Resectability, conversion, metastasectomy and outcome according to RAS and BRAF status for metastatic colorectal cancer in the prospective RAXO study
Uutela, A., Osterlund, E., Halonen, P., Kallio, R., Ålgars, A., Salminen, T., Lamminmäki, A., Soveri, L.-M., Ristamäki, R., Lehtomäki, K., Stedt, H., Heervä, E., Muhonen, T., Kononen, J., Nordin, A., Ovissi, A., Kytölä, S., Keinänen, M., Sundström, J., . . . Osterlund, P. (2022). Resectability, conversion, metastasectomy and outcome according to RAS and BRAF status for metastatic colorectal cancer in the prospective RAXO study. British Journal of Cancer, 127(4), 686-694. https://doi.org/10.1038/s41416-022-01858-8
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British Journal of CancerAuthors
Date
2022Copyright
© 2022 the Authors
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.
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This investigator-initiated RAXO-study was supported by Finska Läkaresällskapet (2016, 2018, 2019, 2020, 2021, 2022); Cancer Foundation Finland (2019–2020, 2021, 2022–2023; Relander’s Foundation (2020–2022); the Competitive State Research Financing of the Expert Responsibility Area of Tampere, Helsinki and Turku (2016, 2017, 2018, 2019, 2020, 2021, 2022); Tampere University Hospital Funds (Tukisäätiö 2019, 2020; OOO 2020); and the Research Fund of Helsinki University Hospital (2019, 2020, 2021). The infrastructure with database and study nurses were partly supported by pharmaceutical companies (Amgen unrestricted grant 2012–2020, Eli Lilly 2012–2017, Merck KGaA 2012–2020, Roche Oy 2012–2020, Sanofi 2012–2017 and Servier unrestricted grant 2016–2020).

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