Salvage Abdominoperineal Resection for Locally Recurrent or Persistent Anal Squamous Cell Carcinoma after Definitive Chemoradiation.

Abstract

Initial treatment for patients with squamous cell carcinoma of the anal canal includes definitive chemoradiation. Salvage abdominoperineal resection (APR) is the treatment of choice for recurrent or persistent disease. Older studies suggest approximately 50% successful salvage of recurrent or persistent disease with APR. Risk factors for failure after salvage APR are incompletely characterized. Using a single institutional database, patients were identified who underwent salvage APR after definitive intensity-modulated radiotherapy-based chemoradiation between 2003 and 2022. Clinical and pathologic variables analyzed included age at APR, sex, race, HIV status, initial cT stage, initial cN stage, radiation dose, recurrent vs persistent disease, recurrent pT stage, recurrent pN stage, the presence of LVSI, PNI or <2mm surgical margins, and the use of either intraoperative radiation or another treatment modality in addition to APR. The log rank test was used to determine differences in time from APR to events (local recurrence, distant metastasis and death) based on clinical and pathologic variables. The Cox Proportional Hazard Model was used to perform multivariable analysis for all factors with a univariate P-value <0.1. Of 628 patients with anal squamous cell carcinoma, 50 (8.0%) were treated with abdominoperineal resection for locally recurrent (n = 29, 58%) or locally persistent (n = 21, 42%) disease. Median [interquartile range] follow up was 40.0 months [15.2-68.0 months] from APR. Median local recurrence-free survival was not reached; 1- and 2-year local recurrence-free survival was 81% (95% CI 72-92%) and 76% (64-89%). On multivariable analysis, pathologic T-stage of the recurrence (3.85 (1.07-13.9); P = .040), the presence of lymphovascular space invasion (9.1 (1.12-73.62); P = .038) and surgical margins <2mm (8.81 (2.11-36.73); P = .003) were all significantly associated with higher rates of local recurrence. Median distant metastasis-free survival was not reached; 1- and 2-year distant metastasis-free survival was 88% (81-98%) and 79% (67-92%). On multivariable analysis, only persistent (versus recurrent) local disease was significantly associated with higher rates of distant metastasis (1.23 (1.05-5.55) P = .043). Median overall survival was not reached; 1- and 2-year overall survival was 90% (81-98%) and 78% (65-90%). On multivariable analysis, only recurrent pT stage (T3/4 vs T1/2) was associated with higher rates of death (5.87 (1.02-33.65); P = .047). APR is a successful salvage modality for anal squamous cell carcinoma with recurrent or persistent disease after chemoradiation results. Patients with pT3/4 disease, lymphovascular space invasion, surgical margins <2 mm may be associated with higher re-recurrence rates and may benefit from more frequent monitoring or treatment escalation.