Impact of locoregional treatment intensification in stampede high-risk M0 prostate cancer patients.

[INTRODUCTION] This study evaluates the efficacy of locoregional treatment intensification with combined modality therapy (CMT) for STAMPEDE high-risk (SHR) nonmetastatic (M0) prostate cancer. We compare metastasis-free survival (MFS) and overall survival (OS) between external beam radiation therapy (EBRT) with androgen deprivation therapy (ADT), CMT with a brachytherapy boost, and up-front surgery.

[MATERIAL AND METHODS] A retrospective cohort of 217 SHR patients from our institutional database was stratified by treatment modality: EBRT + ADT (n = 56), CMT (n = 61), and surgery (n = 100). Median ADT duration was 24 months for the EBRT + ADT group and 6 months for the CMT group. Primary outcomes were MFS and OS, analyzed using Cox proportional hazards regression and Fine-Gray competing risks models, adjusted for PSA, age, and Gleason group.

[RESULTS] CMT significantly improved adjusted MFS compared to EBRT + ADT (HR 0.41; p = 0.004). In contrast, up-front surgery did not significantly improve MFS over EBRT + ADT (HR 0.84; p = 0.471). Adjusted OS was also superior with CMT compared to EBRT + ADT (HR 1.98; p = 0.025). On subgroup analysis, the MFS benefit of CMT persisted for N0 patients but not for N1 patients. A key limitation is the retrospective, nonrandomized nature of the data.

[DISCUSSION AND CONCLUSIONS] Locoregional treatment intensification with CMT and de-intensified ADT offers significant oncologic benefits in men with SHR M0 prostate cancer, particularly in N0 patients. These findings support further investigation into combining brachytherapy and systemic therapy with de-intensified ADT in prospective trials.