Incidence, risk and survival outcomes of second primary malignancy among renal cell carcinoma survivors: A nested case-control study

Abstract Background: Second primary malignancy (SPM) challenges survival and surveillance protocols among renal cell carcinoma (RCC) survivors. The incidence, temporal patterns, survival outcomes, and risk factors of SPM after T1-4N0-1M0 RCC diagnosis need to be investigated. Method: A nested case-control study that was designed using the Surveillance, Epidemiology, and End Results database from 2004-15; A cohort of 6204 SPM were matched with a control group of 37224 non-SPM. Results: SPM shortens the overall survival (hazard ratio [HR], 1.34; 95% confidence interval [CI]: 1.28-1.42, P< 0.001). The median time interval to SPM was 54.5 months. The adjusted standardized incidence ratio (SIR) of SPM increases by survival time (SIR12~35-month: 12.04; SIR36~59-month: 12.67; SIR60~19-month: 16.08; SIR120+-years: 25.01, all P< 0.001), and decreased with age (SIR18~44-years: 86.68; SIR45~59-years: 26.95; SIR60~74-years: 12.43; SIR75+-years: 10.66, all P< 0.001). The second primary RCC onset, especially contralateral kidney, has the highest SIR (SIR: 54.6; 95%CI: 51.0~58.4) among all sites of SPM. Prostate cancer (29.8%) in male and breast cancer (23.5%) in female were the most common SPM site. Older age, black race, male gender, higher family income statues, papillary RCC, and lower TNM stage significantly increases the risk of SPMs diagnosis. A longer time to SPM interval positively associated with a higher tumor stage of a SPM onset (P trend <0.001). The overall survival since the SPM diagnosis was associated with SPM’s stages, site, and surgical treatment, but not associated with time-to-SPM. Conclusion: Collectively, our study described the epidemiological characteristics of SPM among RCC survivors and identified the independent predictors of the SPM onset and its survival outcomes, which provides the clinicians for patients consulting and long-term individual-, tailored site-, and time-specific surveillance to improve survival outcomes.