Prostate Cancer

Key clinical point: In a long-term follow-up, adding short-term androgen deprivation therapy (ADT) to radiotherapy in patients with localized prostate cancer does not show overall survival (OS) benefit after 15 years.

Major finding: The OS curves of the 2 groups converge at 15 years. In the radiotherapy-alone vs combination treatment group, the OS rate at 18 years was 23% vs 23% (hazard ratio, 0.94; P =.94).

Study details: A randomized, phase 3 NRG/RTOG 9408 study of 2,028 patients with localized prostate cancer and prostate-specific antigen of ≤20 ng/mL who were randomly assigned to radiotherapy alone or radiotherapy plus short-term ADT.

Disclosures: This work was supported by National Cancer Institute. The authors performed advisory/consulting roles, received personal fees/grants and/or salary/stipend, chaired committees, and/or were employed by/owned stocks in pharmaceutical companies.

Source: Jones CU et al. Int J Radiat Oncol Biol Phys. 2021 Aug 31. doi: 10.1016/j.ijrobp.2021.08.031.

Key clinical point: In a long-term follow-up, adding short-term androgen deprivation therapy (ADT) to radiotherapy in patients with localized prostate cancer does not show overall survival (OS) benefit after 15 years.

Major finding: The OS curves of the 2 groups converge at 15 years. In the radiotherapy-alone vs combination treatment group, the OS rate at 18 years was 23% vs 23% (hazard ratio, 0.94; P =.94).

Study details: A randomized, phase 3 NRG/RTOG 9408 study of 2,028 patients with localized prostate cancer and prostate-specific antigen of ≤20 ng/mL who were randomly assigned to radiotherapy alone or radiotherapy plus short-term ADT.

Disclosures: This work was supported by National Cancer Institute. The authors performed advisory/consulting roles, received personal fees/grants and/or salary/stipend, chaired committees, and/or were employed by/owned stocks in pharmaceutical companies.

Source: Jones CU et al. Int J Radiat Oncol Biol Phys. 2021 Aug 31. doi: 10.1016/j.ijrobp.2021.08.031.

Key clinical point: In a long-term follow-up, adding short-term androgen deprivation therapy (ADT) to radiotherapy in patients with localized prostate cancer does not show overall survival (OS) benefit after 15 years.

Major finding: The OS curves of the 2 groups converge at 15 years. In the radiotherapy-alone vs combination treatment group, the OS rate at 18 years was 23% vs 23% (hazard ratio, 0.94; P =.94).

Study details: A randomized, phase 3 NRG/RTOG 9408 study of 2,028 patients with localized prostate cancer and prostate-specific antigen of ≤20 ng/mL who were randomly assigned to radiotherapy alone or radiotherapy plus short-term ADT.

Disclosures: This work was supported by National Cancer Institute. The authors performed advisory/consulting roles, received personal fees/grants and/or salary/stipend, chaired committees, and/or were employed by/owned stocks in pharmaceutical companies.

Source: Jones CU et al. Int J Radiat Oncol Biol Phys. 2021 Aug 31. doi: 10.1016/j.ijrobp.2021.08.031.

Key clinical point: Patient-reported outcomes were similar with hypofractionated vs. conventional radiotherapy at 5 years in patients with prostate cancer.

Major finding: There were no differences in the Expanded Prostate Cancer Index Composite or University of California Los Angeles Prostate Cancer Index in the overall bowel, urinary, and sexual symptoms between the 3 groups at 5 years.

Study details: Quality of life substudy of phase 3 randomized CHHiP trial of 2,100 patients with intermediate-risk prostate cancer who received conventional (74 Gy in 37 fractions over 7.4 weeks) or hypofractionated (60 Gy in 20 fractions over 4 weeks or 57 Gy in 19 fractions over 3.8 weeks) radiotherapy.

Disclosures: This study was supported by Cancer Research UK, Institute for Health Research Cancer Research Network, and National Health Service.

Source: Staffurth JN et al. Eur Urol Oncol. 2021 Sep 3. doi: 10.1016/j.euo.2021.07.005.

Key clinical point: Patient-reported outcomes were similar with hypofractionated vs. conventional radiotherapy at 5 years in patients with prostate cancer.

Major finding: There were no differences in the Expanded Prostate Cancer Index Composite or University of California Los Angeles Prostate Cancer Index in the overall bowel, urinary, and sexual symptoms between the 3 groups at 5 years.

Study details: Quality of life substudy of phase 3 randomized CHHiP trial of 2,100 patients with intermediate-risk prostate cancer who received conventional (74 Gy in 37 fractions over 7.4 weeks) or hypofractionated (60 Gy in 20 fractions over 4 weeks or 57 Gy in 19 fractions over 3.8 weeks) radiotherapy.

Disclosures: This study was supported by Cancer Research UK, Institute for Health Research Cancer Research Network, and National Health Service.

Source: Staffurth JN et al. Eur Urol Oncol. 2021 Sep 3. doi: 10.1016/j.euo.2021.07.005.

Key clinical point: Patient-reported outcomes were similar with hypofractionated vs. conventional radiotherapy at 5 years in patients with prostate cancer.

Major finding: There were no differences in the Expanded Prostate Cancer Index Composite or University of California Los Angeles Prostate Cancer Index in the overall bowel, urinary, and sexual symptoms between the 3 groups at 5 years.

Study details: Quality of life substudy of phase 3 randomized CHHiP trial of 2,100 patients with intermediate-risk prostate cancer who received conventional (74 Gy in 37 fractions over 7.4 weeks) or hypofractionated (60 Gy in 20 fractions over 4 weeks or 57 Gy in 19 fractions over 3.8 weeks) radiotherapy.

Disclosures: This study was supported by Cancer Research UK, Institute for Health Research Cancer Research Network, and National Health Service.

Source: Staffurth JN et al. Eur Urol Oncol. 2021 Sep 3. doi: 10.1016/j.euo.2021.07.005.

Key clinical point: Overall health-related quality of life (HRQoL) was maintained with the addition of apalutamide to androgen deprivation therapy (ADT) in patients with nonmetastatic castration-resistant prostate cancer (CRPC).

Major finding: The change in Functional Assessment of Cancer Therapy-Prostate (FACT-P) total score significantly favored apalutamide vs placebo at treatment cycles 21 (P = .0138) and 25 (P = .0009). No difference was seen in the median time to deterioration in scores for FACT-P and subscales.

Study details: HRQoL analysis of phase 3, randomized SPARTAN trial of patients with nmCRPC who were randomly assigned to receive apalutamide or placebo. All patients continued ADT.

Disclosures: This study was funded by Janssen Research & Development. The authors received consulting/personal/advisory/speaker fees, honoraria, royalties, research funding, lectureship fees, and/or travel expenses from various sources. Some authors reported being an investigator in clinical trials and stock ownership in pharmaceutical companies.

Source: Oudard S et al. Eur Urol Focus. 2021 Aug 31. doi: 10.1016/j.euf.2021.08.005.

Key clinical point: Overall health-related quality of life (HRQoL) was maintained with the addition of apalutamide to androgen deprivation therapy (ADT) in patients with nonmetastatic castration-resistant prostate cancer (CRPC).

Major finding: The change in Functional Assessment of Cancer Therapy-Prostate (FACT-P) total score significantly favored apalutamide vs placebo at treatment cycles 21 (P = .0138) and 25 (P = .0009). No difference was seen in the median time to deterioration in scores for FACT-P and subscales.

Study details: HRQoL analysis of phase 3, randomized SPARTAN trial of patients with nmCRPC who were randomly assigned to receive apalutamide or placebo. All patients continued ADT.

Disclosures: This study was funded by Janssen Research & Development. The authors received consulting/personal/advisory/speaker fees, honoraria, royalties, research funding, lectureship fees, and/or travel expenses from various sources. Some authors reported being an investigator in clinical trials and stock ownership in pharmaceutical companies.

Source: Oudard S et al. Eur Urol Focus. 2021 Aug 31. doi: 10.1016/j.euf.2021.08.005.

Key clinical point: Overall health-related quality of life (HRQoL) was maintained with the addition of apalutamide to androgen deprivation therapy (ADT) in patients with nonmetastatic castration-resistant prostate cancer (CRPC).

Major finding: The change in Functional Assessment of Cancer Therapy-Prostate (FACT-P) total score significantly favored apalutamide vs placebo at treatment cycles 21 (P = .0138) and 25 (P = .0009). No difference was seen in the median time to deterioration in scores for FACT-P and subscales.

Study details: HRQoL analysis of phase 3, randomized SPARTAN trial of patients with nmCRPC who were randomly assigned to receive apalutamide or placebo. All patients continued ADT.

Disclosures: This study was funded by Janssen Research & Development. The authors received consulting/personal/advisory/speaker fees, honoraria, royalties, research funding, lectureship fees, and/or travel expenses from various sources. Some authors reported being an investigator in clinical trials and stock ownership in pharmaceutical companies.

Source: Oudard S et al. Eur Urol Focus. 2021 Aug 31. doi: 10.1016/j.euf.2021.08.005.

Nearly 80% of men with metastatic prostate cancer died from their malignancy, according to a retrospective cohort study involving 26,000-plus American men diagnosed with advanced disease in roughly the last 20 years.

The findings fill an information gap because, remarkably, “data are lacking” on causes of death among men whose prostate cancer has spread to other sites, say lead author Ahmed Elmehrath, MD, of Cairo University, Egypt, and colleagues.

“It was an important realization by our team that prostate cancer was the cause of death in 78% of patients,” said senior author Omar Alhalabi, MD, of University of Texas MD Anderson Cancer Center, Houston, in an email.

“Most patients with metastatic prostate cancer die from it, rather than other possible causes of death,” confirm Samuel Merriel, MSc, Tanimola Martins, PhD, and Sarah Bailey, PhD, University of Exeter, United Kingdom, in an accompanying editorial. The study was published last month in JAMA Network Open.

The findings represent the near opposite of a commonly held – and comforting – belief about early-stage disease: “You die with prostate cancer, not from it.”

That old saying is articulated in various ways, such as this from the Prostate Cancer Foundation: “We can confirm that there are those prostate cancers a man may die with and not of, while others are very aggressive.” The American Cancer Society says this: “Prostate cancer can be a serious disease, but most men diagnosed with prostate cancer do not die from it.”

However, these commonplace comments do not cover metastatic disease, which is what the authors of the new study decided to focus on.  

The team used data from the Surveillance, Epidemiology, and End Results Program (SEER) database to gather a sample of 26,168 U.S. men who received a diagnosis of metastatic prostate cancer from January 2000 to December 2016. They then analyzed the data in 2020 and found that 16,732 men (64%) had died during the follow-up period.

The majority of these deaths (77.8%) were from prostate cancer, 5.5% were from other cancers, and 16.7% were from noncancer causes, including cardiovascular diseases, chronic obstructive pulmonary disease, and cerebrovascular diseases.

Senior author Dr. Alhalabi acknowledged a limitation in these findings – that the SEER database relies on causes of death extracted from death certificates. “Death certificates have limited granularity in terms of the details they can contain about the cause of death and also have reporting bias,” he said.

Most of the prostate cancer deaths (59%) occurred within 2 years. The 5-year overall survival rate in the study group was 26%.

The deadliness of metastatic disease “reinforces the need for innovations to promote early-stage diagnosis,” comment the editorialists. Striking a hopeful note, they also say that “new tests for prostate cancer detection may reduce the proportion of patients who receive a diagnosis at a late stage.”
 

Death from other causes

The mean age at metastatic prostate cancer diagnosis in the study was roughly 71 years. Most of the cohort was White (74.5%) and had a diagnosis of stage M1b metastatic prostate cancer (72.7%), which means the cancer had spread to the bones.

Among men in the cohort, the rates of death from septicemia, suicide, accidents, COPD, and cerebrovascular diseases were significantly increased compared with the general U.S. male population, the team observes.

Thus, the study authors were concerned with not only with death from metastatic prostate cancer but death from other causes.

That concern is rooted in the established fact that there is now improved survival among patients with prostate cancer in the U.S., including among men with advanced disease. “Patients tend to live long enough after a prostate cancer diagnosis for non–cancer-related comorbidities to be associated with their overall survival,” they write.

The editorialists agree: Prostate cancer “has a high long-term survival rate compared with almost all other cancer types and signals the need for greater holistic care for patients.”

As noted above, cardiovascular diseases were the most common cause of nonprostate cancer–related deaths in the new study.

As in the management of other cancers, there is concern among clinicians and researchers about the cardiotoxic effects of prostate cancer treatments.

The study authors point to a 2017 analysis that showed that men with prostate cancer and no prior cardiac disease had greater risk of heart failure after taking androgen deprivation therapy (ADT), a common treatment used when the disease recurs after definitive treatment. Another study suggested an association between cardiotoxic effects of ADT and myocardial infarction regardless of medical history in general.

The authors of the current study say that such findings highlight “the importance of multidisciplinary care for such patients and the role of primary care physicians in optimizing cardiovascular risk prevention and providing early referrals to cardiologists.”

Further, the team says that tailoring “ADT to each patient’s needs may be associated with improved survival, especially for patients with factors associated with cardiovascular disease.”

Who should lead the way in multidisciplinary care? “The answer probably is case-by-case,” said Dr. Alhalabi, adding that it might depend on the presence of underlying morbidities such as cardiovascular disease and COPD.

“It is also important for the oncologist (‘the gatekeeper’) to try to mitigate the potential metabolic effects of hormonal deprivation therapy such as weight gain, decreased muscle mass, hyperlipidemia, etc.,” he added.

The study had no specific funding. The study authors and editorialists have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Nearly 80% of men with metastatic prostate cancer died from their malignancy, according to a retrospective cohort study involving 26,000-plus American men diagnosed with advanced disease in roughly the last 20 years.

The findings fill an information gap because, remarkably, “data are lacking” on causes of death among men whose prostate cancer has spread to other sites, say lead author Ahmed Elmehrath, MD, of Cairo University, Egypt, and colleagues.

“It was an important realization by our team that prostate cancer was the cause of death in 78% of patients,” said senior author Omar Alhalabi, MD, of University of Texas MD Anderson Cancer Center, Houston, in an email.

“Most patients with metastatic prostate cancer die from it, rather than other possible causes of death,” confirm Samuel Merriel, MSc, Tanimola Martins, PhD, and Sarah Bailey, PhD, University of Exeter, United Kingdom, in an accompanying editorial. The study was published last month in JAMA Network Open.

The findings represent the near opposite of a commonly held – and comforting – belief about early-stage disease: “You die with prostate cancer, not from it.”

That old saying is articulated in various ways, such as this from the Prostate Cancer Foundation: “We can confirm that there are those prostate cancers a man may die with and not of, while others are very aggressive.” The American Cancer Society says this: “Prostate cancer can be a serious disease, but most men diagnosed with prostate cancer do not die from it.”

However, these commonplace comments do not cover metastatic disease, which is what the authors of the new study decided to focus on.  

The team used data from the Surveillance, Epidemiology, and End Results Program (SEER) database to gather a sample of 26,168 U.S. men who received a diagnosis of metastatic prostate cancer from January 2000 to December 2016. They then analyzed the data in 2020 and found that 16,732 men (64%) had died during the follow-up period.

The majority of these deaths (77.8%) were from prostate cancer, 5.5% were from other cancers, and 16.7% were from noncancer causes, including cardiovascular diseases, chronic obstructive pulmonary disease, and cerebrovascular diseases.

Senior author Dr. Alhalabi acknowledged a limitation in these findings – that the SEER database relies on causes of death extracted from death certificates. “Death certificates have limited granularity in terms of the details they can contain about the cause of death and also have reporting bias,” he said.

Most of the prostate cancer deaths (59%) occurred within 2 years. The 5-year overall survival rate in the study group was 26%.

The deadliness of metastatic disease “reinforces the need for innovations to promote early-stage diagnosis,” comment the editorialists. Striking a hopeful note, they also say that “new tests for prostate cancer detection may reduce the proportion of patients who receive a diagnosis at a late stage.”
 

Death from other causes

The mean age at metastatic prostate cancer diagnosis in the study was roughly 71 years. Most of the cohort was White (74.5%) and had a diagnosis of stage M1b metastatic prostate cancer (72.7%), which means the cancer had spread to the bones.

Among men in the cohort, the rates of death from septicemia, suicide, accidents, COPD, and cerebrovascular diseases were significantly increased compared with the general U.S. male population, the team observes.

Thus, the study authors were concerned with not only with death from metastatic prostate cancer but death from other causes.

That concern is rooted in the established fact that there is now improved survival among patients with prostate cancer in the U.S., including among men with advanced disease. “Patients tend to live long enough after a prostate cancer diagnosis for non–cancer-related comorbidities to be associated with their overall survival,” they write.

The editorialists agree: Prostate cancer “has a high long-term survival rate compared with almost all other cancer types and signals the need for greater holistic care for patients.”

As noted above, cardiovascular diseases were the most common cause of nonprostate cancer–related deaths in the new study.

As in the management of other cancers, there is concern among clinicians and researchers about the cardiotoxic effects of prostate cancer treatments.

The study authors point to a 2017 analysis that showed that men with prostate cancer and no prior cardiac disease had greater risk of heart failure after taking androgen deprivation therapy (ADT), a common treatment used when the disease recurs after definitive treatment. Another study suggested an association between cardiotoxic effects of ADT and myocardial infarction regardless of medical history in general.

The authors of the current study say that such findings highlight “the importance of multidisciplinary care for such patients and the role of primary care physicians in optimizing cardiovascular risk prevention and providing early referrals to cardiologists.”

Further, the team says that tailoring “ADT to each patient’s needs may be associated with improved survival, especially for patients with factors associated with cardiovascular disease.”

Who should lead the way in multidisciplinary care? “The answer probably is case-by-case,” said Dr. Alhalabi, adding that it might depend on the presence of underlying morbidities such as cardiovascular disease and COPD.

“It is also important for the oncologist (‘the gatekeeper’) to try to mitigate the potential metabolic effects of hormonal deprivation therapy such as weight gain, decreased muscle mass, hyperlipidemia, etc.,” he added.

The study had no specific funding. The study authors and editorialists have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Nearly 80% of men with metastatic prostate cancer died from their malignancy, according to a retrospective cohort study involving 26,000-plus American men diagnosed with advanced disease in roughly the last 20 years.

The findings fill an information gap because, remarkably, “data are lacking” on causes of death among men whose prostate cancer has spread to other sites, say lead author Ahmed Elmehrath, MD, of Cairo University, Egypt, and colleagues.

“It was an important realization by our team that prostate cancer was the cause of death in 78% of patients,” said senior author Omar Alhalabi, MD, of University of Texas MD Anderson Cancer Center, Houston, in an email.

“Most patients with metastatic prostate cancer die from it, rather than other possible causes of death,” confirm Samuel Merriel, MSc, Tanimola Martins, PhD, and Sarah Bailey, PhD, University of Exeter, United Kingdom, in an accompanying editorial. The study was published last month in JAMA Network Open.

The findings represent the near opposite of a commonly held – and comforting – belief about early-stage disease: “You die with prostate cancer, not from it.”

That old saying is articulated in various ways, such as this from the Prostate Cancer Foundation: “We can confirm that there are those prostate cancers a man may die with and not of, while others are very aggressive.” The American Cancer Society says this: “Prostate cancer can be a serious disease, but most men diagnosed with prostate cancer do not die from it.”

However, these commonplace comments do not cover metastatic disease, which is what the authors of the new study decided to focus on.  

The team used data from the Surveillance, Epidemiology, and End Results Program (SEER) database to gather a sample of 26,168 U.S. men who received a diagnosis of metastatic prostate cancer from January 2000 to December 2016. They then analyzed the data in 2020 and found that 16,732 men (64%) had died during the follow-up period.

The majority of these deaths (77.8%) were from prostate cancer, 5.5% were from other cancers, and 16.7% were from noncancer causes, including cardiovascular diseases, chronic obstructive pulmonary disease, and cerebrovascular diseases.

Senior author Dr. Alhalabi acknowledged a limitation in these findings – that the SEER database relies on causes of death extracted from death certificates. “Death certificates have limited granularity in terms of the details they can contain about the cause of death and also have reporting bias,” he said.

Most of the prostate cancer deaths (59%) occurred within 2 years. The 5-year overall survival rate in the study group was 26%.

The deadliness of metastatic disease “reinforces the need for innovations to promote early-stage diagnosis,” comment the editorialists. Striking a hopeful note, they also say that “new tests for prostate cancer detection may reduce the proportion of patients who receive a diagnosis at a late stage.”
 

Death from other causes

The mean age at metastatic prostate cancer diagnosis in the study was roughly 71 years. Most of the cohort was White (74.5%) and had a diagnosis of stage M1b metastatic prostate cancer (72.7%), which means the cancer had spread to the bones.

Among men in the cohort, the rates of death from septicemia, suicide, accidents, COPD, and cerebrovascular diseases were significantly increased compared with the general U.S. male population, the team observes.

Thus, the study authors were concerned with not only with death from metastatic prostate cancer but death from other causes.

That concern is rooted in the established fact that there is now improved survival among patients with prostate cancer in the U.S., including among men with advanced disease. “Patients tend to live long enough after a prostate cancer diagnosis for non–cancer-related comorbidities to be associated with their overall survival,” they write.

The editorialists agree: Prostate cancer “has a high long-term survival rate compared with almost all other cancer types and signals the need for greater holistic care for patients.”

As noted above, cardiovascular diseases were the most common cause of nonprostate cancer–related deaths in the new study.

As in the management of other cancers, there is concern among clinicians and researchers about the cardiotoxic effects of prostate cancer treatments.

The study authors point to a 2017 analysis that showed that men with prostate cancer and no prior cardiac disease had greater risk of heart failure after taking androgen deprivation therapy (ADT), a common treatment used when the disease recurs after definitive treatment. Another study suggested an association between cardiotoxic effects of ADT and myocardial infarction regardless of medical history in general.

The authors of the current study say that such findings highlight “the importance of multidisciplinary care for such patients and the role of primary care physicians in optimizing cardiovascular risk prevention and providing early referrals to cardiologists.”

Further, the team says that tailoring “ADT to each patient’s needs may be associated with improved survival, especially for patients with factors associated with cardiovascular disease.”

Who should lead the way in multidisciplinary care? “The answer probably is case-by-case,” said Dr. Alhalabi, adding that it might depend on the presence of underlying morbidities such as cardiovascular disease and COPD.

“It is also important for the oncologist (‘the gatekeeper’) to try to mitigate the potential metabolic effects of hormonal deprivation therapy such as weight gain, decreased muscle mass, hyperlipidemia, etc.,” he added.

The study had no specific funding. The study authors and editorialists have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In the study by Sternberg et al, radiographic progression-free survival (rPFS) and safety were compared between patients aged > 70 and younger than age 70 who were enrolled in the CARD study. In the CARD study, patients with metastatic castrate-resistant prostate cancer (mCRPC) were randomized to cabazitaxel versus abiraterone or enzlutamide after having failed previous treatment. Patients aged > 70 who received cabazitaxel had a higher rPFS than those who received abiraterone or enzalutamide. Grade > 3 adverse effects were identified in 58% of patients receiving cabazitaxel versus 49% in those receiving abiraterone or enzalutamide.

In the study by Smith et al., quality of life (QoL) as measured via time to deterioration of patient report outcomes (PRO) was evaluated in patients enrolled on the ARAMIS trial (darolutamide versus placebo in patients with non-metastatic castrate-resistant prostate cancer (nmCRPC). PRO was assessed via surveys as an exploratory endpoint in this study via FACT-P PCS (prostate cancer subscale) and EORTC QLQ-PR25. Overall, the findings were consistent with either an overall improvement in QoL or improvement in urinary and bowel symptoms over time. In a separate study, Fallah et al conducted a pooled analysis of survival and safety outcomes of 3 second generation androgen receptor blockers (apalutamide, darolutamide, and enzalutamide) in men with nmCRPC. They compared results for men age under 80 versus those 80 and above. Metastasis-free survival and overall survival were higher for the treatment groups compared with placebo groups for both age categories. Side effects were slightly higher in the group aged 80 and above.

In summary, quality of life is an endpoint of critical importance to patients. Inclusion of patient reported outcomes as measured via surveys that provide quantitative assessments aid providers in discussing treatment options with patients. In addition, such QoL instruments aid in assessments based on age. Age bias is common in oncology, and the included studies provide further evidence that age alone should not be a reason to adjust treatment recommendations. Inclusion of geriatric assessments into such studies may further aid in determining risks and benefits of particular prostate cancer treatments in future studies

In the study by Sternberg et al, radiographic progression-free survival (rPFS) and safety were compared between patients aged > 70 and younger than age 70 who were enrolled in the CARD study. In the CARD study, patients with metastatic castrate-resistant prostate cancer (mCRPC) were randomized to cabazitaxel versus abiraterone or enzlutamide after having failed previous treatment. Patients aged > 70 who received cabazitaxel had a higher rPFS than those who received abiraterone or enzalutamide. Grade > 3 adverse effects were identified in 58% of patients receiving cabazitaxel versus 49% in those receiving abiraterone or enzalutamide.

In the study by Smith et al., quality of life (QoL) as measured via time to deterioration of patient report outcomes (PRO) was evaluated in patients enrolled on the ARAMIS trial (darolutamide versus placebo in patients with non-metastatic castrate-resistant prostate cancer (nmCRPC). PRO was assessed via surveys as an exploratory endpoint in this study via FACT-P PCS (prostate cancer subscale) and EORTC QLQ-PR25. Overall, the findings were consistent with either an overall improvement in QoL or improvement in urinary and bowel symptoms over time. In a separate study, Fallah et al conducted a pooled analysis of survival and safety outcomes of 3 second generation androgen receptor blockers (apalutamide, darolutamide, and enzalutamide) in men with nmCRPC. They compared results for men age under 80 versus those 80 and above. Metastasis-free survival and overall survival were higher for the treatment groups compared with placebo groups for both age categories. Side effects were slightly higher in the group aged 80 and above.

In summary, quality of life is an endpoint of critical importance to patients. Inclusion of patient reported outcomes as measured via surveys that provide quantitative assessments aid providers in discussing treatment options with patients. In addition, such QoL instruments aid in assessments based on age. Age bias is common in oncology, and the included studies provide further evidence that age alone should not be a reason to adjust treatment recommendations. Inclusion of geriatric assessments into such studies may further aid in determining risks and benefits of particular prostate cancer treatments in future studies

In the study by Sternberg et al, radiographic progression-free survival (rPFS) and safety were compared between patients aged > 70 and younger than age 70 who were enrolled in the CARD study. In the CARD study, patients with metastatic castrate-resistant prostate cancer (mCRPC) were randomized to cabazitaxel versus abiraterone or enzlutamide after having failed previous treatment. Patients aged > 70 who received cabazitaxel had a higher rPFS than those who received abiraterone or enzalutamide. Grade > 3 adverse effects were identified in 58% of patients receiving cabazitaxel versus 49% in those receiving abiraterone or enzalutamide.

In the study by Smith et al., quality of life (QoL) as measured via time to deterioration of patient report outcomes (PRO) was evaluated in patients enrolled on the ARAMIS trial (darolutamide versus placebo in patients with non-metastatic castrate-resistant prostate cancer (nmCRPC). PRO was assessed via surveys as an exploratory endpoint in this study via FACT-P PCS (prostate cancer subscale) and EORTC QLQ-PR25. Overall, the findings were consistent with either an overall improvement in QoL or improvement in urinary and bowel symptoms over time. In a separate study, Fallah et al conducted a pooled analysis of survival and safety outcomes of 3 second generation androgen receptor blockers (apalutamide, darolutamide, and enzalutamide) in men with nmCRPC. They compared results for men age under 80 versus those 80 and above. Metastasis-free survival and overall survival were higher for the treatment groups compared with placebo groups for both age categories. Side effects were slightly higher in the group aged 80 and above.

In summary, quality of life is an endpoint of critical importance to patients. Inclusion of patient reported outcomes as measured via surveys that provide quantitative assessments aid providers in discussing treatment options with patients. In addition, such QoL instruments aid in assessments based on age. Age bias is common in oncology, and the included studies provide further evidence that age alone should not be a reason to adjust treatment recommendations. Inclusion of geriatric assessments into such studies may further aid in determining risks and benefits of particular prostate cancer treatments in future studies

Nearly 50,000 veterans are diagnosed with cancer within the Veterans Health Administration annually with prostate cancer (PC) being the most frequently diagnosed, accounting for 29% of all cancers diagnosed.¹ The treatment of PC depends on the stage and risk group at presentation and patient preference. Men with early stage, localized PC can be managed with prostatectomy, radiation therapy, or active surveillance.²

Within the Veterans Health Administration, more patients are treated with radiation therapy than with radical prostatectomy.³ This is in contrast to the civil health system, where more patients are treated with radical prostatectomy than with radiation therapy.^4,5 Radiation therapy for PC can be given externally with external beam radiation therapy or internally with brachytherapy (BT). BT is categorized by the rate at which the radiation dose is delivered and generally grouped as low-dose rate (LDR) or high-dose rate (HDR). LDRBT consists of permanently implanting radioactive seeds, which slowly deliver a radiation dose over an extended period. HDRBT consists of implanting catheters that allow delivery of a radioactive source to be placed temporarily in the prostate and removed after treatment. The utilization of HDRBT has become more common as treatment has evolved to consist of fewer, larger fractions in a shorter time, making it a convenient treatment option for men with PC.⁶ The veteran population has singular medical challenges. These patients differ from the general population and are often underrepresented in medical research and published studies.⁷ There are no studies exploring the treatment-associated toxicities from HDRBT treatment for PC specifically in the veteran population. The objective of this study is to report our findings regarding the veteran-reported and physician-graded toxicities associated with HDRBT as monotherapy in veterans treated through the US Department of Veterans Affairs (VA) for PC.

Methods

We performed a retrospective cohort study of a prospectively maintained, institutional review board-approved database of patients treated with HDRBT for PC. Veterans were seen in consultation at Edward Hines, Jr. VA Hospital (EHJVAH) in Hines, Illinois. This is the only VA hospital in Illinois that offers radiation therapy, so it acted as a tertiary center, receiving referrals from other, neighboring VA hospitals. If the veteran was deemed a good BT candidate and elected to proceed with HDRBT, HDR treatment was performed at a partnering academic institution equipped to provide HDRBT (Loyola University Medical Center).

We selected patients with National Cancer Center Network (NCCN) low- or intermediate-risk PC undergoing definitive HDRBT as monotherapy using 13.5 Gy x 2 fractions delivered over 2 implants that were 1 to 2 weeks apart. Patients who received androgen deprivation therapy (ADT) were excluded from this study. No patients received supplemental external beam radiation. Men with unfavorable intermediate risk PC were offered ADT and BT in accordance with NCCN guidelines. However, patients with unfavorable intermediate-risk PC who declined ADT or who were deemed poor ADT candidates due to comorbidities were treated with HDR as monotherapy and included in this study.⁸

HDR Treatment

Our HDRBT implant procedure and treatment planning details have been previously described.⁹ In brief, patients were implanted with between 17 and 22 catheters based on gland size under transrectal ultrasound guidance. After implantation, computed tomography and, when possible, magnetic resonance imaging of the prostate were obtained and registered for target delineation. The prostate was segmented, and an asymmetric planning target volume of 0 to 5 mm was created and extended to encompass the proximal seminal vesicles. The second fraction was given 1 to 2 weeks after initial treatment, based on patient, physician, and operating room availability.

Health-Related Quality of Life Assessment

Veteran-reported genitourinary (GU), gastrointestinal (GI), and sexual health-related quality of life (hrQOL) were assessed using the validated International Prostate Symptom Score (IPSS) and the Expanded Prostate Cancer Index Composite Short Form (EPIC-26) instruments.^10,11 Baseline veteran-reported hrQOL scores in the GU, GI, and sexual domains were obtained prior to each veteran’s first HDR treatment. Veteran-reported hrQOL scores were assessed at each of the patient’s follow-up appointments. Physician-graded toxicity was assessed Common Terminology Criteria for Adverse Events (CTCAE) v 4.03 criteria.¹² Physician-graded toxicity was assessed at each follow-up visit and reported as the highest grade reported during any follow-up examination.

Follow-up appointments typically occurred at 1 month, 3 months, 6 months, 12 months, and subsequently every 6 months after the second HDR treatment. Follow-up appointments were conducted in the radiation oncology department at EHJVAH.

Minimal Clinically Important Differences

To evaluate the veteran-reported hrQOL, we characterized statistically significant differences in IPSS or EPIC-26 scores over time as compared with baseline values as clinically important or not clinically important through the use of reported minimal clinically important difference (MCID) assessments.^13-15 For the IPSS, we used reported data that showed a change of ≥ 3.0 points represented a clinically meaningful change in urinary function.¹⁴ For the EPIC-26 scores, we used reported data that showed a change of ≥ 6 points for urinary incontinence score, ≥ 5 points for urinary obstruction score, ≥ 4 points for bowel score, and ≥ 10 points for sexual score to represent an MCID.¹⁵

Statistical Analysis

Changes in veteran-reported hrQOL over time were compared using mixed linear effects models, with the time since the last BT implant serving as the fixed variable. Effects were deemed statistically significant if P < .05. If a statistically significant difference from baseline was found at any time point, additional evaluation was done to see if the numerical difference in the assessment led to an MCID as described above. IBM SPSS Statistics for Windows, version 25.0 was used for data analysis.

Results

Seventy-four veterans were included in the study. The median follow-up was 18 months (range 1-43). The demographic and oncologic specifics of the treated veterans are outlined in Table 1.

There was a significant increase in IPSS (P < .001) with reciprocal decline in EPIC-26 urinary incontinence (P = .008) and EPIC-26 urinary obstruction scores (P = .001) from baseline over time (Table 2 and Figure 1). At the 18-month follow-up assessment, there was no longer a significant difference in the EPIC-26 urinary obstruction score from baseline (88.7 vs 84.0, P = .31). The increases in IPSS at the 1-, 3-, and 6-month assessments met the criteria for MCID. The decrease in EPIC-26 urinary incontinence scores at the 1-, 3-, 6-, 12-, and 18-month assessments were found to be an MCID, as were the decrease in EPIC-26 urinary obstruction scores at the 1-, 3-, 6-, and 12-month assessments.

Discussion

We performed a retrospective study of veterans with low- or intermediate-risk PC undergoing definitive HDR prostate BT as monotherapy. We found that veterans experienced immediate declines in GU, GI, and sexual hrQOL after treatment. However, each trended toward a return to baseline over time, with the EPIC-26 urinary obstruction and the EPIC-26 bowel scores showing no difference from the baseline value within 18 months and 12 months, respectively. The physician-reported toxicities were low, with only 1 incidence of grade 3 GU toxicity, no grade 3 GI or sexual toxicities, and no grade 4 or 5 toxicity. This suggests that HDRBT is a well-tolerated and safe, definitive treatment for veterans with localized PC.

In a series similar to ours, Gaudet and colleagues reported on their single institutional results of treating 30 low- or intermediate-risk PC patients with HDRBT as monotherapy.¹⁶ Patients included in their study were civilians from the general population, treated in a similar fashion to the veterans treated in our study. Each patient received 27 Gy in 2 fractions given over 2 implants. The authors collected patient-reported hrQOL results using the IPSS and EPIC questionnaires and found that 57% of patients treated experienced moderate-to-severe urinary symptoms at the 1-month assessment after implantation, with a rapid recovery toward baseline over time. In contrast, GI symptoms did not change from baseline, while sexual symptoms worsened after implantation and failed to return to baseline.

Limitations

To the authors’ knowledge, there are no other studies exploring HDR prostate BT toxicity in a veteran-specific population, and our study is novel in addressing this question. One limitation of the study is the relatively short median follow-up time of 18 months. With this limitation, our data were not yet sufficiently mature to perform biochemical control or overall survival analyses. The next step in our study is to calculate these clinical endpoints from our data after longer follow-up.

An additional limitation to our study is the single institutional nature of the design. While veterans from neighboring VA hospitals were included in the study by way of referral and treatment at our center, the only VA hospital in the state to provide radiation therapy, our patient population remains limited. Further multi-institutional and prospective data are needed to validate our findings.

Conclusions

HDR prostate BT as monotherapy is feasible with a favorable veteran-reported hrQOL and physician-graded toxicity profile. Veterans should be educated about this treatment modality when considering the optimal treatment for their localized prostate cancer.

Nearly 50,000 veterans are diagnosed with cancer within the Veterans Health Administration annually with prostate cancer (PC) being the most frequently diagnosed, accounting for 29% of all cancers diagnosed.¹ The treatment of PC depends on the stage and risk group at presentation and patient preference. Men with early stage, localized PC can be managed with prostatectomy, radiation therapy, or active surveillance.²

Within the Veterans Health Administration, more patients are treated with radiation therapy than with radical prostatectomy.³ This is in contrast to the civil health system, where more patients are treated with radical prostatectomy than with radiation therapy.^4,5 Radiation therapy for PC can be given externally with external beam radiation therapy or internally with brachytherapy (BT). BT is categorized by the rate at which the radiation dose is delivered and generally grouped as low-dose rate (LDR) or high-dose rate (HDR). LDRBT consists of permanently implanting radioactive seeds, which slowly deliver a radiation dose over an extended period. HDRBT consists of implanting catheters that allow delivery of a radioactive source to be placed temporarily in the prostate and removed after treatment. The utilization of HDRBT has become more common as treatment has evolved to consist of fewer, larger fractions in a shorter time, making it a convenient treatment option for men with PC.⁶ The veteran population has singular medical challenges. These patients differ from the general population and are often underrepresented in medical research and published studies.⁷ There are no studies exploring the treatment-associated toxicities from HDRBT treatment for PC specifically in the veteran population. The objective of this study is to report our findings regarding the veteran-reported and physician-graded toxicities associated with HDRBT as monotherapy in veterans treated through the US Department of Veterans Affairs (VA) for PC.

Methods

We performed a retrospective cohort study of a prospectively maintained, institutional review board-approved database of patients treated with HDRBT for PC. Veterans were seen in consultation at Edward Hines, Jr. VA Hospital (EHJVAH) in Hines, Illinois. This is the only VA hospital in Illinois that offers radiation therapy, so it acted as a tertiary center, receiving referrals from other, neighboring VA hospitals. If the veteran was deemed a good BT candidate and elected to proceed with HDRBT, HDR treatment was performed at a partnering academic institution equipped to provide HDRBT (Loyola University Medical Center).

We selected patients with National Cancer Center Network (NCCN) low- or intermediate-risk PC undergoing definitive HDRBT as monotherapy using 13.5 Gy x 2 fractions delivered over 2 implants that were 1 to 2 weeks apart. Patients who received androgen deprivation therapy (ADT) were excluded from this study. No patients received supplemental external beam radiation. Men with unfavorable intermediate risk PC were offered ADT and BT in accordance with NCCN guidelines. However, patients with unfavorable intermediate-risk PC who declined ADT or who were deemed poor ADT candidates due to comorbidities were treated with HDR as monotherapy and included in this study.⁸

HDR Treatment

Our HDRBT implant procedure and treatment planning details have been previously described.⁹ In brief, patients were implanted with between 17 and 22 catheters based on gland size under transrectal ultrasound guidance. After implantation, computed tomography and, when possible, magnetic resonance imaging of the prostate were obtained and registered for target delineation. The prostate was segmented, and an asymmetric planning target volume of 0 to 5 mm was created and extended to encompass the proximal seminal vesicles. The second fraction was given 1 to 2 weeks after initial treatment, based on patient, physician, and operating room availability.

Health-Related Quality of Life Assessment

Veteran-reported genitourinary (GU), gastrointestinal (GI), and sexual health-related quality of life (hrQOL) were assessed using the validated International Prostate Symptom Score (IPSS) and the Expanded Prostate Cancer Index Composite Short Form (EPIC-26) instruments.^10,11 Baseline veteran-reported hrQOL scores in the GU, GI, and sexual domains were obtained prior to each veteran’s first HDR treatment. Veteran-reported hrQOL scores were assessed at each of the patient’s follow-up appointments. Physician-graded toxicity was assessed Common Terminology Criteria for Adverse Events (CTCAE) v 4.03 criteria.¹² Physician-graded toxicity was assessed at each follow-up visit and reported as the highest grade reported during any follow-up examination.

Follow-up appointments typically occurred at 1 month, 3 months, 6 months, 12 months, and subsequently every 6 months after the second HDR treatment. Follow-up appointments were conducted in the radiation oncology department at EHJVAH.

Minimal Clinically Important Differences

To evaluate the veteran-reported hrQOL, we characterized statistically significant differences in IPSS or EPIC-26 scores over time as compared with baseline values as clinically important or not clinically important through the use of reported minimal clinically important difference (MCID) assessments.^13-15 For the IPSS, we used reported data that showed a change of ≥ 3.0 points represented a clinically meaningful change in urinary function.¹⁴ For the EPIC-26 scores, we used reported data that showed a change of ≥ 6 points for urinary incontinence score, ≥ 5 points for urinary obstruction score, ≥ 4 points for bowel score, and ≥ 10 points for sexual score to represent an MCID.¹⁵

Statistical Analysis

Changes in veteran-reported hrQOL over time were compared using mixed linear effects models, with the time since the last BT implant serving as the fixed variable. Effects were deemed statistically significant if P < .05. If a statistically significant difference from baseline was found at any time point, additional evaluation was done to see if the numerical difference in the assessment led to an MCID as described above. IBM SPSS Statistics for Windows, version 25.0 was used for data analysis.

Results

Seventy-four veterans were included in the study. The median follow-up was 18 months (range 1-43). The demographic and oncologic specifics of the treated veterans are outlined in Table 1.

There was a significant increase in IPSS (P < .001) with reciprocal decline in EPIC-26 urinary incontinence (P = .008) and EPIC-26 urinary obstruction scores (P = .001) from baseline over time (Table 2 and Figure 1). At the 18-month follow-up assessment, there was no longer a significant difference in the EPIC-26 urinary obstruction score from baseline (88.7 vs 84.0, P = .31). The increases in IPSS at the 1-, 3-, and 6-month assessments met the criteria for MCID. The decrease in EPIC-26 urinary incontinence scores at the 1-, 3-, 6-, 12-, and 18-month assessments were found to be an MCID, as were the decrease in EPIC-26 urinary obstruction scores at the 1-, 3-, 6-, and 12-month assessments.

Discussion

We performed a retrospective study of veterans with low- or intermediate-risk PC undergoing definitive HDR prostate BT as monotherapy. We found that veterans experienced immediate declines in GU, GI, and sexual hrQOL after treatment. However, each trended toward a return to baseline over time, with the EPIC-26 urinary obstruction and the EPIC-26 bowel scores showing no difference from the baseline value within 18 months and 12 months, respectively. The physician-reported toxicities were low, with only 1 incidence of grade 3 GU toxicity, no grade 3 GI or sexual toxicities, and no grade 4 or 5 toxicity. This suggests that HDRBT is a well-tolerated and safe, definitive treatment for veterans with localized PC.

In a series similar to ours, Gaudet and colleagues reported on their single institutional results of treating 30 low- or intermediate-risk PC patients with HDRBT as monotherapy.¹⁶ Patients included in their study were civilians from the general population, treated in a similar fashion to the veterans treated in our study. Each patient received 27 Gy in 2 fractions given over 2 implants. The authors collected patient-reported hrQOL results using the IPSS and EPIC questionnaires and found that 57% of patients treated experienced moderate-to-severe urinary symptoms at the 1-month assessment after implantation, with a rapid recovery toward baseline over time. In contrast, GI symptoms did not change from baseline, while sexual symptoms worsened after implantation and failed to return to baseline.

Limitations

To the authors’ knowledge, there are no other studies exploring HDR prostate BT toxicity in a veteran-specific population, and our study is novel in addressing this question. One limitation of the study is the relatively short median follow-up time of 18 months. With this limitation, our data were not yet sufficiently mature to perform biochemical control or overall survival analyses. The next step in our study is to calculate these clinical endpoints from our data after longer follow-up.

An additional limitation to our study is the single institutional nature of the design. While veterans from neighboring VA hospitals were included in the study by way of referral and treatment at our center, the only VA hospital in the state to provide radiation therapy, our patient population remains limited. Further multi-institutional and prospective data are needed to validate our findings.

Conclusions

HDR prostate BT as monotherapy is feasible with a favorable veteran-reported hrQOL and physician-graded toxicity profile. Veterans should be educated about this treatment modality when considering the optimal treatment for their localized prostate cancer.

Nearly 50,000 veterans are diagnosed with cancer within the Veterans Health Administration annually with prostate cancer (PC) being the most frequently diagnosed, accounting for 29% of all cancers diagnosed.¹ The treatment of PC depends on the stage and risk group at presentation and patient preference. Men with early stage, localized PC can be managed with prostatectomy, radiation therapy, or active surveillance.²

Within the Veterans Health Administration, more patients are treated with radiation therapy than with radical prostatectomy.³ This is in contrast to the civil health system, where more patients are treated with radical prostatectomy than with radiation therapy.^4,5 Radiation therapy for PC can be given externally with external beam radiation therapy or internally with brachytherapy (BT). BT is categorized by the rate at which the radiation dose is delivered and generally grouped as low-dose rate (LDR) or high-dose rate (HDR). LDRBT consists of permanently implanting radioactive seeds, which slowly deliver a radiation dose over an extended period. HDRBT consists of implanting catheters that allow delivery of a radioactive source to be placed temporarily in the prostate and removed after treatment. The utilization of HDRBT has become more common as treatment has evolved to consist of fewer, larger fractions in a shorter time, making it a convenient treatment option for men with PC.⁶ The veteran population has singular medical challenges. These patients differ from the general population and are often underrepresented in medical research and published studies.⁷ There are no studies exploring the treatment-associated toxicities from HDRBT treatment for PC specifically in the veteran population. The objective of this study is to report our findings regarding the veteran-reported and physician-graded toxicities associated with HDRBT as monotherapy in veterans treated through the US Department of Veterans Affairs (VA) for PC.

Methods

We performed a retrospective cohort study of a prospectively maintained, institutional review board-approved database of patients treated with HDRBT for PC. Veterans were seen in consultation at Edward Hines, Jr. VA Hospital (EHJVAH) in Hines, Illinois. This is the only VA hospital in Illinois that offers radiation therapy, so it acted as a tertiary center, receiving referrals from other, neighboring VA hospitals. If the veteran was deemed a good BT candidate and elected to proceed with HDRBT, HDR treatment was performed at a partnering academic institution equipped to provide HDRBT (Loyola University Medical Center).

We selected patients with National Cancer Center Network (NCCN) low- or intermediate-risk PC undergoing definitive HDRBT as monotherapy using 13.5 Gy x 2 fractions delivered over 2 implants that were 1 to 2 weeks apart. Patients who received androgen deprivation therapy (ADT) were excluded from this study. No patients received supplemental external beam radiation. Men with unfavorable intermediate risk PC were offered ADT and BT in accordance with NCCN guidelines. However, patients with unfavorable intermediate-risk PC who declined ADT or who were deemed poor ADT candidates due to comorbidities were treated with HDR as monotherapy and included in this study.⁸

HDR Treatment

Our HDRBT implant procedure and treatment planning details have been previously described.⁹ In brief, patients were implanted with between 17 and 22 catheters based on gland size under transrectal ultrasound guidance. After implantation, computed tomography and, when possible, magnetic resonance imaging of the prostate were obtained and registered for target delineation. The prostate was segmented, and an asymmetric planning target volume of 0 to 5 mm was created and extended to encompass the proximal seminal vesicles. The second fraction was given 1 to 2 weeks after initial treatment, based on patient, physician, and operating room availability.

Health-Related Quality of Life Assessment

Veteran-reported genitourinary (GU), gastrointestinal (GI), and sexual health-related quality of life (hrQOL) were assessed using the validated International Prostate Symptom Score (IPSS) and the Expanded Prostate Cancer Index Composite Short Form (EPIC-26) instruments.^10,11 Baseline veteran-reported hrQOL scores in the GU, GI, and sexual domains were obtained prior to each veteran’s first HDR treatment. Veteran-reported hrQOL scores were assessed at each of the patient’s follow-up appointments. Physician-graded toxicity was assessed Common Terminology Criteria for Adverse Events (CTCAE) v 4.03 criteria.¹² Physician-graded toxicity was assessed at each follow-up visit and reported as the highest grade reported during any follow-up examination.

Follow-up appointments typically occurred at 1 month, 3 months, 6 months, 12 months, and subsequently every 6 months after the second HDR treatment. Follow-up appointments were conducted in the radiation oncology department at EHJVAH.

Minimal Clinically Important Differences

To evaluate the veteran-reported hrQOL, we characterized statistically significant differences in IPSS or EPIC-26 scores over time as compared with baseline values as clinically important or not clinically important through the use of reported minimal clinically important difference (MCID) assessments.^13-15 For the IPSS, we used reported data that showed a change of ≥ 3.0 points represented a clinically meaningful change in urinary function.¹⁴ For the EPIC-26 scores, we used reported data that showed a change of ≥ 6 points for urinary incontinence score, ≥ 5 points for urinary obstruction score, ≥ 4 points for bowel score, and ≥ 10 points for sexual score to represent an MCID.¹⁵

Statistical Analysis

Changes in veteran-reported hrQOL over time were compared using mixed linear effects models, with the time since the last BT implant serving as the fixed variable. Effects were deemed statistically significant if P < .05. If a statistically significant difference from baseline was found at any time point, additional evaluation was done to see if the numerical difference in the assessment led to an MCID as described above. IBM SPSS Statistics for Windows, version 25.0 was used for data analysis.

Results

Seventy-four veterans were included in the study. The median follow-up was 18 months (range 1-43). The demographic and oncologic specifics of the treated veterans are outlined in Table 1.

There was a significant increase in IPSS (P < .001) with reciprocal decline in EPIC-26 urinary incontinence (P = .008) and EPIC-26 urinary obstruction scores (P = .001) from baseline over time (Table 2 and Figure 1). At the 18-month follow-up assessment, there was no longer a significant difference in the EPIC-26 urinary obstruction score from baseline (88.7 vs 84.0, P = .31). The increases in IPSS at the 1-, 3-, and 6-month assessments met the criteria for MCID. The decrease in EPIC-26 urinary incontinence scores at the 1-, 3-, 6-, 12-, and 18-month assessments were found to be an MCID, as were the decrease in EPIC-26 urinary obstruction scores at the 1-, 3-, 6-, and 12-month assessments.

Discussion

We performed a retrospective study of veterans with low- or intermediate-risk PC undergoing definitive HDR prostate BT as monotherapy. We found that veterans experienced immediate declines in GU, GI, and sexual hrQOL after treatment. However, each trended toward a return to baseline over time, with the EPIC-26 urinary obstruction and the EPIC-26 bowel scores showing no difference from the baseline value within 18 months and 12 months, respectively. The physician-reported toxicities were low, with only 1 incidence of grade 3 GU toxicity, no grade 3 GI or sexual toxicities, and no grade 4 or 5 toxicity. This suggests that HDRBT is a well-tolerated and safe, definitive treatment for veterans with localized PC.

In a series similar to ours, Gaudet and colleagues reported on their single institutional results of treating 30 low- or intermediate-risk PC patients with HDRBT as monotherapy.¹⁶ Patients included in their study were civilians from the general population, treated in a similar fashion to the veterans treated in our study. Each patient received 27 Gy in 2 fractions given over 2 implants. The authors collected patient-reported hrQOL results using the IPSS and EPIC questionnaires and found that 57% of patients treated experienced moderate-to-severe urinary symptoms at the 1-month assessment after implantation, with a rapid recovery toward baseline over time. In contrast, GI symptoms did not change from baseline, while sexual symptoms worsened after implantation and failed to return to baseline.

Limitations

To the authors’ knowledge, there are no other studies exploring HDR prostate BT toxicity in a veteran-specific population, and our study is novel in addressing this question. One limitation of the study is the relatively short median follow-up time of 18 months. With this limitation, our data were not yet sufficiently mature to perform biochemical control or overall survival analyses. The next step in our study is to calculate these clinical endpoints from our data after longer follow-up.

An additional limitation to our study is the single institutional nature of the design. While veterans from neighboring VA hospitals were included in the study by way of referral and treatment at our center, the only VA hospital in the state to provide radiation therapy, our patient population remains limited. Further multi-institutional and prospective data are needed to validate our findings.

Conclusions

HDR prostate BT as monotherapy is feasible with a favorable veteran-reported hrQOL and physician-graded toxicity profile. Veterans should be educated about this treatment modality when considering the optimal treatment for their localized prostate cancer.