Adding radiation therapy to surgery was associated with better survival for patients with head and neck cutaneous squamous cell carcinoma (CSCC) and either perineural invasion (PNI) or regional adenopathy, a retrospective multi-center study found.
In subgroup analyses of the 349-patient study, improvements in disease-free survival (DFS) and overall survival (OS) were observed for those with PNI who went on to receive radiotherapy after resection (HR 0.47, 95% CI 0.23-0.93; HR 0.44, 95% CI 0.24-0.86; respectively), according to Arnaud Bewley, MD, of the University of California Davis in Sacramento, and colleagues.
And also for those with regional disease (HR 0.36, 95% CI 0.15-0.84; HR 0.30, 95% CI 0.15-0.61; respectively), as reported in JAMA Otolaryngology — Head & Neck Surgery.
On multivariate analysis, patients with periorbital tumors (HR 2.48, 95% CI 1.00-6.16), PNI (HR 1.90, 95% CI 1.12-3.19), or ≥N2 disease (HR 2.16, 95% CI 1.13-4.16) had worse DFS overall. And immunosuppressed patients (HR 2.17, 95% CI 1.12-4.17) and those with ≥N2 disease (HR 2.43, 95% CI 1.42-4.17) had worse OS.
The authors noted that guidelines on the role of adjuvant therapy in CSCC of the head and neck are “ill-defined” and data on whether it provides benefit are inconsistent. They said prospective studies to evaluate its efficacy and determine optimal patient selection are needed.
“In the present series, patients with tumors with PNI, increased diameter, poor differentiation, or regionally metastatic disease were more likely to undergo adjuvant therapy,” they wrote. “Although these findings have been described as high-risk features for CSCC, only PNI and regional disease are currently recognized indications for adjuvant therapy.”
They also found that adjuvant therapy was more common among younger immunosuppressed patients.
“The study is highly thought-provoking and adds convincing support for the benefit of adjuvant radiation therapy for patients with PNI with [CSCC of the head and neck],” Ajay Bhatnagar, MD, of Alliance Cancer Care Arizona, told MedPage Today.
“I am pleasantly surprised that there is an OS benefit in addition to a local control benefit, which is typically the primary objective for radiation therapy in the setting of non-melanoma skin cancer,” he said. “Therefore, the benefit of radiation therapy for these patients may be greater than we initially thought.”
But Bhatnagar, who was not involved in the study, cautioned that this OS benefit needs to be viewed in context, pointing to the retrospective design as a limitation of the findings.
Christopher A. Barker, MD, of Memorial Sloan Kettering Cancer Center in New York, agreed that the design limits the strength of its conclusions, and he echoed the authors’ assessment regarding inconsistent data in this setting.
“It is worth noting that the recently published TROG 05.01 trial demonstrated disease control outcomes with surgery and adjuvant radiotherapy that were remarkably superior to the present report,” said Barker, who also was not involved in the study.
For the current study, Bewley’s group identified a total of 349 patients with CSCCs of the head and neck who underwent primary surgery at two tertiary referral centers from 2008 to 2016. Median patient age was 72 (range 32-94) and 86% were men.
At study enrollment, 58% of tumors were recurrent; 39% of patients had PNI, 19% had extracapsular tumor extension, 24% had poorly differentiated histologic features, and 37% had regional disease. The mean follow-up time was 37 months. There were 97 documented recurrences, of which 66% were local.
Overall, about 50% of patients received adjuvant radiation therapy, and another 4% (often patients with extracapsular tumor extension or positive margins) received adjuvant chemoradiation therapy. Looking at the entire cohort on univariate analysis, adjuvant therapy was not associated with improvements in DFS or OS, but on multivariate analysis an association was seen for improved OS (HR 0.59, 95% CI 0.38-0.90).
The authors noted that study limitations included the retrospective nature and inherent selection bias for patients who received adjuvant radiation therapy, and potential variations in administration of adjuvant radiation treatment at outside institutions, noting that additional research on radiation dose and field design would be of value.
“Given the increasing incidence of CSCC and the high morbidity and mortality of this disease, more data are needed to help guide adjuvant treatment recommendations to improve survival outcomes,” they concluded.
Bewley had no disclosures. One co-author reported being a faculty member for AO North America.