Perioperative and Clinicopathologic Outcomes of Patients with Young-Onset Renal Cell Carcinoma.

INTRODUCTION Young-onset renal cell carcinoma (RCC) exhibits distinct clinicopathologic features. We retrospectively compared outcomes and survival dynamics between young- and older-onset RCC cohorts. PATIENTS AND

Methods

We included RCC patients undergoing partial or radical nephrectomy (2015-2024), categorized as young-(≤ 46 years) or older-onset (> 46 years) based on age at surgery. Outcomes included recurrence-free survival (RFS), overall survival (OS), metastasis-free survival (MFS), and cumulative incidence of RCC-related deaths. Chi-squared/Fisher's and Wilcoxon rank sum test were used for intergroup comparisons, Kaplan-Meier and log-rank tests for estimating oncologic outcomes, and multivariable Cox proportional hazards models for identifying predictors of OS/RFS.

Results

Of 812 patients, 109 (13%) had young-onset and 703 (87%) older-onset RCC. Young-onset patients showed higher 5-year OS (92.4% vs. 80.9%). Clinical T2 stage showed worse OS (HR 2.46 [95% CI, 1.53, 3.97]) and RFS (HR 2.81 [95% CI, 1.64, 4.83]). Obesity (HR 0.50 [95% CI, 0.32, 0.79] showed improved OS (all P < .05). Non-RCC mortality was significantly higher in older-onset patients at 1 and 5 years (3.6% vs. 14% and 0.97% vs. 6.3%) compared to young-onset patients. Among older-onset patients, obesity (BMI ≥ 30) demonstrated higher OS at 1 and 5 years (95.5% vs. 94.3% and 84.7% vs. 78.1%) (P = .006). Young-onset patients had a significantly higher frequency of germline alterations in FANCI, POLD1, PTCH1, and RINT1 genes (all P < .05).

Conclusions

Young-onset RCC patients demonstrated higher OS and comparable RFS and MFS to patients with older-onset RCC. Obesity was associated with improved OS, suggesting a potential role of metabolic reserve in this group.