Prognosis of the 8th TNM Staging System for Penile Cancer and Refinement of Prognostication by Incorporating High Risk Human Papillomavirus Status

Purpose: We evaluated the prognostic value of the 8th TNM staging system and assessed a modified N stage incorporating high risk human papillomavirus status in a multicenter cohort. Materials and Methods: Included in analysis were 292 patients with M0 penile squamous cell carcinoma from a total of 6 referral centers. High risk human papillomavirus status was examined. The Chinese multicenter cohort of 230 patients was used to validate the 8th TNM staging system and propose a modified N classification. The modified classification was further validated in an independent cohort of 62 patients at Moffitt Cancer Center. Results: Median followup was 48.9 months. Of the patients 42% had node positive disease. In the primary cohort the 8th TNM staging system achieved better discriminative ability compared with the 7th edition (C-index 0.769 vs 0.751, p=0.029). The 8th N category better stratified survival between pN1 and pN2 (p <0.001) and reclassified 15% of node positive cases into pN1 with 64% 5-year overall survival. High risk human papillomavirus status further stratified pN2-3 disease (p=0.040) and pN2-3 high risk human papillomavirus negative status was associated with 32% 5-year survival. The newly proposed 3-tier classification (1dpN1, 2dpN2-3 high risk human papillomavirus positive and 3dpN2-3 high risk human papillomavirus negative) significantly increased the C-index from 0.620 to 0.666 compared with the 8th N classification of pN1 and pN2-3 (p=0.04). In the external validation cohort significantly improved results were observed using the modified N classification (C-index 0.567-0.641, p=0.027). Conclusions: The 8th edition of the AJCC (American Joint Committee on Cancer) Staging System for penile cancer showed better discriminative ability for prognostic stratification. Adding high risk human papillomavirus status further improved the prognostic stratification in patients with node positive disease.