Paraneoplastic Resolution Holds Prognostic Utility in Patients with Metastatic Renal Cell Carcinoma.

Simple Summary: This is the first comprehensive study to examine the impact of paraneoplastic syndrome (PNS) resolution on overall and cancer-specific survival in patients with metastatic renal cell carcinoma (mRCC). PNS can manifest as hematologic, metabolic, immunologic, or constitutional abnormalities, and their presence prior to surgery is associated with worse survival. The PNS we assessed were those previously described by Moldovan et al., including neutrophil–lymphocyte. We found that resolution of one or more PNS by one year after surgery was independently associated with improved overall survival and cancer-specific survival. Furthermore, patients categorized as favorable risk in current mRCC risk models (SCREEN, IMDC, MSKCC) did not experience PNS resolution more often than patients categorized as poor risk. This suggests that PNS resolution may provide distinct prognostic information to better risk stratify patients. Background/Objectives: The presence of paraneoplastic syndromes (PNS) in patients with renal cell carcinoma (RCC) is associated with worse survival; however, little is known about whether resolution of PNS after intervention has any prognostic value. We sought to determine if resolution of PNS by one year after cytoreductive nephrectomy was significantly associated with improved overall survival (OS) and cancer-specific survival (CSS). Methods: We retrospectively reviewed a prospectively maintained nephrectomy database for patients with any histology metastatic RCC (mRCC) who underwent nephrectomy between 2000 and 2022. Patients with the necessary laboratory studies available within 90 days before and by one year after surgery were included for study. PNS resolution was defined as an abnormal value compared to established laboratory cutoffs by one year after surgery. Multiple PNS in one patient was allowed, and resolution of each PNS was measured separately. OS and CSS were assessed using Kaplan–Meier curves and Cox proportional hazards models. Results: A total of 253 patients met inclusion criteria. A total of 177 patients (70.0%) met criteria for at least one PNS resolution by one year. Five-year OS and CSS rates were 15.7% and 36.2% for no PNS resolved, 24.5% and 31.6% for 1 PNS resolved, and 43.0% and 58.2% for ≥2 PNS resolved, respectively (p < 0.001). On multivariable analysis, no PNS resolution was associated with worse OS (HR 2.75, p < 0.001) and CSS (HR 2.62, p < 0.001) compared to ≥2 PNS resolved. Conclusions: Resolution of preoperative PNS abnormalities by one year following surgery is associated with improved OS and CSS in patients with mRCC. [ABSTRACT FROM AUTHOR]