Primary tumor staging for oral cancer and a proposed modification incorporating depth of invasion: An international multicenter retrospective study

Ardalan Ebrahimi, Ziv Gil, Moran Amit, Tzu Chen Yen, Chun Ta Liao, Pankaj Chaturvedi, Jai Prakash Agarwal, Luiz P. Kowalski, Matthias Kreppel, Claudio R. Cernea, Jose Brandao, Gideon Bachar, Andrea Bolzoni Villaret, Dan Fliss, Eran Fridman, K. Thomas Robbins, Jatin P. Shah, Snehal G. Patel, Jonathan R. Clark, The International Consortium for Outcome Research (ICOR) in Head and Neck Cancer

Research output: Contribution to journalArticlepeer-review

203 Scopus citations


IMPORTANCE: The current American Joint Committee on Cancer (AJCC) staging system for oral cancer demonstrates wide prognostic variability within each primary tumor stage and provides suboptimal staging and prognostic information for some patients. OBJECTIVE To determine if a modified staging system for oral cancer that integrates depth of invasion (DOI) into the T categories improves prognostic performance compared with the current AJCC T staging. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of 3149 patients with oral squamous cell carcinoma treated with curative intent at 11 comprehensive cancer centers worldwide between 1990 and 2011 with surgery ± adjuvant therapy, with a median follow-up of 40 months. MAIN OUTCOMES AND MEASURES: We assessed the impact of DOI on disease-specific and overall survival in multivariable Cox proportional hazard models and investigated for institutional heterogeneity using 2-stage random effects meta-analyses. Candidate staging systems were developed after identification of optimal DOI cutpoints within each AJCC T category using the Akaike information criterion (AIC) and likelihood ratio tests. Staging systems were evaluated using the Harrel concordance index (C-index), AIC, and visual inspection for stratification into distinct prognostic categories, with internal validation using bootstrapping techniques. RESULTS: The mean and median DOI were 12.9mmand 10.0 mm, respectively. On multivariable analysis, DOI was a significantly associated with disease-specific survival (P < .001), demonstrated no institutional prognostic heterogeneity (I2 = 6.3%; P = .38), and resulted in improved model fit compared with T category alone (lower AIC, P < .001). Optimal cutpoints of 5mmin T1 and 10mmin T2-4 category disease were used to develop a modified T staging system that was preferred to the AJCC system on the basis of lower AIC, visual inspection of Kaplan-Meier curves, and significant improvement in bootstrapped C-index. CONCLUSIONS AND RELEVANCE: We propose an improved oral cancer T staging system based on incorporation of DOI that should be considered in future versions of the AJCC staging system after external validation.

Original languageEnglish (US)
Pages (from-to)1138-1148
Number of pages11
JournalJAMA Otolaryngology - Head and Neck Surgery
Issue number12
StatePublished - Dec 1 2014

ASJC Scopus subject areas

  • Surgery
  • Otorhinolaryngology


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