Ten Year Results of Extensive Nodal Radiotherapy and Moderately Hypofractionated Simultaneous Integrated Boost in Unfavorable Intermediate-, High-, and Very High-Risk Prostate Cancer

SIMPLE SUMMARY: Several phase III randomized trials of moderate hypofractionation, including a higher proportion of high-risk prostate cancer patients treated only to the prostate, failed to demonstrate the superiority of hypofractionated regimens. There is only one randomized phase III trial, of moderately hypofractionated high-dose radiotherapy to the prostate-only versus pelvic irradiation and prostate boost, with a sufficiently long follow-up. It demonstrated better biochemical and disease-free survival when lymph nodal radiotherapy was added. Here we present the 10-year results of our experience based on an Institutional protocol adopted after a phase I–II study, on patients with unfavorable intermediate- (UIR), high- (HR), and very high-risk (VHR) prostate cancer (PCa) treated with pelvic lymph nodal irradiation (WPRT) and moderately hypofractionated high-dose (HD) simultaneous integrated boost (SIB) to the prostate. Prognostic factors for relapse, as well as acute and late gastro-intestinal (GI) and genito-urinary (GU) toxicity were also analyzed. ABSTRACT: Aims: To report 10-year outcomes of WPRT and HD moderately hypofractionated SIB to the prostate in UIR, HR, and VHR PCa. Methods: From 11/2005 to 12/2015, 224 UIR, HR, and VHR PCa patients underwent WPRT at 51.8 Gy/28 fractions and SIB at 74.2 Gy (EQD2 88 Gy) to the prostate. Androgen deprivation therapy (ADT) was prescribed in up to 86.2% of patients. Results: Median follow-up was 96.3 months (IQR: 71–124.7). Median age was 75 years (IQR: 71.3–78.1). At last follow up, G3 GI–GU toxicity was 3.1% and 8%, respectively. Ten-year biochemical relapse-free survival (bRFS) was 79.8% (95% CI: 72.3–88.1%), disease-free survival (DFS) 87.8% (95% CI: 81.7–94.3%), overall survival (OS) 65.7% (95% CI: 58.2–74.1%), and prostate cancer-specific survival (PCSS) 94.9% (95% CI: 91.0–99.0%). Only two patients presented local relapse. At univariate analysis, VHR vs. UIR was found to be a significant risk factor for biochemical relapse (HR: 2.8, 95% CI: 1.17–6.67, p = 0.021). After model selection, only Gleason Score ≥ 8 emerged as a significant factor for biochemical relapse (HR = 2.3, 95% CI: 1.12–4.9, p = 0.023). Previous TURP (HR = 3.5, 95% CI: 1.62–7.54, p = 0.001) and acute toxicity ≥ G2 (HR = 3.1, 95% CI = 1.45–6.52, p = 0.003) were significant risk factors for GU toxicity ≥ G3. Hypertension was a significant factor for GI toxicity ≥ G3 (HR = 3.63, 95% CI: 1.06–12.46, p = 0.041). ADT (HR = 0.31, 95% CI: 0.12–0.8, p = 0.015) and iPsa (HR = 0.37, 95% CI: 0.16–0.83, p = 0.0164) played a protective role. Conclusions: WPRT and HD SIB to the prostate combined with long-term ADT, in HR PCa, determine good outcomes with acceptable toxicity.