Treatment of stage I-III squamous cell anal cancer: a comparative effectiveness systematic review.

Troester A, Parikh R, Southwell B, Ester E, Sultan S, Greeno E, Arsoniadis E, Church TR, Wilt T, Butler M, Goffredo P. Treatment of stage I-III squamous cell anal cancer: a comparative effectiveness systematic review. Journal of the National Cancer Institute. 2025 Feb 1; 117(2):240-252.

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Abstract:

BACKGROUND: We sought to assess the effectiveness and harms of initial treatment strategies for stage I through III anal squamous cell anal cancer. METHODS: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials between January 1, 2000, and March 2024, for randomized controlled trials and nonrandomized studies of interventions comparing initial treatment strategies. Individual study risk of bias and overall strength of evidence were evaluated for a prespecified outcome list using standardized methods. RESULTS: We identified 33 eligible studies and extracted data. Six were deemed low to moderate risk of bias. Compared with radiation therapy alone, chemoradiation therapy (CRT) with 5-fluorouracil (5-FU) and mitomycin C probably shows a benefit in locoregional failure, disease-specific survival, and colostomy-free survival (moderate strength of evidence) yet may result in greater overall and acute hematological toxicity, with no difference in late harms (low strength of evidence). CRT with 5-FU plus mitomycin C may show a benefit in locoregional failure, disease-specific survival, and colostomy-free survival rates compared with 5-FU alone (low strength of evidence). CRT with 5-FU plus cisplatin vs 5-FU plus mitomycin C probably results in no differences in several effectiveness outcomes or overall acute or late harms and probably increases hematological toxicity with mitomycin C (moderate strength of evidence). Compared with CRT using capecitabine plus mitomycin C, CRT with capecitabine plus mitomycin C and paclitaxel may improve overall survival, disease-specific survival, and colostomy-free survival yet cause more acute harms (low strength of evidence). Evidence was insufficient for remaining comparisons. CONCLUSIONS: CRT with 5-FU plus mitomycin C or 5-FU plus cisplatin is likely more effective yet incurs greater acute hematological toxicity than radiation therapy alone or single-agent CRT. Adding paclitaxel to capecitabine plus mitomycin C may increase treatment efficacy and toxicity. Evidence is insufficient comparing posttreatment surveillance strategies and patient-reported outcomes, highlighting research opportunities.