Subclassification of pN3 staging systems for penile cancer: Proposal for modification of the current TNM classification

Abstract

Objective: To validate the clinical and prognostic significance of our proposed pN3 subclassification in penile cancer.

Materials and methods: A retrospective analysis of 509 patients with penile cancer undergoing partial, total penectomy or inguinal lymphadenectomy or pelvic lymphadenectomy at Sun Yat-sen University Cancer Center was reevaluated by pathologists. pN3 stage was subclassified into pN3a (extranodal extension of any inguinal lymph node [LN] metastasis only) and pN3b (pelvic LN metastasis). The t test and chi-square test were applied to assess the comparability of pN3a and pN3b with clinicopathologic features. Univariable and multivariable statistical analyses were used to evaluate prognostic effect with cancer-specific survival.

Results: Among 509 patients, 71 patients with pN3 stage cancer were divided into 39 with pN3a and 32 with pN3b. The median number of LNs removed and the number of positive LNs were 27 and 3, respectively. The 3-year cancer-specific survival in pN3a and pN3b groups was significantly different at 47.9% and 28.6% (P = 0.003). In multivariable analysis, pN3 subclassification was an independent predictor for cancer-specific mortality (hazard ratio = 2.77; 95% CI: 1.170-6.558; P = 0.02). Adding pN3 subclassification to a multivariable model including pT stage, tumor grade, side involvement, lymphovascular invasion, number of positive LNs, and adjuvant therapy increased predictive accuracy for cancer-specific mortality from 0.665 to 0.695 (P<0.001).

Conclusions: Subclassification helps better distinguish patients with pN3 penile cancer with increased risk of disease progression and cancer-related mortality.

Keywords: Lymph nodes; Neoplasm metastasis; Neoplasm staging; Penile neoplasms; Penis.