Primary Cancer vs Competing Causes of Death in Survivors of Head and Neck Cancer

Approximately 436 000 survivors of head and neck cancer (HNC) currently live in the United States, the number increasing because of decreasing smoking rates and increasing human papillomavirus incidence.¹ Survivors, however, face several comorbidities that increase their risk of death from competing causes other than primary HNC.²

To our knowledge, no model exists estimating the survival time point when death from competing causes becomes likelier than death from primary HNC. Developing such models may improve clinicians’ long-term surveillance of HNC sequelae.¹ We aimed to determine the probability and estimate the time point after diagnosis when death from competing causes becomes more common than that from primary HNC.

We retrospectively queried the Surveillance, Epidemiology, and End Results (SEER) 18 database³ from 2000 through 2014 for eligible cases of adults with head and neck squamous cell carcinoma (first or only cancer with known cause of death). Because SEER is a publicly available database with deidentified data, this study was exempt from consideration by the Saint Louis University Institutional Review Board. Binomial logistic regression analysis used year of follow-up as predictor, and cause of death (primary HNC and competing causes) as the outcome variables, while controlling for covariates (sex, race, marital status, treatment modality, stage, anatomic site, and county-level median family income). Reported adjusted odds ratios (aORs) were not adjusted using the multiple comparison analysis method.

Conditional probabilities (CP) of failure for both causes of death were plotted by year of follow-up. Statistical analyses were performed using SAS, version 9.4 (SAS Institute). Tests were 2 tailed and conducted at α = .05.

There were 151 155 patients in the cohort. Each increasing year of survival was associated with 26% increased odds of death from competing causes (aOR, 1.26; 95% CI, 1.25-1.27). Male sex (aOR, 1.21; 95% CI, 1.16-1.26), divorced or separated status (aOR, 1.17; 95% CI, 1.11-1.23), and oral cavity cancer (aOR, 1.06; 95% CI, 1.01-1.11) were all associated with greater odds of death from competing causes compared with the variables’ reference groups. Black patients (aOR, 0.93; 95% CI, 0.88-0.98) had lower odds of death from competing causes compared with whites (Table).

Median survival time for the entire cohort was 80 months (range, 0-180 months). The first 56 months after diagnosis, primary HNC accounted for 73.4% of deaths. However, death from competing causes became more common than death from primary HNC after 57 months and later (competing cause CP at 57 months, 0.0023; 95% CI, 0.0020-0.0026; HNC death CP, 0.0027; 95% CI, 0.0025-0.0030) (Figure). Primary HNC accounted for 38.8% of deaths 6 to 10 years after diagnosis. By 11 to 15 years after diagnosis, primary HNC only accounted for 30.6% of deaths. The most common competing causes of death were cardiovascular disease, second primary cancers, and chronic obstructive pulmonary disease.

We showed that each increasing year after HNC diagnosis was associated with a 26% increase in the odds of dying from competing causes, and death from competing causes became more common than primary HNC 5 years after diagnosis. This time point could guide the multidisciplinary cancer team to focus on competing risks that could cause death in HNC survivors, independent of primary disease or recurrence.

Eleven years after diagnosis, only 30.6% died from primary HNC. It is critical to develop lifelong surveillance for competing causes of death, which by this time accounted for greater than two-thirds of deaths. Besides preventing deaths from competing causes, surveillance could help mitigate treatment-related quality-of life issues.

The most common competing causes of death in this cohort were cardiovascular disease, chronic obstructive pulmonary disease, and second primary lung cancer, all linked to tobacco use.⁴ Despite decreasing national smoking rates, up to 80% of patients with HNC are either current or former smokers.^5,6 Thus, tobacco cessation should be standard care for patients with HNC from diagnosis and throughout their lifetime.

In conclusion, more patients with HNC die from competing causes than primary cancer 5 years after diagnosis, and less than 1 in 3 die from primary HNC 11 years after diagnosis. Our study reaffirms the need for a multidisciplinary focus on HNC competing causes of death.

Corresponding Author: Nosayaba Osazuwa-Peters, BDS, MPH, CHES, Department of Otolaryngology-Head and Neck Surgery, Saint Louis University School of Medicine, 3635 Vista Ave, Sixth Floor, Desloge Towers, St Louis, MO 63110-2539 (nosazuwa@slu.edu).

Accepted for Publication: October 10, 2017.

Published Online: December 28, 2017. doi:10.1001/jamaoncol.2017.4478

Author Contributions: Mr Simpson and Dr Osazuwa-Peters had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Simpson, Massa, Varvares, Osazuwa-Peters.

Acquisition, analysis, or interpretation of data: Simpson, Massa, Adjei Boakye, Antisdel, Stamatakis, Osazuwa-Peters.

Drafting of the manuscript: Simpson, Adjei Boakye, Osazuwa-Peters.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Simpson, Massa, Adjei Boakye.

Administrative, technical, or material support: Simpson, Massa, Antisdel, Osazuwa-Peters.

Study supervision: Massa, Antisdel, Varvares, Osazuwa-Peters.

Conflict of Interest Disclosures: None reported.