Ambispective registry study reveals comparable survival but higher toxicity in females with metastatic renal cell carcinoma, highlighting potential age- and hormone-related differences.
Background Sex-related biological differences may affect cancer immunity and outcomes with immune checkpoint inhibitors (ICIs) in patients with metastatic renal cell carcinoma (mRCC). This sub-analysis aimed to explore sex-based differences in a real-world cohort of patients with mRCC treated with first-line systemic therapy within the Meet-URO 33 (REGAL) study. Methods The Meet-URO 33 study is a multicentre ambispective registry collecting real-world data on patients with mRCC. Clinical-pathological features, haematological parameters, toxicities, and outcomes were compared by sex and age (< 50 vs ≥ 50 years). Results Among 1560 patients, 401 were females, and 1159 were males. Females presented with lower BMI (≤ 25 kg/m2, 52% vs 43%, p = 0.008) and lower median NLR (2.8 vs 3.1, p = 0.005), and had worse baseline characteristics, such as liver metastases (18% vs 11%, p = 0.002) and sarcomatoid variant (20.3% vs 14.5%, p = 0.025). Grade 3–4 adverse events (AEs) were more frequent in females (35% vs 28%, p = 0.012), but no sex-related differences emerged in the pattern of AEs and discontinuation rates. No significant differences were observed in PFS (14.8 vs 17.6 months) and OS (39.3 vs 39.7 months). Females < 50 years experienced a shorter PFS (8.5 vs 19.6 months, HR 2.02, p = 0.009), Fig 1. In multivariable Cox complete-case analyses, sex was not independently associated with either PFS (HR 1.21, 95% CI: 0.97–1.51, p = 0.099) or OS (HR 1.16, 95% CI: 0.87–1.55, p = 0.307), and sensitivity analysis based on multiple imputation produced consistent results. Conclusions Female patients with mRCC presented with more adverse baseline features and experienced higher severe toxicity rates, although PFS and OS were comparable to male patients. However, multivariable analyses demonstrate that sex does not have an independent prognostic value. Subgroup analysis in female patients aged < 50 years showed worse PFS, suggesting a potential hormonal influence warranting further investigation. Stronger female representation and translational research are needed to guide sex-tailored strategies in advanced RCC. Acknowledgements The authors thank Meet-URO33 centres and investigators.
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Ronzoni et al. (2026) studied this question.