Original Study| Volume 15, ISSUE 6, e1095-e1106, December 2017

Validation of the Eighth AJCC New Substages for Bladder Cancer Among Different Staging Contexts

  • Omar Abdel-Rahman
    Address for correspondence: Dr. Omar Abdel-Rahman, MD, Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Lotfy Elsayed Street, Cairo 11566, Egypt
    Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
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Published:August 02, 2017DOI:



      To validate the prognostic value of the new American Joint Committee on Cancer (AJCC) staging system (eighth edition) among different staging contexts (clinical vs. pathologic).


      Surveillance, Epidemiology, and End Results (SEER) database (2010-2014) was accessed through SEER*Stat program and both AJCC seventh and eighth edition stages were assigned for each patient. Overall and cancer-specific survival analyses according to both editions were conducted through Kaplan-Meier analysis. Concordance index (c-index) was assessed for each edition.


      A total of 7074 patients with pathologically staged and 26,698 with clinically staged urinary bladder carcinoma were identified in the period from 2010 to 2014. Among patients with pathologically staged disease without neoadjuvant treatment, P values for all pairwise comparisons among different stages (according to AJCC seventh and eighth systems) were significant for both overall and cancer-specific survivals (< .01). Moreover, within the same cohort, c-index (using death from urinary bladder cancer as the dependent variable) for AJCC seventh system was 0.714 (SE 0.008; 95% CI, 0.699-0.729); whereas the c-index for the AJCC eighth system was 0.718 (SE 0.008; 95% CI, 0.702-0.733). Likewise, among patients with clinically staged disease, P values for all pairwise comparisons among different AJCC eighth stages were significant for overall survival (< .05) except for stage IIIA versus stage IIIB; whereas P values for all pairwise comparisons among different AJCC eighth stages were significant for cancer-specific survival (P < .05).


      This analysis supports the prognostic relevance of the added substages described within AJCC eighth edition stages III and IV for clinically staged and pathologically staged disease without neoadjuvant treatment.


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        • International Agency for Research on Cancer
        GLOBOCAN 2012.
        (Available at:) (Accessed: November 27, 2016)
        • Abdel-Rahman O.
        Squamous cell carcinoma of the bladder: a SEER database analysis.
        Clin Genitourin Cancer. 2017; 15: e463-e468
        • Galsky M.D.
        • Domingo-Domenech J.
        • Sfakianos J.P.
        • Ferket B.S.
        Definitive management of primary bladder tumors in the context of metastatic disease: who, how, when, and why?.
        J Clin Oncol. 2016; 34: 3495-3498
        • Griffiths G.
        • Hall R.
        • Sylvester R.
        • Raghavan D.
        • Parmar M.K.
        International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial.
        J Clin Oncol. 2011; 29: 2171-2177
        • Grossman H.B.
        • Natale R.B.
        • Tangen C.M.
        • et al.
        Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer.
        N Engl J Med. 2003; 349: 859-866
        • Amin M.B.
        • Greene F.L.
        • Edge S.B.
        • et al.
        The Eighth Edition AJCC Cancer Staging Manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging.
        CA Cancer J Clin. 2017; 67: 93-99
      1. Surveillance, Epidemiology and End Results Program. About the SEER Program.
        (Available at:) (Accessed: June 25, 2016)
        • Bellmunt J.
        • Orsola A.
        • Leow J.J.
        • Wiegel T.
        • De Santis M.
        • Horwich A.
        Bladder cancer: ESMO Practice Guidelines for diagnosis, treatment and follow-up.
        Ann Oncol. 2014; 25: iii40-iii48
        • Witjes J.A.
        • Comperat E.
        • Cowan N.C.
        • et al.
        EAU guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2013 guidelines.
        Eur Urol. 2014; 65: 778-792
        • Clark P.E.
        • Agarwal N.
        • Biagioli M.C.
        • et al.
        Bladder cancer.
        J Natl Compr Canc Netw. 2013; 11: 446-475
        • Patel A.R.
        • Cohn J.A.
        • Abd El Latif A.
        • et al.
        Validation of new AJCC exclusion criteria for subepithelial prostatic stromal invasion from pT4a bladder urothelial carcinoma.
        J Urol. 2013; 189: 53-58
        • Tilki D.
        • Reich O.
        • Karakiewicz P.I.
        • et al.
        Validation of the AJCC TNM substaging of pT2 bladder cancer: deep muscle invasion is associated with significantly worse outcome.
        Eur Urol. 2010; 58: 112-117
        • Gakis G.
        • Schilling D.
        • Renninger M.
        • Seibold J.
        • Sievert K.D.
        • Stenzl A.
        Comparison of the new American Joint Committee on Cancer substratification in node-negative pT2 urothelial carcinoma of the bladder: analysis of patient outcomes in a contemporary series.
        BJU Int. 2011; 107: 919-923
        • Oweira H.
        • Petrausch U.
        • Helbling D.
        • et al.
        Prognostic value of site-specific metastases in pancreatic adenocarcinoma: a Surveillance Epidemiology and End Results database analysis.
        World J Gastroenterol. 2017; 23: 1872-1880
        • Oweira H.
        • Petrausch U.
        • Helbling D.
        • et al.
        Prognostic value of site-specific extra-hepatic disease in hepatocellular carcinoma: a SEER database analysis.
        Expert Rev Gastroenterol Hepatol. 2017; 11: 695-701