Local Recurrence Rates in Locally Advanced Rectal Cancer Are Higher with KRAS Codon 13 Mutations

Despite advances in oncology regimens and standardization of technical approaches such as total mesorectal excision (TME), local recurrences (LR) remain a significant concern in rectal cancer. This may be due to the complex interplay of genetic mutations driving the disease progression, leading to recurrence associated morbidity and mortality. The association of KRAS mutations on local recurrences in locally advanced rectal cancer (LARC) patients has been less investigated.

Patients from a single-center retrospective database with LARC (2018-2023) were identified and divided into two cohorts: KRAS mutated and KRAS wild-type. A propensity score was used to match the two groups, adjusting for cT/pT stage, tumour grade, extra-mural vessel invasion, lymphovascular/perineural invasion, surgical margins, TME quality, tumour budding, neoadjuvant/adjuvant radiotherapy. Propensity score matching was assessed with Chi-squared tests. Univariate Cox regression analyses were performed to assess KRAS mutations' influence on LR.

136 patients were included (68 KRAS mutated; 68 KRAS wild-type). The overall LR rate was 8.1%. Adjusted Cox regression analysis revealed that the mutations in codon 13 of KRAS (G13D/G13C) were a significant risk factor for LR (HR = 7.06, p-value = 0.001), with a 33.3% LR rate in those patients. Conversely, other KRAS mutations did not appear to be risk factors for LR (p-value > 0.05).

This study suggests codon 13 KRAS mutations may be associated with LR in LARC. However, given the small number patients and events, these findings should be cautiously interpreted until confirmed by larger studies. Preoperative genetic testing for KRAS mutations is suggested to enhance risk stratification.