Laboratory paraneoplastic syndrome resolution is associated with reduced recurrence and improved survival in non-metastatic renal cell carcinoma

In patients with paraneoplastic syndrome (PNS) and non-metastatic renal cell carcinoma, complete tumor resection/non-recurrence should theoretically result in PNS resolution. This study aims to evaluate whether postoperative PNS resolution/non-resolution is associated with recurrence and/or survival in non-metastatic renal cell carcinoma (RCC).

Following institutional review board approval, the nephrectomy database at our institution was reviewed for patients with non-metastatic RCC and at least 1 documented laboratory-based PNS undergoing nephrectomy between 2000 and 2022. PNS resolution was defined as the normalization of ≥1 PNS-related laboratory abnormality within 30 days to 1-year post-nephrectomy. Primary endpoints were 5-year and all-time disease-free survival (DFS) and overall survival (OS). Kaplan-Meier curves were illustrated and multivariable Cox proportional hazards models adjusted for relevant confounders.

A total of 473 patients met inclusion criteria, 303 (64.1%) of which demonstrated postoperative PNS resolution. PNS non-resolution was associated with a 1.60-fold (HR 1.60, 95%CI 1.01-2.55, P = 0.046) increased in 5-year recurrence and a 2.64-fold (HR 2.64, 95%CI 1.47-4.75, P = 0.001) increase in 5-year all-cause mortality. PNS non-resolution was associated with a 1.40-fold (HR 1.40, 95%CI 1.01-1.93, P = 0.041) increase in study period recurrence and a 1.63-fold (HR 1.63, 95%CI 1.14-2.32, P = 0.008) increase in study period all-cause mortality.

In this analysis of patients with paraneoplastic syndrome and non-metastatic RCC, paraneoplastic syndrome non-resolution was independently associated with poor 5-year/all-time DFS and OS. This association maintained significance despite patients with PNS resolution demonstrating higher grade/stage tumors. Validation of our findings and further research into these associations is encouraged.