Timothy J Wilt1, Tien N Vo2, Lisa Langsetmo2, Philipp Dahm3, Thomas Wheeler4, William J Aronson5, Matthew R Cooperberg6, Brent C Taylor7, Michael K Brawer8. 1. Minneapolis VA Center for Care Delivery and Outcomes Research, Minneapolis, MN, USA; Section of General Medicine, University of Minnesota School of Medicine, Minneapolis MN, USA. Electronic address: Tim.wilt@va.gov. 2. University of Minnesota School of Public Health, University of Minnesota, Minneapolis, MN, USA. 3. Minneapolis VA Section of Urology, Minneapolis MN, USA; Department of Urology, University of Minnesota, Minneapolis MN, USA. 4. Baylor College of Medicine, Houston, TX, USA. 5. VA Medical Center, Greater Los Angeles Healthcare System, Los Angeles, CA, USA; Department of Urology, University of California at Los Angeles, Los Angeles, CA, USA. 6. Department of Urology, University of California at San Francisco, CA, USA; Department of Urology and Epidemiology and Biostatistics, University of California at San Francisco, CA, USA. 7. Minneapolis VA Center for Care Delivery and Outcomes Research, Minneapolis, MN, USA; Section of General Medicine, University of Minnesota School of Medicine, Minneapolis MN, USA. 8. MDx Health, Irvine, CA, USA; Nanospectra Biosciences, Houston, TX, USA.
Abstract
BACKGROUND: Very long-term mortality in men with early prostate cancer treated with surgery versus observation is uncertain. OBJECTIVE: To determine long-term effects of surgery versus observation on all-cause mortality for men with early prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: This study evaluated long-term follow-up of a randomized trial conducted at the US Department of Veterans Affairs and National Cancer Institute sites. The participants were men (n=731) ≤75yr of age with localized prostate cancer, prostate-specific antigen (PSA) <50ng/ml, life expectancy ≥10yr, and medically fit for surgery. INTERVENTION: Radical prostatectomy versus observation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: All-cause mortality was assessed in the entire cohort and patient and tumor subgroups. Intention-to-treat analysis was conducted using Kaplan-Meier methods with log-rank tests and Cox proportional hazard models; cumulative mortality incidence, between-group differences, and relative risks were also assessed at predefined time periods. RESULTS AND LIMITATIONS: During 22.1yr (median follow-up for survivors=18.6yr; interquartile range: 16.6-20.0), 515 men died; 246 of 346 men (68%) were assigned to surgery versus 269 of 367 (73%) assigned to observation (hazard ratio 0.84 [95% confidence interval {CI}: 0.70-1.00]; p= 0.044 [absolute risk reduction = 5.7 percentage points, 95% CI: -0.89 to 12%]; relative risk: 0.92 [95% CI: 0.84-1.01]). The restricted mean survival in the surgical group was 13.6 yr (95% CI: 12.9-14.3) versus 12.6 yr (95% CI: 11.8-13.3) in the observation group; a mean of 1 life-year was gained with surgery. Results did not significantly vary by patient or tumor characteristics, although differences were larger favoring surgery among men aged <65 yr, of white race, and having better health status, fewer comorbidities, ≥34% positive prostate biopsy cores, and intermediate-risk disease. Results were not adjusted for multiple comparisons, and we could not assess outcomes other than all-cause mortality. CONCLUSIONS: Surgery was associated with small very long-term reductions in all-cause mortality and increases in years of life gained. Absolute effects did not vary markedly by patient characteristics. Absolute effects and mean survival were much smaller in men with low-risk disease, but were greater in men with intermediate-risk disease although not in men with high-risk disease. PATIENT SUMMARY: In this randomized study, we evaluated death from any cause in men with early prostate cancer treated with either surgery or observation. Overall, surgery may provide small very long-term reductions in death from any cause and increases in years of life gained. Absolute effects were much smaller in men with low-risk disease, but were greater in men with intermediate-risk disease although not in men with high-risk disease. Strategies are needed to identify men needing and benefitting from surgery while reducing ineffective treatment and overtreatment. Published by Elsevier B.V.
RCT Entities:
BACKGROUND: Very long-term mortality in men with early prostate cancer treated with surgery versus observation is uncertain. OBJECTIVE: To determine long-term effects of surgery versus observation on all-cause mortality for men with early prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: This study evaluated long-term follow-up of a randomized trial conducted at the US Department of Veterans Affairs and National Cancer Institute sites. The participants were men (n=731) ≤75yr of age with localized prostate cancer, prostate-specific antigen (PSA) <50ng/ml, life expectancy ≥10yr, and medically fit for surgery. INTERVENTION: Radical prostatectomy versus observation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: All-cause mortality was assessed in the entire cohort and patient and tumor subgroups. Intention-to-treat analysis was conducted using Kaplan-Meier methods with log-rank tests and Cox proportional hazard models; cumulative mortality incidence, between-group differences, and relative risks were also assessed at predefined time periods. RESULTS AND LIMITATIONS: During 22.1yr (median follow-up for survivors=18.6yr; interquartile range: 16.6-20.0), 515 men died; 246 of 346 men (68%) were assigned to surgery versus 269 of 367 (73%) assigned to observation (hazard ratio 0.84 [95% confidence interval {CI}: 0.70-1.00]; p= 0.044 [absolute risk reduction = 5.7 percentage points, 95% CI: -0.89 to 12%]; relative risk: 0.92 [95% CI: 0.84-1.01]). The restricted mean survival in the surgical group was 13.6 yr (95% CI: 12.9-14.3) versus 12.6 yr (95% CI: 11.8-13.3) in the observation group; a mean of 1 life-year was gained with surgery. Results did not significantly vary by patient or tumor characteristics, although differences were larger favoring surgery among men aged <65 yr, of white race, and having better health status, fewer comorbidities, ≥34% positive prostate biopsy cores, and intermediate-risk disease. Results were not adjusted for multiple comparisons, and we could not assess outcomes other than all-cause mortality. CONCLUSIONS: Surgery was associated with small very long-term reductions in all-cause mortality and increases in years of life gained. Absolute effects did not vary markedly by patient characteristics. Absolute effects and mean survival were much smaller in men with low-risk disease, but were greater in men with intermediate-risk disease although not in men with high-risk disease. PATIENT SUMMARY: In this randomized study, we evaluated death from any cause in men with early prostate cancer treated with either surgery or observation. Overall, surgery may provide small very long-term reductions in death from any cause and increases in years of life gained. Absolute effects were much smaller in men with low-risk disease, but were greater in men with intermediate-risk disease although not in men with high-risk disease. Strategies are needed to identify men needing and benefitting from surgery while reducing ineffective treatment and overtreatment. Published by Elsevier B.V.
Entities:
Keywords:
Outcome; Prognosis; Prostate cancer; Surgery
Authors: Robin Wm Vernooij; Michelle Lancee; Anne Cleves; Philipp Dahm; Chris H Bangma; Katja Kh Aben Journal: Cochrane Database Syst Rev Date: 2020-06-04
Authors: Xiaoyu Song; Meng Ru; Zoe Steinsnyder; Kaitlyn Tkachuk; Ryan P Kopp; John Sullivan; Zeynep H Gümüş; Kenneth Offit; Vijai Joseph; Robert J Klein Journal: Cancer Epidemiol Biomarkers Prev Date: 2022-07-01 Impact factor: 4.090
Authors: Okyaz Eminaga; Eugene Shkolyar; Bernhard Breil; Axel Semjonow; Martin Boegemann; Lei Xing; Ilker Tinay; Joseph C Liao Journal: Cancers (Basel) Date: 2022-06-26 Impact factor: 6.575
Authors: Mario Rivera-Izquierdo; Javier Pérez de Rojas; Virginia Martínez-Ruiz; Miguel Ángel Arrabal-Polo; Beatriz Pérez-Gómez; José Juan Jiménez-Moleón Journal: Prostate Cancer Prostatic Dis Date: 2022-01-06 Impact factor: 5.455
Authors: Simon John Christoph Soerensen; I-Chun Thomas; Bogdana Schmidt; Timothy J Daskivich; Ted A Skolarus; Christian Jackson; Thomas F Osborne; Glenn M Chertow; James D Brooks; David H Rehkopf; John T Leppert Journal: Urology Date: 2021-06-15 Impact factor: 2.633
Authors: Denise Garcia; Julie B Siegel; David A Mahvi; Biqi Zhang; David M Mahvi; E Ramsay Camp; Whitney Graybill; Stephen J Savage; Antonio Giordano; Sara Giordano; Denise Carneiro-Pla; Mahsa Javid; Aaron P Lesher; Andrea Abbott; Nancy Klauber DeMore Journal: Clin Oncol Res Date: 2020-06-26