patients may have a reduced likelihood of developing KRAS mutation in the presence of Bifidobacterium and Akkermansia.

Analyses of biological pathways of gut microbiota associated with KRAS mutation status in CRC revealed a significantly higher abundance of the isoflavonoid biosynthesis pathway in the KRAS wild-type group compared with the KRAS mutant group.

“In comparison to KRAS mutant CRC, it is postulated that KRAS wild-type CRC may be less aggressive due to the upregulation of the isoflavonoid biosynthesis pathway, which may inhibit CRC development and progression,” the authors wrote.

Promising Predictive Model

Dr. Tang and colleagues also developed a machine learning model to predict KRAS mutation status in CRC patients based on the gut microbiota signature in KRAS mutant CRC. 

The initial results underscore the model’s predictive efficacy and suggest that it has “considerable potential for clinical application, offering a novel dimension in the prediction of KRAS mutation status among CRC patients in a clinical setting,” the authors wrote. 

They caution that the model requires data from a larger cohort to improve its efficacy, and they plan to do larger studies to validate the findings. 

The study had no commercial funding. The authors declared no relevant conflicts of interest. 

A version of this article appeared on Medscape.com.

Gut microbiota signatures associated with KRAS mutations in patients with colorectal cancer (CRC) have been identified by researchers.

Their findings suggest that the gut microbes may serve as noninvasive biomarkers to help identify subtypes of CRC and guide personalized treatment recommendations.

“Our new work contributes to the growing body of evidence highlighting the significance of microbiota-driven mechanisms in cancer pathogenesis,” lead investigator Weizhong Tang, MD, with Guangxi Medical University Cancer Hospital in Nanning, China, said in a statement. 

The research was recently published online in Microbiology Spectrum. 

The onset and growth of CRC has been linked both to imbalances in the gut microbiome and to mutations in the KRAS gene — about 40% of people with CRC have a KRAS mutation. Yet, the interplay between gut dysbiosis and KRAS mutations in CRC remains unclear. 

To investigate further, Dr. Tang and colleagues used 16s rRNA sequencing to analyze stool samples from 94 patients with CRC, including 24 with KRAS-mutated CRC and 70 with KRAS wild-type (nonmutated) CRC. 

The researchers identified 26 distinct types of gut microbiota with statistically significant differences in abundance between the KRAS mutant and KRAS wild-type CRC patients.

At the genus level, Fusobacterium, Clostridium, and Shewanella were all abundant in the KRAS mutant group. 

Fusobacterium is a Gram-negative microbe found in the gastrointestinal tract and the oral cavity. Recent studies have established a strong link between Fusobacterium and CRC development. Other work found elevated levels of Fusobacterium nucleatum were not only closely associated with KRAS mutation but also correlated with chemoresistance in CRC.

Clostridium produces metabolites in the large intestine, which are known to cause DNA damage and trigger inflammatory responses, thereby increasing the risk of CRC development. 

Similarly, Shewanella has been proven to be a contributor to CRC development.

The researchers say it’s “plausible” to consider all three as potential noninvasive biomarkers for identifying KRAS mutation in CRC patients.

In contrast, Bifidobacterium and Akkermansia were abundant in the KRAS wild-type group. 

Bifidobacterium is a probiotic with antitumor activity and Akkermansia is a Gram-negative anaerobic bacterium abundant in the gut and currently recognized as a potential probiotic. 

The researchers speculated that CRC patients may have a reduced likelihood of developing KRAS mutation in the presence of Bifidobacterium and Akkermansia.

Analyses of biological pathways of gut microbiota associated with KRAS mutation status in CRC revealed a significantly higher abundance of the isoflavonoid biosynthesis pathway in the KRAS wild-type group compared with the KRAS mutant group.

“In comparison to KRAS mutant CRC, it is postulated that KRAS wild-type CRC may be less aggressive due to the upregulation of the isoflavonoid biosynthesis pathway, which may inhibit CRC development and progression,” the authors wrote.

Promising Predictive Model

Dr. Tang and colleagues also developed a machine learning model to predict KRAS mutation status in CRC patients based on the gut microbiota signature in KRAS mutant CRC. 

The initial results underscore the model’s predictive efficacy and suggest that it has “considerable potential for clinical application, offering a novel dimension in the prediction of KRAS mutation status among CRC patients in a clinical setting,” the authors wrote. 

They caution that the model requires data from a larger cohort to improve its efficacy, and they plan to do larger studies to validate the findings. 

The study had no commercial funding. The authors declared no relevant conflicts of interest. 

A version of this article appeared on Medscape.com.

Gut microbiota signatures associated with KRAS mutations in patients with colorectal cancer (CRC) have been identified by researchers.

Their findings suggest that the gut microbes may serve as noninvasive biomarkers to help identify subtypes of CRC and guide personalized treatment recommendations.

“Our new work contributes to the growing body of evidence highlighting the significance of microbiota-driven mechanisms in cancer pathogenesis,” lead investigator Weizhong Tang, MD, with Guangxi Medical University Cancer Hospital in Nanning, China, said in a statement. 

The research was recently published online in Microbiology Spectrum. 

The onset and growth of CRC has been linked both to imbalances in the gut microbiome and to mutations in the KRAS gene — about 40% of people with CRC have a KRAS mutation. Yet, the interplay between gut dysbiosis and KRAS mutations in CRC remains unclear. 

To investigate further, Dr. Tang and colleagues used 16s rRNA sequencing to analyze stool samples from 94 patients with CRC, including 24 with KRAS-mutated CRC and 70 with KRAS wild-type (nonmutated) CRC. 

The researchers identified 26 distinct types of gut microbiota with statistically significant differences in abundance between the KRAS mutant and KRAS wild-type CRC patients.

At the genus level, Fusobacterium, Clostridium, and Shewanella were all abundant in the KRAS mutant group. 

Fusobacterium is a Gram-negative microbe found in the gastrointestinal tract and the oral cavity. Recent studies have established a strong link between Fusobacterium and CRC development. Other work found elevated levels of Fusobacterium nucleatum were not only closely associated with KRAS mutation but also correlated with chemoresistance in CRC.

Clostridium produces metabolites in the large intestine, which are known to cause DNA damage and trigger inflammatory responses, thereby increasing the risk of CRC development. 

Similarly, Shewanella has been proven to be a contributor to CRC development.

The researchers say it’s “plausible” to consider all three as potential noninvasive biomarkers for identifying KRAS mutation in CRC patients.

In contrast, Bifidobacterium and Akkermansia were abundant in the KRAS wild-type group. 

Bifidobacterium is a probiotic with antitumor activity and Akkermansia is a Gram-negative anaerobic bacterium abundant in the gut and currently recognized as a potential probiotic. 

The researchers speculated that CRC patients may have a reduced likelihood of developing KRAS mutation in the presence of Bifidobacterium and Akkermansia.

Analyses of biological pathways of gut microbiota associated with KRAS mutation status in CRC revealed a significantly higher abundance of the isoflavonoid biosynthesis pathway in the KRAS wild-type group compared with the KRAS mutant group.

“In comparison to KRAS mutant CRC, it is postulated that KRAS wild-type CRC may be less aggressive due to the upregulation of the isoflavonoid biosynthesis pathway, which may inhibit CRC development and progression,” the authors wrote.

Promising Predictive Model

Dr. Tang and colleagues also developed a machine learning model to predict KRAS mutation status in CRC patients based on the gut microbiota signature in KRAS mutant CRC. 

The initial results underscore the model’s predictive efficacy and suggest that it has “considerable potential for clinical application, offering a novel dimension in the prediction of KRAS mutation status among CRC patients in a clinical setting,” the authors wrote. 

They caution that the model requires data from a larger cohort to improve its efficacy, and they plan to do larger studies to validate the findings. 

The study had no commercial funding. The authors declared no relevant conflicts of interest. 

A version of this article appeared on Medscape.com.