Clinicopathological features and prognosis of alpha‐fetoprotein‐producing colorectal adenocarcinoma

Aims Alpha‐fetoprotein (AFP)‐producing colorectal adenocarcinoma (AFPCRA) is uncommon, with obscure clinicopathological features and prognosis. Methods and Results In this retrospective comparison study on surgically resected colorectal adenocarcinomas (CRA, n = 2389), we investigated and compared clinicopathological and prognostic features between AFPCRA cases with elevated pre‐operative serum AFP levels, as the AFPCRA study group ( n = 49, 2.1%), and the exact sex‐, age‐ and stage‐matched CRA cases as the control group at a 1:2 ratio during the study period from 2011 to 2021. The AFPCRA group was further divided into low and high serum AFP‐level subgroups at the cut‐off of 8.4 ng/ml. Compared to the control group, the AFPCR group showed a significantly higher frequency in extramural venous invasion, intermediate/high tumour budding grade, poor tumour differentiation, liver and distant metastases, mixed and hepatoid adenocarcinomas. The 5‐year overall survival rate was significantly lower in the AFPCRA group (69.2%) than in the control (87.2%) ( P = 0.002). The high AFP‐level AFPCRA subgroup displayed a significantly higher prevalence of the left colon location than the low AFP‐level subgroup. Risk factors of overall survival for the AFPCRA group included lymphovascular, perineural and extramural venous invasion, poor tumour differentiation, tumour budding grade, distant metastasis, pN, pM and pathological summary stages, while distant metastasis was the only independent prognostic risk factor. Conclusions AFPCRA was rare and may be associated with aggressive behaviour and poor prognosis. These preliminary findings in this single‐centre study remain to be validated by future studies with larger samples.