The prognostic impact of RAS on overall survival following liver resection in early versus late-onset colorectal cancer patients

Abstract

Background The impact of molecular aberrations on survival after resection of colorectal liver metastases (CLM) in patients with early-age-onset (EOCRC) versus late-age-onset colorectal cancer (LOCRC) is unknown. Methods Patients who underwent liver resection for CLM with known RAS, BRAF and MSI status were retrospectively studied. The prognostic impact of RAS mutations by age was analysed with age as a categorical variable and a continuous variable. Results The study included 573 patients, 192 with EOCRC and 381 with LOCRC. The younger the age of onset of CRC, the greater the negative impact on overall survival of RAS mutations in the LOCRC, EOCRC, and ≤40 years (hazard ratio (HR), 1.64 (95% confidence interval (CI), 1.23–2.20), 2.03 (95% CI, 1.30–3.17), and 2.97 (95% CI, 1.44–6.14), respectively. Age-specific mortality risk and linear regression analysis also demonstrated that RAS mutations had a greater impact on survival in EOCRC than in LOCRC (slope: −4.07, 95% CI −8.10 to 0.04, P = 0.047, R2 = 0.08). Conclusion Among patients undergoing CLM resection, RAS mutations have a greater negative influence on survival in patients with EOCRC, more so in patients ≤40 years, than in patients with LOCRC and should be considered as a prognostic factor in multidisciplinary treatment planning.

Impact of Age of Onset on Survival after Hepatectomy for Patients with Colorectal Cancer Liver Metastasis: A Real-World Single-Center Experience

“…Surgery remains the cornerstone of potentially curative treatment for CRLM. In light of the prognostic effect of age after hepatectomy, our results were in conflict with previous studies [ 19 , 20 ]. Our study showed that the prognosis of early-onset patients with CRLM is worse than that of IOCRLM.…”

“…Numerous studies have shown that RAS mutation is associated with poorer survival following curative resection of CRLM [ 14 , 29 , 30 ]. However, some studies have recently suggested that RAS mutations have different roles when predicting prognosis in CRLM with distinct clinical characteristics [ 20 , 31 ]. Similar to previous reports, our study also showed that RAS mutation did not have the same prognostic effect among patients of different ages [ 20 , 32 ].…”

“…Several retrospective studies have suggested that older people have a poorer prognosis than younger people [ 17 , 18 ], while another study reported that age above 60 years was not associated with poorer long-term survival [ 19 ]. In addition, Alexandre et al found that early-onset CRLM (EOCRLM) demonstrated comparable long-term survival to late-onset CRLM (LOCRLM) and showed that age may affect the prognostic value of RAS mutations [ 20 ].…”

Efficacy of neoadjuvant chemotherapy for initially resectable colorectal liver metastases: A retrospective cohort study

“…Second, its retrospective nature introduces the inevitable risk of selection bias, which could not be completely eradicated, despite using propensity score matching to reduce confounding by indication. Lastly, it has been reported that molecular biological factors, such as RAS status and microsatellite instability, are prognostic[ 20 , 21 ]. However, this information was unavailable in the present study.…”

The reality of early-onset colorectal cancer: highlighting the needs in a unique but emerging population

“…Additionally, Jácome et al . showed a greater negative impact of certain biomarkers for EOCRC in patients with CRC liver metastectomy ( 23 ) Analyses such as these and the fact that traditional standard of care therapy was studied in an older population, practitioners often took the approach of providing more aggressive treatment strategies (front-line triplet chemotherapy; more metastatic surgical approaches; overtreatment via adjuvant therapy). Kneuertz et al .…”