The identification of clinicopathological features predictive of recurrence following lymphadenectomy in penile cancer: A systematic review

Recurrence following inguinal and/or pelvic lymph node dissection (I/PLND) for penile squamous cell carcinoma (PSCC) is associated with poor survival, yet predictors of post-I/PLND recurrence and optimal salvage strategies remain unclear. We conducted a systematic review to identify clinicopathological features predictive of recurrence after I/PLND. This systematic review followed PRISMA 2020 guidelines and was prospectively registered on PROSPERO. Major bibliographic databases were searched from inception to November 13th 2025. Eligible studies evaluated clinicopathological factors associated with local, regional (inguinal/pelvic), or distant recurrence after I/PLND. Risk of bias was assessed using the Newcastle-Ottawa Scale. Owing to substantial heterogeneity, results were synthesized narratively. Fifteen retrospective studies comprising 2,973 patients were included; most exhibited moderate to high risk of bias. Recurrence-free survival (RFS) was reported in 12 studies (n = 2,515), with 3-year RFS ranging from 43 to 70% and 5-year RFS from 0 - 60%. Median time to recurrence (n = 1,208) ranging from 5.3 - 44.5 mo. Recurrence was consistently associated with higher pN stage, ≥3 positive inguinal lymph nodes, extranodal extension, pelvic nodal involvement, lymphovascular invasion, and adverse primary-tumor features (pT3-pT4, positive margins, urethral invasion). Early ILND (≤3 months) and higher total lymph node yield (≥15 for ILND; ≥9 for PLND) were associated with improved outcomes. Median OS after recurrence ranged from 3.1 to 23.0 mo. Meta-analysis was not feasible. Post-I/PLND recurrence risk in PSCC is primarily driven by nodal burden and extranodal or pelvic disease. Given the poor prognosis of regional and distant recurrence, risk-adapted surveillance and early, multimodal management are essential, while prospective studies are urgently needed.