Stage I Squamous Cell Carcinoma of the Anus: Is Radiation Therapy Alone Sufficient Treatment?

Abstract

Simple SummaryThe optimal treatment of early stage anal cancer is unknown. This patient population was relatively under-represented on the trials, which defined radiation therapy with concurrent chemotherapy as the standard treatment for anal cancer, thus radiation therapy alone may be an effective alternative treatment. The aim of this study was to use a large national database of anal cancer patients to compare overall survival of patients treated with radiation therapy alone to those treated with radiation therapy with concurrent chemotherapy. We found that patients who received radiation therapy alone were more likely to be ≥70 years old and less likely to be female. Treatment with radiation and concurrent chemotherapy was associated with a 31% reduction in the risk of death compared to treatment with radiation alone. Our results suggest that radiation with concurrent chemotherapy should be the standard treatment for early stage anal cancer patients.The optimal treatment for stage I squamous cell carcinoma of the anus (SCCA) remains undefined. Recently, wide local excision alone was found to have comparable survival to those treated with chemoradiation (CRT). Given that local excision may be sufficient for the treatment of stage I SCCA, we hypothesized that radiation therapy (RT) alone, compared to CRT would result in equivalent overall survival (OS) in this population. We identified non-surgically treated patients with stage I SCCA from the National Cancer Database from 2004–2015. We included only patients treated either with CRT (45–59.4 Gy with chemotherapy initiated within 14 days of RT) or RT alone (45–59.4 Gy with no chemotherapy). The primary endpoint was OS between CRT and RT patients. Propensity-score matched (PSM) analysis was performed to determine the effect of concurrent chemotherapy on OS using a Cox proportional hazards model with robust standard error to account for clustering in matched pairs. We identified 3552 stage I patients treated with CRT and 287 treated with RT. Compared to patients treated with CRT, those that received RT were more likely to be ≥70 years old (33.1% vs. 19.7%, p < 0.001) and less likely to be female (63.1% vs. 71.0%, p < 0.001). The proportion of patients with a Charlson-Deyo score of 0 was similar in both groups (80.8% RT vs. 82.7% CRT, p = 0.164). The PSM cohort consisted of 287 pairs of patients with median follow-up 48.3 months (interquartile range, 24.4–85.1 months) and 151 deaths (86 RT, 65 CRT). CRT was associated with a 31% reduction in the risk of death (HR = 0.69, 95% CI 0.50–0.95, p = 0.023). We found that CRT was associated with improved OS, compared to RT alone, in patients with non-surgically treated stage I SCCA. These data suggest that de-intensification of therapy in stage I SCCA must be used with caution. However, given the retrospective nature of the data, prospective trials are required.