Combination of Androgen Deprivation Therapy with Radical Local Therapy Versus Androgen Deprivation Therapy Alone for Newly Diagnosed Oligometastatic Prostate Cancer: A Phase II Randomized Controlled Trial

Abstract

Background: Previous studies suggested that men with metastatic prostate cancer might benefit from local treatment of the primary tumor.

Objective: To determine whether radical local therapy (RLT) improves survival for men with oligometastatic prostate cancer (OMPCa).

Design, setting, and participants: This open-label randomized controlled trial included patients with newly diagnosed OMPCa defined as five or fewer bone or extrapelvic lymph node metastases and no visceral metastases.

Intervention: Patients were randomly allocated to androgen deprivation therapy (ADT) or ADT and RLT. Men allocated RLT received either cytoreductive radical prostatectomy (RP) or prostate radiation therapy (RT) with a radical dose schedule.

Outcome measurements and statistical analysis: The primary outcome was radiographic progression-free survival (rPFS). Secondary outcomes were overall survival (OS) and prostate-specific antigen (PSA) progression-free survival.

Results and limitations: Between September 2015 and March 2019, 200 patients were randomized, with 100 men allocated to each group. The median age was 68 yr and the median PSA at diagnosis was 99 ng/ml. In the study group, 96 patients underwent RLT (85 RP and 11 RT). In the control group, 17 patients eventually received RLT (15 RP and two RT). All patients were included for an intention-to-treat analysis. After a median follow-up of -48 mo, the median rPFS was not reached in the study group and was 40 mo in the control group (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.27-0.70; p = 0.001). The 3-yr OS rate was 88% for the study group and 70% for the control group (HR 0.44, 95% CI 0.24-0.81; p = 0.008).

Conclusions: Men with newly diagnosed OMPCa who received ADT plus RLT (mainly prostatectomy) had significantly higher rates of rPFS and OS than those who received ADT alone.

Patient summary: This study investigated the effect of radical local therapy (RLT) of the primary tumor on survival in patents with oligometastatic prostate cancer. In our group, RLT improved radiographic progression-free and overall survival.

Trial registration: ClinicalTrials.gov NCT02742675.

Keywords: Androgen deprivation therapy; Oligometastatic prostate cancer; Prostate radiation therapy; Prostatectomy; Radiographic progression-free survival.