Prognostic impact and clinical management of pT4N0 colon cancer: data from a large, multicenter, international, real-world dataset

Background: T4 is one of the most important prognostic factors in localized colon cancer (CC), especially in stage II (pT4N0). However, the optimal adjuvant treatment in this subset of patients remains unclear. We present a large, multicenter, international, real-world analysis of pT4N0 CC patients. Patients and methods: A real-world database regarding clinicopathological characteristics of patients with stage II pT4N0 CC surgically removed between 2010 and 2021 was queried. Primary endpoints were overall survival (OS) and relapse-free survival (RFS), and analyses were adjusted on age (with a cut-off of 75 years) to reduce selection bias. Results: Our study included 492 patients; outcomes data were available for 390 patients. Median age was 73 years. Microsatellite status was assessed in 294 (75%), including 74 (25%) mismatch repair deficient (dMMR)/microsatellite instability (MSI). Adjuvant chemotherapy was prescribed in 204 patients (52%), mostly oxaliplatin-based (70%). After a median follow-up of 46.8 months, 6 months of adjuvant chemotherapy was associated with a significant improvement in OS [hazard ratio (HR) age-adjusted 0.22, P < 0.001] when compared with no adjuvant. The benefit was seen also with 3 months of adjuvant chemotherapy, even if the benefit was lower (HR age-adjusted 0.60, P < 0.001). Similar results were observed in terms of RFS, with a statistically significant benefit both in the 6-month group (HR age-adjusted 0.47, P = 0.001) and in the 3-month group (HR age-adjusted 0.71, P = 0.001). Considering the regimen and the duration of treatment, 6 months of oxaliplatin-based chemotherapy was associated with a significant improvement in both OS and RFS (P < 0.001). In univariate analysis, MMR status was not associated with OS nor RFS. Conclusions: T4 was confirmed to be a poor prognostic factor. Adjuvant chemotherapy provided a large benefit, with a significant reduction in risk of recurrence and death. The benefit was proportional to its duration, and oxaliplatin-based chemotherapy may be better than monotherapy.