Prognostic Value of Fusobacterium nucleatum after Abdominoperineal Resection for Anal Squamous Cell Carcinoma

SIMPLE SUMMARY: The main prognostic factors of localized/locally advanced anal squamous cell carcinoma (ASCC) are insufficient to predict 10–20% of metastatic relapses. Fusobacterium nucleatum is among the most studied bacteria in digestive tract cancers and has been described as a poor prognostic factor in several digestive cancers. We retrospectively analyzed surgical samples from a homogeneous multicenter cohort of 166 patients with ASCC who underwent abdominoperineal resection. This study showed that F. nucleatum was an independent predictor of favorable overall survival and disease-free survival. This allowed the identification of a patient subgroup with a good prognosis (upper tercile). Our current work strengthens the new insight into the prognostic role of intratumoral F. nucleatum in cancer patients. Validation of these findings would allow to guide therapeutic strategies in dedicated trials by proposing intensification or de-escalation of systemic treatments and follow-up according to F. nucleatum loads. ABSTRACT: Main prognostic factors of anal squamous cell carcinoma (ASCC) are tumor size, differentiation, lymph node involvement, and male gender. However, they are insufficient to predict relapses after exclusive radiotherapy (RT) or chemoradiotherapy (CRT). Fusobacterium nucleatum has been associated with poor prognosis in several digestive cancers. In this study, we assessed the association between intratumoral F. nucleatum load and clinico-pathological features, relapse, and survival in patients with ASCC who underwent abdominoperineal resection (APR) after RT/CRT. We retrospectively analyzed surgical samples from a cohort of 166 patients with ASCC who underwent APR. F. nucleatum 16S rRNA gene sequences were quantified using real-time quantitative PCR. We associated F. nucleatum load with classical clinicopathological features, overall survival (OS), disease-free survival (DFS), and metastasis-free survival (MFS) using Cox regression univariate and multivariate analyses. Tumors harboring high loads of F. nucleatum (highest tercile) showed longer OS and DFS (median: not reached vs. 50.1 months, p = 0.01, and median: not reached vs. 18.3 months, p = 0.007, respectively). High F. nucleatum load was a predictor of longer OS (HR = 0.55, p = 0.04) and DFS (HR = 0.50, p = 0.02) in multivariate analysis. High F. nucleatum load is an independent favorable prognostic factor in patients with ASCC who underwent APR.