Unraveling the safety of adjuvant radiotherapy in prostate cancer: impact of older age and hypofractionated regimens on acute and late toxicity - a multicenter comprehensive analysis

BackgroundThe objective of this study was to assess the impact of age and other patient and treatment characteristics on toxicity in prostate cancer patients receiving adjuvant radiotherapy (RT).Materials and methodsThis observational study (ICAROS-1) evaluated both acute (RTOG) and late (RTOG/EORTC) toxicity. Patient- (age; Charlson’s comorbidity index) and treatment-related characteristics (nodal irradiation; previous TURP; use, type, and duration of ADT, RT fractionation and technique, image-guidance systems, EQD2 delivered to the prostate bed and pelvic nodes) were recorded and analyzed.ResultsA total of 381 patients were enrolled. The median EQD2 to the prostate bed (α/β=1.5) was 71.4 Gy. The majority of patients (75.4%) were treated with intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). Acute G3 gastrointestinal (GI) and genitourinary (GU) toxicity rates were 0.5% and 1.3%, respectively. No patients experienced >G3 acute toxicity. The multivariable analysis of acute toxicity (binomial logistic regression) showed a statistically significant association between older age (> 65) and decreased odds of G≥2 GI acute toxicity (OR: 0.569; 95%CI: 0.329-0.973; p: 0.040) and decreased odds of G≥2 GU acute toxicity (OR: 0.956; 95%CI: 0.918-0.996; p: 0.031). The 5-year late toxicity-free survival rates for G≥3 GI and GU toxicity were 98.1% and 94.5%, respectively. The only significant correlation found (Cox’s regression model) was a reduced risk of late GI toxicity in patients undergoing hypofractionation (HR: 0.38; 95% CI: 0.18-0.78; p: 0.008).ConclusionsThe unexpected results of this analysis could be explained by a “response shift bias” concerning the protective effect of older age and by treatment in later periods (using IMRT/VMAT) concerning the favorable effect of hypofractionation. However, overall, the study suggests that age should not be a reason to avoid adjuvant RT and that the latter is well-tolerated even with moderately hypofractionated regimens

Hypofractionated postoperative IMRT in prostate carcinoma: A phase I/II study

Aim: To report the outcome of hypofractionated radiotherapy after radical prostatectomy (RP) for prostate cancer (PCa) using simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT). Patients and Methods: A total of 124 patients with PCa at high risk of relapse after RP or diagnosis of biochemical relapse were included. Patients received 62.5 Gy to the prostate bed and 45 Gy to pelvic nodes in 25 fractions. Androgen-suppressive therapy was prescribed based on National Comprehensive Cancer Network risk categories. Results: Median follow-up was 30 months. Only two patients (1.6%) developed grade 3 or more acute toxicity: one grade 3 skin toxicity (0.8%) and one grade 4 genitourinary toxicity (0.8%). Grade 2 acute gastrointestinal and genitourinary toxicity was recorded in 24.2% and 17.7% of patients, respectively. Five-year grade 2 or more gastrointestinal and genitourinary toxicity was 1.1% and 7.3%, respectively. Five-year biochemical relapse-free survival was 86.5%. Conclusion: After RP, hypofractionated IMRT-SIB demonstrated a favorable toxicity profile and encouraging results in terms of relapse-free survival