The Substantial Omission of Indicated Postoperative Radiotherapy in Patients With Advanced-Stage Oral Cancer in the US—A Call to Action

Abstract

This cohort study aims to identify factors associated with omission of adjuvant postoperative radiotherapy in patients with advanced-stage oral squamous cell cancers in the US.

While primary surgical resection remains the mainstay of cancer management in patients with oral squamous cell cancers (OSCCs), recurrence rates are high in the setting of adverse pathologic features. Adjuvant postoperative radiotherapy (PORT) is therefore critical to improving oncologic outcomes.^1,2,3 Nevertheless, many patients may refuse PORT, not be offered PORT, or receive suboptimal dosing.⁴ The current study aims to identify factors associated with PORT omission in patients with advanced stage OSCCs and evaluate its effect on survival.

Methods

The 2015 participant user file from the National Cancer Database (NCDB) was analyzed. Patients with standard keratinizing OSCC who underwent up-front definitive surgery were included. To obtain a homogenous cohort with unambiguous pathological indications for PORT, patients with pathological stage III or IV OSCC were included. Patients with pathological T1-2N1 disease were excluded. A complete list of inclusion and exclusion criteria is detailed in the Supplement.

Data collection included relevant sociodemographic, comorbidity, tumor, and treatment factors available in the NCDB data set. Statistical analysis was performed using SPSS (SPSS version 24, IBM). Multivariable Cox survival analyses were used to evaluate the effects of PORT omission on mortality. Factors associated with receipt of PORT were investigated with univariable and multivariable logistic regression analyses. The Medical College of Wisconsin Institutional Review Board deemed this study exempt from review, and deidentified data were used.

Results

A total of 89 402 patients diagnosed with OSCC were identified, of whom 7084 patients met inclusion criteria. All patients had American Joint Committee on Cancer (AJCC), 7th edition, pathological stage III (n = 820, 12%) or stage IV (n = 6264, 88%) disease. A total of 2140 patients (30%) did not undergo any PORT. Reasons for omission included: 1614 (76%) for whom PORT was listed as not part of the first course of treatment, 346 (16%) who refused recommended PORT, 103 (5%) for whom PORT was contraindicated owing to patient risk factors, and 68 (3%) for whom radiation was recommended and not given without documented reason.

In the NCDB, when radiation is listed as not part of the first course of treatment, this is defined specifically as “the treatment plan offered multiple alternative treatment options and the patient selected treatment that did not include radiation therapy” (https://www.facs.org/-/media/files/quality-programs/cancer/ncdb/puf_data_dictionary_2018.ashx). Therefore, while it is possible that some small number of these patients may still have received PORT at a facility not accredited by the Commission on Cancer (CoC), we believe this metric to be highly accurate for PORT omission.

For analysis, 56 Gy or lower was considered incomplete total PORT dosing.⁵ Receipt of PORT higher than 56 Gy as compared with no PORT was significantly associated with improved overall survival in every age category when adjusting for relevant covariates (Figure 1). Despite this, PORT omission increased for each decade from 60 to 90 years (Figure 2). Age younger than 65 years and distance less than 25 miles from the treatment facility were the most significant sociodemographic factors associated with receipt of PORT (age: odds ratio [OR], 1.96; 95% CI, 1.73-2.21; distance: OR, 1.61; 95% CI, 1.44-1.80).

Figure 1. Kaplan-Meier Estimates of Overall Survival in Patients Who Did Not Receive Any PORT, and Patients Who Received Adequate PORT (>56 Gy) Within Different Age Groups.

HR indicates hazard ratio; PORT, postoperative radiotherapy. Omission of PORT was significantly associated with decreased overall survival within each age group.

Figure 2. Percentages of Patients Who Did Not Receive PORT by Age Group.

PORT indicates postoperative radiotherapy.

Discussion

Nearly one-third of patients included in this study, and more than 40% of patients older than 70 years, did not receive PORT despite clear National Comprehensive Cancer Network recommendations. Importantly, this omission was associated with decreased survival in every age category. While the addition of PORT adds treatment-related morbidity and requires an individualized informed risk and benefit assessment, there appears to be substantial, and possibly preventable, mortality related to PORT omission.

While PORT omission was associated with decreased survival, it is important to recognize that its usage may be a surrogate for differences in access to care.⁶ Omission of PORT in the present study was associated with older age and distance from the treatment facility. Omission may therefore be related to the extended duration of current PORT regimens (6-7 weeks) combined with long travel distances and physical challenges related to advancing age. These factors could serve as targets for further investigation with potential interventions focusing on education, accessibility, and care coordination.

Limitations of the present study are related to the absence of highly granular data in the NCDB. Although each patient included had a documented reason for omitting PORT, specific details of patient and physician decision-making are largely absent. Furthermore, while the NCDB provides specific guidelines for inputting data, misinterpretation of these instructions may result in miscategorization of reasons for PORT omission. Particularly, while the NCDB offers a category intended to include patients in whom PORT receipt is unknown, it is possible that some patients who received PORT at non-CoC facilities were miscategorized as having omitted PORT entirely. Lastly, certain pathologic variables known to affect oncologic outcomes were also unavailable. Despite these limitations, this study suggests that PORT is inappropriately omitted in a large portion of patients with advanced-stage OSCC, and this omission is associated with reduced patient survival and requires further investigation.

Supplement.

eFigure. Inclusion and Exclusion Criteria