Risk-adapted intensification therapy in high-risk prostate cancer: how relevant is the role of radiation dose.

Background/purpose: Dose escalation has demonstrated a significant improvement in biochemical recurrence in high-risk prostate cancer (HRPCa). We evaluated the impact on overall survival (OS) of dose intensification with external beam radiation therapy (EBRT) in a cohort of HRPCa patients treated in a single institution.

Methods and materials: Between January 1997 and January 2024, a total of 1451 consecutive localized PCa patients were treated with primary EBRT alone as part of a prospective institutional program for risk-adapted dose-intensification radiotherapy. For the present analysis, we specifically selected a cohort of 424 consecutive HRPCa patients with a minimum follow-up (FU) of 5 years. The median RT dose was 79.2 Gy (interquartile range [IQR] 74.9-80.3). Short and long-term hormones were administered in 56 (13%) and 350 (83%) of patients respectively. Kaplan-Meier curves were used to calculate overall survival (OS). Cumulative incidence of distant metastasis (DM), and cause specific survival (CSS) were estimated using competing risk regression.

Results: Median patient age was 69 years (IQR 65-72) and median FU was 118 months (IQR 88.0-135.0). At the time of analysis, 54 of 424 patients (13%) had died. The leading cause of death was cardiovascular disease in 16/54 patients (4%), followed by PCa in 15 patients (3%). At 10 and 15 years, the KM estimated OS rates were 91% (95% CI 87-93) and 71% (95% CI 61-79), respectively. The corresponding rates for MFS were 87% (95% CI 83-90) and 60% (95% CI 49-68), and for CSS were 97% (95% CI 95-99) and 90% (95% CI 49-81), respectively. In multivariate analysis, when adjusted for patient age, T stage, Gleason/ISUP group, PSA and length of hormone-therapy, higher radiation dose remained significantly associated with an improved OS (HR 0.89; 95% CI 0.84-0.94), MFS (HR 0.94; 95% CI 0.90-0.98) and CSS (HR 0.89; 95% CI 0.84-0.94).

Conclusions: The present study confirms that radiation dose intensification is paramount in the treatment of HRPCa with independence of duration of ADT.