Prognostic impact of anal cancer morphology on survival and local recurrence: A 20-year regional cohort study.

aimThe relationship between macroscopic tumour morphology and clinical outcomes has previously been demonstrated for malignant melanoma and gastric cancers, but not for anal squamous cell cancer (ASCC). This study investigated the effect of the morphology of ASCC on oncological outcomes.

methodsThe morphology of all ASCC patients presenting between 2003 and 2022 was analysed retrospectively and classified as Exophytic, Ulcerated or Mixed. The primary outcome was 5-year overall survival (OS). Secondary outcomes were complete response to treatment, local recurrence (LR) and 5-year disease-free survival (DFS).

resultsOf 622 patients referred to the anal MDT, 515 were included for analysis: 290 exophytic, 179 ulcerated and 46 mixed morphology. Ulcerated morphology was associated with a significantly lower percentage of patients surviving at 5 years compared to exophytic and mixed groups (25.1% vs. 67.9% vs. 65.2% p < 0.001). Ulcerated and mixed morphology patients presented with significantly larger tumours (T4- 30.7% vs. 28.3% vs. 10.0% p < 0.001) and greater nodal involvement (N2- 26.3% vs. 17.2% vs. 15.2% p = 0.042). Exophytic morphology patients had significantly greater complete response at 95.9%, compared to 82.6% for mixed and 45.8% for ulcerated tumours (p < 0.001). Morphology remained significant in both univariable and multivariable Cox regression models across 5-year OS, DFS and LR. Ulcerated [HR 5.160 (3.338-7.979) p < 0.001] and mixed morphology [HR 2.299 (1.179-4.482) p = 0.015] had significantly worse risk of 5-year overall survival compared to exophytic morphology.

conclusionUlcerated morphology is associated with advanced tumours, poor response to chemoradiotherapy, resulting in a higher incidence of recurrent disease and worse overall- and disease-free survival.