Kiri A Sandler1, Ryan R Cook2, Jay P Ciezki3, Ashley E Ross4, Mark M Pomerantz5, Paul L Nguyen6, Talha Shaikh7, Phuoc T Tran8, Richard G Stock9, Gregory S Merrick10, David Jeffrey Demanes1, Daniel E Spratt11, Eyad I Abu-Isa11, Trude B Wedde12, Wolfgang Lilleby12, Daniel J Krauss13, Grace K Shaw5, Ridwan Alam4, Chandana A Reddy4, Daniel Y Song8, Eric A Klein3, Andrew J Stephenson3, Jeffrey J Tosoian4, John V Hegde1, Sun Mi Yoo1, Ryan Fiano10, Anthony V D'Amico5, Nicholas G Nickols14, William J Aronson15, Ahmad Sadeghi16, Stephen C Greco8, Curtiland Deville8, Todd McNutt8, Theodore L DeWeese8, Robert E Reiter17, Jonathan W Said18, Michael L Steinberg1, Eric M Horwitz7, Patrick A Kupelian1, Christopher R King1, Amar U Kishan19. 1. Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA. 2. Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA. 3. Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH, USA. 4. Department of Urology, The James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. 5. Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. 6. Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. 7. Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA. 8. Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. 9. Department of Radiation Oncology, The Icahn School of Medicine at Mount Sinai, New York City, NY, USA. 10. Schiffler Cancer Center, Wheeling Hospital, Wheeling Jesuit University, Wheeling, WV, USA. 11. Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA. 12. Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway. 13. Oakland University William Beaumont School of Medicine, Royal Oak, MI, USA. 14. Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA; Department of Radiation Oncology, Veteran Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA. 15. Department of Radiation Oncology, Veteran Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA; Department of Urology, University of California, Los Angeles, Los Angeles, CA, USA. 16. Department of Radiation Oncology, Veteran Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA. 17. Department of Urology, University of California, Los Angeles, Los Angeles, CA, USA. 18. Department of Pathology, University of California, Los Angeles, Los Angeles, CA, USA. 19. Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: aukishan@mednet.ucla.edu.
Abstract
BACKGROUND: The role of elective whole-pelvis radiotherapy (WPRT) remains controversial. Few studies have investigated it in Gleason grade group (GG) 5 prostate cancer (PCa), known to have a high risk of nodal metastases. OBJECTIVE: To assess the impact of WPRT on patients with GG 5 PCa treated with external-beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT). DESIGN, SETTING, AND PARTICIPANTS: We identified 1170 patients with biopsy-proven GG 5 PCa from 11 centers in the United States and one in Norway treated between 2000 and 2013 (734 with EBRT and 436 with EBRT+BT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific survival (PCSS) were compared using Cox proportional hazards models with propensity score adjustment. RESULTS AND LIMITATIONS: A total of 299 EBRT patients (41%) and 320 EBRT+BT patients (73%) received WPRT. The adjusted 5-yr bRFS rates with WPRT in the EBRT and EBRT+BT groups were 66% and 88%, respectively. Without WPRT, these rates for the EBRT and EBRT+BT groups were 58% and 78%, respectively. The median follow-up was 5.6yr. WPRT was associated with improved bRFS among patients treated with EBRT+BT (hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.2-0.9, p=0.02), but no evidence for improvement was found in those treated with EBRT (HR 0.8, 95% CI 0.6-1.2, p=0.4). WPRT was not significantly associated with improved DMFS or PCSS in the EBRT group (HR 1.1, 95% CI 0.7-1.7, p=0.8 for DMFS and HR 0.7, 95% CI 0.4-1.1, p=0.1 for PCSS), or in the EBRT+BT group (HR 0.6, 95% CI 0.3-1.4, p=0.2 for DMFS and HR 0.5 95% CI 0.2-1.2, p=0.1 for PCSS). CONCLUSIONS: WPRT was not associated with improved PCSS or DMFS in patients with GG 5 PCa who received either EBRT or EBRT+BT. However, WPRT was associated with a significant improvement in bRFS among patients receiving EBRT+BT. Strategies to optimize WPRT, potentially with the use of advanced imaging techniques to identify occult nodal disease, are warranted. PATIENT SUMMARY: When men with a high Gleason grade prostate cancer receive radiation with external radiation and brachytherapy, the addition of radiation to the pelvis results in a longer duration of prostate-specific antigen control. However, we did not find a difference in their survival from prostate cancer or in their survival without metastatic disease. We also did not find a benefit for radiation to the pelvis in men who received radiation without brachytherapy.
BACKGROUND: The role of elective whole-pelvis radiotherapy (WPRT) remains controversial. Few studies have investigated it in Gleason grade group (GG) 5 prostate cancer (PCa), known to have a high risk of nodal metastases. OBJECTIVE: To assess the impact of WPRT on patients with GG 5 PCa treated with external-beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT). DESIGN, SETTING, AND PARTICIPANTS: We identified 1170 patients with biopsy-proven GG 5 PCa from 11 centers in the United States and one in Norway treated between 2000 and 2013 (734 with EBRT and 436 with EBRT+BT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific survival (PCSS) were compared using Cox proportional hazards models with propensity score adjustment. RESULTS AND LIMITATIONS: A total of 299 EBRTpatients (41%) and 320 EBRT+BTpatients (73%) received WPRT. The adjusted 5-yr bRFS rates with WPRT in the EBRT and EBRT+BT groups were 66% and 88%, respectively. Without WPRT, these rates for the EBRT and EBRT+BT groups were 58% and 78%, respectively. The median follow-up was 5.6yr. WPRT was associated with improved bRFS among patients treated with EBRT+BT (hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.2-0.9, p=0.02), but no evidence for improvement was found in those treated with EBRT (HR 0.8, 95% CI 0.6-1.2, p=0.4). WPRT was not significantly associated with improved DMFS or PCSS in the EBRT group (HR 1.1, 95% CI 0.7-1.7, p=0.8 for DMFS and HR 0.7, 95% CI 0.4-1.1, p=0.1 for PCSS), or in the EBRT+BT group (HR 0.6, 95% CI 0.3-1.4, p=0.2 for DMFS and HR 0.5 95% CI 0.2-1.2, p=0.1 for PCSS). CONCLUSIONS:WPRT was not associated with improved PCSS or DMFS in patients with GG 5 PCa who received either EBRT or EBRT+BT. However, WPRT was associated with a significant improvement in bRFS among patients receiving EBRT+BT. Strategies to optimize WPRT, potentially with the use of advanced imaging techniques to identify occult nodal disease, are warranted. PATIENT SUMMARY: When men with a high Gleason grade prostate cancer receive radiation with external radiation and brachytherapy, the addition of radiation to the pelvis results in a longer duration of prostate-specific antigen control. However, we did not find a difference in their survival from prostate cancer or in their survival without metastatic disease. We also did not find a benefit for radiation to the pelvis in men who received radiation without brachytherapy.
Authors: Mack Roach; Jennifer Moughan; Colleen A F Lawton; Adam P Dicker; Kenneth L Zeitzer; Elizabeth M Gore; Young Kwok; Michael J Seider; I-Chow Hsu; Alan C Hartford; Eric M Horwitz; Kosj Yamoah; Christopher U Jones; Jeff M Michalski; W Robert Lee; Thomas M Pisansky; Rachel Rabinovitch; Marvin Rotman; Rodger M Pryzant; Harold E Kim; Charles R Thomas; William U Shipley; Howard M Sandler Journal: Lancet Oncol Date: 2018-10-10 Impact factor: 41.316
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
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