Role of lymphatic invasion in predicting biochemical recurrence after radical prostatectomy

Objective: Lymphatic invasion in prostate cancer is associated with poor prognosis. However, there is no consensus regarding the clinical and prognostic value of lymphatic invasion. This study aimed to investigate the prognostic value of lymphatic invasion in biochemical recurrence (BCR) and compare the recurrence rates between patients with lymphatic invasion and lymph node metastasis.Methods: We retrospectively analyzed 2,207 patients who underwent radical prostatectomy (RP) without pelvic lymph node dissection (PLND) and 742 patients who underwent RP with PLND for clinically localized or locally advanced prostate cancer, between 1993 and 2020, at Seoul National University Hospital. Kaplan-Meier analysis was performed to estimate BCR-free survival (BCRFS) using the log-rank test. The Cox proportional hazards model was used to identify the significant factors for BCR. Propensity score matching was performed with a 1:2 ratio to match age, initial PSA level, pathological T stage, and Gleason score to exclude confounding effects.Results: Of the 2,207 patients who underwent RP without PLND, lymphatic invasion (L1Nx) was observed in 79 (3.5%) individuals. Among the 742 patients who underwent RP with PLND, lymph node metastases were found in 105 patients (14.2%). In patients with lymph node metastasis, lymphatic invasion was observed in 50 patients (47.6%), whereas lymphatic invasion was observed in 53 patients (8.3%) among those without lymph node metastasis. In patients who underwent RP without PLND, Kaplan-Meier analysis showed significantly poorer BCR-free survival in the L1Nx group than in the L0Nx group (p < 0.001). In patients who underwent RP with PLND, the L1N0, L0N1, and L1N1 groups showed significantly worse prognoses than the L0N0 group (p < 0.001). However, there was no significant difference in BCRFS between the L1N0 and lymph node metastasis groups, including the L0N1 and L1N1 groups. After propensity score matching at a 1:2 ratio, the L1Nx group showed significantly poorer outcomes in terms of BCRFS than the L0Nx group (p = 0.05). In addition, the L1N0 group showed a significantly worse prognosis than the L0N0 group after propensity score matching.Conclusion: Lymphatic invasion in radical prostatectomy specimens is an independent prognostic factor, which can complement lymph node status for predicting biochemical recurrence. Considering lymphatic invasion as an adverse pathological finding, similar to lymph node metastasis, adjuvant therapy could be considered in patients with lymphatic invasion.