Application of Hereditary Renal Cell Carcinoma Risk Criteria to a Large Prospective Database.

AIMS: To evaluate the clinical impact of the Canadian criteria for identifying patients and families at risk for hereditary renal cell carcinoma (RCC). MATERIALS AND METHODS: The Canadian hereditary RCC risk criteria were applied to patients from 16 centres in the Canadian Kidney Cancer information system (CKCis) prospective database. The primary end point was the proportion of patients who met at least one criterion. RESULTS: Between January 2011 and May 2017, 8388 patients were entered in the database; 291 had inadequate risk data; 2827 (35%) met at least one criterion for genetic testing (at-risk population). Most (83%) met just one criterion. The criterion of non-clear cell histology contributed the largest proportion of at-risk patients (59%), followed by age ≤ 45 years (28%). Sixty-one patients had documentation of genetic testing, with 56 being classified at-risk (2% of at-risk). Twenty patients (35%) of the patients at risk and tested for hereditary RCC were found to harbour a germline mutation. CONCLUSIONS: Application of the Canadian hereditary RCC risk criteria to a large prospective database resulted in 35% of patients being identified at risk for hereditary RCC who could qualify for genetic testing. However, the true incidence of hereditary RCC in this population is unknown as most patients did not have documented genetic testing carried out and, thus, the sensitivity and specificity of the criteria cannot be determined. The low proportion of at-risk patients who underwent genetic testing is disappointing and highlights that there may be gaps in reporting, knowledge and/or barriers in access to genetic testing.

Use of targeted therapy in patients with metastatic renal cell carcinoma: clinical and economic impact in a Canadian real-life setting.

Introduction: Outside of randomized controlled clinical trials, the understanding of the effectiveness and costs associated with targeted therapies for metastatic renal cell carcinoma (mrcc) is limited in Canada. The purpose of the present study was to use real-world prospective data to assess the effectiveness and cost of targeted therapies for patients with mrcc. Methods: The Canadian Kidney Cancer Information System, a pan-Canadian database, was used to identify prospectively collected data relating to patients with mrcc. First- and subsequent-line time to treatment termination (ttt) was determined from therapy initiation time (sunitinib or pazopanib) to discontinuation of therapy. Kaplan-Meier survival curves were used to estimate the unadjusted and adjusted overall survival (os) by treatment. Unit treatment cost was used to estimate the cost by line of treatment and the total cost of therapy for the management of patients with mrcc. Results: The study included 475 patients receiving sunitinib or pazopanib in the first-line setting. Patients were treated mostly with sunitinib (81%); 19% of patients were treated with pazopanib. The median ttt in the first line was 7.7 months for patients receiving sunitinib and 4.6 months for those receiving pazopanib (p < 0.001). The adjusted os was 32 months with sunitinib and 21 months with pazopanib (hazard ratio: 1.61; p < 0.01). The total median cost of first- and second-line treatments was $56,476 (interquartile range: $23,738-$130,447) for patients in the sunitinib group and $46,251 (interquartile range: $28,167-$91,394) for those in the pazopanib group. Conclusions: For the two therapies, os differed significantly, with a higher median os being observed in the sunitinib group. The cost of treatment was higher in the sunitinib group, which is to be expected with longer survival.

The risk of venous thromboembolism in renal cell carcinoma patients with residual tumor thrombus.

BACKGROUND: The clinical importance of tumor thrombus in patients with renal cell carcinoma is unknown. We sought to determine the long-term risk of venous thromboembolism (VTE) in patients with residual tumor thrombus postextraction, and to evaluate the impact of residual tumor thrombus on overall survival. PATIENTS/METHODS: A cohort study of patients with stage III-IV renal cell carcinoma undergoing nephrectomy was undertaken. The primary endpoint was the risk of VTE during a 2-year follow-up period. The secondary endpoint was 2-year overall survival. RESULTS: A total of 170 surgical renal cell carcinoma patients were included, 97 (57.1%) of whom had tumor thrombus. Patients with residual tumor thrombus following surgery had a higher risk of developing VTE than those with complete tumor thrombus resection (hazard ratio [HR] 8.7, 95% confidence interval [CI] 1.7-43.4) and no tumor thrombus (HR 6.5, 95% CI 1.7-24.7). Patient with residual tumor thrombus did not have worse overall survival than those with tumor thrombus completely resected or those without tumor thrombus. CONCLUSIONS: The presence of residual tumor thrombus is an important risk factor for VTE among renal cell carcinoma patients.

Increased risk of preoperative venous thromboembolism in patients with renal cell carcinoma and tumor thrombus.

BACKGROUND: The clinical impact of a tumor thrombus in renal cell carcinoma (RCC) patients awaiting radical nephrectomy and thrombectomy is unknown. OBJECTIVE: To determine the incidence of venous thromboembolism (VTE) in RCC patients with tumor thrombus prior to nephrectomy. PATIENTS AND METHODS: We conducted a retrospective cohort study including all late-stage (stage 3-4 excluding T1-2 N0M0) RCC patients who underwent radical nephrectomy at our institution between 1 January 2005 and 1 July 2012. Tumor thrombus was defined as the presence of an intraluminal filling defect in the renal vein, hepatic vein, portal vein, or inferior vena cava, directly extending from a renal mass detected on computed tomography. RESULTS: A total of 176 patients were included in the study. Fifty-three (30.1%) patients had tumor thrombus diagnosed on imaging Three patients with tumor thrombus (5.7%; 95% confidence interval [CI] 1.4-16.8) developed a VTE while awaiting radical nephrectomy, whereas none (0%; 95% CI 0-2.9) of the patients without a tumor thrombus had an event (P = 0.026). All three events were deep vein thrombosis. Times from tumor thrombus diagnosis to VTE were 5, 15 and 21 days. CONCLUSIONS: Tumor thrombus on imaging is a frequent finding among RCC patients awaiting nephrectomy. The presence of tumor thrombus in these patients increases the incidence of preoperative VTE.