Extended Results and Independent Validation of a Phase 2 Trial of Metastasis-Directed Therapy for Molecularly Defined Oligometastatic Prostate Cancer

Purpose: The role of metastasis-directed therapy (MDT) in molecularly defined oligorecurrent prostate cancer (PCa) remains irresolute. We present extended follow-up and an independent validation cohort of a prospective trial.Methods and Materials: This study consists of 2 sequential single-arm phase-2 trials of patients with biochemical recurrence (prostate specific antigen [PSA] 0.4-3.0 ng/mL) and negative conventional imaging after radical prostatectomy and postopera-tive radiation therapy. All patients underwent [18F]DCFPyL positron emission tomography/computed tomography. Patients with molecularly defined oligorecurrent prostate cancer underwent MDT with stereotactic body radiation therapy or surgery, without androgen deprivation therapy (ADT). The primary end point was biochemical response (>= 50% PSA decline from baseline). Secondary end points included PSA progression-free survival and ADT-free survival. The sample size of 37 MDT patients was determined based on a Simon's 2-stage design with biochemical response rate >20%, and this design was also applied for the subsequent independent validation cohort.Results: Seventy-four patients underwent MDT: 37 each in the initial and validation cohorts. Both cohorts met the prespeci-fied biochemical response rate and completed the planned 2-stages of accrual. For the pooled cohort, the median number of prostate specific membrane antigen positron emission tomography avid lesions was 2 and most (87%) recurrences were nodal. Sixty-four (87%) had stereotactic body radiation therapy and 10 (13%) had surgery. Median follow-up (interquartile range [IQR]) for the initial, validation and combined cohorts were 41 (35-46) months, 14 months (7-21), and 24 months (14-41), respectively. The biochemical response rates for the initial, validation and combined cohorts were 59%, 43%, and 51%, respec-tively. For the combined cohort, median biochemical progression-free survival was 21 months (95% confidence interval, 13 -not reached), and median ADT-free survival was 45 months (95% confidence interval, 31-not reached). Conclusions: Half of patients treated with MDT for molecularly defined-only oligorecurrent prostate cancer exhibited a bio-chemical response. This study provides necessary and validated evidence to support randomized trials aiming to determine whether MDT (alone or with systemic therapy) can affect clinically meaningful end points. (c) 2022 Elsevier Inc. All rights reserved.