2838 - Preserving Function with Induction therapy: High Local Control Rates for Locally Advanced Anal Cancer

Purpose/Objective(s): Anal squamous cell carcinoma (SSC) is primarily managed with radiotherapy with fluoropyrimidine (fluorouracil or capecitabine) and mitomycin. In patients with more advanced features—adjacent organ invasion, tumor size >5cm, or pelvic nodal disease—pooled analyses report 5 year local control (LC) of only 40–50%, with local failure often requiring APR (Gunderson et al., 2013). Prior attempts at induction therapy or dose escalation have shown inconsistent benefit and may increase toxicity (Vendrely et al., 2025). Carbo/Taxol has demonstrated tumoricidal activity with favorable toxicity in unresectable or recurrent disease (Rao et al., 2020 InterAAct Trial). We hypothesize that induction carbo/Taxol in locally advanced (LA) anal SCC (defined as T3-T4, N0-1, M0) could improve LC.

Materials/Methods: Single-institution, retrospective review (January 2010–December 2025). Relevant clinical variables, treatment regimen and responses were abstracted. Response was assessed by clinical exams, endoscopy and cross-sectional imaging. Patients receiving at least one cycle induction carbo/Taxol prior to definitive chemoradiotherapy were included. Interval response to induction therapy was assessed with MRI or PET/CT. CTCAE V5.0 was utilized in toxicity grading. Statistical analyses were performed in R (v4.4.2) via RStudio (Posit, PBC).

Results: In 400 patients with anal SCC, 33 met criteria for LA disease treated with induction therapy. Median age was 64.5 years (27 female, 6 male). Median craniocaudal tumor length was 6.97cm (range 3.5-17.1). Genitourinary invasion was the prostate/bladder in 2 patients, and the vagina in 21. Additional AJCC 9th edition staging is available is in Table 1. Patients received a median of 3 induction cycles (range 3-4). During induction two patients experienced =G3 toxicity (one Taxol-related pneumonitis, one neutropenic fever). Interval imaging by RECIST criteria showed progression in 2, mixed response in 2, stable disease in 2, and decreased tumor burden in 27. Mean primary tumor SUVmax decreased from 20.2 (7.7–33.9) to 9.41 (0–39.5). Definitive chemoradiotherapy consisted of 5-FU/MMC with 4500cGy to the elective pelvic nodes, and 5000-5400cGy to gross disease with a 1-2cm margin. At a median follow-up of 45 months (range 4–118), LC was 97%, with one local failure at 17 months, salvaged by APR (initially cT3N1a, primary tumor 14cm craniocaudally; pT1N0). 6 patients had upfront diverting colostomies due to anovaginal fistula or perforated anus; 4 underwent reversal an average of 18 months post treatment and maintained continence to date.

Conclusion: In this single-institution experience, induction carbo/Taxol prior to standard chemoradiation yielded excellent LC in LA anal SCC, with successful organ preservation and ostomy reversals in a subset of patients. Further investigation of induction carbo/Taxol as a strategy to enhance LC and organ preservation in LA anal SCC is indicated.