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Julia Kohn*1, Alexander Troester1, Qi Wang2, Robert Madoff1, Imran Hassan3, Wolfgang B. Gaertner1, Schelomo Marmor1, Paolo Goffredo1
1University of Minnesota Academic Health Center, Minneapolis, MN; 2University of Minnesota Twin Cities, Minneapolis, MN; 3University of Iowa Hospitals and Clinics, Iowa City, IA

Introduction: Due to its rarity, anal adenocarcinoma (AA) does not have a standardized staging system. The tumor (T) stage of an adenocarcinoma arising from the anal canal could be based on depth of invasion, as for rectal adenocarcinoma, or on size, as in anal squamous cell carcinoma. We hypothesized that staging by adenocarcinoma histology, rather than anal location, would be most accurate in predicting survival of AA patients.

Methods: Adults with AA were identified in the Surveillance, Epidemiology, and End Results database between 2004 and 2019. Exclusion criteria were overlapping lesions of the anus/rectum, >1 lifetime diagnosis of cancer, and missing tumor size or extension. All patient stages were categorized according to the American Joint Committee on Cancer (AJCC) classifications of rectal adenocarcinoma (AJCC-rectum) and anal squamous cell carcinoma (AJCC-anus). Kaplan-Meier curves were used to determine 5-year overall (OS) and disease-specific survival (DSS) rates. Cox proportional hazard regressions, adjusting for age, gender, race, marital status, tumor grade, and treatment received, analyzed the association between prognosis and both overall and T stages.

Results: Of 424 patients, 55% were male, 63% were Caucasian, and 23% had distant metastases. Median age was 65 (interquartile ratio 53-75) years. Thirty-four percent of patients underwent chemoradiation (CRT) and abdominoperineal resection (APR), 15% CRT with local excision (LE), 26% CRT alone, 11% upfront APR, and 15% LE only. When patients were classified by AJCC-rectum staging, 36% had stage I disease, 25% stage II, and 23% stage III. Conversely, according to AJCC-anus, there were 19% stage I, 38% stage II, and 20% stage III patients. Both classifications included the same 97 patients (23%) with stage IV disease. The unadjusted 5-year DSS and OS were similar for early stages, while both classifications similarly differentiated more advanced disease (Figure 1). After adjustment, stages I and II maintained similar OS and DSS in both staging systems, while stages III and IV had significantly worse prognosis (Table 1). In contrast, when analyzing T stage alone (node-negative, non-metastatic patients), multivariable analyses demonstrated significant, incrementally lower OS and DSS for stage T1 to T4 for AJCC-rectum, but not for AJCC-anus (Table 1).

Conclusion: In this population-based cohort, neither staging system was able to accurately risk stratify stage I and II tumors, although both classifications appropriately differentiated the prognosis of more advanced disease. These observations suggest that a 3-tier localized, regional, and distant system could provide a more pragmatic option for prognostication. However, AJCC-rectum staging better discriminated between T stages, indicating that providers should consider utilizing this system in the clinical assessment of AA.

Figure 1. 5-year overall and disease-specific survival rates by AJCC-rectum and AJCC-anus staging systems (all patients, n=424).

Table 1. Multivariable analyses of 5-year overall and disease-specific survival by AJCC-anus and AJCC-rectum staging for overall and T anal and rectal stages. All are adjusted for age, gender, race, marital status, tumor grade, and treatment received.

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