The 8th American Joint Committee on Cancer tumor-node-metastasis (AJCC-TNM) staging system is based on a few retrospective single-center studies. We aimed to test the prognostic validity of the staging system and to determine whether a modified clinicopathological tumor staging system that includes lymphovascular embolization could increase the accuracy of prognostic prediction for patients with stage T2-3 penile cancer.
A training cohort of 411 patients who were treated at 2 centers in China and Brazil between 2000 and 2015 were staged according to the 8th AJCC-TNM staging system. The internal validation was analyzed by bootstrap-corrected C-indexes (resampled 1000 times). Data from 436 patients who were treated at 15 centers over four continents were used for external validation.
A survivorship overlap was observed between T2 and T3 patients (P = 0.587) classified according to the 8th AJCC-TNM staging system. Lymphovascular embolization was a significant prognostic factor for metastasis and survival (all P < 0.001). Based on the multivariate analysis, only lymphovascular embolization showed a significant influence on cancer-specific survival (CSS) (hazard ratio = 1.587, 95% confidence interval = 1.253-2.011; P = 0.001). T2 and T3 patients with lymphovascular embolization showed significantly shorter CSS than did those without lymphovascular embolization (P < 0.001). Therefore, a modified clinicopathological staging system was proposed, with the T2 and T3 categories of the 8th AJCC-TNM staging system being subdivided into two new categories as follows: t2 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra without lymphovascular invasion, and t3 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra with lymphovascular invasion. The modified staging system involving lymphovascular embolization showed improved prognostic stratification with significant differences in CSS among all categories (all P < 0.005) and exhibited higher accuracy in predicting patient prognoses than did the 8th AJCC-TNM staging system (C-index, 0.739 vs. 0.696). These results were confirmed in the external validation cohort.
T2-3 penile cancers are heterogeneous, and a modified clinicopathological staging system that incorporates lymphovascular embolization may better predict the prognosis of patients with penile cancer than does the 8th AJCC-TNM staging system. Trial registration This study was retrospectively registered on Chinese Clinical Trail Registry: ChiCTR16008041 (2016-03-02). http://www.chictr.org.cn.
Cancer communications (London, England). 2018 Nov 23*** epublish ***
Zai-Shang Li, Antonio Augusto Ornellas, Christian Schwentner, Xiang Li, Alcides Chaux, Georges Netto, Arthur L Burnett, Yong Tang, JiunHung Geng, Kai Yao, Xiao-Feng Chen, Bin Wang, Hong Liao, Nan Liu, Peng Chen, Yong-Hong Lei, Qi-Wu Mi, Hui-Lan Rao, Ying-Ming Xiao, Qi-Lin Wang, Zi-Ke Qin, Zhuo-Wei Liu, Yong-Hong Li, Zi-Jun Zou, Jun-Hang Luo, Hui Li, Hui Han, Fang-Jian Zhou
Department of Urology, Shenzhen People's Hospital, The Second Clinical College of Jinan University, Shenzhen, 518060, Guangdong, P. R. China., Section of Urology, National Institute of Cancer, Rio de Janeiro, Brazil., Department of Urology, Diakonie Klinikum Stuttgart, 70174, Stuttgart, Germany., Urological Department, Urological Institute, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, P. R. China., Department of Scientific Research, Norte University, 1001-1925, Asunción, Paraguay., Department of Pathology, Johns Hopkins University, Baltimore, MD, 21218, USA., Department of Urology, Johns Hopkins University, Baltimore, MD, 21218, USA., Department of Urology, Affiliated Cancer Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, P. R. China., Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, 807, China., Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China., Department of Urology, The First People's Hospital of Chenzhou, Chenzhou, 423000, Hunan, P. R. China., Department of Urology, Cancer Center of Guangzhou Medical University, Guangzhou, 510000, Guangdong, P. R. China., Department of Urology, Sichuan Cancer Hospital, Chengdu, 610041, Sichuan, P. R. China., Department of Urology Oncological Surgery, Chongqing Cancer Hospital & Institute & Cancer Center, Chongqing, 400040, China., Department of Urology, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, 830011, Xinjiang, P. R. China., Department of Urology, Yunnan Provincial Tumor Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, Yunnan, P. R. China., Department of Urology, Dongguan People's Hospital, Dongguan, 523059, Guangdong, P. R. China., Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China., Department of Urology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510000, Guangdong, P. R. China., Department of Pathology, The Chinese University of Hong Kong, Hong Kong, 999077, P. R. China., Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China. ., Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China. .