Renal Cell Carcinoma

In contrast to other recent studies, androgen deprivation therapy (ADT) had no link to dementia in a observational cohort study of more than 45,000 men with prostate cancer who received definitive radiotherapy, investigators have reported.

No significant associations were found between ADT and Alzheimer’s disease or vascular dementia, or between shorter or longer courses of ADT and any dementia studied, according to Rishi Deka, PhD, of Veterans Affairs San Diego Health Care System, La Jolla, Calif., and coinvestigators.

“These results may mitigate concerns regarding the long-term risks of ADT on cognitive health in the treatment of prostate cancer,” Dr. Deka and colleagues wrote in JAMA Oncology.

Two other recent studies showed strong, statistically significant associations between ADT and dementia in prostate cancer. However, those studies combined patients with local and metastatic disease, receiving ADT in the upfront or recurrent settings, while the present study looked specifically at men with nonmetastatic prostate cancer who received radiotherapy.

“Different treatment modalities and disease stages are associated with substantial selection bias that may predispose results to false associations,” noted Dr. Deka and coauthors.

Their observational cohort study comprised 45,218 men diagnosed with nonmetastatic prostate cancer at the U.S. Department of Veterans Affairs who underwent radiotherapy with or without ADT. The investigators excluded men who had a diagnosis of dementia within 1 year of the prostate cancer diagnosis or who had prior diagnoses of dementia, stroke, or cognitive impairment.

A total of 1,497 patients were diagnosed with dementia over a median of 6.8 years of follow-up: 404 with Alzheimer disease, 335 with vascular dementia, and 758 with other types or unclassified dementias.

The investigators found no significant association between use of ADT and development of any dementia, the primary outcome of the analysis (subdistribution hazard ratio [SHR], 1.04; 95% confidence interval, 0.94-1.16; P = .43).

Likewise, there was no association between ADT and vascular dementia, specifically, with an SHR of 1.20 (95% CI, 0.97-1.50; P = .10) or Alzheimer’s disease, with an SHR of 1.11 (95% CI, 0.91-1.36; P = .29).

Duration of ADT longer than 1 year was not significantly associated with dementia, nor was duration shorter than 1 year, with SHRs, of 1.08 and 1.01 respectively, the analysis shows.

The SHRs in these and other analysis reported ranged from 1.00 to 1.21. That is substantially lower than hazard ratios of 1.66 to 2.32 in one previous study linking ADT to dementia, according to the investigators, suggesting that the results of the current analysis were not due to inadequate power to detect differences.

Nevertheless, the findings may not be generalizable to some other populations, they cautioned, since it was focused demographically on veterans, and was limited to radiotherapy-treated patients.

Dr. Deka and coauthors reported no conflict of interest. Their study was funded by grants from the University of California San Diego Center for Precision Radiation Medicine.

SOURCE: Deka R et al. JAMA Oncol. 2018 Oct 11. doi: 10.1001/jamaoncol.2018.4423.

In contrast to other recent studies, androgen deprivation therapy (ADT) had no link to dementia in a observational cohort study of more than 45,000 men with prostate cancer who received definitive radiotherapy, investigators have reported.

No significant associations were found between ADT and Alzheimer’s disease or vascular dementia, or between shorter or longer courses of ADT and any dementia studied, according to Rishi Deka, PhD, of Veterans Affairs San Diego Health Care System, La Jolla, Calif., and coinvestigators.

“These results may mitigate concerns regarding the long-term risks of ADT on cognitive health in the treatment of prostate cancer,” Dr. Deka and colleagues wrote in JAMA Oncology.

Two other recent studies showed strong, statistically significant associations between ADT and dementia in prostate cancer. However, those studies combined patients with local and metastatic disease, receiving ADT in the upfront or recurrent settings, while the present study looked specifically at men with nonmetastatic prostate cancer who received radiotherapy.

“Different treatment modalities and disease stages are associated with substantial selection bias that may predispose results to false associations,” noted Dr. Deka and coauthors.

Their observational cohort study comprised 45,218 men diagnosed with nonmetastatic prostate cancer at the U.S. Department of Veterans Affairs who underwent radiotherapy with or without ADT. The investigators excluded men who had a diagnosis of dementia within 1 year of the prostate cancer diagnosis or who had prior diagnoses of dementia, stroke, or cognitive impairment.

A total of 1,497 patients were diagnosed with dementia over a median of 6.8 years of follow-up: 404 with Alzheimer disease, 335 with vascular dementia, and 758 with other types or unclassified dementias.

The investigators found no significant association between use of ADT and development of any dementia, the primary outcome of the analysis (subdistribution hazard ratio [SHR], 1.04; 95% confidence interval, 0.94-1.16; P = .43).

Likewise, there was no association between ADT and vascular dementia, specifically, with an SHR of 1.20 (95% CI, 0.97-1.50; P = .10) or Alzheimer’s disease, with an SHR of 1.11 (95% CI, 0.91-1.36; P = .29).

Duration of ADT longer than 1 year was not significantly associated with dementia, nor was duration shorter than 1 year, with SHRs, of 1.08 and 1.01 respectively, the analysis shows.

The SHRs in these and other analysis reported ranged from 1.00 to 1.21. That is substantially lower than hazard ratios of 1.66 to 2.32 in one previous study linking ADT to dementia, according to the investigators, suggesting that the results of the current analysis were not due to inadequate power to detect differences.

Nevertheless, the findings may not be generalizable to some other populations, they cautioned, since it was focused demographically on veterans, and was limited to radiotherapy-treated patients.

Dr. Deka and coauthors reported no conflict of interest. Their study was funded by grants from the University of California San Diego Center for Precision Radiation Medicine.

SOURCE: Deka R et al. JAMA Oncol. 2018 Oct 11. doi: 10.1001/jamaoncol.2018.4423.

In contrast to other recent studies, androgen deprivation therapy (ADT) had no link to dementia in a observational cohort study of more than 45,000 men with prostate cancer who received definitive radiotherapy, investigators have reported.

No significant associations were found between ADT and Alzheimer’s disease or vascular dementia, or between shorter or longer courses of ADT and any dementia studied, according to Rishi Deka, PhD, of Veterans Affairs San Diego Health Care System, La Jolla, Calif., and coinvestigators.

“These results may mitigate concerns regarding the long-term risks of ADT on cognitive health in the treatment of prostate cancer,” Dr. Deka and colleagues wrote in JAMA Oncology.

Two other recent studies showed strong, statistically significant associations between ADT and dementia in prostate cancer. However, those studies combined patients with local and metastatic disease, receiving ADT in the upfront or recurrent settings, while the present study looked specifically at men with nonmetastatic prostate cancer who received radiotherapy.

“Different treatment modalities and disease stages are associated with substantial selection bias that may predispose results to false associations,” noted Dr. Deka and coauthors.

Their observational cohort study comprised 45,218 men diagnosed with nonmetastatic prostate cancer at the U.S. Department of Veterans Affairs who underwent radiotherapy with or without ADT. The investigators excluded men who had a diagnosis of dementia within 1 year of the prostate cancer diagnosis or who had prior diagnoses of dementia, stroke, or cognitive impairment.

A total of 1,497 patients were diagnosed with dementia over a median of 6.8 years of follow-up: 404 with Alzheimer disease, 335 with vascular dementia, and 758 with other types or unclassified dementias.

The investigators found no significant association between use of ADT and development of any dementia, the primary outcome of the analysis (subdistribution hazard ratio [SHR], 1.04; 95% confidence interval, 0.94-1.16; P = .43).

Likewise, there was no association between ADT and vascular dementia, specifically, with an SHR of 1.20 (95% CI, 0.97-1.50; P = .10) or Alzheimer’s disease, with an SHR of 1.11 (95% CI, 0.91-1.36; P = .29).

Duration of ADT longer than 1 year was not significantly associated with dementia, nor was duration shorter than 1 year, with SHRs, of 1.08 and 1.01 respectively, the analysis shows.

The SHRs in these and other analysis reported ranged from 1.00 to 1.21. That is substantially lower than hazard ratios of 1.66 to 2.32 in one previous study linking ADT to dementia, according to the investigators, suggesting that the results of the current analysis were not due to inadequate power to detect differences.

Nevertheless, the findings may not be generalizable to some other populations, they cautioned, since it was focused demographically on veterans, and was limited to radiotherapy-treated patients.

Dr. Deka and coauthors reported no conflict of interest. Their study was funded by grants from the University of California San Diego Center for Precision Radiation Medicine.

SOURCE: Deka R et al. JAMA Oncol. 2018 Oct 11. doi: 10.1001/jamaoncol.2018.4423.

Renal cell carcinoma (RCC) incidence rates increased in recent years, but have stabilized, while mortality rates have dropped precipitously, according to an analysis of more than 20 years of U.S. cancer registry data.

The introduction of antiangiogenic agents is likely one key factor that led to the mortality decrease, said authors of the analysis of Surveillance, Epidemiology, and End Results data from 1992 to 2015.

Incidence trends are likely more complex and may reflect the interplay between increased detection, on one hand, and decreases in modifiable risk factors such as smoking on the other, the authors reported in Clinical Genitourinary Cancer.

The analysis, conducted by Anas M. Saad, a final-year medical student at Ain Shams University, Cairo; Thai H. Ho, MD, PhD, of Mayo Clinic Cancer Center, Phoenix; and coinvestigators, included a total of 104,584 patients with an RCC diagnosis, of whom nearly 64% were male and 80% were white. The majority of tumors were small and localized at diagnosis, and clear cell was the histologic subtype in 44%, according to the report.

Overall incidence of RCC was 11.3 per 100,000 person-years over the 1992-2015 study period, Dr. Saad and coauthors said in their report.

The incidence rate increased by about 2.4% per year, averaged over the course of the entire study period, though the plateau in rates began around 2008, according to the investigators. A figure in their report shows that the age-adjusted rate was just over 8 per 100,000 person-years in 1992; it climbed steadily until 2008, at which point it remained in the range of about 12-14 per 100,000 person-years for the next 7 years.

The uptick in incidence from 1992 to 2008 was concentrated mostly in localized and regional RCC, rather than distant disease, according to Dr. Saad and colleagues.

The overall incidence-based mortality rate for RCC was 5.3 per 100,000 person-years from 1992 to 2015, Dr. Saad and coauthors said.

Mortality rates increased from 1992 and peaked in 2001, at which point they started to drop at an ever accelerating pace. The annual percent decrease in that mortality rate was 1.5% between 2001 and 2008, 9.3% between 2008 and 2013, and 32.2% from 2013 to 2015, according to the report.

Incidence rate trends are probably affected by increases in incidental diagnoses and changes in RCC risk factor prevalence, investigators noted. For example, there has been a significant increase in use of advanced abdominal imaging, which has improved sensitivity in picking up renal masses, but cannot reliably distinguish between benign and malignant features, they said. On the other hand, smoking, which increases risk of RCC, has been trending downward for decades, which they said correlated with RCC trends.

Authors said RCC survival has been improved by antiangiogenic agents known as vascular endothelial growth factor inhibitors, and more recently immune checkpoint therapies, as clinical trials have shown.

“The decreasing mortality trend starting in 2007 and continuing until 2015 is associated with the introduction of such therapies for RCC treatment,” Dr. Saad and coauthors said in their report.

Support for the study came from the National Cancer Institute and the Department of Defense. Dr. Saad and coauthors declared that they had no conflicts of interest.

SOURCE: Saad AM et al. Clin Genitourin Cancer. 2018. doi: 10.1016/j.clgc.2018.10.002.

Renal cell carcinoma (RCC) incidence rates increased in recent years, but have stabilized, while mortality rates have dropped precipitously, according to an analysis of more than 20 years of U.S. cancer registry data.

The introduction of antiangiogenic agents is likely one key factor that led to the mortality decrease, said authors of the analysis of Surveillance, Epidemiology, and End Results data from 1992 to 2015.

Incidence trends are likely more complex and may reflect the interplay between increased detection, on one hand, and decreases in modifiable risk factors such as smoking on the other, the authors reported in Clinical Genitourinary Cancer.

The analysis, conducted by Anas M. Saad, a final-year medical student at Ain Shams University, Cairo; Thai H. Ho, MD, PhD, of Mayo Clinic Cancer Center, Phoenix; and coinvestigators, included a total of 104,584 patients with an RCC diagnosis, of whom nearly 64% were male and 80% were white. The majority of tumors were small and localized at diagnosis, and clear cell was the histologic subtype in 44%, according to the report.

Overall incidence of RCC was 11.3 per 100,000 person-years over the 1992-2015 study period, Dr. Saad and coauthors said in their report.

The incidence rate increased by about 2.4% per year, averaged over the course of the entire study period, though the plateau in rates began around 2008, according to the investigators. A figure in their report shows that the age-adjusted rate was just over 8 per 100,000 person-years in 1992; it climbed steadily until 2008, at which point it remained in the range of about 12-14 per 100,000 person-years for the next 7 years.

The uptick in incidence from 1992 to 2008 was concentrated mostly in localized and regional RCC, rather than distant disease, according to Dr. Saad and colleagues.

The overall incidence-based mortality rate for RCC was 5.3 per 100,000 person-years from 1992 to 2015, Dr. Saad and coauthors said.

Mortality rates increased from 1992 and peaked in 2001, at which point they started to drop at an ever accelerating pace. The annual percent decrease in that mortality rate was 1.5% between 2001 and 2008, 9.3% between 2008 and 2013, and 32.2% from 2013 to 2015, according to the report.

Incidence rate trends are probably affected by increases in incidental diagnoses and changes in RCC risk factor prevalence, investigators noted. For example, there has been a significant increase in use of advanced abdominal imaging, which has improved sensitivity in picking up renal masses, but cannot reliably distinguish between benign and malignant features, they said. On the other hand, smoking, which increases risk of RCC, has been trending downward for decades, which they said correlated with RCC trends.

Authors said RCC survival has been improved by antiangiogenic agents known as vascular endothelial growth factor inhibitors, and more recently immune checkpoint therapies, as clinical trials have shown.

“The decreasing mortality trend starting in 2007 and continuing until 2015 is associated with the introduction of such therapies for RCC treatment,” Dr. Saad and coauthors said in their report.

Support for the study came from the National Cancer Institute and the Department of Defense. Dr. Saad and coauthors declared that they had no conflicts of interest.

SOURCE: Saad AM et al. Clin Genitourin Cancer. 2018. doi: 10.1016/j.clgc.2018.10.002.

Renal cell carcinoma (RCC) incidence rates increased in recent years, but have stabilized, while mortality rates have dropped precipitously, according to an analysis of more than 20 years of U.S. cancer registry data.

The introduction of antiangiogenic agents is likely one key factor that led to the mortality decrease, said authors of the analysis of Surveillance, Epidemiology, and End Results data from 1992 to 2015.

Incidence trends are likely more complex and may reflect the interplay between increased detection, on one hand, and decreases in modifiable risk factors such as smoking on the other, the authors reported in Clinical Genitourinary Cancer.

The analysis, conducted by Anas M. Saad, a final-year medical student at Ain Shams University, Cairo; Thai H. Ho, MD, PhD, of Mayo Clinic Cancer Center, Phoenix; and coinvestigators, included a total of 104,584 patients with an RCC diagnosis, of whom nearly 64% were male and 80% were white. The majority of tumors were small and localized at diagnosis, and clear cell was the histologic subtype in 44%, according to the report.

Overall incidence of RCC was 11.3 per 100,000 person-years over the 1992-2015 study period, Dr. Saad and coauthors said in their report.

The incidence rate increased by about 2.4% per year, averaged over the course of the entire study period, though the plateau in rates began around 2008, according to the investigators. A figure in their report shows that the age-adjusted rate was just over 8 per 100,000 person-years in 1992; it climbed steadily until 2008, at which point it remained in the range of about 12-14 per 100,000 person-years for the next 7 years.

The uptick in incidence from 1992 to 2008 was concentrated mostly in localized and regional RCC, rather than distant disease, according to Dr. Saad and colleagues.

The overall incidence-based mortality rate for RCC was 5.3 per 100,000 person-years from 1992 to 2015, Dr. Saad and coauthors said.

Mortality rates increased from 1992 and peaked in 2001, at which point they started to drop at an ever accelerating pace. The annual percent decrease in that mortality rate was 1.5% between 2001 and 2008, 9.3% between 2008 and 2013, and 32.2% from 2013 to 2015, according to the report.

Incidence rate trends are probably affected by increases in incidental diagnoses and changes in RCC risk factor prevalence, investigators noted. For example, there has been a significant increase in use of advanced abdominal imaging, which has improved sensitivity in picking up renal masses, but cannot reliably distinguish between benign and malignant features, they said. On the other hand, smoking, which increases risk of RCC, has been trending downward for decades, which they said correlated with RCC trends.

Authors said RCC survival has been improved by antiangiogenic agents known as vascular endothelial growth factor inhibitors, and more recently immune checkpoint therapies, as clinical trials have shown.

“The decreasing mortality trend starting in 2007 and continuing until 2015 is associated with the introduction of such therapies for RCC treatment,” Dr. Saad and coauthors said in their report.

Support for the study came from the National Cancer Institute and the Department of Defense. Dr. Saad and coauthors declared that they had no conflicts of interest.

SOURCE: Saad AM et al. Clin Genitourin Cancer. 2018. doi: 10.1016/j.clgc.2018.10.002.

Among patients with stage III renal cell carcinoma (RCC) by current staging criteria, survival outcomes are worse for those who have pathological nodal involvement, results of a retrospective study suggest.

Survival was significantly shorter for stage III patients with nodal involvement versus those with no involvement, and was “equivalent” to survival in stage IV RCC patients, according to study author Jose A. Karam, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his coauthors.

“If these findings are validated in other studies, consideration should be given to reclassifying patients with stage III, pN1 disease as having stage IV disease,” Dr. Karam and his coauthors wrote in Cancer.

Dr. Karam and his colleagues looked at records for patients with RCC of any histologic subtype who had undergone radical or partial nephrectomy between 1993 and 2012. Their analysis included a total of 389 patients with stage III disease, including 274 with node-positive disease (pT3N0M0) and 115 with node-negative disease (pT123N1M0), along with 523 patients who had stage IV disease.

They found that median overall survival was just 2.4 years (95% confidence interval, 1.7-4.1) for stage III, node-positive disease patients, compared with 10.2 years (95% CI, 8.7-not estimable [NE]) for stage III, node-negative disease and 2.4 years (95% CI, 2.1-3.0) for stage IV disease.

There was a significant difference in overall survival between the three groups, but no significant difference between patients with stage III node-positive disease and stage IV disease, the investigators wrote.

Similarly, median cancer-specific survival was 2.8 years (95% CI, 1.8-4.8) for stage III node-positive disease, not reached (95% CI, 10.2-NE) for stage III node-negative disease, and 2.4 years (95% CI, 2.1-3.0) for stage IV disease, the investigators wrote.

In multivariate analysis, pathological lymph node involvement in the stage III patients was independently associated with worse overall and cancer-specific survival.

Dr. Karam and his coauthors wrote that it may be prudent to revise the current staging system to reclassify node-positive patients if further research confirms their findings. By the current American Joint Committee on Cancer tumor, nodes, and metastases staging manual, patients can be classified as stage III on the basis of either primary tumor status (pT3) or pathological lymph node involvement, they said.

The incidence of pathological, node-positive disease in RCC ranges from 2%-10% in studies, with 5-year survival rates that are “poor” at 5%-30%, the authors noted in their report.

“Even in the targeted therapy era, adjuvant therapy with tyrosine kinase inhibitors does not appear to improve on these outcomes in patients with pN-positive disease,” they wrote.

Funding support for the research came from the National Institutes of Health/National Cancer Institute. Dr. Karam reported serving as a consultant/advisory board member for Pfizer, EMD Serono, Novartis, and Roche/Genentech, and that the MD Anderson Cancer Center has received clinical trial research funding from Roche/Genentech, though none of these disclosures were related to the current report.

SOURCE: Karam JA et al. Cancer. 2018 Oct 1. doi: 10.1002/cncr.31661.

Among patients with stage III renal cell carcinoma (RCC) by current staging criteria, survival outcomes are worse for those who have pathological nodal involvement, results of a retrospective study suggest.

Survival was significantly shorter for stage III patients with nodal involvement versus those with no involvement, and was “equivalent” to survival in stage IV RCC patients, according to study author Jose A. Karam, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his coauthors.

“If these findings are validated in other studies, consideration should be given to reclassifying patients with stage III, pN1 disease as having stage IV disease,” Dr. Karam and his coauthors wrote in Cancer.

Dr. Karam and his colleagues looked at records for patients with RCC of any histologic subtype who had undergone radical or partial nephrectomy between 1993 and 2012. Their analysis included a total of 389 patients with stage III disease, including 274 with node-positive disease (pT3N0M0) and 115 with node-negative disease (pT123N1M0), along with 523 patients who had stage IV disease.

They found that median overall survival was just 2.4 years (95% confidence interval, 1.7-4.1) for stage III, node-positive disease patients, compared with 10.2 years (95% CI, 8.7-not estimable [NE]) for stage III, node-negative disease and 2.4 years (95% CI, 2.1-3.0) for stage IV disease.

There was a significant difference in overall survival between the three groups, but no significant difference between patients with stage III node-positive disease and stage IV disease, the investigators wrote.

Similarly, median cancer-specific survival was 2.8 years (95% CI, 1.8-4.8) for stage III node-positive disease, not reached (95% CI, 10.2-NE) for stage III node-negative disease, and 2.4 years (95% CI, 2.1-3.0) for stage IV disease, the investigators wrote.

In multivariate analysis, pathological lymph node involvement in the stage III patients was independently associated with worse overall and cancer-specific survival.

Dr. Karam and his coauthors wrote that it may be prudent to revise the current staging system to reclassify node-positive patients if further research confirms their findings. By the current American Joint Committee on Cancer tumor, nodes, and metastases staging manual, patients can be classified as stage III on the basis of either primary tumor status (pT3) or pathological lymph node involvement, they said.

The incidence of pathological, node-positive disease in RCC ranges from 2%-10% in studies, with 5-year survival rates that are “poor” at 5%-30%, the authors noted in their report.

“Even in the targeted therapy era, adjuvant therapy with tyrosine kinase inhibitors does not appear to improve on these outcomes in patients with pN-positive disease,” they wrote.

Funding support for the research came from the National Institutes of Health/National Cancer Institute. Dr. Karam reported serving as a consultant/advisory board member for Pfizer, EMD Serono, Novartis, and Roche/Genentech, and that the MD Anderson Cancer Center has received clinical trial research funding from Roche/Genentech, though none of these disclosures were related to the current report.

SOURCE: Karam JA et al. Cancer. 2018 Oct 1. doi: 10.1002/cncr.31661.

Among patients with stage III renal cell carcinoma (RCC) by current staging criteria, survival outcomes are worse for those who have pathological nodal involvement, results of a retrospective study suggest.

Survival was significantly shorter for stage III patients with nodal involvement versus those with no involvement, and was “equivalent” to survival in stage IV RCC patients, according to study author Jose A. Karam, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his coauthors.

“If these findings are validated in other studies, consideration should be given to reclassifying patients with stage III, pN1 disease as having stage IV disease,” Dr. Karam and his coauthors wrote in Cancer.

Dr. Karam and his colleagues looked at records for patients with RCC of any histologic subtype who had undergone radical or partial nephrectomy between 1993 and 2012. Their analysis included a total of 389 patients with stage III disease, including 274 with node-positive disease (pT3N0M0) and 115 with node-negative disease (pT123N1M0), along with 523 patients who had stage IV disease.

They found that median overall survival was just 2.4 years (95% confidence interval, 1.7-4.1) for stage III, node-positive disease patients, compared with 10.2 years (95% CI, 8.7-not estimable [NE]) for stage III, node-negative disease and 2.4 years (95% CI, 2.1-3.0) for stage IV disease.

There was a significant difference in overall survival between the three groups, but no significant difference between patients with stage III node-positive disease and stage IV disease, the investigators wrote.

Similarly, median cancer-specific survival was 2.8 years (95% CI, 1.8-4.8) for stage III node-positive disease, not reached (95% CI, 10.2-NE) for stage III node-negative disease, and 2.4 years (95% CI, 2.1-3.0) for stage IV disease, the investigators wrote.

In multivariate analysis, pathological lymph node involvement in the stage III patients was independently associated with worse overall and cancer-specific survival.

Dr. Karam and his coauthors wrote that it may be prudent to revise the current staging system to reclassify node-positive patients if further research confirms their findings. By the current American Joint Committee on Cancer tumor, nodes, and metastases staging manual, patients can be classified as stage III on the basis of either primary tumor status (pT3) or pathological lymph node involvement, they said.

The incidence of pathological, node-positive disease in RCC ranges from 2%-10% in studies, with 5-year survival rates that are “poor” at 5%-30%, the authors noted in their report.

“Even in the targeted therapy era, adjuvant therapy with tyrosine kinase inhibitors does not appear to improve on these outcomes in patients with pN-positive disease,” they wrote.

Funding support for the research came from the National Institutes of Health/National Cancer Institute. Dr. Karam reported serving as a consultant/advisory board member for Pfizer, EMD Serono, Novartis, and Roche/Genentech, and that the MD Anderson Cancer Center has received clinical trial research funding from Roche/Genentech, though none of these disclosures were related to the current report.

SOURCE: Karam JA et al. Cancer. 2018 Oct 1. doi: 10.1002/cncr.31661.

A comparison of the genomic landscapes of both primary and metastatic clear cell renal cell carcinoma (ccRCC) found no significant differences in gene expression or mutational burden between the disease states, suggesting that there is no single genetic driver of metastases, investigators reported.

An analysis of targeted next-generation sequencing of both primary tumors and metastases in two independent patient cohorts showed that only the gene encoding for the tumor suppressor TP53 was significantly more frequently mutated in metastases, compared with primary tumors, but this finding did not pass a false positive test (false discovery rate), noted Toni K. Choueiri, MD, from the Dana-Farber Cancer Institute in Boston, and his colleagues, in the British Journal of Cancer.

“No other gene had significant difference in the cohort frequency of mutations between the metastases and primary tumors. Mutation burden was not significantly different between the metastases and primary tumors or between metastatic sites,” they wrote.

Frequently mutated genes in ccRCC include VHL, the gene encoding for von Hippel–Lindau syndrome, as well as tumor suppressor genes such as PBRM1, SEDT2, BAP1 and KDM5C, but few mutations are clinically actionable, the investigators noted. “However, the value of genomic alterations will be determined by understanding the interactions between acquired genetic alterations, treatments received, heterogeneity, and the dynamics of mutations during evolution of disease.”

To see whether they could improve understanding of the genomic differences between primary and metastatic ccRCC and potentially develop personalized therapies, the investigators studied targeted next-generation sequencing data from two separate cohorts.

The first cohort included data on 349 ccRCC primary tumors and 229 unmatched cases of metastatic ccRCC from the Foundation Medicine database. The second, a validation cohort, included data on 177 ccRCC primary tumors and 80 metastases from patients treated at Dana-Farber. In each cohort, sequencing was performed on 275 genes and intronic regions in 30 genes for a total of 282 unique genes.

In cohort 1, which included tumor samples from 417 men and 169 women with a median age of 58 years, the frequency of mutations was similar in primary tumors and metastases. As noted before, mutations in TP53 were significantly more frequent in metastases than in primary tumors, detected in 14.85% versus 8.90% of samples, respectively (P = .031). This difference did not, however, pass the false discovery rate test (q = 0.21). Two other tumor suppressor genes, PBRM1 and KDM5C, were numerically but not significantly more frequent in metastases.

There were no differences in median tumor mutational burden between primary and metastatic samples and no difference in either mutations or mutational burden across different metastatic sites.

In cohort 2 there were no significantly different mutational frequencies between primary and metastatic samples for any gene and no differences in median tumor mutational burden.

An analysis comparing the frequency of gene mutations in primary tumors of patients in this cohort who went on to develop metastatic disease versus those of patients with only localized disease showed that, after a median follow-up of 21.9 months, there were no significant differences in either mutational frequency or tumor mutational burden.

“It is currently unknown if cohortwide genomic alterations in RCC metastases have a different genomic profile, including potential actionable mutations, compared to samples derived from the primary site. To our knowledge, our analysis is the largest genomic ccRCC study that compares cohortwide mutational differences between metastases and primary tumors,” the investigators wrote.

They acknowledged that because they did not match primary tumors with metastatic tumors in the same patients they were unable to evaluate how individual tumors evolve over time or how systemic therapies may alter the tumor genomic landscape.

Dr. Choueri is supported in part by the Dana-Farber/Harvard Cancer Center Kidney SPORE, the Kohlberg Chair at Harvard Medical School and the Trust Family, Michael Brigham, and Loker Pinard Funds for Kidney Cancer Research at the Dana-Farber Cancer Institute. Six of the study’s coauthors are employed by Foundation Medicine. The remaining authors declared no competing interests.

SOURCE: Choueiri TK et al. Br J Cancer. 2018 May;118(9):1238-42.

A comparison of the genomic landscapes of both primary and metastatic clear cell renal cell carcinoma (ccRCC) found no significant differences in gene expression or mutational burden between the disease states, suggesting that there is no single genetic driver of metastases, investigators reported.

An analysis of targeted next-generation sequencing of both primary tumors and metastases in two independent patient cohorts showed that only the gene encoding for the tumor suppressor TP53 was significantly more frequently mutated in metastases, compared with primary tumors, but this finding did not pass a false positive test (false discovery rate), noted Toni K. Choueiri, MD, from the Dana-Farber Cancer Institute in Boston, and his colleagues, in the British Journal of Cancer.

“No other gene had significant difference in the cohort frequency of mutations between the metastases and primary tumors. Mutation burden was not significantly different between the metastases and primary tumors or between metastatic sites,” they wrote.

Frequently mutated genes in ccRCC include VHL, the gene encoding for von Hippel–Lindau syndrome, as well as tumor suppressor genes such as PBRM1, SEDT2, BAP1 and KDM5C, but few mutations are clinically actionable, the investigators noted. “However, the value of genomic alterations will be determined by understanding the interactions between acquired genetic alterations, treatments received, heterogeneity, and the dynamics of mutations during evolution of disease.”

To see whether they could improve understanding of the genomic differences between primary and metastatic ccRCC and potentially develop personalized therapies, the investigators studied targeted next-generation sequencing data from two separate cohorts.

The first cohort included data on 349 ccRCC primary tumors and 229 unmatched cases of metastatic ccRCC from the Foundation Medicine database. The second, a validation cohort, included data on 177 ccRCC primary tumors and 80 metastases from patients treated at Dana-Farber. In each cohort, sequencing was performed on 275 genes and intronic regions in 30 genes for a total of 282 unique genes.

In cohort 1, which included tumor samples from 417 men and 169 women with a median age of 58 years, the frequency of mutations was similar in primary tumors and metastases. As noted before, mutations in TP53 were significantly more frequent in metastases than in primary tumors, detected in 14.85% versus 8.90% of samples, respectively (P = .031). This difference did not, however, pass the false discovery rate test (q = 0.21). Two other tumor suppressor genes, PBRM1 and KDM5C, were numerically but not significantly more frequent in metastases.

There were no differences in median tumor mutational burden between primary and metastatic samples and no difference in either mutations or mutational burden across different metastatic sites.

In cohort 2 there were no significantly different mutational frequencies between primary and metastatic samples for any gene and no differences in median tumor mutational burden.

An analysis comparing the frequency of gene mutations in primary tumors of patients in this cohort who went on to develop metastatic disease versus those of patients with only localized disease showed that, after a median follow-up of 21.9 months, there were no significant differences in either mutational frequency or tumor mutational burden.

“It is currently unknown if cohortwide genomic alterations in RCC metastases have a different genomic profile, including potential actionable mutations, compared to samples derived from the primary site. To our knowledge, our analysis is the largest genomic ccRCC study that compares cohortwide mutational differences between metastases and primary tumors,” the investigators wrote.

They acknowledged that because they did not match primary tumors with metastatic tumors in the same patients they were unable to evaluate how individual tumors evolve over time or how systemic therapies may alter the tumor genomic landscape.

Dr. Choueri is supported in part by the Dana-Farber/Harvard Cancer Center Kidney SPORE, the Kohlberg Chair at Harvard Medical School and the Trust Family, Michael Brigham, and Loker Pinard Funds for Kidney Cancer Research at the Dana-Farber Cancer Institute. Six of the study’s coauthors are employed by Foundation Medicine. The remaining authors declared no competing interests.

SOURCE: Choueiri TK et al. Br J Cancer. 2018 May;118(9):1238-42.

A comparison of the genomic landscapes of both primary and metastatic clear cell renal cell carcinoma (ccRCC) found no significant differences in gene expression or mutational burden between the disease states, suggesting that there is no single genetic driver of metastases, investigators reported.

An analysis of targeted next-generation sequencing of both primary tumors and metastases in two independent patient cohorts showed that only the gene encoding for the tumor suppressor TP53 was significantly more frequently mutated in metastases, compared with primary tumors, but this finding did not pass a false positive test (false discovery rate), noted Toni K. Choueiri, MD, from the Dana-Farber Cancer Institute in Boston, and his colleagues, in the British Journal of Cancer.

“No other gene had significant difference in the cohort frequency of mutations between the metastases and primary tumors. Mutation burden was not significantly different between the metastases and primary tumors or between metastatic sites,” they wrote.

Frequently mutated genes in ccRCC include VHL, the gene encoding for von Hippel–Lindau syndrome, as well as tumor suppressor genes such as PBRM1, SEDT2, BAP1 and KDM5C, but few mutations are clinically actionable, the investigators noted. “However, the value of genomic alterations will be determined by understanding the interactions between acquired genetic alterations, treatments received, heterogeneity, and the dynamics of mutations during evolution of disease.”

To see whether they could improve understanding of the genomic differences between primary and metastatic ccRCC and potentially develop personalized therapies, the investigators studied targeted next-generation sequencing data from two separate cohorts.

The first cohort included data on 349 ccRCC primary tumors and 229 unmatched cases of metastatic ccRCC from the Foundation Medicine database. The second, a validation cohort, included data on 177 ccRCC primary tumors and 80 metastases from patients treated at Dana-Farber. In each cohort, sequencing was performed on 275 genes and intronic regions in 30 genes for a total of 282 unique genes.

In cohort 1, which included tumor samples from 417 men and 169 women with a median age of 58 years, the frequency of mutations was similar in primary tumors and metastases. As noted before, mutations in TP53 were significantly more frequent in metastases than in primary tumors, detected in 14.85% versus 8.90% of samples, respectively (P = .031). This difference did not, however, pass the false discovery rate test (q = 0.21). Two other tumor suppressor genes, PBRM1 and KDM5C, were numerically but not significantly more frequent in metastases.

There were no differences in median tumor mutational burden between primary and metastatic samples and no difference in either mutations or mutational burden across different metastatic sites.

In cohort 2 there were no significantly different mutational frequencies between primary and metastatic samples for any gene and no differences in median tumor mutational burden.

An analysis comparing the frequency of gene mutations in primary tumors of patients in this cohort who went on to develop metastatic disease versus those of patients with only localized disease showed that, after a median follow-up of 21.9 months, there were no significant differences in either mutational frequency or tumor mutational burden.

“It is currently unknown if cohortwide genomic alterations in RCC metastases have a different genomic profile, including potential actionable mutations, compared to samples derived from the primary site. To our knowledge, our analysis is the largest genomic ccRCC study that compares cohortwide mutational differences between metastases and primary tumors,” the investigators wrote.

They acknowledged that because they did not match primary tumors with metastatic tumors in the same patients they were unable to evaluate how individual tumors evolve over time or how systemic therapies may alter the tumor genomic landscape.

Dr. Choueri is supported in part by the Dana-Farber/Harvard Cancer Center Kidney SPORE, the Kohlberg Chair at Harvard Medical School and the Trust Family, Michael Brigham, and Loker Pinard Funds for Kidney Cancer Research at the Dana-Farber Cancer Institute. Six of the study’s coauthors are employed by Foundation Medicine. The remaining authors declared no competing interests.

SOURCE: Choueiri TK et al. Br J Cancer. 2018 May;118(9):1238-42.

An updated analysis of interim results for JAVELIN Renal 101 will be presented at a Presidential Symposium during the annual congress of the European Society for Medical Oncology (ESMO 2018), to be held Oct. 19-23 in Munich.

The phase 3 trial compared avelumab (Bavencio) in combination with axitinib (Inlyta) to sunitinib monotherapy as first-line treatment, in patients with advanced renal cell carcinoma (RCC). Interim analysis results announced by the company in a September press release indicated the combination of immunotherapy and a tyrosine kinase inhibitor showed “a statistically significant improvement in progression-free survival by central review for patients treated with the combination whose tumors had programmed death ligand-1‒positive (PD-L1+) expression greater than 1% (primary objective), as well as in the entire study population regardless of PD-L1 tumor expression (secondary objective).”

An updated analysis of progression-free survival and overall response rates will be presented at ESMO 2018 by Robert J. Motzer, MD of Memorial Sloan Kettering Cancer Center, New York.

A phase 1b study (JAVELIN Renal 100), published in Lancet Oncology, found the safety profile of the combination to be similar to either drug alone.

For the phase 3 trial, more than 800 patients with advanced RCC were randomized to first-line treatment with the combination of avelumab (10 mg/kg IV every 2 weeks) plus axitinib (5 mg orally, twice daily) or monotherapy with sunitinib (50 mg orally once daily, 4 weeks on/2 weeks off). The overall survival results will be presented at the Presidential Symposium 2 on Oct. 21.

This article was updated on 10/15/18 to reflect the fact that interim results will be presented.






 

An updated analysis of interim results for JAVELIN Renal 101 will be presented at a Presidential Symposium during the annual congress of the European Society for Medical Oncology (ESMO 2018), to be held Oct. 19-23 in Munich.

The phase 3 trial compared avelumab (Bavencio) in combination with axitinib (Inlyta) to sunitinib monotherapy as first-line treatment, in patients with advanced renal cell carcinoma (RCC). Interim analysis results announced by the company in a September press release indicated the combination of immunotherapy and a tyrosine kinase inhibitor showed “a statistically significant improvement in progression-free survival by central review for patients treated with the combination whose tumors had programmed death ligand-1‒positive (PD-L1+) expression greater than 1% (primary objective), as well as in the entire study population regardless of PD-L1 tumor expression (secondary objective).”

An updated analysis of progression-free survival and overall response rates will be presented at ESMO 2018 by Robert J. Motzer, MD of Memorial Sloan Kettering Cancer Center, New York.

A phase 1b study (JAVELIN Renal 100), published in Lancet Oncology, found the safety profile of the combination to be similar to either drug alone.

For the phase 3 trial, more than 800 patients with advanced RCC were randomized to first-line treatment with the combination of avelumab (10 mg/kg IV every 2 weeks) plus axitinib (5 mg orally, twice daily) or monotherapy with sunitinib (50 mg orally once daily, 4 weeks on/2 weeks off). The overall survival results will be presented at the Presidential Symposium 2 on Oct. 21.

This article was updated on 10/15/18 to reflect the fact that interim results will be presented.






 

An updated analysis of interim results for JAVELIN Renal 101 will be presented at a Presidential Symposium during the annual congress of the European Society for Medical Oncology (ESMO 2018), to be held Oct. 19-23 in Munich.

The phase 3 trial compared avelumab (Bavencio) in combination with axitinib (Inlyta) to sunitinib monotherapy as first-line treatment, in patients with advanced renal cell carcinoma (RCC). Interim analysis results announced by the company in a September press release indicated the combination of immunotherapy and a tyrosine kinase inhibitor showed “a statistically significant improvement in progression-free survival by central review for patients treated with the combination whose tumors had programmed death ligand-1‒positive (PD-L1+) expression greater than 1% (primary objective), as well as in the entire study population regardless of PD-L1 tumor expression (secondary objective).”

An updated analysis of progression-free survival and overall response rates will be presented at ESMO 2018 by Robert J. Motzer, MD of Memorial Sloan Kettering Cancer Center, New York.

A phase 1b study (JAVELIN Renal 100), published in Lancet Oncology, found the safety profile of the combination to be similar to either drug alone.

For the phase 3 trial, more than 800 patients with advanced RCC were randomized to first-line treatment with the combination of avelumab (10 mg/kg IV every 2 weeks) plus axitinib (5 mg orally, twice daily) or monotherapy with sunitinib (50 mg orally once daily, 4 weeks on/2 weeks off). The overall survival results will be presented at the Presidential Symposium 2 on Oct. 21.

This article was updated on 10/15/18 to reflect the fact that interim results will be presented.






 

Epacadostat, a highly selective oral inhibitor of the indoleamine 2,3-dioxygenase 1 (IDO1) enzyme, was well tolerated when combined with pembrolizumab and demonstrated encouraging antitumor activity in multiple types of advanced solid tumors, according to the results of a phase l/ll trial.

Tumors may evade immunosurveillance through upregulation of the IDO1 enzyme, and thus there is a great interest in developing combination therapies that can target various immune evasion pathways to improve therapeutic response and outcomes. In this study, the authors evaluated the investigational agent epacadostat combined with pembrolizumab in 62 patients with advanced solid tumors.

In the dose escalation phase, patents received increasing doses of oral epacadostat (25, 50, 100, or 300 mg) twice per day plus intravenous pembrolizumab 2 mg/kg or 200 mg every 3 weeks. During the safety expansion, epacadostat at 50, 100, or 300 mg was given twice per day, plus pembrolizumab 200 mg every 3 weeks. The maximum tolerated dose of epacadostat in combination with pembrolizumab was not reached.

Objective responses (per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) occurred in 12 (55%) of 22 patients with melanoma and in patients with non–small-cell lung cancer, renal cell carcinoma, endometrial adenocarcinoma, urothelial carcinoma, and squamous cell carcinoma of the head and neck, reported Tara C. Mitchell, MD, of the Abramson Cancer Center, University of Pennsylvania, Philadelphia, and her colleagues. The report is in the Journal of Clinical Oncology.

The authors observed that there was antitumor activity at all epacadostat doses and in several tumor types. A complete response was achieved by 8 patients (treatment naive melanoma [5 patients] and previously treated for advanced/ metastatic melanoma, endometrial adenocarcinoma [EA], or urothelial carcinoma [UC] [1 patient each]), while 17 patients achieved a partial response (treatment-naive melanoma [6 patients], non–small cell lung cancer [NSCLC] [5 patients], renal cell carcinoma [RCC] and UC [2 patients each], and EA and squamous cell carcinoma of the head and neck [1 patient each]).

Most patients (n = 52, 84%) experienced treatment-related adverse events (TRAEs), the most frequently observed being fatigue (36%), rash (36%), arthralgia (24%), pruritus (23%), and nausea (21%). Grade 3/4 TRAEs occurred in 24% of patients, and 7 patients (11%) discontinued their treatment because of TRAEs. There were no deaths associated with TRAEs.

“The safety profile observed with epacadostat plus pembrolizumab compares favorably with studies of other combination immunotherapies,” wrote Dr. Mitchell and her colleagues. “Although not powered to evaluate efficacy, the phase I portion of this study showed that epacadostat plus pembrolizumab had encouraging and durable antitumor activity,” they said.

SOURCE: Mitchell TC et al. J Clin Oncol. 2018 Sep 28. doi: 10.1200/JCO.2018.78.9602.

Epacadostat, a highly selective oral inhibitor of the indoleamine 2,3-dioxygenase 1 (IDO1) enzyme, was well tolerated when combined with pembrolizumab and demonstrated encouraging antitumor activity in multiple types of advanced solid tumors, according to the results of a phase l/ll trial.

Tumors may evade immunosurveillance through upregulation of the IDO1 enzyme, and thus there is a great interest in developing combination therapies that can target various immune evasion pathways to improve therapeutic response and outcomes. In this study, the authors evaluated the investigational agent epacadostat combined with pembrolizumab in 62 patients with advanced solid tumors.

In the dose escalation phase, patents received increasing doses of oral epacadostat (25, 50, 100, or 300 mg) twice per day plus intravenous pembrolizumab 2 mg/kg or 200 mg every 3 weeks. During the safety expansion, epacadostat at 50, 100, or 300 mg was given twice per day, plus pembrolizumab 200 mg every 3 weeks. The maximum tolerated dose of epacadostat in combination with pembrolizumab was not reached.

Objective responses (per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) occurred in 12 (55%) of 22 patients with melanoma and in patients with non–small-cell lung cancer, renal cell carcinoma, endometrial adenocarcinoma, urothelial carcinoma, and squamous cell carcinoma of the head and neck, reported Tara C. Mitchell, MD, of the Abramson Cancer Center, University of Pennsylvania, Philadelphia, and her colleagues. The report is in the Journal of Clinical Oncology.

The authors observed that there was antitumor activity at all epacadostat doses and in several tumor types. A complete response was achieved by 8 patients (treatment naive melanoma [5 patients] and previously treated for advanced/ metastatic melanoma, endometrial adenocarcinoma [EA], or urothelial carcinoma [UC] [1 patient each]), while 17 patients achieved a partial response (treatment-naive melanoma [6 patients], non–small cell lung cancer [NSCLC] [5 patients], renal cell carcinoma [RCC] and UC [2 patients each], and EA and squamous cell carcinoma of the head and neck [1 patient each]).

Most patients (n = 52, 84%) experienced treatment-related adverse events (TRAEs), the most frequently observed being fatigue (36%), rash (36%), arthralgia (24%), pruritus (23%), and nausea (21%). Grade 3/4 TRAEs occurred in 24% of patients, and 7 patients (11%) discontinued their treatment because of TRAEs. There were no deaths associated with TRAEs.

“The safety profile observed with epacadostat plus pembrolizumab compares favorably with studies of other combination immunotherapies,” wrote Dr. Mitchell and her colleagues. “Although not powered to evaluate efficacy, the phase I portion of this study showed that epacadostat plus pembrolizumab had encouraging and durable antitumor activity,” they said.

SOURCE: Mitchell TC et al. J Clin Oncol. 2018 Sep 28. doi: 10.1200/JCO.2018.78.9602.

Epacadostat, a highly selective oral inhibitor of the indoleamine 2,3-dioxygenase 1 (IDO1) enzyme, was well tolerated when combined with pembrolizumab and demonstrated encouraging antitumor activity in multiple types of advanced solid tumors, according to the results of a phase l/ll trial.

Tumors may evade immunosurveillance through upregulation of the IDO1 enzyme, and thus there is a great interest in developing combination therapies that can target various immune evasion pathways to improve therapeutic response and outcomes. In this study, the authors evaluated the investigational agent epacadostat combined with pembrolizumab in 62 patients with advanced solid tumors.

In the dose escalation phase, patents received increasing doses of oral epacadostat (25, 50, 100, or 300 mg) twice per day plus intravenous pembrolizumab 2 mg/kg or 200 mg every 3 weeks. During the safety expansion, epacadostat at 50, 100, or 300 mg was given twice per day, plus pembrolizumab 200 mg every 3 weeks. The maximum tolerated dose of epacadostat in combination with pembrolizumab was not reached.

Objective responses (per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) occurred in 12 (55%) of 22 patients with melanoma and in patients with non–small-cell lung cancer, renal cell carcinoma, endometrial adenocarcinoma, urothelial carcinoma, and squamous cell carcinoma of the head and neck, reported Tara C. Mitchell, MD, of the Abramson Cancer Center, University of Pennsylvania, Philadelphia, and her colleagues. The report is in the Journal of Clinical Oncology.

The authors observed that there was antitumor activity at all epacadostat doses and in several tumor types. A complete response was achieved by 8 patients (treatment naive melanoma [5 patients] and previously treated for advanced/ metastatic melanoma, endometrial adenocarcinoma [EA], or urothelial carcinoma [UC] [1 patient each]), while 17 patients achieved a partial response (treatment-naive melanoma [6 patients], non–small cell lung cancer [NSCLC] [5 patients], renal cell carcinoma [RCC] and UC [2 patients each], and EA and squamous cell carcinoma of the head and neck [1 patient each]).

Most patients (n = 52, 84%) experienced treatment-related adverse events (TRAEs), the most frequently observed being fatigue (36%), rash (36%), arthralgia (24%), pruritus (23%), and nausea (21%). Grade 3/4 TRAEs occurred in 24% of patients, and 7 patients (11%) discontinued their treatment because of TRAEs. There were no deaths associated with TRAEs.

“The safety profile observed with epacadostat plus pembrolizumab compares favorably with studies of other combination immunotherapies,” wrote Dr. Mitchell and her colleagues. “Although not powered to evaluate efficacy, the phase I portion of this study showed that epacadostat plus pembrolizumab had encouraging and durable antitumor activity,” they said.

SOURCE: Mitchell TC et al. J Clin Oncol. 2018 Sep 28. doi: 10.1200/JCO.2018.78.9602.

The link between obesity and renal cell carcinoma (RCC) appears to be complex and may provide insight into differing etiologies for various histologic subtypes of this cancer, according to a nested case-control study and subsequent meta-analysis.

Investigators led by Catherine L. Callahan, PhD, a postdoctoral fellow with the Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Md., first analyzed data from the Kaiser Permanente Northern California health care network. They matched 685 patients with RCC (421 clear cell, 65 papillary, 24 chromophobe, 35 other, and 140 not otherwise specified) with 4,266 unaffected control patients on age, sex, race/ethnicity, duration of network membership, and medical center of diagnosis.

Compared with normal-weight counterparts (body mass index less than 25 kg/m²), obese patients (body mass index of at least 30 kg/m²), had a significantly elevated risk of clear cell RCC (odds ratio, 1.5) and a nonsignificantly elevated risk of chromophobe RCC (2.5), but a similar risk of papillary RCC (1.0), according to results reported in Cancer Epidemiology. Associations weakened when cases were restricted to stage II or higher RCC, suggesting potential bias from incidental diagnoses related to abdominal imaging. Patients who were overweight (body mass index of 25 to 29.9 kg/m²) did not have significantly elevated risks of any subtype of RCC.

The investigators next conducted a meta-analysis, including this new study and three others. Results showed a significant link between obesity and clear cell RCC (summary relative risk, 1.8) and chromophobe RCC (2.2), but not papillary RCC (1.2). Here, however, patients who were overweight also had elevated risks of clear cell RCC (1.3) and chromophobe RCC (1.9).

“Our results provide support for the hypothesis that histologic subtypes of RCC represent distinct etiologic pathways, and that obesity is more strongly associated with risk of clear cell RCC. Additional research to elucidate the underlying biology of specific subtypes of RCC is warranted,” wrote Dr. Callahan and her coinvestigators. “More generally, our findings underscore the importance of accounting for histologic subtype in investigations of RCC etiology.”

The investigators disclosed that they had no conflicts of interest. The research was supported by the Intramural Research Program of the NIH and the National Cancer Institute.

SOURCE: Callahan CL et al. Cancer Epidemiol. 2018 Jul 18, doi: 10.1016/j.canep.2018.07.002.

The link between obesity and renal cell carcinoma (RCC) appears to be complex and may provide insight into differing etiologies for various histologic subtypes of this cancer, according to a nested case-control study and subsequent meta-analysis.

Investigators led by Catherine L. Callahan, PhD, a postdoctoral fellow with the Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Md., first analyzed data from the Kaiser Permanente Northern California health care network. They matched 685 patients with RCC (421 clear cell, 65 papillary, 24 chromophobe, 35 other, and 140 not otherwise specified) with 4,266 unaffected control patients on age, sex, race/ethnicity, duration of network membership, and medical center of diagnosis.

Compared with normal-weight counterparts (body mass index less than 25 kg/m²), obese patients (body mass index of at least 30 kg/m²), had a significantly elevated risk of clear cell RCC (odds ratio, 1.5) and a nonsignificantly elevated risk of chromophobe RCC (2.5), but a similar risk of papillary RCC (1.0), according to results reported in Cancer Epidemiology. Associations weakened when cases were restricted to stage II or higher RCC, suggesting potential bias from incidental diagnoses related to abdominal imaging. Patients who were overweight (body mass index of 25 to 29.9 kg/m²) did not have significantly elevated risks of any subtype of RCC.

The investigators next conducted a meta-analysis, including this new study and three others. Results showed a significant link between obesity and clear cell RCC (summary relative risk, 1.8) and chromophobe RCC (2.2), but not papillary RCC (1.2). Here, however, patients who were overweight also had elevated risks of clear cell RCC (1.3) and chromophobe RCC (1.9).

“Our results provide support for the hypothesis that histologic subtypes of RCC represent distinct etiologic pathways, and that obesity is more strongly associated with risk of clear cell RCC. Additional research to elucidate the underlying biology of specific subtypes of RCC is warranted,” wrote Dr. Callahan and her coinvestigators. “More generally, our findings underscore the importance of accounting for histologic subtype in investigations of RCC etiology.”

The investigators disclosed that they had no conflicts of interest. The research was supported by the Intramural Research Program of the NIH and the National Cancer Institute.

SOURCE: Callahan CL et al. Cancer Epidemiol. 2018 Jul 18, doi: 10.1016/j.canep.2018.07.002.

The link between obesity and renal cell carcinoma (RCC) appears to be complex and may provide insight into differing etiologies for various histologic subtypes of this cancer, according to a nested case-control study and subsequent meta-analysis.

Investigators led by Catherine L. Callahan, PhD, a postdoctoral fellow with the Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Md., first analyzed data from the Kaiser Permanente Northern California health care network. They matched 685 patients with RCC (421 clear cell, 65 papillary, 24 chromophobe, 35 other, and 140 not otherwise specified) with 4,266 unaffected control patients on age, sex, race/ethnicity, duration of network membership, and medical center of diagnosis.

Compared with normal-weight counterparts (body mass index less than 25 kg/m²), obese patients (body mass index of at least 30 kg/m²), had a significantly elevated risk of clear cell RCC (odds ratio, 1.5) and a nonsignificantly elevated risk of chromophobe RCC (2.5), but a similar risk of papillary RCC (1.0), according to results reported in Cancer Epidemiology. Associations weakened when cases were restricted to stage II or higher RCC, suggesting potential bias from incidental diagnoses related to abdominal imaging. Patients who were overweight (body mass index of 25 to 29.9 kg/m²) did not have significantly elevated risks of any subtype of RCC.

The investigators next conducted a meta-analysis, including this new study and three others. Results showed a significant link between obesity and clear cell RCC (summary relative risk, 1.8) and chromophobe RCC (2.2), but not papillary RCC (1.2). Here, however, patients who were overweight also had elevated risks of clear cell RCC (1.3) and chromophobe RCC (1.9).

“Our results provide support for the hypothesis that histologic subtypes of RCC represent distinct etiologic pathways, and that obesity is more strongly associated with risk of clear cell RCC. Additional research to elucidate the underlying biology of specific subtypes of RCC is warranted,” wrote Dr. Callahan and her coinvestigators. “More generally, our findings underscore the importance of accounting for histologic subtype in investigations of RCC etiology.”

The investigators disclosed that they had no conflicts of interest. The research was supported by the Intramural Research Program of the NIH and the National Cancer Institute.

SOURCE: Callahan CL et al. Cancer Epidemiol. 2018 Jul 18, doi: 10.1016/j.canep.2018.07.002.

Credit improvements in therapy rather than diagnosis at an earlier stage for improved survival of renal cell carcinoma in recent years, investigators say.

A review of records on nearly 263,000 patients diagnosed with renal cell carcinoma (RCC ) from 2004 through 2015 showed that better 5-year overall survival (OS) in later years was likely attributable to better treatments rather than an uptick in detection of cancers at an earlier stage, a trend known as “stage migration,” reported Hiten D. Patel, MD, of the Brady Urological Institute at Johns Hopkins Medicine in Baltimore, and his colleagues.

“While survival has improved over time when considering all RCC patients, the primary benefit was observed in advanced RCC (stage III–IV), with 5-year survival increasing from 9.8% in 2004 to 13.2% in 2010 for patients with distant metastatic disease. The results indicate that stage migration no longer contributes to improvements in survival for RCC, and additional gains reflect improvements in advanced treatment options,” they wrote in European Urology Oncology.

Dr. Patel and colleagues noted that the incidence of RCC has been on the rise worldwide for nearly 3 decades because of both environmental risk factors and improvements in medical imaging that have resulted in an increase in incidental cancers.

“Data from the National Cancer Database (NCDB) indicated an increase in the proportion of patients presenting with cT1 RCC from 40% before 1993 to 60% through 2004. However, it is unknown if clinical stage migration has continued into recent years, which has implications for patient outcomes,” they wrote.

To try to answer this question, they sifted through data on 262,597 patients diagnosed with RCC from 2004 through 2015 at more than 1,500 facilities covered by the U.S. National Cancer Database.

They found that, up to 2007, there were statistically significant trends toward more frequent diagnosis of clinical stage I disease (70% of cases) and less frequent diagnoses of stage III (8%) and stage IV (11%; P less than .001 for all comparisons). From 2008 through 2015, however, the respective rates stabilized.

They also noticed a trend throughout the study period for decreased size of localized tumors at diagnosis, with a mean decrease of 0.22 cm for stage I lesions, and 1.24 cm for stage II tumors.

When they looked at 5-year overall survival by Kaplan-Meier analysis, they saw that it improved from 67.9% in 2004 to 72.3% in 2010. As noted before, most of the benefit was attributable to gains in survival among patients with stage III or IV disease.

In multivariable Cox proportional hazard models, diagnosis in recent years was a statistically significant predictor of improved survival, even after adjustment for stage distribution. In addition, receipt of systemic therapy was associated with improved survival, with a hazard ratio of 0.811 (P less than .001).

The authors acknowledged that a limitation of the findings is the reliance on the NCDB, which includes data on most cancer diagnoses in the United States, but is not a population-based sample.

No study funding source was reported. Dr. Patel and coauthors reported having no conflicts of interest to disclose.

SOURCE: Patel HD et al. Eur Urol Oncol. 2018 Sep 25. doi: 10.1016/j.euo.2018.08.023.
 

Credit improvements in therapy rather than diagnosis at an earlier stage for improved survival of renal cell carcinoma in recent years, investigators say.

A review of records on nearly 263,000 patients diagnosed with renal cell carcinoma (RCC ) from 2004 through 2015 showed that better 5-year overall survival (OS) in later years was likely attributable to better treatments rather than an uptick in detection of cancers at an earlier stage, a trend known as “stage migration,” reported Hiten D. Patel, MD, of the Brady Urological Institute at Johns Hopkins Medicine in Baltimore, and his colleagues.

“While survival has improved over time when considering all RCC patients, the primary benefit was observed in advanced RCC (stage III–IV), with 5-year survival increasing from 9.8% in 2004 to 13.2% in 2010 for patients with distant metastatic disease. The results indicate that stage migration no longer contributes to improvements in survival for RCC, and additional gains reflect improvements in advanced treatment options,” they wrote in European Urology Oncology.

Dr. Patel and colleagues noted that the incidence of RCC has been on the rise worldwide for nearly 3 decades because of both environmental risk factors and improvements in medical imaging that have resulted in an increase in incidental cancers.

“Data from the National Cancer Database (NCDB) indicated an increase in the proportion of patients presenting with cT1 RCC from 40% before 1993 to 60% through 2004. However, it is unknown if clinical stage migration has continued into recent years, which has implications for patient outcomes,” they wrote.

To try to answer this question, they sifted through data on 262,597 patients diagnosed with RCC from 2004 through 2015 at more than 1,500 facilities covered by the U.S. National Cancer Database.

They found that, up to 2007, there were statistically significant trends toward more frequent diagnosis of clinical stage I disease (70% of cases) and less frequent diagnoses of stage III (8%) and stage IV (11%; P less than .001 for all comparisons). From 2008 through 2015, however, the respective rates stabilized.

They also noticed a trend throughout the study period for decreased size of localized tumors at diagnosis, with a mean decrease of 0.22 cm for stage I lesions, and 1.24 cm for stage II tumors.

When they looked at 5-year overall survival by Kaplan-Meier analysis, they saw that it improved from 67.9% in 2004 to 72.3% in 2010. As noted before, most of the benefit was attributable to gains in survival among patients with stage III or IV disease.

In multivariable Cox proportional hazard models, diagnosis in recent years was a statistically significant predictor of improved survival, even after adjustment for stage distribution. In addition, receipt of systemic therapy was associated with improved survival, with a hazard ratio of 0.811 (P less than .001).

The authors acknowledged that a limitation of the findings is the reliance on the NCDB, which includes data on most cancer diagnoses in the United States, but is not a population-based sample.

No study funding source was reported. Dr. Patel and coauthors reported having no conflicts of interest to disclose.

SOURCE: Patel HD et al. Eur Urol Oncol. 2018 Sep 25. doi: 10.1016/j.euo.2018.08.023.
 

Credit improvements in therapy rather than diagnosis at an earlier stage for improved survival of renal cell carcinoma in recent years, investigators say.

A review of records on nearly 263,000 patients diagnosed with renal cell carcinoma (RCC ) from 2004 through 2015 showed that better 5-year overall survival (OS) in later years was likely attributable to better treatments rather than an uptick in detection of cancers at an earlier stage, a trend known as “stage migration,” reported Hiten D. Patel, MD, of the Brady Urological Institute at Johns Hopkins Medicine in Baltimore, and his colleagues.

“While survival has improved over time when considering all RCC patients, the primary benefit was observed in advanced RCC (stage III–IV), with 5-year survival increasing from 9.8% in 2004 to 13.2% in 2010 for patients with distant metastatic disease. The results indicate that stage migration no longer contributes to improvements in survival for RCC, and additional gains reflect improvements in advanced treatment options,” they wrote in European Urology Oncology.

Dr. Patel and colleagues noted that the incidence of RCC has been on the rise worldwide for nearly 3 decades because of both environmental risk factors and improvements in medical imaging that have resulted in an increase in incidental cancers.

“Data from the National Cancer Database (NCDB) indicated an increase in the proportion of patients presenting with cT1 RCC from 40% before 1993 to 60% through 2004. However, it is unknown if clinical stage migration has continued into recent years, which has implications for patient outcomes,” they wrote.

To try to answer this question, they sifted through data on 262,597 patients diagnosed with RCC from 2004 through 2015 at more than 1,500 facilities covered by the U.S. National Cancer Database.

They found that, up to 2007, there were statistically significant trends toward more frequent diagnosis of clinical stage I disease (70% of cases) and less frequent diagnoses of stage III (8%) and stage IV (11%; P less than .001 for all comparisons). From 2008 through 2015, however, the respective rates stabilized.

They also noticed a trend throughout the study period for decreased size of localized tumors at diagnosis, with a mean decrease of 0.22 cm for stage I lesions, and 1.24 cm for stage II tumors.

When they looked at 5-year overall survival by Kaplan-Meier analysis, they saw that it improved from 67.9% in 2004 to 72.3% in 2010. As noted before, most of the benefit was attributable to gains in survival among patients with stage III or IV disease.

In multivariable Cox proportional hazard models, diagnosis in recent years was a statistically significant predictor of improved survival, even after adjustment for stage distribution. In addition, receipt of systemic therapy was associated with improved survival, with a hazard ratio of 0.811 (P less than .001).

The authors acknowledged that a limitation of the findings is the reliance on the NCDB, which includes data on most cancer diagnoses in the United States, but is not a population-based sample.

No study funding source was reported. Dr. Patel and coauthors reported having no conflicts of interest to disclose.

SOURCE: Patel HD et al. Eur Urol Oncol. 2018 Sep 25. doi: 10.1016/j.euo.2018.08.023.
 

The oral, multitargeted tyrosine kinase inhibitor pazopanib (Votrient) is active and safe in patients with renal cell carcinoma and other neoplasms caused by von Hippel-Lindau disease, a phase 2 trial has found.

Eric Jonasch, MD, and his coinvestigators at the University of Texas MD Anderson Cancer Center, Houston, conducted the single-arm trial among 31 adult patients with clinical manifestations of von Hippel-Lindau disease, an autosomal dominant disorder that currently has no approved treatment.

All patients were treated with open-label pazopanib (800 mg daily with dose reductions permitted) for 24 weeks, with an option to continue thereafter. Pazopanib derives its antiangiogenic and antineoplastic activity from its selective inhibition of vascular endothelial growth factor receptors (VEGFR)–1, –2, and –3; c-KIT; and platelet-derived growth factor receptor (PDGFR). It is currently approved by the FDA for treatment of advanced renal cell carcinoma and advanced soft-tissue sarcoma.

The trial was stopped before attaining planned enrollment because accrual slowed and it met a prespecified toxicity stopping threshold, according to results reported in Lancet Oncology.

At a median follow-up of 12 months, 42% of patients overall had an objective response to pazopanib. By site, response was seen in 52% of 59 renal cell carcinomas, 53% of 17 pancreatic lesions (mainly serous cystadenomas), and 4% of 49 CNS hemangioblastomas; the median reduction in tumor size was 40.5%, 30.5%, and 13%, respectively.

Slightly more than half of patients, 52%, opted to stay on pazopanib after 24 weeks, with the longest duration being 60 months at data cutoff.

Some 13% of patients withdrew from the study because of grade 3 or 4 transaminitis, and 10% stopped treatment because of general intolerance related to multiple grade 1 and 2 toxicities. There were three treatment-related serious adverse events: one case of appendicitis, one case of gastritis, and one case of fatal CNS bleeding after a fall.

“Pazopanib was associated with encouraging preliminary activity in von Hippel-Lindau disease, with a side effect profile consistent with that seen in previous trials,” the investigators concluded. “Pazopanib could be considered as a treatment choice for patients with von Hippel-Lindau disease and growing lesions, or to reduce the size of unresectable lesions in these patients.”

Dr. Jonasch disclosed that he receives research support and honoraria from Novartis. The study was funded by Novartis and by a National Institutes of Health National Cancer Institute core grant.

SOURCE: Jonasch E et al. Lancet Oncol. 2018 Sep 17. doi: 10.1016/S1470-2045(18)30487-X,

The oral, multitargeted tyrosine kinase inhibitor pazopanib (Votrient) is active and safe in patients with renal cell carcinoma and other neoplasms caused by von Hippel-Lindau disease, a phase 2 trial has found.

Eric Jonasch, MD, and his coinvestigators at the University of Texas MD Anderson Cancer Center, Houston, conducted the single-arm trial among 31 adult patients with clinical manifestations of von Hippel-Lindau disease, an autosomal dominant disorder that currently has no approved treatment.

All patients were treated with open-label pazopanib (800 mg daily with dose reductions permitted) for 24 weeks, with an option to continue thereafter. Pazopanib derives its antiangiogenic and antineoplastic activity from its selective inhibition of vascular endothelial growth factor receptors (VEGFR)–1, –2, and –3; c-KIT; and platelet-derived growth factor receptor (PDGFR). It is currently approved by the FDA for treatment of advanced renal cell carcinoma and advanced soft-tissue sarcoma.

The trial was stopped before attaining planned enrollment because accrual slowed and it met a prespecified toxicity stopping threshold, according to results reported in Lancet Oncology.

At a median follow-up of 12 months, 42% of patients overall had an objective response to pazopanib. By site, response was seen in 52% of 59 renal cell carcinomas, 53% of 17 pancreatic lesions (mainly serous cystadenomas), and 4% of 49 CNS hemangioblastomas; the median reduction in tumor size was 40.5%, 30.5%, and 13%, respectively.

Slightly more than half of patients, 52%, opted to stay on pazopanib after 24 weeks, with the longest duration being 60 months at data cutoff.

Some 13% of patients withdrew from the study because of grade 3 or 4 transaminitis, and 10% stopped treatment because of general intolerance related to multiple grade 1 and 2 toxicities. There were three treatment-related serious adverse events: one case of appendicitis, one case of gastritis, and one case of fatal CNS bleeding after a fall.

“Pazopanib was associated with encouraging preliminary activity in von Hippel-Lindau disease, with a side effect profile consistent with that seen in previous trials,” the investigators concluded. “Pazopanib could be considered as a treatment choice for patients with von Hippel-Lindau disease and growing lesions, or to reduce the size of unresectable lesions in these patients.”

Dr. Jonasch disclosed that he receives research support and honoraria from Novartis. The study was funded by Novartis and by a National Institutes of Health National Cancer Institute core grant.

SOURCE: Jonasch E et al. Lancet Oncol. 2018 Sep 17. doi: 10.1016/S1470-2045(18)30487-X,

The oral, multitargeted tyrosine kinase inhibitor pazopanib (Votrient) is active and safe in patients with renal cell carcinoma and other neoplasms caused by von Hippel-Lindau disease, a phase 2 trial has found.

Eric Jonasch, MD, and his coinvestigators at the University of Texas MD Anderson Cancer Center, Houston, conducted the single-arm trial among 31 adult patients with clinical manifestations of von Hippel-Lindau disease, an autosomal dominant disorder that currently has no approved treatment.

All patients were treated with open-label pazopanib (800 mg daily with dose reductions permitted) for 24 weeks, with an option to continue thereafter. Pazopanib derives its antiangiogenic and antineoplastic activity from its selective inhibition of vascular endothelial growth factor receptors (VEGFR)–1, –2, and –3; c-KIT; and platelet-derived growth factor receptor (PDGFR). It is currently approved by the FDA for treatment of advanced renal cell carcinoma and advanced soft-tissue sarcoma.

The trial was stopped before attaining planned enrollment because accrual slowed and it met a prespecified toxicity stopping threshold, according to results reported in Lancet Oncology.

At a median follow-up of 12 months, 42% of patients overall had an objective response to pazopanib. By site, response was seen in 52% of 59 renal cell carcinomas, 53% of 17 pancreatic lesions (mainly serous cystadenomas), and 4% of 49 CNS hemangioblastomas; the median reduction in tumor size was 40.5%, 30.5%, and 13%, respectively.

Slightly more than half of patients, 52%, opted to stay on pazopanib after 24 weeks, with the longest duration being 60 months at data cutoff.

Some 13% of patients withdrew from the study because of grade 3 or 4 transaminitis, and 10% stopped treatment because of general intolerance related to multiple grade 1 and 2 toxicities. There were three treatment-related serious adverse events: one case of appendicitis, one case of gastritis, and one case of fatal CNS bleeding after a fall.

“Pazopanib was associated with encouraging preliminary activity in von Hippel-Lindau disease, with a side effect profile consistent with that seen in previous trials,” the investigators concluded. “Pazopanib could be considered as a treatment choice for patients with von Hippel-Lindau disease and growing lesions, or to reduce the size of unresectable lesions in these patients.”

Dr. Jonasch disclosed that he receives research support and honoraria from Novartis. The study was funded by Novartis and by a National Institutes of Health National Cancer Institute core grant.

SOURCE: Jonasch E et al. Lancet Oncol. 2018 Sep 17. doi: 10.1016/S1470-2045(18)30487-X,

Radiofrequency ablation (RFA) of small renal tumors is safe and effective, and is associated with high rates of disease-free survival, according to a study that followed patients for up to 10 years.

In 106 patients who had a total of 112 tumors and who were followed for a median 79 months, 10 recurrences were seen, after an initial procedural success rate of 97%.

Over a 6-year period, Kaplan-Meier disease-free survival (DFS) was 89%, and cancer-specific survival (CSS) was 96%. In the subgroup followed for 10 years, DFS was 82%, CSS was 94%, and overall survival (OS) was 49%.

Tumors were, on average, small (mean 2.5 cm), but for patients whose tumors were larger than 3 cm, the DFS rate fell to 68%. Patients were included in the study if they had a solitary renal mass; those who had metastatic renal cell carcinoma (RCC) or a hereditary kidney cancer syndrome were excluded.

Brett Johnson, MD, and his collaborators from the University of Texas Southwestern, Dallas, noted that an additional 29 patients received RFA but also had partial nephrectomy; these patients were excluded. “Healthier patients with larger tumors may have been advised to undergo partial nephrectomy, thereby selecting for more comorbid patients for RFA,” they noted in discussing their findings. The report was published in The Journal of Urology

Within these parameters, Dr. Johnson and his colleagues conducted a retrospective review of clinic patients whose renal tumors were successfully treated with RFA between the years 2000 and 2007. Patients were followed with yearly imaging, and were considered to have a recurrence if contrast enhancement was seen within the ablation zone at any point after a negative imaging study.

Of the 10 recurrences that were seen, eight were local and two were local and metastatic. An additional patient developed metastatic RCC without evidence of local recurrence; all patients with metastases died of their disease, said Dr. Johnson and his coauthors.

For patients whose tumors recurred, the mean initial tumor size was 3.2 cm, compared with 2.4 cm in those whose tumors didn’t recur (P = .005). Looking at the tumor size data another way, tumor size “was an independent risk factor for cancer recurrence,” with an odds ratio of 3.01 (P = .025), wrote Dr. Johnson and his collaborators.

They noted that it was not routine practice for biopsies to be performed during the initial study period; the seven patients with recurrences who had biopsy data all had clear cell RCC. Median time to local recurrence was 26 months, with no recurrences seen after 5 years.

At the time of the initial procedure, patients were a mean 63.1 years old. The relatively low OS in the subgroup with 10 years of follow-up was likely related to advancing age.

In the subgroup analysis of patients for whom 10-year data were available, the investigators used only data from patients whose initial tumors were biopsied when calculating CSS and metastasis-free survival; these rates were both 94% for those analyzed.

“Age, gender, and time of follow-up had no statistically significant effect on disease-free recurrence” in a univariate analysis, said Dr. Johnson and his colleagues.

“Nephron sparing surgery is the gold standard for treatment of small renal masses,” and the study bolsters the safety and durable efficacy of RFA by using actual survival data rather than actuarial disease survival, said the investigators.

The current study is unique in having such a long duration of follow-up and a subgroup of individuals with 10 years of annual imaging data. In addition, experienced urologists at a single site all used a uniform technique to perform thermal ablation on solitary tumors, noted Dr. Johnson and his coauthors. Successful ablations were followed only by surveillance, in keeping with current American Urological Association recommendations.

However, the study’s retrospective, nonrandomized nature introduces the possibility of selection bias, and variations in follow-up protocols may be a source of ascertainment bias, they said.

The authors reported no conflicts of interest and no outside sources of funding.

SOURCE: Johnson B et al. J Urol. 2018. doi:10.1016/j.juro.2018.08.045.

Radiofrequency ablation (RFA) of small renal tumors is safe and effective, and is associated with high rates of disease-free survival, according to a study that followed patients for up to 10 years.

In 106 patients who had a total of 112 tumors and who were followed for a median 79 months, 10 recurrences were seen, after an initial procedural success rate of 97%.

Over a 6-year period, Kaplan-Meier disease-free survival (DFS) was 89%, and cancer-specific survival (CSS) was 96%. In the subgroup followed for 10 years, DFS was 82%, CSS was 94%, and overall survival (OS) was 49%.

Tumors were, on average, small (mean 2.5 cm), but for patients whose tumors were larger than 3 cm, the DFS rate fell to 68%. Patients were included in the study if they had a solitary renal mass; those who had metastatic renal cell carcinoma (RCC) or a hereditary kidney cancer syndrome were excluded.

Brett Johnson, MD, and his collaborators from the University of Texas Southwestern, Dallas, noted that an additional 29 patients received RFA but also had partial nephrectomy; these patients were excluded. “Healthier patients with larger tumors may have been advised to undergo partial nephrectomy, thereby selecting for more comorbid patients for RFA,” they noted in discussing their findings. The report was published in The Journal of Urology

Within these parameters, Dr. Johnson and his colleagues conducted a retrospective review of clinic patients whose renal tumors were successfully treated with RFA between the years 2000 and 2007. Patients were followed with yearly imaging, and were considered to have a recurrence if contrast enhancement was seen within the ablation zone at any point after a negative imaging study.

Of the 10 recurrences that were seen, eight were local and two were local and metastatic. An additional patient developed metastatic RCC without evidence of local recurrence; all patients with metastases died of their disease, said Dr. Johnson and his coauthors.

For patients whose tumors recurred, the mean initial tumor size was 3.2 cm, compared with 2.4 cm in those whose tumors didn’t recur (P = .005). Looking at the tumor size data another way, tumor size “was an independent risk factor for cancer recurrence,” with an odds ratio of 3.01 (P = .025), wrote Dr. Johnson and his collaborators.

They noted that it was not routine practice for biopsies to be performed during the initial study period; the seven patients with recurrences who had biopsy data all had clear cell RCC. Median time to local recurrence was 26 months, with no recurrences seen after 5 years.

At the time of the initial procedure, patients were a mean 63.1 years old. The relatively low OS in the subgroup with 10 years of follow-up was likely related to advancing age.

In the subgroup analysis of patients for whom 10-year data were available, the investigators used only data from patients whose initial tumors were biopsied when calculating CSS and metastasis-free survival; these rates were both 94% for those analyzed.

“Age, gender, and time of follow-up had no statistically significant effect on disease-free recurrence” in a univariate analysis, said Dr. Johnson and his colleagues.

“Nephron sparing surgery is the gold standard for treatment of small renal masses,” and the study bolsters the safety and durable efficacy of RFA by using actual survival data rather than actuarial disease survival, said the investigators.

The current study is unique in having such a long duration of follow-up and a subgroup of individuals with 10 years of annual imaging data. In addition, experienced urologists at a single site all used a uniform technique to perform thermal ablation on solitary tumors, noted Dr. Johnson and his coauthors. Successful ablations were followed only by surveillance, in keeping with current American Urological Association recommendations.

However, the study’s retrospective, nonrandomized nature introduces the possibility of selection bias, and variations in follow-up protocols may be a source of ascertainment bias, they said.

The authors reported no conflicts of interest and no outside sources of funding.

SOURCE: Johnson B et al. J Urol. 2018. doi:10.1016/j.juro.2018.08.045.

Radiofrequency ablation (RFA) of small renal tumors is safe and effective, and is associated with high rates of disease-free survival, according to a study that followed patients for up to 10 years.

In 106 patients who had a total of 112 tumors and who were followed for a median 79 months, 10 recurrences were seen, after an initial procedural success rate of 97%.

Over a 6-year period, Kaplan-Meier disease-free survival (DFS) was 89%, and cancer-specific survival (CSS) was 96%. In the subgroup followed for 10 years, DFS was 82%, CSS was 94%, and overall survival (OS) was 49%.

Tumors were, on average, small (mean 2.5 cm), but for patients whose tumors were larger than 3 cm, the DFS rate fell to 68%. Patients were included in the study if they had a solitary renal mass; those who had metastatic renal cell carcinoma (RCC) or a hereditary kidney cancer syndrome were excluded.

Brett Johnson, MD, and his collaborators from the University of Texas Southwestern, Dallas, noted that an additional 29 patients received RFA but also had partial nephrectomy; these patients were excluded. “Healthier patients with larger tumors may have been advised to undergo partial nephrectomy, thereby selecting for more comorbid patients for RFA,” they noted in discussing their findings. The report was published in The Journal of Urology

Within these parameters, Dr. Johnson and his colleagues conducted a retrospective review of clinic patients whose renal tumors were successfully treated with RFA between the years 2000 and 2007. Patients were followed with yearly imaging, and were considered to have a recurrence if contrast enhancement was seen within the ablation zone at any point after a negative imaging study.

Of the 10 recurrences that were seen, eight were local and two were local and metastatic. An additional patient developed metastatic RCC without evidence of local recurrence; all patients with metastases died of their disease, said Dr. Johnson and his coauthors.

For patients whose tumors recurred, the mean initial tumor size was 3.2 cm, compared with 2.4 cm in those whose tumors didn’t recur (P = .005). Looking at the tumor size data another way, tumor size “was an independent risk factor for cancer recurrence,” with an odds ratio of 3.01 (P = .025), wrote Dr. Johnson and his collaborators.

They noted that it was not routine practice for biopsies to be performed during the initial study period; the seven patients with recurrences who had biopsy data all had clear cell RCC. Median time to local recurrence was 26 months, with no recurrences seen after 5 years.

At the time of the initial procedure, patients were a mean 63.1 years old. The relatively low OS in the subgroup with 10 years of follow-up was likely related to advancing age.

In the subgroup analysis of patients for whom 10-year data were available, the investigators used only data from patients whose initial tumors were biopsied when calculating CSS and metastasis-free survival; these rates were both 94% for those analyzed.

“Age, gender, and time of follow-up had no statistically significant effect on disease-free recurrence” in a univariate analysis, said Dr. Johnson and his colleagues.

“Nephron sparing surgery is the gold standard for treatment of small renal masses,” and the study bolsters the safety and durable efficacy of RFA by using actual survival data rather than actuarial disease survival, said the investigators.

The current study is unique in having such a long duration of follow-up and a subgroup of individuals with 10 years of annual imaging data. In addition, experienced urologists at a single site all used a uniform technique to perform thermal ablation on solitary tumors, noted Dr. Johnson and his coauthors. Successful ablations were followed only by surveillance, in keeping with current American Urological Association recommendations.

However, the study’s retrospective, nonrandomized nature introduces the possibility of selection bias, and variations in follow-up protocols may be a source of ascertainment bias, they said.

The authors reported no conflicts of interest and no outside sources of funding.

SOURCE: Johnson B et al. J Urol. 2018. doi:10.1016/j.juro.2018.08.045.