Evolving Management for Locally Advanced Prostate Cancer

Men with high-risk non-metastatic prostate cancer are frequently managed with external beam radiotherapy (EBRT) along with two to three years of androgen deprivation therapy (ADT). In the metastatic setting, there is compelling evidence from phase 3 trials of an overall survival benefit from ADT intensification with docetaxel or next-generation hormonal therapy agents (abiraterone, enzalutamide, and apalutamide); data in the high-risk locally advanced setting are more limited.

In a meta-analysis, investigators pooled data from two prospective, randomized, phase 3 STAMPEDE trials that compared ADT for three years to either ADT plus abiraterone acetate or ADT plus abiraterone acetate plus enzalutamide for two years in men with locally advanced, high-risk prostate cancer. Eligible patients had an ECOG performance status of 0–2, no metastases on conventional imaging, and no significant cardiovascular risk factors, and were either node positive or had other high-risk features.

Of 1974 patients, median age was 68, median prostate-specific antigen concentration was 34 ng/mL, and 39% were node positive. Median follow-up was at least 5 years in both studies.

Metastasis-free survival (MFS) — the primary endpoint — was significantly longer in the intensification groups (P< 0.0001); 6-year MFS was 82% in the intensification group compared to 69% in the control group. Of note, there was no difference in MFS when abiraterone was administered with enzalutamide or without (P=0·91). Overall survival also was significantly longer in the intensification groups than in the controls (P<0.0001); 6-year overall survival was 86% in the intensification groups versus 77% in the control group. Seven deaths occurred, none in the control group. More grade 3 or higher adverse events occurred in the combined abiraterone–enzalutamide group than in the abiraterone-alone arm.