239 - Efficacy of All-Site Radiotherapy at the Hormone-Sensitive Stage in Combination with Systemic Therapy in Grade Group 5 Metastatic Prostate Cancer: Long-Term Data from a Single-Institution

Purpose/Objective(s):

Prostate radiotherapy is recommended for low tumor-burden metastatic hormone-sensitive prostate cancer (mHSPC). All-site radiotherapy (RT) has become a focus of research as a potential treatment strategy. Gleason grade group 5 (GG5) mHSPC represents a high-risk subgroup of patients with a more aggressive biological profile. This study aims to compare the survival benefit of all-site RT in the mHSPC stage, in addition to standard systemic therapies, for patients with GG5 metastatic prostate cancer, and to explore a comprehensive treatment approach for this population.

Materials/Methods:

This study consecutively enrolled patients diagnosed with prostate adenocarcinoma (GG5) from 2018 to 2024. All participants had confirmed distant metastases via imaging. In the RT group, patients received all-site radiotherapy after 3-6 months of standard systemic therapy at the time of initial diagnosis. Those who did not receive radiotherapy during the mHSPC stage were divided into the non-RT group and later received radiotherapy upon progression to castration-resistant prostate cancer (CRPC). Radiotherapy regimens included all-site radiotherapy for oligometastatic patients (with fewer than 10 metastases) and residual lesion radiotherapy for those with extensive metastatic disease after systemic therapy. The systemic treatment includes androgen deprivation therapy (ADT) with novel hormonal therapy (NHT) with or without docetaxel (Doc). The primary endpoint was CRPC-free survival. Statistical analyses were performed using the Kaplan-Meier method, log-rank test, and Cox regression analysis.

Results:

A total of 200 patients were included in the study. The median age was 67.5 years (46-89 years), and the median follow-up time was 17.7 months (0.8-76.8 months). All of these patients received ADT+NHT. 166 patients initiated all-site radiotherapy during the HSPC stage (RT group), with 39 (23.5%) of them undergoing intensive Doc treatment. 34 patients received salvage radiotherapy upon progression to CRPC (non-RT group), with 13 (38.2%) receiving Doc. In terms of survival, the intervention of all-site radiotherapy at the HSPC stage significantly prolonged CRPC-free survival in patients with any systemic treatment strategy. In the ADT+NHT group, the 6-year CRPC-free survival was 76.7% in patients who received all-site radiotherapy compared to 9.5% in those who did not (p=0.00047). Similarly, in the ADT+NHT+Doc group, the 6-year CRPC-free survival was 50.9% with all-site radiotherapy, compared to 7.7% in the non-RT group (p=0.00021). Interestingly, when only systemic therapy was administered during the HSPC stage, patients treated with ADT+NHT+Doc had significantly better survival compared to those receiving ADT+NHT alone (p=0.00075).

Conclusion:

The 6-year survival results show that in patients with GG5 mHSPC, early all-site radiotherapy to the primary and all metastatic lesions at the HSPC stage provides a survival benefit without castration resistance.