Analysis of classical high risk factors in stage III colon cancer: Experience at University Hospital Ramon y Cajal (UHRyC)
Authors: J. Serrano Domingo, R. Martín Huertas, A. Barquín García, E. Corral de la Fuente, C. Saavedra Serrano, M. Villamayor Delgado, O. Martínez Saez, F. Longo Muñoz, V Pachón Olmos, M. Rodriguez Garrote, M. Vaz, P Reguera Puertas, R. Fuentes, A. Carrato, R. Ferreiro Monteagudo
Journal: Annals of Oncology (2018)

Introduction: In colon cancer (CC), surgery is a curative treatment but, because of recurrence risk factors, postoperative adjuvant chemotherapy (AC) is widely accepted, at least for stage III. However, the benefit in stage II remains uncertain and indication of AC is based on risk factors. Nevertheless, the role of these high-risk factors (HRF) in stage III it is not clear. Methods: We conducted an observational unicentric retrospective study. Patients with stage III resected CC between 2009 and 2014 were identified, and data was collected for predefined variables including patients and tumor characteristics, treatment procedures and oncological outcomes. Univariate analyses were performed for classic stage II HRF in patients with stage III CC, and those with a p < 0.05 were incorporated in a multivariant model. We analyzed the relapse free survival (RFS) and overall survival (OS) rates according to the presence of at least one classic HRF. Finally, we studied the benefit of AC on patients depending on the presence or absence of risk factors. Cox regression was employed for the analysis. Stata 13.1 was used for the statistical analysis. Results: 268 patients with stage III CC were identified. 53.16% were men. Median age was 77 years (range 28-97). Most patients received AC (65.43%) most of them with oxaliplatin (78.86%). 71.38% had at least one HRF. In univariate analysis for RFS the perineural infiltration and the KRAS mutation (KRASm) were significant (hazard ratio (HR) 1.88 and 2.1 respectively). We incorporated them in a prognostic multivariate model were KRASm was identified as an independent risk factor for stage III (HR 3.17). On the other hand for OS, no HRF were significant. For RFS, patients with at least one HRF receiving AC had benefit (HR 0.43, p < 0.001), whereas there was no benefit in those without HRF (HR 0.7, 95% CI 0.26-1.86, p 0.48). For OS, both patients with at least one HRF and those without any of them, obtained benefit with AC (HR 0.16, p < 0.001 and HR 0.21, p 0.008). Oxaliplatin based chemotherapy showed benefit in terms of RFS in those patients with at least one risk factor (HR 0.38 p 0.006) whereas no benefit was obtained in those without any HRF (HR 1.69, 95% CI: 0.37-7.73, p 0.497). For OS, the addition of oxaliplatin to fluoropyrimidines had benefit in patients with any HRF (HR 0.25, p 0.02), and there is a trend to improve OS in those with none of the HRF (HR 0.12, p 0.085). Conclusion: Patients with at least one HRF, benefit from AC in terms of RFS and OS, especially those receiving oxaliplatin based treatment. In those without HRF, the role of AC is not clear in reducing the risk of relapse even with the addition of oxaliplatin. In these patients, there is benefit in terms of OS with AC, but oxaliplatin does not seem to be a determinant.