Abstract

Simple SummaryThis multi-institutional study analyzed the patterns of care and outcomes of external beam radiotherapy (EBRT) in localized prostate cancer to identify the optimal EBRT strategy for each risk-stratified patient subgroup for clinical practice implementation. In 1573 patients from 17 institutions, EBRT treated prostate cancer effectively. Also, among various risk classification tools, NCCN classification revealed the highest predictive power. The modern RT techniques and dose escalation (≥179 Gy1.5) enhanced therapeutic effects of RT significantly, especially in the high-risk group. On the other hand, modest doses (≥170 Gy1.5) was a significant factor in the intermediate-risk group and no significant impact of dose was observed in the low-risk group. IMRT+ ≥179 Gy1.5+ hypofractionation resulted in higher biochemical failure-free survival in all risk groups, and it translated into survival benefits in the high-risk group. Therefore, risk-adapted RT (more intense RT, high-risk patients; moderate-dose RT, low-risk patients) can be considered, although further prospective studies are warranted.Purpose: This nationwide multi-institutional study analyzed the patterns of care and outcomes of external beam radiotherapy (EBRT) in localized prostate cancer patients. We compared various risk classification tools and assessed the need for refinements in current radiotherapy (RT) schemes. Methods and Materials: We included non-metastatic prostate cancer patients treated with primary EBRT from 2001 to 2015 in this study. Data of 1573 patients from 17 institutions were analyzed and re-grouped using a risk stratification tool with the highest predictive power for biochemical failure-free survival (BCFFS). We evaluated BCFFS, overall survival (OS), and toxicity rates. Results: With a median follow-up of 75 months, 5- and 10-year BCFFS rates were 82% and 60%, and 5- and 10-year OS rates were 95% and 83%, respectively. NCCN risk classification revealed the highest predictive power (AUC = 0.556, 95% CI 0.524–0.588; p < 0.001). Gleason score, iPSA < 12 ng/mL, intensity-modulated RT (IMRT), and ≥179 Gy1.5 (EQD2, 77 Gy) were independently significant for BCFFS (all p < 0.05). IMRT and ≥179 Gy1.5 were significant factors in the high-risk group, whereas ≥170 Gy1.5 (EQD2, 72 Gy) was significant in the intermediate-risk group and no significant impact of dose was observed in the low-risk group. Both BCFFS and OS improved significantly when ≥179 Gy1.5 was delivered using IMRT and hypofractionation in the high-risk group without increasing toxicities. Conclusions: With NCCN risk classification, dose escalation with modern high-precision techniques might increase survivals in the high-risk group, but not in the low-risk group, although mature results of prospective studies are awaited.

Highlights

  • External-beam radiotherapy (EBRT) is a well-established local therapy for non-metastatic prostate cancer [1,2]

  • Concurrent Androgen deprivation therapy (ADT) was performed in 61% National Comprehensive Cancer Network (NCCN) high-risk group patients and 55% NCCN very-high-risk group patients

  • Higher doses were delivered with the selection of more hypofractionated schedules (Dmean: conventional, 167.9 Gy; HF, 185.5 Gy; and ultra-HF, 214.9 Gy; p < 0.001) (Figure S1a) or more modern RT techniques (Dmean: 3D, 166.0 Gy; intensity-modulated RT (IMRT), 185.1 Gy, and proton therapy, 191.3 Gy; p < 0.001) (Figure S1b)

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Summary

Introduction

External-beam radiotherapy (EBRT) is a well-established local therapy for non-metastatic prostate cancer [1,2]. Localized prostate cancer patients can be stratified into risk groups by clinicopathological parameters. Prostate cancer patients receive a 64–70 Gy EBRT dose, no clear cutoff is recommended. Recent studies suggested these doses to be insufficient for tumor control, and dose escalation was proposed for the best biochemical control with the development of modern RT techniques [8,9,10,11,12,13,14,15,16,17,18,19]. Studies analyzing the effects of dose escalation with modern RT techniques in each risk group are scarce

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