Paraneoplastic syndromes are associated with adverse prognosis among patients with renal cell carcinoma undergoing nephrectomy.

Objectives: To analyze the association of paraneoplastic syndromes (PNS) with progression-free (PFS) and cancer-specific survival (CSS) among patients with renal cell carcinoma (RCC) undergoing nephrectomy.

Methods: We performed a retrospective analysis of 2865 patients undergoing nephrectomy for localized RCC at Mayo Clinic from 1990 to 2010. PNS analyzed were anemia, polycythemia, hypercalcemia, recent-onset hypertension, and liver dysfunction. PFS and CSS were estimated using Kaplan-Meier method and compared with Cox proportional hazard models, unadjusted and adjusted for clinicopathologic features.

Results: A total of 661 (23 %) patients had anemia, 37 (1 %) had polycythemia, 177 (9 %) had hypercalcemia, 51 (2 %) had recent-onset hypertension, and 224 (10 %) had liver dysfunction at time of nephrectomy. Patients with PNS were more likely to have high-grade tumors and advanced disease stages. A total of 675 (24 %) patients developed progression and 1171 (41 %) died of RCC, over a median follow-up of 8.2 years. On univariable analysis, the presence of any PNS was associated with inferior CSS [hazard ratio (HR) = 1.86, p = 0.007] and a trend toward shorter PFS (HR = 1.33, p = 0.07) compared with patients without PNS. Specifically, anemia, polycythemia, hypercalcemia, and liver dysfunction were each associated with inferior CSS and PFS (all p < 0.05). However, on multivariable analysis PNS (overall or each individual syndrome) did not remain independently associated with CSS or PFS.

Conclusions: Patients with RCC undergoing nephrectomy presenting with PNS have worse oncologic outcome than those with incidentally found tumors. However, the adverse outcome among PNS patients seems to be largely explained by adverse pathologic features of these tumors.