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Brief Report
January 05, 2017

Comparison of Survival Outcomes Among Human Papillomavirus–Negative cT1-2 N1-2b Patients With Oropharyngeal Squamous Cell Cancer Treated With Upfront Surgery vs Definitive Chemoradiation TherapyAn Observational Study

Author Affiliations
  • 1Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut
  • 2Division of Otolaryngology, Department of Surgery, Yale School of Medicine, New Haven, Connecticut
  • 3Department of Medical Oncology, Yale School of Medicine, New Haven, Connecticut
JAMA Oncol. Published online January 5, 2017. doi:10.1001/jamaoncol.2016.5769
Key Points

Question  Does upfront surgery improve overall survival in patients with cT1-2 N1-2b human papillomavirus (HPV)-negative oropharyngeal squamous cell carcinoma (OPSCC)?

Findings  Upfront surgical intensification of treatment does not improve overall survival in patients with cT1-2 N1-2b HPV-negative OPSCC, including a subset analysis of patients with margin-negative surgery. Nearly 60% of surgical patients received trimodal therapy with adjuvant chemoradiation.

Meaning  Given that upfront surgical intensification is not associated with improved overall survival, further research should focus on better selection of surgical patients who are less likely to require adjuvant CRT, as trimodal therapy increases treatment-related toxic effects.

Abstract

Importance  Human papillomavirus (HPV)-negative oropharyngeal squamous cell carcinoma (OPSCC) has shown resistance to conventional concurrent chemoradiation (CRT) therapy and carries a relatively poor prognosis in comparison with HPV-positive disease, with decreased locoregional control and overall survival (OS). In the present analysis, we examine whether upfront surgical resection improves overall survival in a large national sample.

Objective  To compare survival outcomes among patients with newly diagnosed cT1-2 N1-2b HPV-negative OPSCC when treated with primary surgical resection vs CRT.

Design, Setting, and Participants  This was an observational study of factors associated with primary treatment modality were identified using multivariable logistic regression. Overall survival was compared using Kaplan-Meier analysis with log-rank tests, multivariable Cox regression, and propensity score matching. Statistical tests were 2-sided. Patients newly diagnosed as having cT1-2 N1-2b pathologically confirmed HPV-negative OPSCC in 2010 to 2012 were identified using the National Cancer Data Base, which includes more than 70% of patients newly diagnosed as having cancer in the United States.

Exposures  Primary surgical resection vs definitive CRT.

Main Outcomes and Measures  Overall survival.

Results  We identified 1044 patients, among whom 460 (44.1%) received upfront surgery and 584 (55.9%) received CRT. Median age was 59 years (range, 25-90 years); 812 patients were male (77.8%), 232 were female (22.2%). Median follow-up was 30 months. Approximately 59% of surgical patients received adjuvant CRT. On multivariable Cox regression, upfront surgery was not associated with increased OS when compared with CRT (adjusted hazard ratio [HR], 1.01; 95% CI, 0.74-1.39; P = .93). Propensity score-matching identified a cohort of 822 patients and redemonstrated equivalent OS (HR, 1.14; 95% CI, 0.81-1.62; P = .46). Lack of OS benefit with upfront surgery persisted in a subset analysis of patients with margin-negative resection (HR, 0.97; 95% CI, 0.66-1.45; P = .88).

Conclusions and Relevance  In this observational study, OS was similar for patients with HPV-negative OPSCC when treated with primary surgery vs CRT. Most surgical patients received trimodal therapy with adjuvant CRT. Our data may have implications for future research focusing on optimal patient selection for surgery.

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