Prognostic impact of paraneoplastic syndromes on patients with non-metastatic renal cell carcinoma undergoing surgery: Results from Canadian Kidney Cancer information system

Abstract

Introduction: The impact of paraneoplastic syndromes (PNS) on survival in patients with renal cell carcinoma (RCC) is uncertain. This study was conducted to analyze the association of PNS with recurrence and survival of patients with non-metastatic RCC undergoing nephrectomy.
 Methods: The Canadian Kidney Cancer information system is a multi-institutional cohort of patients started in January 2011. Patients with nephrectomy for non-metastatic RCC were identified. PNS included anemia, polycythemia, hypercalcemia, and weight loss. Associations between PNS and recurrence or death were assessed using Kaplan-Meier curves and multivariable analysis.
 Results: Of 4337 patients, 1314 (30.3%) had evidence of one or more PNS. Patients with PNS, were older, had higher comorbidity, and had more advanced clinical and pathological tumor characteristics as compared to patients without PNS (all p<0.05). Kaplan-Meier five-year estimated recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were significantly worse in patients with PNS (63.7%, 84.3%, and 79.6%, respectively for patients with PNS vs. 73.9%, 90.8%, and 90.1%, respectively for patients without PNS, all p<0.005). On univariable analysis, presence of PNS increased risk of recurrence (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.48–1.90, p<0.0001) and cancer-related death (HR 1.85, 95% CI 1.34–2.54, p=0.0002). Adjusting for known prognostic factors, PNS was not associated with recurrence or survival.
 Conclusions: In non-metastatic RCC patients undergoing surgery, presence of PNS is associated with older age, higher Charlson comorbidity index score, advanced tumor stage, and aggressive tumor histology. Following surgery, baseline PNS is not strongly independently associated with recurrence or death.

European Association of Urology Guidelines on Renal Cell Carcinoma: The 2019 Update

“…Many patients with RCC only present with symptomatic disease (bone pain, deterioration of performance status, or persistent cough) in advanced stages [16] (LE: 3). The majority of RCCs are detected incidentally via noninvasive imaging for investigation of various nonspecific symptoms and other abdominal diseases.…”

Clinical Significance of Extracellular Vesicles in Prostate and Renal Cancer

“…With respect to mRNA, studies have reported that undifferentiated tumor cells and CSCs release EVs containing multiple pro-angiogenic mRNAs, including vascular endothelial growth factor (VEGF), FGF, angiopoietin 1, ephrin A3, MMP-2, and MMP-9 [121]. These mRNAs play a crucial role in promoting endothelial cells' growth, invasion, and survival, which ultimately support the progression of tumors and angiogenesis (Figure 3).…”

“…About 90% of these cancers are renal cell carcinoma (RCC), and about 70% of all renal cancers have a clear cell histology (ccRCC), with other less common histology including papillary and chromophobe [117][118][119][120]. Although some patients only present in the advanced stage of the disease with systemic symptoms or symptomatic pain, most cases are detected incidentally with imaging for the workup of other abdominal diseases or nonspecific symptoms, a phenomenon that is continually increasing with the rising use of medical imaging and subsequence incidence of RCC [121][122][123]. The welldescribed triad of RCC, including flank pain, hematuria, and a palpable mass is very rarely identified and represents very aggressive disease [122].…”