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

• Published in: British journal of cancer Vol. 127; no. 4; pp. 686 - 694
• Main Authors: Uutela, Aki, Osterlund, Emerik, Halonen, Päivi, Kallio, Raija, Ålgars, Annika, Salminen, Tapio, Lamminmäki, Annamarja, Soveri, Leena-Maija, Ristamäki, Raija, Lehtomäki, Kaisa, Stedt, Hanna, Heervä, Eetu, Muhonen, Timo, Kononen, Juha, Nordin, Arno, Ovissi, Ali, Kytölä, Soili, Keinänen, Mauri, Sundström, Jari, Nieminen, Lasse, Mäkinen, Markus J., Kuopio, Teijo, Ristimäki, Ari, Isoniemi, Helena, Osterlund, Pia
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2022; Nature Publishing Group
• Subjects: 692/4028/546; 692/4028/67/1504/1885; 692/4028/67/322; 692/53/2422; Biomedical and Life Sciences; Biomedicine; Cancer Research; Colorectal cancer; Colorectal carcinoma; Drug Resistance; Epidemiology; Medicin och hälsovetenskap; Metastases; Metastasis; Molecular Medicine; Oncology; Patients; Survival
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/s41416-022-01858-8

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 BRAF wt), 529 with RAS mutated ( RAS mt) and 88 with BRAF mutated ( BRAF mt) mCRC. Metastatic prevalence varied between the RAS and BRAF wt/ RAS mt/ BRAF mt 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 RAS a and BRAF wt/ RAS mt/ BRAF mt, 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 BRAF wt/ RAS mt/ BRAF mt, 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 BRAF wt 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