Survival in N3 penile cancer: Does pelvic lymphadenopathy predict a worse prognosis than inguinal extra-nodal extension?

Abstract

Introduction & Objectives: Penile squamous cell cancer (PSCC) with lymph node (LN) disease has a poor overall survival (OS). The current TNM classification system defines clinical N3 (cN3) stage as the presence of fixed inguinal LN metastasis or pelvic lymphadenopathy (PLN), and pathologic N3 (pN3) stage as metastasis in pelvic LN and/or extra-nodal extension (ENE) in any LN. This study has examined whether N3 stage can be further stratified based on ENE and PLN status. We hypothesised a worse OS for patients with PLN on cross-sectional imaging compared to those with ENE present in inguinal LN (iENE) and without PLN. Materials & Methods: We analysed retrospective data for patients treated at a UK tertiary referral centre between 2003 and 2021 with PSCC and suspicion of LN disease (cN+) at diagnosis. We excluded patients with extra-pelvic LN or distant metastatic disease at diagnosis and those without available cross-sectional imaging of the abdomen and pelvis within 6 months of definitive primary (penile) treatment. The primary outcome of OS (time from definitive primary surgery to death, censored for last follow-up) was stratified by PLN present (PLN+) vs PLN absent and iENE present (PLN-iENE+). The PLN absent and iENE absent (PLN-iENE-) group has been included as a reference for OS comparison. Audit approval was obtained from the host clinical governance committee. Results: 199 patients met inclusion criteria, of which 110 were categorised as PLN-iENE-, 58 as PLN-iENE+ and 31 as PLN+. Baseline characteristics of age, primary tumour stage and grade were similar across all groups. Univariate Cox regression analysis demonstrated an increased risk of death in the PLN-iENE+ group (HR=2.23, 95% CI 1.38-3.61, p=0.001) and the PLN+ group (HR=4.08, 95% CI 2.39-6.97, p<0.001) compared to the reference PLN-iENE- group (figure 1).