De-Escalation of Therapy for Patients with Early-Stage Squamous Cell Carcinoma of the Anus

Abstract

The incidence of squamous cell carcinoma of the anus (SCCA) is increasing, particularly in the elderly, with increased mortality in this age group. While the current standard of care for localized SCCA remains chemoradiation (CRT), completion of this treatment can be challenging with risks for severe acute and late toxicity. It remains unclear if full course CRT is required for the management of early-stage SCCA or if de-escalation of treatment is possible without compromising patient outcomes. Alternative therapies include radiation therapy alone or local excision for appropriate patients. Modifying standard CRT may also reduce toxicity including the routine use of intensity-modulated radiation therapy for treatment delivery, modification of treatment volumes, and selection and dosing of concurrent systemic therapy agents. Finally, we provide an overview of currently accruing prospective trials focused on defining the role of de-escalation of therapy in patients with early-stage SCCA.

Cure Rates According to Dose-Intensity of Chemoradiation in T2N0 Squamous Cell Carcinoma of the Anal Canal

“…The primary tumour and pelvis receive a dose 41.4 and 34.5 Gy for T1N0 and T2N0 disease, respectively, with concurrent mitomycin (single dose of 10 mg/m 2 ) and 1 cycle of infusional 5-FU/capecitabine. 15 The ACT-IV (NCT04640168) is a randomised phase II trial comparing reduced RT dose (41.4 Gy) to standarddose (50.4 Gy) during CRT for patients with T1N0 or T2N0 SCCA.…”

High dose rate brachytherapy in the management of anal cancer: A review

“…Dose de-escalation has been suggested for HPV positive cancers [28]. Presently, there are various prospective trials investigating de-escalation in HPV related anal cancers; these trials are assessing loco-regional failure rate (ACT3) or the ability to sufficiently control disease while improving health-related quality of life (QOL) (ACT4) [29]. At our institution we have successfully implemented lower-dose EBRT regimens for HPV-related anal cancers.…”

Local excision versus radical surgery for anal squamous cell carcinoma: a multicenter study in Japan

“…Additionally, CRT is a risk for secondary carcinogenesis [ 6 ]. Therefore, there is an argument that CRT may be over-treatment for early-stage anal cancer [ 7 ]. In fact, satisfactory long-term outcomes of local excision for cT1N0 anal cancer were recently demonstrated [ 8 – 12 ].…”