Standard of Care Versus Metastases-directed Therapy for PET-detected Nodal Oligorecurrent Prostate Cancer Following Multimodality Treatment: A Multi-institutional Case-control Study

Background: Most prostate cancer (PCa) patients with a biochemical failure following primary multimodality treatment (surgery and postoperative radiotherapy) relapse in the nodes. Objective: To perform a matched-case analysis in men with lymph node recurrent PCa comparing standard of care (SOC) with metastasis-directed therapy (MDT). Design, setting, and participants: PCa patients with a prostate-specific antigen (PSA) progression following multimodality treatment were included in this retrospective multi-institutional analysis. Intervention: The SOC cohort (n = 1816) received immediate or delayed androgen deprivation therapy administered at PSA progression. The MDT cohort (n = 263) received either salvage lymph node dissection (n = 166) or stereotactic body radiotherapy (n = 97) at PSA progression to a positron emission tomography-detected nodal recurrence. Outcome measurements and statistical analysis: The primary endpoint, cancer-specific survival (CSS), was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched analyses. Results and limitations: At a median follow-up of 70 (interquartile range: 48–98) mo, MDT was associated with an improved CSS on univariate (p = 0.029) and multivariate analysis (hazard ratio: 0.33, 95% confidence interval [CI]: 0.17–0.64) adjusted for the year of radical prostatectomy (RP), age at RP, PSA at RP, time from RP to PSA progression, Gleason score, surgical margin status, pT- and pN-stage. In total, 659 men were matched (3:1 ratio). The 5-yr CSS was 98.6% (95% CI: 94.3–99.6) and 95.7% (95% CI: 93.2–97.3) for MDT and SOC, respectively (p = 0.005, log-rank). The main limitations of our study are its retrospective design and lack of standardization of systemic treatment in the SOC cohort. Conclusions: MDT for nodal oligorecurrent PCa improves CSS as compared with SOC. These retrospective data from a multi-institutional pooled analysis should be considered as hypothesis-generating and inform future randomized trials in this setting. Patient summary: Prostate cancer patients experiencing a lymph node recurrence might benefit from local treatments directed at these lymph nodes.