Prostate-Only Versus Whole-Pelvic Radiation Therapy in High-Risk and Very High-Risk Prostate Cancer (POP-RT): Outcomes From Phase III Randomized Controlled Trial | Journal of Clinical Oncology
Prostate-Only Versus Whole-Pelvic Radiation Therapy in High-Risk and Very High-Risk Prostate Cancer (POP-RT): Outcomes From Phase III Randomized Controlled Trial
PURPOSE
We report the clinical outcomes of a randomized trial comparing prophylactic whole-pelvic nodal radiotherapy to prostate-only radiotherapy (PORT) in high-risk prostate cancer.
METHODS
This phase III, single center, randomized controlled trial enrolled eligible patients undergoing radical radiotherapy for node-negative prostate adenocarcinoma, with estimated nodal risk ≥ 20%. Randomization was 1:1 to PORT (68 Gy/25# to prostate) or whole-pelvic radiotherapy (WPRT, 68 Gy/25# to prostate, 50 Gy/25# to pelvic nodes, including common iliac) using computerized stratified block randomization, stratified by Gleason score, type of androgen deprivation, prostate-specific antigen at diagnosis, and prior transurethral resection of the prostate. All patients received image-guided, intensity-modulated radiotherapy and minimum 2 years of androgen deprivation therapy. The primary end point was 5-year biochemical failure-free survival (BFFS), and secondary end points were disease-free survival (DFS) and overall survival (OS).
RESULTS
From November 2011 to August 2017, a total of 224 patients were randomly assigned (PORT = 114, WPRT = 110). At a median follow-up of 68 months, 36 biochemical failures (PORT = 25, WPRT = 7) and 24 deaths (PORT = 13, WPRT = 11) were recorded. Five-year BFFS was 95.0% (95% CI, 88.4 to 97.9) with WPRT versus 81.2% (95% CI, 71.6 to 87.8) with PORT, with an unadjusted hazard ratio (HR) of 0.23 (95% CI, 0.10 to 0.52; P < .0001). WPRT also showed higher 5-year DFS (89.5% v 77.2%; HR, 0.40; 95% CI, 0.22 to 0.73; P = .002), but 5-year OS did not appear to differ (92.5% v 90.8%; HR, 0.92; 95% CI, 0.41 to 2.05; P = .83). Distant metastasis-free survival was also higher with WPRT (95.9% v 89.2%; HR, 0.35; 95% CI, 0.15 to 0.82; P = .01). Benefit in BFFS and DFS was maintained across prognostic subgroups.
CONCLUSION
Prophylactic pelvic irradiation for high-risk, locally advanced prostate cancer improved BFFS and DFS as compared with PORT, but OS did not appear to differ.
© 2021 by American Society of Clinical Oncology
CONTEXT
Key Objective
To address the longstanding question regarding the efficacy of prophylactic pelvic nodal irradiation in high-risk prostate cancer. The present trial incorporates the contemporary standards of staging, radiotherapy dose, technique, nodal volumes, and duration of androgen deprivation therapy.
Knowledge Generated
Prophylactic pelvic radiotherapy resulted in significantly improved biochemical failure-free survival and disease-free survival as compared with prostate-only radiotherapy. Modest increase was observed in the incidence of grade ≥ 2 late genitourinary toxicity with pelvic radiotherapy, with low incidence of GI toxicity in both the arms.
Relevance
Prophylactic pelvic irradiation using contemporary dose and technique of radiation along with long-term androgen deprivation for high-risk and very high-risk prostate cancer should be routinely considered as standard for these patients.
The results of secondary outcomes of acute and late toxicities and patient-reported quality of life from this study have been published previously (doi.org/10.1016/j.radonc.2019.12.006). The results of final survival outcomes have been presented as a Plenary Lecture at the annual meeting of the European Society of Therapeutic Radiology and Oncology (ESTRO39), Vienna, Austria, November 30, 2020.
The POP-RT trial is supported by intramural funding from Tata Memorial Center and the Terry Fox Foundation.
AUTHOR CONTRIBUTIONS
Conception and design: Vedang Murthy, Sadhana Kannan, Ganesh Bakshi, Reena Phurailatpam, Palak Popat, Kumar Prabhash, Umesh Mahantshetty
Administrative support: Dipika Chaurasiya, Kumar Prabhash
Provision of study materials or patients: Gitanjali Panigrahi, Ganesh Bakshi, Mahendra Pal, Smruti Mokal, Venkatesh Rangarajan, Amit Joshi, Vanita Noronha, Umesh Mahantshetty
Collection and assembly of data: Vedang Murthy, Priyamvada Maitre, Sadhana Kannan, Gitanjali Panigrahi, Rahul Krishnatry, Ganesh Bakshi, Gagan Prakash, Mahendra Pal, Dipika Chaurasiya, Palak Popat, Archi Agarwal, Venkatesh Rangarajan, Amit Joshi, Vanita Noronha, Kumar Prabhash, Umesh Mahantshetty
Data analysis and interpretation: Vedang Murthy, Priyamvada Maitre, Sadhana Kannan, Rahul Krishnatry, Mahendra Pal, Santosh Menon, Smruti Mokal, Palak Popat, Nilesh Sable, Vanita Noronha, Kumar Prabhash
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors
AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Prostate Only Versus Whole Pelvic Radiation Therapy in High-Risk and Very High-Risk Prostate Cancer (POP-RT): Outcomes From Phase III Randomized Controlled Trial
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.
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Vanita Noronha
Research Funding: Amgen, Sanofi/Aventis, Dr Reddy's Laboratories, Intas, AstraZeneca
Kumar Prabhash
Research Funding: Biocon, Dr Reddy's Laboratories, Fresenius Kabi, Alkem Laboratories, Natco Pharma, BDR Pharmaceutics, Roche
Umesh Mahantshetty
Research Funding: Varian Medical Systems
No other potential conflicts of interest were reported.
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