To evaluate the prognostic value of the 8th TNM staging system and assess a modified N stage that incorporates high-risk human papillomavirus (hrHPV) status in a multicenter cohort.

292 patients with M0 penile squamous cell carcinoma from six referral centers were included, and hrHPV status was examined. The Chinese multicenter cohort (n=230) 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 (n=62) from Moffitt Cancer Center.

The median follow-up was 48.9 months, and 42% of patients had node-positive disease. In the primary cohort, the 8th TNM staging system achieved better discriminative ability compared with the 7th edition, with a C-index of 0.769 versus 0.751 (p=0.029). The 8th N category could better stratify survival between pN1 and pN2 (p<0.001) and reclassified 15% of node-positive disease into pN1 with a 5-year overall survival of 64%. HrHPV status further stratified pN2-3 disease (p=0.040) and pN2-3/hrHPV- disease had a 5-year survival of 32%. The newly proposed three-tier classification (pN1, pN2-3/hrHPV+, pN2-3/hrHPV-) significantly increased the C-index from 0.620 to 0.666 compared with the 8th N classification (pN1, pN2-3) (p=0.04). Significantly improved results (C-index: 0.567-0.641, p=0.027) were observed in the external validation cohort using the modified N classification.

The 8th edition of the AJCC staging system for penile cancer showed better discriminative ability in prognostic stratification. Adding hrHPV status further improved the prognostic stratification in node-positive disease.

The Journal of urology. 2019 Oct 09 [Epub ahead of print]

Beihe Wang, Weijie Gu, Fangning Wan, Yu Wei, Wenjun Xiao, Xiaolin Lu, Guiming Zhang, Jiaquan Zhou, Qifeng Wang, Xuefei Ding, Mounsif Azizi, Philippe E Spiess, DingWei Ye, Yao Zhu

Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China., Department of Urology, Affiliated Hospital of Qingdao University, Qingdao, China., Department of Urology, Hainan General Hospital, Hainan, China., Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China., Department of Urology, Northern Jiangsu People’s Hospital, Yangzhou, China., Department of GU Oncology and Tumor Biology, Moffitt Cancer Center, Florida.