Prognostic factors associated with worse outcomes following chemoradiation therapy in patients with anal carcinoma.

Aim: Chemoradiation therapy (CRT) is considered as the first line of treatment for patients with squamous cell carcinoma of the anal canal. Following initial CRT, patients who present with either persistent or locally recurrent disease are treated by surgical intervention. The aim of our study is to determine the prognostic factors associated with failure of CRT and overall mortality in patients with anal squamous cell carcinoma (SCC).

Methods: We performed a 14-year analysis (2004-2017) of the National Cancer Database and included patients diagnosed with non-metastatic SCC of the anal canal who underwent CRT. Baseline patient characteristics including demographics, comorbidities and tumour characteristics were analysed. Outcome measures were needed for operative intervention after 4 months of initiation of CRT (failure of CRT) and 5-year overall mortality. Multivariate logistic regression analysis identified prognostic factors independently associated with failure of CRT.

Results: We included a total of 37 615 patients with anal SCC who received CRT. Predictors of operative intervention included male sex, higher Deyo-Charlson Comorbidity Index (DCCI) and higher primary tumour stage. The 5-year overall survival rate was 77.6%, and 2.4% of patients failed CRT, defined as requiring and undergoing surgical intervention within 4 months post-initiation of CRT. Median follow-up time was 47 (95% CI 24-84) months. Independent predictors of overall mortality within the first 5 years of diagnosis were increased age, male sex, Black race, non-insured status, higher DCCI, higher primary tumour grade, and higher primary tumour and lymph node stage. The 5-year survival rate was significantly lower in patients who underwent operative intervention compared to those who received CRT alone (57.4% vs. 78.1%; P < 0.01).

Conclusion: Our study showed that male sex, younger age, DCCI of 1 and 3, and increased tumour size were predictive of CRT failure among patients with anal SCC. Increased age, male sex, Black race, non-insured status, increased DCCI, and more aggressive tumour characteristics were associated with increased 5-year overall mortality. More importantly, patients who failed CRT had worse 5-year overall survival. Our findings support increased emphasis on intensive surveillance for these high-risk patient cohorts.