Recurrence patterns in primary urethral carcinoma: Prognostic impact of inguinal and pelvic lymphadenectomy

Primary urethral carcinoma (PUC) is a rare, aggressive malignancy with limited evidence to guide management. This study aimed to characterize recurrence patterns and identify clinicopathological predictors of recurrence-free survival (RFS), focusing on nodal management.

We retrospectively analyzed adults treated for PUC at 2 academic centers. Patients with concurrent bladder cancer, upper tract urothelial carcinoma, or urethral involvement from another malignancy were excluded. Management included transurethral resection, partial or radical urethrectomy (with or without cystectomy), and selective inguinal and/or pelvic lymph node dissection (ILND/PLND). Some patients received radiotherapy or systemic therapy. The primary endpoint was RFS, defined as the interval from initial treatment to first recurrence. Kaplan-Meier and Cox regression identified independent predictors.

Fifty patients were included (median age 68.5 years; 78% male): 44 treated at University Hospital Tübingen and 6 at Fundeni Clinical Institute. Histology comprised urothelial carcinoma (50%), squamous cell carcinoma (20%), and others (30%). At diagnosis, 28% were cN+ and 12% cM1. ILND and PLND were performed in 28% and 36% of cases, respectively. Overall, 48% developed recurrence (12% local, 12% regional, 24% distant) at a median of 14.5 months. RFS was 71% at 12 months and 23% at 36 months. On multivariable analysis, age ≥ 70 years (HR 0.07; P = 0.01) was independently associated with a reduced risk of recurrence. PLND demonstrated a protective trend (HR 0.08; P = 0.07), and a similar tendency was observed for ILND (HR 0.23; P = 0.053). In contrast, posterior tumor location was associated with an increased risk of overall recurrence (P = 0.023), and grade 3 tumors with a higher risk of local recurrence (P = 0.047). The retrospective design and small sample limit generalizability.

Recurrence after PUC treatment is frequent and early. PLND and older age predict improved RFS, supporting risk-adapted, multimodal management and extended follow-up at expert centers.