Efficacy and Safety Analyses of Cytoreductive Non-Regional Lymph Node Radiotherapy in Addition to Prostate-Directed Local Therapy in Low Metastatic Burden Prostate Cancer

Background: To evaluate the efficacy and safety of cytoreductive non-regional lymph node radiotherapy (NRLNRT) in addition to prostate-directed local therapy (PDLT) in low metastatic burden prostate cancer (LMBPC). Methods: From August 2009 to February 2021, 88 LMBPC patients with NRLN metastasis were identified. Patients receiving cytoreductive NRLN RT in addition to PDLT (NRLN RT group) were matched by one-to-one propensity score to patients without cytoreductive NRLN radiotherapy (control group). Kaplan-Meier method and Cox proportional hazards model were used for prognostic analyses. Results: The median follow-up was 43.3 months. PSA response after NRLN RT was 70.6%, and the median PFS after NRLN RT was 29.5 months. The 4-year OS for NRLN RT group and control group was 62% and 46%, respectively ( P = 0.037). NRLN RT (HR 0.22, P = 0.001), HSPC (HR 0.32, P = 0.003), bone metastases (HR 3.79, P = 0.000) and androgen-receptor-axis-targeted agents (HR 0.40, P =0.007) were independent prognostic factors of OS. Subgrou p analyses showed HSPC at the time of NRLNM and patients with ＜5 NRLNM had greater magnitude of benefit than the counterpart (HR 0.28, 95% CI 0.08-0.94, P = 0.039; HR 0.16, 95% CI 0.04-0.69, P = 0.014). After PSM, NRLN RT was still associated with improved OS (HR 0.39, 95% CI 0.16-0.96, P = 0.040). NRLN RT related AEs were 11 cases (32.4%) of acute gastrointestinal AEs, 3 cases (8.8%) of acute skin AEs, 10 cases (29.4%) of acute bone marrow suppression (BMS) and 5 cases (14.7%) of chronic BMS. All were grade 1-2 AEs. Conclusions: It was beneficial and safe to apply cytoreductive NRLN radiotherapy in addition to PDLT in LMBPC. HSPC at the time of NRLNM and patients with < 5 NRLNM may be the potential beneficiaries. Prospective studies were needed for verification.