Anusha Kalbasi1, Jiaqi Li2, Abigail Berman1, Samuel Swisher-McClure3, Marc Smaldone4, Robert G Uzzo4, Dylan S Small5, Nandita Mitra6, Justin E Bekelman7. 1. Department of Radiation Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia. 2. Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia3Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia. 3. Department of Radiation Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia4Leonard Davis Institute of Health, Perelman School of Medicine at the University of Pennsylvania, Philadelphia. 4. Division of Urologic Oncology, Department of Surgery, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania. 5. Leonard Davis Institute of Health, Perelman School of Medicine at the University of Pennsylvania, Philadelphia6Department of Statistics, The Wharton School at the University of Pennsylvania, Philadelphia. 6. Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia. 7. Department of Radiation Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia7Department of Medical Ethics and Health Policy, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
Abstract
IMPORTANCE: In 5 published randomized clinical trials, dose-escalated external-beam radiation therapy (EBRT) for prostate cancer resulted in improved biochemical and local control. However, scarce evidence addresses whether dose escalation improves overall survival. OBJECTIVE: To examine the association between dose-escalated EBRT and overall survival among men with nonmetastatic prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective, nonrandomized comparative effectiveness study of dose-escalated vs standard-dose EBRT for prostate cancer diagnosed from 2004 to 2006 using the National Cancer Database (NCDB), which includes data from patients treated at Commission on Cancer-accredited community, academic, and comprehensive cancer facilities. Three cohorts were evaluated: men with low-risk (n = 12,229), intermediate-risk (n = 16,714), or high-risk (n = 13,538) prostate cancer. EXPOSURES: We categorized patients in each risk cohort into 2 treatment groups: standard-dose (from 68.4 Gy to <75.6 Gy) or dose-escalated (≥75.6 Gy to 90 Gy) EBRT (1 Gy = 100 rad). MAIN OUTCOMES AND MEASURES: We compared overall survival between treatment groups in each analytic cohort using Cox proportional hazard models with an inverse probability weighted propensity score (IPW-PS) approach. In secondary analyses, we evaluated dose response for survival. RESULTS: Dose-escalated EBRT was associated with improved survival in the intermediate-risk (IPW-PS adjusted hazard ratio [HR], 0.84; 95% CI, 0.80-0.88; P < .001) and high-risk groups (HR, 0.82; 95% CI, 0.78-0.85; P < .001) but not the low-risk group (HR, 0.98; 95% CI, 0.92-1.05; P = .54). For every incremental increase of about 2 Gy in dose, there was a 7.8% (95% CI, 5.4%-10.2%; P < .001) and 6.3% (95% CI, 3.3%-9.1%; P < .001) reduction in the hazard of death for intermediate- and high-risk patients, respectively. CONCLUSIONS AND RELEVANCE: Dose-escalated EBRT is associated with improved overall survival in men with intermediate- and high-risk prostate cancer but not low-risk prostate cancer. These results add to the evidence questioning aggressive local treatment strategies in men with low-risk prostate cancer but supporting such treatment in men with greater disease severity.
IMPORTANCE: In 5 published randomized clinical trials, dose-escalated external-beam radiation therapy (EBRT) for prostate cancer resulted in improved biochemical and local control. However, scarce evidence addresses whether dose escalation improves overall survival. OBJECTIVE: To examine the association between dose-escalated EBRT and overall survival among men with nonmetastatic prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective, nonrandomized comparative effectiveness study of dose-escalated vs standard-dose EBRT for prostate cancer diagnosed from 2004 to 2006 using the National Cancer Database (NCDB), which includes data from patients treated at Commission on Cancer-accredited community, academic, and comprehensive cancer facilities. Three cohorts were evaluated: men with low-risk (n = 12,229), intermediate-risk (n = 16,714), or high-risk (n = 13,538) prostate cancer. EXPOSURES: We categorized patients in each risk cohort into 2 treatment groups: standard-dose (from 68.4 Gy to <75.6 Gy) or dose-escalated (≥75.6 Gy to 90 Gy) EBRT (1 Gy = 100 rad). MAIN OUTCOMES AND MEASURES: We compared overall survival between treatment groups in each analytic cohort using Cox proportional hazard models with an inverse probability weighted propensity score (IPW-PS) approach. In secondary analyses, we evaluated dose response for survival. RESULTS: Dose-escalated EBRT was associated with improved survival in the intermediate-risk (IPW-PS adjusted hazard ratio [HR], 0.84; 95% CI, 0.80-0.88; P < .001) and high-risk groups (HR, 0.82; 95% CI, 0.78-0.85; P < .001) but not the low-risk group (HR, 0.98; 95% CI, 0.92-1.05; P = .54). For every incremental increase of about 2 Gy in dose, there was a 7.8% (95% CI, 5.4%-10.2%; P < .001) and 6.3% (95% CI, 3.3%-9.1%; P < .001) reduction in the hazard of death for intermediate- and high-risk patients, respectively. CONCLUSIONS AND RELEVANCE: Dose-escalated EBRT is associated with improved overall survival in men with intermediate- and high-risk prostate cancer but not low-risk prostate cancer. These results add to the evidence questioning aggressive local treatment strategies in men with low-risk prostate cancer but supporting such treatment in men with greater disease severity.
Authors: Rebecca G Levin-Epstein; Naomi Y Jiang; Xiaoyan Wang; Shrinivasa K Upadhyaya; Sean P Collins; Simeng Suy; Nima Aghdam; Constantine Mantz; Alan J Katz; Leszek Miszczyk; Aleksandra Napieralska; Agnieszka Namysl-Kaletka; Nicholas Prionas; Hilary Bagshaw; Mark K Buyyounouski; Minsong Cao; Nzhde Agazaryan; Audrey Dang; Ye Yuan; Patrick A Kupelian; Nicholas G Zaorsky; Daniel E Spratt; Osama Mohamad; Felix Y Feng; Brandon A Mahal; Paul C Boutros; Arun U Kishan; Jesus Juarez; David Shabsovich; Tommy Jiang; Sartajdeep Kahlon; Ankur Patel; Jay Patel; Nicholas G Nickols; Michael L Steinberg; Donald B Fuller; Amar U Kishan Journal: Radiother Oncol Date: 2020-10-07 Impact factor: 6.280
Authors: Amar U Kishan; Ryan R Cook; Jay P Ciezki; Ashley E Ross; Mark M Pomerantz; Paul L Nguyen; Talha Shaikh; Phuoc T Tran; Kiri A Sandler; Richard G Stock; Gregory S Merrick; D Jeffrey Demanes; Daniel E Spratt; Eyad I Abu-Isa; Trude B Wedde; Wolfgang Lilleby; Daniel J Krauss; Grace K Shaw; Ridwan Alam; Chandana A Reddy; Andrew J Stephenson; Eric A Klein; Daniel Y Song; Jeffrey J Tosoian; John V Hegde; Sun Mi Yoo; Ryan Fiano; Anthony V D'Amico; Nicholas G Nickols; William J Aronson; Ahmad Sadeghi; Stephen Greco; Curtiland Deville; Todd McNutt; Theodore L DeWeese; Robert E Reiter; Johnathan W Said; Michael L Steinberg; Eric M Horwitz; Patrick A Kupelian; Christopher R King Journal: JAMA Date: 2018-03-06 Impact factor: 56.272
Authors: W Robert Lee; James J Dignam; Mahul B Amin; Deborah W Bruner; Daniel Low; Gregory P Swanson; Amit B Shah; David P D'Souza; Jeff M Michalski; Ian S Dayes; Samantha A Seaward; William A Hall; Paul L Nguyen; Thomas M Pisansky; Sergio L Faria; Yuhchyau Chen; Bridget F Koontz; Rebecca Paulus; Howard M Sandler Journal: J Clin Oncol Date: 2016-04-04 Impact factor: 44.544
Authors: Andrew McPartlin; Lucy Kershaw; Alan McWilliam; Marcus Ben Taylor; Clare Hodgson; Marcel van Herk; Ananya Choudhury Journal: Ther Adv Urol Date: 2018-10-11