Development of a New Classification Method for Penile Squamous Cell Carcinoma Based on Lymph Node Density and Standard Pathological Risk Factors: The ND Staging System

Object: In this study, we evaluated the role of lymph node density (LND) and validated whether LND increases the accuracy of survival prediction when combined with the American Joint Committee on Cancer (AJCC) pathological node (N) staging system for penile cancer (7(th) edition). Methods: A total of 270 Chinese penile cancer patients treated between March 1999 and October 2014 were retrospectively analyzed. LND was analyzed as a trichotomous variable for the prediction of DSS in this cohort. We developed a new prediction model, which we refer to as the ND staging system, that is based on LND and pathological N staging. The predictive accuracy of this model was further assessed using the concordance index. Results: LND was correlated with the laterality of lymph node metastasis, extranodal extension, pelvic lymph node metastases, and pathologic tumor (T) and N stages (P<0.05). In separate multivariate Cox regression models, the LND (hazard ratio [HR], 1.966, 95% confidence interval [CI], (1.112-3.473, P=0.020) yielded independent effects on the outcome. According to the LND classification, the 3-year disease-specific survival (DSS) rates for patients with LNDs <7.0%, 7.0 to 16.9%, and ≥17.0% were 90.9%, 66.5%, and 22.2%, respectively (P(<7.0%; 7.0%-16.9%)=0.006; P(7.0-16.9%; ≥17.0%)=0.001). The corresponding rates were 95.7%, 76.7%, and 28.1% for the ND1, ND2, and ND3 patients, respectively (P(ND1-ND2)=0.047; P(ND2-ND3)<0.001). The indexes indicated that the accuracy of the pathological ND category that incorporated LND was significantly increased. Conclusion: LND was associated with some prognosticators and is thus a prognostic factor. The ND staging system that incorporates the LND better reflects the prognoses of penile cancer patients.