76 Defining Young-Onset Renal Cell Carcinoma (YORCC): a Registry-Based Analysis of Incidence Trends

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Abstract Background While RCC typically arises in the 6th decade, the incidence of YORCC is rising globally. Studies investigating YO cancers, particularly YORCC, have been largely inconsistent in defining the age threshold, deriving the cutoff based on convention or prior literature. Herein, we aim to define the age cutoff for YORCC by examining incidence trends over time and evaluate these trends across different sociodemographic groups. Methods We analyzed population-based data from 21 National Cancer Institute SEER registries (2025 submission) between 2000 and 2023. Records from patients (pts) diagnosed at the age of 15 years (y) and older, with primary site of kidney (ICD-O-3 code: C64.9), and any RCC-specific ICD-O-3 morphological codes (8260/3, 8290/3, 8310/3, 8311/3, 8312/3, 8316/3, 8317/3, 8318/3, 8319/3 and 8320/3) were included. SEER*Stat Version 9.0.43.0 calculated incidence rates per 100,000 persons, age adjusted to the 2000 US Standard Population. The Annual Percent Change (APC) in incidence rates was computed using the weighted least squares method, and the Average APCs (AAPC) were computed using the Joinpoint Regression Program Version 5.4.0.0. The age cutoff was defined by comparing APCs – and AAPCs, where model fit permitted – and generating a difference variable (ΔAPC and ΔAAPC) between YORCC and non-YORCC (nYORCC) defined across sequential 5-year age thresholds (e.g. 40, 45, 50). The Monte Carlo Permutation method assessed parallelism for incidence trends and AAPCs across age and sociodemographic groups (sex, race, ethnicity and rural-urban residence), while two-sample Wald test compared APCs and AAPCs for age groups and RCC subtypes. Results We included 472,766 RCC records. An increasing incidence trend was observed in the whole RCC cohort over the study period (AAPC: 1.82%, 95% CI: 1.57-2.24). The relationship between sequential age cutoffs and ΔAPC demonstrated two local maxima with higher APCs for the young groups at the 25y cutoff (ΔAPC = 2.20%, 95% CI: 0.82-3.58) and between the ages of 40 (ΔAPC = 1.70%, 95% CI: 0.96-2.44) and 50y (ΔAPC = 1.60%, 95% CI: 1.17-2.03) (adjusted p < 0.05). Subsequent sensitivity analysis comparing the YORCC and nYORCC for the sequential age cutoffs of 45 and 50 demonstrated significantly different trends between the groups for both age cutoffs (cutoff 45y: YO AAPC: 2.89%, 95% CI: 2.21-3.57 vs nYO AAPC: 1.63%, 95% CI: 1.09-2.17; cutoff 50: YO AAPC: 3.08%, 95% CI: 2.49-3.69 vs nYO AAPC: 1.51%, 95% CI: 1.04-1.97) (pairwise parallelism p < 0.001), with significantly higher AAPC for the young groups (cutoff 45y: ΔAAPC: 1.26%, 95% CI: 0.39-2.13, p = 0.004; cutoff 50y: ΔAAPC: 1.58%, 95% CI: 0.82-2.34, p = 4.5x10-5). As such, the age cutoff separating YORCC and nYORCC was defined at 50y, despite the consistently higher incidence rates of nYORCC (29.6-43.3 per 100,000 persons) compared to YORCC (3-6.3 per 100,000 persons) over the study period. The YORCC group had significantly higher APC for clear-cell subtype than nYORCC (YORCC: 5.4%, 95% CI: 4.3-6.6; nYORCC: 3.8%, 95% CI: 2.9-4.8; p = 0.035), but not for papillary (p = 0.095) and chromophobe (p = 0.75) histologies. The AAPCs across different sociodemographic groups for both YO and nYORCC are presented in the Table. Conclusions This nation-wide analysis demonstrates an increasing trend in incidence of RCC diagnosis for people under the age of 50, while highlighting trend differences between races, ethnicities and rural-urban residences. Efforts to further characterize YORCC clinically and translationally are ongoing.

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