Optimizing External Beam Radiotherapy as per the Risk Group of Localized Prostate Cancer: A Nationwide Multi-Institutional Study (KROG 18-15)

SIMPLE SUMMARY: This 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 Gy(1.5)) enhanced therapeutic effects of RT significantly, especially in the high-risk group. On the other hand, modest doses (≥170 Gy(1.5)) was a significant factor in the intermediate-risk group and no significant impact of dose was observed in the low-risk group. IMRT+ ≥179 Gy(1.5)+ 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. ABSTRACT: 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 Gy(1.5) (EQD2, 77 Gy) were independently significant for BCFFS (all p < 0.05). IMRT and ≥179 Gy(1.5) were significant factors in the high-risk group, whereas ≥170 Gy(1.5) (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 Gy(1.5) 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.