Clinical Investigation
Total Laryngectomy Versus Larynx Preservation for T4a Larynx Cancer: Patterns of Care and Survival Outcomes

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Purpose

To examine practice patterns and compare survival outcomes between total laryngectomy (TL) and larynx preservation chemoradiation (LP-CRT) in the setting of T4a larynx cancer, using a large national cancer registry.

Methods and Materials

Using the National Cancer Database, we identified 969 patients from 2003 to 2006 with T4a squamous cell larynx cancer receiving definitive treatment with either initial TL plus adjuvant therapy or LP-CRT. Univariate and multivariable logistic regression were used to assess predictors of undergoing surgery. Survival outcomes were compared using Kaplan-Meier and propensity score–adjusted and inverse probability of treatment–weighted Cox proportional hazards methods. Sensitivity analyses were performed to account for unmeasured confounders.

Results

A total of 616 patients (64%) received LP-CRT, and 353 (36%) received TL. On multivariable logistic regression, patients with advanced nodal disease were less likely to receive TL (N2 vs N0, 26.6% vs 43.4%, odds ratio [OR] 0.52, 95% confidence interval [CI] 0.37-0.73; N3 vs N0, 19.1% vs 43.4%, OR 0.23, 95% CI 0.07-0.77), whereas patients treated in high case-volume facilities were more likely to receive TL (46.1% vs 31.5%, OR 1.78, 95% CI 1.27-2.48). Median survival for TL versus LP was 61 versus 39 months (P<.001). After controlling for potential confounders, LP-CRT had inferior overall survival compared with TL (hazard ratio 1.31, 95% CI 1.10-1.57), and with the inverse probability of treatment–weighted model (hazard ratio 1.25, 95% CI 1.05-1.49). This survival difference was shown to be robust on additional sensitivity analyses.

Conclusions

Most patients with T4a larynx cancer receive LP-CRT, despite guidelines suggesting TL as the preferred initial approach. Patients receiving LP-CRT had more advanced nodal disease and worse overall survival. Previous studies of (non-T4a) locally advanced larynx cancer showing no difference in survival between LP-CRT and TL may not apply to T4a disease, and patients should be counseled accordingly.

Introduction

In 2014 the estimated incidence of larynx cancer in the United States will be 12,630, with 3610 deaths (1). The Department of Veterans Affairs (VA) Laryngeal Cancer Study established larynx preservation (LP) as a viable alternative to total laryngectomy (TL) for those with locally advanced disease (2). Radiation Therapy Oncology Group (RTOG) protocol 91-11 demonstrated that concurrent cisplatin/radiation (LP-CRT) achieved higher rates of LP than radiation therapy (RT) alone or sequential CRT, resulting in concurrent chemoradiation being adapted as the dominant form of LP 3, 4.

The optimal treatment for advanced-stage larynx cancer remains unclear. The randomized trials infrequently included patients with T4a disease, comprising 26% of patients on the VA study (2) and 10% on RTOG 91-11 (in which patients with tumor penetrating through the thyroid cartilage or >1 cm into the base of tongue were ineligible) (3). In the VA study, >50% of those with T4a disease receiving LP ultimately needed salvage laryngectomy. Guideline recommendations for T4a larynx cancer specify TL as the initial treatment of choice 5, 6. However, some advocate that well-selected, low-volume T4a disease may be appropriate for LP, given good pretreatment larynx function and limited thyroid cartilage destruction (7).

Concerns that LP is being offered too broadly and inappropriately have been fueled by evidence of declining survival, concurrent with the rise of LP and the declining use of TL (8). Furthermore, it was reported that patients with stage IV disease had improved overall survival with TL compared with LP (9). A population-based analysis in Canada revealed that TL resulted in better survival among T4a patients relative to LP (with 37% undergoing LP) (10). It is unclear how often T4a disease is treated with TL versus CRT in a non-study, practice-based setting in the United States. Our study aimed to: (1) determine what proportion of T4a patients receive the recommended standard treatment (TL); (2) report disease outcomes associated with TL versus CRT; and (3) identify factors that account for differences in treatment and outcomes. Our results will have implications on patient counseling for treatment, with the aim of changing practice patterns to comply with current treatment paradigms/guidelines.

Section snippets

Study design and data source

This was a retrospective, observational, cohort study conducted with data from the National Cancer Data Base (NCDB). The NCDB is a large national cancer registry sponsored by the American College of Surgeons Commission on Cancer (COC) and the American Cancer Society. Approximately 70% of incident cancer cases in the United States are reported to the NCDB (11). The study was reviewed and determined to have exempt status by our institutional review board.

Cohort

The study cohort is illustrated in Figure 1

Patient characteristics

Patient characteristics are shown in Table 1. Factors predictive of TL from multivariable logistic regression are shown in Table 2. Sixty-four percent of patients received LP-CRT versus TL (36%). Patients with advanced nodal disease (N2 vs N0: 26.6% vs 43.4%; OR 0.52, 95% CI 0.37-0.73, P<.001) and supraglottic (vs glottis) location (31.3% vs 47.5%; OR 0.51, 95% CI 0.36-0.72, P<.001) were less likely to undergo TL. Patients treated at high case-volume facilities were more likely to undergo TL

Discussion

Although the efficacy and safety of organ preservation in the treatment of advanced larynx cancer has been well established 2, 3, 4, previous studies suggested worse survival with organ preservation compared with TL for stage IV larynx cancer 9, 20. Laryngeal cancer comprises a wide spectrum of tumor and nodal stage, and patient selection is important, as reflected in the guidelines supporting initial TL for patients with T4a disease 5, 6. As recently as 1998 the majority of patients with stage

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    Note—An online CME test for this article can be taken at http://astro.org/MOC.

    S.G. and S.S.-M. contributed equally to this work.

    Conflict of interest: none.

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