Genomic Alterations and Outcomes with VEGF-Targeted Therapy in Patients with Clear Cell Renal Cell Carcinoma.

Background: Mutations in VHL, PBRM1, SETD2, BAP1, and KDM5C are common in clear cell renal cell carcinoma (ccRCC), and presence of certain mutations has been associated with outcomes in patients with non-metastatic disease. Limited information is available regarding the correlation between genomic alterations and outcomes in patients with metastatic disease, including response to VEGF-targeted therapy. Objective: To explore correlations between mutational profiles and cancer-specific outcomes, including response to standard VEGF-targeted agents, in patients with metastatic cc RCC. Methods: A retrospective review of 105 patients with metastatic ccRCC who had received systemic therapy and had targeted next-generation sequencing of tumors was conducted. Genomic alterations were correlated to outcomes, including overall survival and time to treatment failure to VEGF-targeted therapy. Results: The most frequent mutations were detected in VHL (83%), PBRM1 (51%), SETD2 (35%), BAP1 (24%), KDM5C (16%), and TERT (14%). Time to treatment failure with VEGF-targeted therapy differed significantly by PBRM1 mutation status (p = 0.01, median 12.0 months for MT versus 6.9 months for WT) and BAP1 mutation status (p = 0.01, median 6.4 months for MT versus 11.0 months for WT). Shorter overall survival was associated with TERT mutations (p = 0.03, median 29.6 months for MT versus 52.6 months for WT) or BAP1 mutations (p = 0.02, median 28.7 months for MT versus not reached for WT). Conclusions: Genomic alterations in ccRCC tumors have prognostic implications in patients with metastatic disease. BAP1 and TERT promoter mutations may be present in higher frequency than previously thought, and based on this data, deserve further study for their association with poor prognosis.

Outcomes in patients undergoing nephrectomy for renal cancer on chronic anticoagulation therapy.

AIMS: To report our experience on surgical resection of renal tumors for patients with a history of chronic anticoagulation (ACT) or aspirin use. METHODS: We performed a retrospective analysis of 2473 patients who underwent surgery for renal tumors between 2005 and 2012. Prior to surgery, 172 were on chronic ACT and 695 on aspirin. Multivariable linear and logistic regression models were used to compare transfusion and overall complication rates between patients undergoing renal surgery who were on therapy to patients who were on aspirin and to patients with no therapy. RESULTS: Compared to no therapy and aspirin patients those on ACT were older (57.3 (IQR 48.4-66.10) vs 63.9, (IQR 57.3-71.5) vs 68.4, (IQR 60.4-73.5); p < 0.001), with a higher percentage having an ASA score of 3 or 4 (42.4 vs 57.9 vs 82.6%; p < 0.001), respectively. ACT patients had a higher 30-day transfusion rate, 22.7% vs 7.6% vs 6.9%, and 90-day complication rate, 17.4% vs 7.2% vs 7.3%, both p < 0.001. The median length of stay differed statistically between groups (p < 0.001), with a modest longer stay in the anticoagulation group (OR 1.11 SE 0.26; p < 0.001). Transfusion and complication rates for patients on therapy undergoing minimally invasive surgery vs open surgery were not statistically different. CONCLUSIONS: Patients on chronic ACT had higher transfusion and overall complication rates compared to patients on no treatment or on chronic aspirin. These findings did not correlate to clinical differences in length of stay or grade 3-5 complications.

Treatment outcome with mTOR inhibitors for metastatic renal cell carcinoma with nonclear and sarcomatoid histologies.

BACKGROUND: The clinical trials that reported benefit of the rapalogs temsirolimus and everolimus in advanced renal cell carcinoma (RCC) were primarily conducted in patients with clear-cell histology (ccRCC). We assessed outcome with these mammalian target of rapamicin (mTOR) inhibitors in two subsets of kidney cancer: sarcomatoid variant ccRCC and nonclear-cell RCC. PATIENTS AND METHODS: Baseline clinical features, information on prior treatment, and histologic subtypes were collected for patients previously treated with rapalogs for metastatic RCC of either nonclear phenotype or ccRCC with sarcomatoid features. Outcome was assessed centrally by a dedicated research radiologist for determination of tumor response, progression-free survival (PFS), and overall survival (OS). RESULTS: Eighty-five patients received temsirolimus (n = 59) or everolimus (n = 26). Nonclear-cell phenotypes included papillary (n = 14), chromophobe (n = 9), collecting duct (n = 4), translocation-associated (n = 3), and unclassified (n = 32) RCC. Twenty-three patients had clear-cell histology with sarcomatoid features. The response rate in assessable patients (n = 82) was 7% (all partial responses); 49% of patients achieved stable disease, and 44% had progressive disease as their best response. Tumor shrinkage was observed in 26 patients (32%). Median PFS and OS were 2.9 and 8.7 months, respectively. Nine patients (11%) were treated for ≥1 year, including cases of papillary (n = 3), chromophobe (n = 2), unclassified (n = 3) RCC, and ccRCC with sarcomatoid features (n = 1). No tumor shrinkages were observed for patients with collecting duct or translocation-associated RCC. CONCLUSIONS: A subset of patients with nonclear-cell and sarcomatoid variant ccRCC subtypes benefit from mTOR inhibitors, but most have poor outcome. Histologic subtype does not appear to be helpful in selecting patients for rapalog therapy. Future efforts should include the identification of predictive tissue biomarkers.

Renal insufficiency is an independent risk factor for complications after partial nephrectomy.

PURPOSE: We identify and describe the postoperative outcomes of a single surgeon partial nephrectomy cohort. We performed univariate and multivariate analysis on preoperative patient characteristics, and their association with increased length of stay and postoperative complication rates. MATERIALS AND METHODS: Perioperative characteristics of 146 consecutive patients undergoing partial nephrectomy were recorded. Postoperative complications were defined as those occurring within 30 days using the Clavien postoperative complication scale. We conducted logistic regression analysis to evaluate the development of complications and linear regression analysis to determine the effect on length of stay. RESULTS: In a linear regression model patients with renal insufficiency had a mean of 1.7 +/- 0.6 days longer length of stay compared to those with normal renal function (p = 0.006). Complications occurred in 48.5% in the renal insufficiency group compared with 16.8% in the other cohort (p = 0.0004). There were no mortalities. On univariable analysis 4 factors were significantly associated with the development of complications including race (p = 0.03), preoperative Modification of Diet in Renal Disease less than 60 (p <0.0001), tumor size greater than 4 cm (p = 0.03) and estimated blood loss (p = 0.04). On multivariable analysis the 2 factors of Modification of Diet in Renal Disease less than 60 (p = 0.003) and race (p = 0.03) remained significant. The odds ratio for complications comparing patients with renal insufficiency to the normal cohort, adjusting for confounding factors, was 4.58 (95% CI 1.65-12.65). CONCLUSIONS: Preoperative renal insufficiency defined as Modification of Diet in Renal Disease less than 60 and non African-American race, which may be related to Modification of Diet in Renal Disease, are predictive of complications after partial nephrectomy. Decreased Modification of Diet in Renal Disease is an independent risk factor for increased length of hospital stay and increased complication rate in partial nephrectomy.

Laparoscopic nephrectomy for the management of renal medullary carcinoma in a child.

Renal medullary carcinoma is a lethal subtype of renal cancer that afflicts patients with sickle-cell hemoglobinopathies. Here we present the case of a 13-year-old boy with renal medullary carcinoma who is the first, to our knowledge, to be managed using a planned laparoscopic radical nephrectomy.