Table 2.

Summary of current de-escalation studies for early-stage squamous cell carcinoma of the anus.

Study	Key Inclusion Criteria	Study Design/Treatment	Primary Endpoint
DECREASE (NCT04166318)	T1–2 (with tumor size ≤4 cm) N0 anal canal or anal margin squamous cell carcinoma; specific radiographic criteria for lymph node evaluation.	Randomized phase II in 1:2 fashion to standard-dose CRT vs. deintensified CRT. Doses of RT based on T stage.	To determine if deintensified CRT results in 2-year disease control ≥85% while improving health-related quality of life compared to standard CRT.
ACT 3 (ISRCTN88455282)	T1 N0 anal margin squamous cell carcinoma treated with local excision.	Nonrandomized phase II: patients with tumor margins >1 mm will undergo observation, while those with margins ≤1 mm will receive adjuvant CRT.	To assess the 3-year locoregional failure rate.
ACT 4 (ISRCTN88455282)	T1–2 (with tumor size ≤4 cm) N0 anal canal or T2 (with tumor size ≤4 cm) N0 anal margin squamous cell carcinoma.	Randomized phase II in 1:2 fashion to standard-dose CRT vs. deintensified CRT.	To assess the 3-year locoregional failure rate.