Impact of primary tumor sidedness on survival after resection of colorectal liver metastases (CRLM).

Abstract

694 Background: The impact of primary tumour sidedness has recently been demonstrated in patients with metastatic colorectal cancer (mCRC). Differences in right (R) versus left (L) sided mCRC may be due to differences in consensus molecular subtyping. Clinically predictive mutations in ras, ( kras, nras and braf) may also help drive some of the differences in outcome. However, patients with mCRC who undergo surgical resection of CRLM often have a good prognosis. The aim of this study was to assess the impact of tumour sidedness on OS after resection of CRLM. Methods: Patients who underwent resection of CRLM in the province of Alberta, Canada were identified from 2004-2016. Tumour sidedness was determined by chart review, with R from the cecum to transverse and L from splenic flexure to sigmoid. Where available, ras mutational status was collected. OS was measured from the time of CRLM resection to death or last follow-up using the Kaplan-meier method. R and L were compared using the log-rank test and a Cox regression model. Results: 471 patients were identified who underwent resection of CRLM for mCRC, including 204 R and 267 L. Median age was 65, 63% male, with 54% synchronous metastatic disease, and 67% with a Charleson comorbidity index of 0. All ras wildtype was present in 22% of cases, any ras mutation was detected in 21% and 57% were unknown at the time of analysis. The median OS of R was 45 months, compared to 72 months for L, log-rank p = 0.01. After adjusting for potential confounders with a Cox-proportional hazard model, R compared to L remained significant, with a HR of 1.4 (95% CI 1.0-1.9, p = 0.02). ras mutational status was also significant for ras mutant, HR 2.4 (95% CI 1.7-3.3) and ras unknown HR 2.2 (95% CI 1.5-3.1) compared to ras wildtype p < 0.01. Conclusions: Primary tumour sidedness continues to have an impact on OS in mCRC, even when disease is managed surgically with resection of CRLM. Though limited by numbers, the impact remained significant even after controlling for potential confounders, including ras mutational status. Additional ras testing is underway. Further molecular classification may provide a biologic rationale for the observed differences.

Is primary sidedness a prognostic factor in patients with resected colon cancer liver metastases (CLM)?

“…17 In the two studies from the United States, the proportion of patients with right-sided colon tumors was higher than that reported in our study (43.3% and 36%, respectively). 15,16 In turn, the study from Japan reported a R:L tumor ratio similar to that of our case series (15.6%). It is possible that differences in the results are because of differences in the selection criteria; however, the lack of information on these populations limits conclusions on the subject.…”

“…Few studies to date evaluated cases of resected metastatic disease. The three studies presented at the ASCO 2017 Gastrointestinal Cancers Symposium demonstrated the impact of sidedness of tumor origin on OS alone, [15][16][17] and in the study from Japan, this impact was less evident and was observed only after the Cox regression model was fit to the confounding factors (UV: P = 0.547; MV: P = 0.047). 17 In the two studies from the United States, the proportion of patients with right-sided colon tumors was higher than that reported in our study (43.3% and 36%, respectively).…”

“…Few studies to date have evaluated patients with resected metastatic disease. Retrospective analyses presented at the ASCO 2017 Gastrointestinal Cancers Symposium (including two American populations and one Japanese population) considered patients who underwent resection of liver metastases, and the results suggest that patients with right‐sided colon tumors had an inferior overall survival (OS) but no significant difference in disease‐free survival (DFS) . However, these results are recent have not yet been applied in clinical practice.…”