Sex-based differences in peri-operative and long-term oncologic outcomes after primary surgical treatment for kidney cancer: A comprehensive analysis from a high-volume tertiary center.

BACKGROUND

Sex-related differences in kidney cancer incidence and tumor biology are well established; however, their impact on peri‑operative performance and long-term oncologic outcomes after surgery remains incompletely characterized. We evaluated the association between biological sex and surgical, pathological, and oncologic outcomes in a large contemporary cohort.

MATERIALS AND

METHODS

We retrospectively analyzed a prospectively maintained institutional database including patients undergoing partial or radical nephrectomy as primary treatment for kidney cancer at a high-volume tertiary center (1987-2024). Peri-operative outcomes, adverse pathological features, and long-term oncologic endpoints were compared according to biological sex. Multivariable regression models were used to adjust for baseline clinical, surgical, and tumor-related confounders. Survival outcomes were assessed using Kaplan-Meier estimates and Cox proportional hazards models. In addition, a sensitivity analysis restricted to patients treated between 2005 and 2020 (n = 2,227) was performed to evaluate the robustness and contemporary applicability of the findings.

RESULTS

Overall, 3,956 patients were included, of whom 30.5% were female. After multivariable adjustment, male sex was independently associated with longer operative time (β: 13, 95% confidence interval [CI] 6.3-19; P < 0.001) and a higher risk of post-operative acute kidney injury (odds ratio [OR] 1.49, 95% CI 1.21-1.84; P < 0.001), but not with major complications, peri‑operative transfusions, or prolonged length of stay (all P > 0.5). From a pathological standpoint, male patients were more likely to harbor high-grade tumors (OR 1.52, 95% CI 1.19-1.96; P = 0.001) and tumor necrosis (OR 1.38, 95% CI 1.10-1.75; P = 0.006). While biological sex was not independently associated with relapse-free, progression-free, or overall survival (all P > 0.1), male patients exhibited a significantly higher risk of progression at unfavorable metastatic sites (hazard ratio 1.78, 95% CI 1.09-2.89; P = 0.02). Importantly, these findings showed consistent directionality and statistical significance in the contemporary surgical era sensitivity analysis.

CONCLUSIONS

Biological sex emerged as a relevant determinant of peri‑operative outcomes, tumor aggressiveness, and patterns of disease progression in surgically treated kidney cancer patients. Male sex was independently associated with less favorable peri‑operative metrics, adverse pathological features, and a higher risk of progression at unfavorable metastatic sites, although these differences did not independently translate into worse long-term relapse-free, progression-free, or overall survival.