Rising Trends of Aggressive Renal Cell Carcinoma Among Younger Adults: Insights From the National Cancer Database

To evaluate trends, and characteristics of renal cell carcinoma (RCC) in younger adults, as its rise has been primarily attributed to increasing incidental discovery of small renal masses in older adults.

We utilized the National Cancer Database to examine RCC patients aged 20-39 years between 2004 and 2021. Annual Average Percent Change (AAPC) was estimated via negative binomial regression. Aggressive RCC was defined as pT3+, high-grade (G3/G4), pN1, or metastatic disease. Logistic regression identified risk factors for aggressive RCC. Kaplan-Meier and Cox models assessed survival impact.

Among 30,849 RCC cases, 8,465 (27.45%) were classified as aggressive RCC. The number of diagnosed cases increased over time (AAPC: 3.53%, P < .001), with aggressive RCC increasing at a similar rate (AAPC: 3.58%, P < .001). Compared to clear cell RCC, papillary (OR = 1.49, P < .001), chromophobe (OR = 1.14, P = .006), collecting duct (OR = 35.68, P < .001), and RCC NOS (OR = 1.51, P < .001) had higher odds of aggressive RCC. Black (OR = 1.53, P < .001) and Asian/Pacific Islander patients (OR = 1.51, P < .001) were more likely to present with aggressive RCC compared to White patients. Uninsured (OR = 1.18, P = .001) and unknown insurance status patients (OR = 1.49, P < .001) had significantly higher odds of aggressive RCC compared to privately insured patients. At 120 months, survival was significantly lower for aggressive vs nonaggressive RCC (65.0% vs. 91.7%, P < .001). The negative impact of aggressive RCC on survival was attenuated in patients aged ≥ 35 years (HR = 0.78, P = .001) CONCLUSION: Rising RCC cases in younger adults are accompanied by an increase in aggressive disease, not attributable to stage migration. The drivers for this rise are unclear and demand more investigation.