Intensity-modulated radiation therapy (IMRT) is widely accepted as the preferred approach for managing anal squamous cell carcinoma (SCCA), yet comprehensive data from large cohorts on treatment results and side effects are scarce. This single-institution review retrospectively examines clinical results and adverse events following IMRT combined with chemotherapy for SCCA, assesses whether increasing the radiation dose beyond 54 Gy provides benefits, and contrasts the use of fluoropyrimidine-based regimens paired with either mitomycin or cisplatin as sensitizing agents. The analysis encompassed individuals who underwent IMRT combined with chemotherapy at The University of Texas MD Anderson Cancer Center from 2003 through 2018. Estimates of time to local-regional relapse, need for permanent colostomy, and overall survival were derived via Kaplan-Meier analysis. Four hundred twenty-eight cases were reviewed, with an average follow-up period of 4.4 years. Most patients (334, or 78%) received cisplatin plus a fluoropyrimidine concurrently, while 160 (about 37%) were given radiation doses higher than 54 Gy. At two years and five years post-treatment, rates of freedom from local-regional recurrence stood at 86.5% and 81.2%; avoidance of colostomy at 90.0% and 88.3%; and overall survival at 93.6% and 85.8%. Higher radiation doses or mitomycin-containing chemotherapy did not yield superior tumor control or survival. However, mitomycin regimens correlated with roughly 2.5-fold higher rates of severe (grade 3+) short-term side effects, and doses exceeding 54 Gy linked to approximately 2.6-fold greater long-term severe toxicities. Findings indicate that combining IMRT with cisplatin and a fluoropyrimidine offers an effective and tolerable strategy for SCCA, likely with reduced short-term adverse effects compared to mitomycin alternatives. Benefits from escalating radiation doses remain unproven and warrant additional prospective evaluation.
