Impact of gender on demographics, resectability, resections, systemic treatment, adverse events and outcomes in metastatic colorectal cancer (mCRC) patients (RAXO-study)

Gender impacts tumour sidedness, RAS/BRAF mutations and adverse events, but data on resectability and conversion rates and outcomes are scarce. The prospective Finnish real-life RAXO study included 1086 patients 2012-2018 (Osterlund et al TLRHE 2021). We assessed repeated centralized resectability in mCRC, and overall survival (OS), adverse events, and Quality of life (QoL) with 15D after metastasectomy, local ablative therapy (LAT) and systemic therapy. Bonferroni corrected ꭓ2 <0.05 denoted with*. Kaplan-Meier estimates and Cox regression were analysed. Males (n=656, 60%) versus females (n=430) had more comorbidities, rectal primaries, liver metastases, or RAS mutations*. Females had more right-sided primaries, poorly differentiated tumours, peritoneal metastases, rare metastases, BRAF mutations, MSI-H, anaemia, thrombocytosis, elevated CRP or ALP*. No differences were seen for age, ECOG PS, leucocytosis, lung, or lymph node metastases. Upfront resectable were 28/29% of males/females, borderline 17/16%, and non-resectable 55/55%. In upfront local vs centralised assessment resectability was underestimated in 39% of both genders. Successfully converted were 19/16%. R0/1-resections were performed in 30/30%, R2-resection/LAT in 7/7%; with liver procedure in 31/27%, lung 8/7%, cytoreductive 2/8%*, and rare metastasectomies 5/10%*. Median OS was 30.2/29.4 months (HR 1.03, CI 95% 0.89-1.19). OS was similar in R0/1-resected, R2/LAT, or “Systemic only” groups. Gr 5 toxicity was seen in 1.1/0.5%. Worst haematologic toxicity was gr 3-4 in 26/34%* and non-haematologic gr 3-5 in 62/66%, with more gr 3-4 anaemia, neutropenia, and nausea in females. Mean QoL with 15D during neoadjuvant therapy was 0.91/0.86*, <6 months from resection 0.90/0.85*, 6-18 months 0.91/0.91, >18 months 0.89/0.90, and during 1st line systemic 0.86/0.87. Sidedness, RAS/BRAF mutations, MSI-H, and metastatic sites and thus metastasectomies differed between genders. Resectability and conversion rates were similar. Resection/LAT was performed in 37% of both genders, with excellent and similar survival. Adverse event differences were noted.