Resectability, conversion, metastasectomy and outcome according to RAS and BRAF status for metastatic colorectal cancer in the prospective RAXO study

Abstract

Background Outcomes after metastasectomy for metastatic colorectal cancer (mCRC) vary with RAS and BRAF mutational status, but their effects on resectability and conversion rates have not been extensively studied. Methods This substudy of the prospective RAXO trial included 906 patients recruited between 2011 and 2018. We evaluated repeated centralised resectability assessment, conversion/resection rates and overall survival (OS), according to RAS and BRAF status. Results Patients included 289 with RAS and BRAF wild-type (RAS and BRAFwt), 529 with RAS mutated (RASmt) and 88 with BRAF mutated (BRAFmt) mCRC. Metastatic prevalence varied between the RAS and BRAFwt/RASmt/BRAFmt groups, for liver (78%/74%/61%), lung (24%/35%/28%) and peritoneal (15%/15%/32%) metastases, respectively. Upfront resectability (32%/29%/15%), conversion (16%/13%/7%) and resection/local ablative therapy (LAT) rates (45%/37%/17%) varied for RASa and BRAFwt/RASmt/BRAFmt, respectively. Median OS for patients treated with resection/LAT (n = 342) was 83/69/30 months, with 5-year OS-rates of 67%/60%/24%, while systemic therapy-only patients (n = 564) had OS of 29/21/15 months with 5-year OS-rates of 11%/6%/2% in RAS and BRAFwt/RASmt/BRAFmt, respectively. Resection/LAT was associated with improved OS in all subgroups. Conclusions There were significant differences in resectability, conversion and resection/LAT rates according to RAS and BRAF status. OS was also significantly longer for RAS and BRAFwt versus either mutant. Patients only receiving systemic therapy had poorer long-term survival, with variation according to molecular status. Clinical trial registration NCT01531621/EudraCT2011-003158-24

Impact of Primary Tumor Location on Demographics, Resectability, Outcomes, and Quality of Life in Finnish Metastatic Colorectal Cancer Patients (Subgroup Analysis of the RAXO Study)

“…Right colon PTL was, as discussed above, associated with a higher incidence of BRAF mt and dMMR, and also high RAS mt rates, which were associated with lower metastasectomy rates [ 7 , 43 , 44 ]. This is not unexpected, since BRAF mt patients often have metastases in organs considered unresectable, such as the peritoneum and distant lymph nodes, while RAS mt patients have metastases in lungs and brain.…”

Resectability and resection rates of colorectal liver metastases according to RAS and BRAF mutational status: prospective study

“…RAXO was a prospective, investigator-initiated, nationwide Finnish study (NCT01531621, EudraCT 2011-003158-24) that included 1086 patients with metastatic colorectal cancer between 2012 and 2018. The main protocol 12 , liver metastases group 13 , and RAS / BRAF mutations in studies of metastatic colorectal cancer 14 have been published previously. This substudy included patients with known RAS/BRAF status and CRLMs.…”

Colorectal Cancer Pulmonary Metastasectomy: When, Why and How

“…The selection of these two settings of patients is very important due to the different median survival rates [57]. Molecular characterization of the tumor, that is, baseline RAS/BRAF status-MMR status, seems to be associated with different metastatic profiles at baseline, as well as with resectability rates and survival rates [58]. Lung metastases, for example, are more common among RAS mutant patients.…”