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Background: Temsirolimus has level 1 evidence for initial treatment of poor-risk patients with advanced renal cell carcinoma (mRCC), but its efficacy has not been directly compared with an antiangiogenic tyrosine kinase inhibitor (vascular endothelial growth factor receptor tyrosine kinase inhibitor [VEGFR TKi]) in this setting., Objective: To evaluate temsirolimus versus pazopanib as first-line therapy in patients with mRCC, predominant clear-cell features, and clinical characteristics of a poor prognosis., Design, Setting, and Participants: A randomized (1:1) phase II trial in 69 treatment-naïve mRCC patients and with three or more predictors of short survival for temsirolimus was conducted during 2012-2017 in a single academic cancer center. Crossover to the alternative treatment upon discontinuation of the first-line agent was permitted., Intervention: Mechanistic target of rapamycin inhibitor temsirolimus and VEGFR TKi pazopanib., Outcome Measurements and Statistical Analysis: The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), safety, and patient-reported outcomes (PROs). Radiographic response was assessed by blinded radiologists. Efficacy outcomes were adjusted by prior nephrectomy status, prior interleukin-2 treatment, and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score., Results and Limitations: Thirty-five patients received temsirolimus and 34 received pazopanib upfront; 72% overall had poor risk by IMDC. Median PFS in the first line was 2.7mo with temsirolimus and 5.2mo with pazopanib (adjusted hazard ratio [HR] 1.36, 95% confidence interval [CI] 0.84-2.22; p=0.210). Median OS was 7.1mo with temsirolimus and 11.9mo with pazopanib (adjusted HR 1.16, 95% CI 0.70-1.93; p=0.558), and ORRs were 5.9% and 21.2%, respectively (adjusted odds ratio 5.2, 95% CI 0.9-29.3; p=0.062). PRO measures favored pazopanib. Five patients discontinued first-line therapy due to adverse events., Conclusions: Temsirolimus and pazopanib had modest activity in patients with poor-risk clear-cell mRCC, and therefore their use should be discouraged in this setting., Patient Summary: We evaluated outcomes of advanced renal cell carcinoma patients presenting with aggressive features when treated with temsirolimus or pazopanib as first-line therapy. Survival was <1yr for most, suggesting that more efficacious alternative treatments should be favored for these patients., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate how many patients could have undergone partial nephrectomy (PN) rather than radical nephrectomy (RN) before and after neoadjuvant axitinib therapy, as assessed by five independent urological oncologists, and to study the variability of inter-observer agreement., Patients and Methods: Pre- and post-systemic treatment computed tomography scans from 22 patients with clear cell renal cell carcinoma in a phase II neoadjuvant axitinib trial were reviewed by five independent urological oncologists. R.E.N.A.L. nephrometry score and κ statistics were calculated., Results: The median R.E.N.A.L. nephrometry score changed from 11 before treatment to 10 after treatment (P = 0.002). Five tumours with moderate complexity before axitinib treatment remained moderate complexity after treatment. Of 17 tumours with high complexity before axitinib treatment, three became moderate complexity after treatment. The overall κ statistic was 0.611. Moderate-complexity κ was 0.611 vs a high-complexity κ of 0.428. Before axitinib treatment the κ was 0.550 vs 0.609 after treatment. After treatment with axitinib, all five reviewers agreed that only five patients required RN (instead of eight before treatment) and that 10 patients could now undergo PN (instead of three before treatment). The odds of PN feasibility were 22.8-times higher after treatment with axitinib., Conclusions: There is considerable variability in inter-observer agreement on the feasibility of PN in patients treated with neoadjuvant targeted therapy. Although more patients were candidates for PN after neoadjuvant axitinib therapy, it remains difficult to identify these patients a priori., (© 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.)

Background: Indeterminate pulmonary nodules (IPN) are of uncertain significance in patients with renal cell carcinoma., Objective: We sought to determine predictors of IPN progression to pulmonary metastasis and develop a tool for individualized risk stratification of patients who present with IPN on preoperative chest imaging in the setting of localized or locally advanced renal cell carcinoma., Design, Setting, and Participants: We reviewed all patients who had radical nephrectomy with no evidence of distant metastases at a single institution from 2005-2009 who had ≥1 IPN on chest computed tomography that measured <2 cm. All chest computed tomographies were rereviewed by a radiologist who was blinded to outcomes, to independently determine number, size, and location of nodules., Outcome Measurements and Statistical Analysis: The primary objective of the study was to develop a prognostic model to predict pulmonary metastases among radical nephrectomy patients who present with IPN based on readily available preoperative imaging and postoperative pathological criteria. Univariable and multivariable Cox regression models were used to assess the predictive factors for development of pulmonary metastasis. We developed a nomogram that predicted the 3-yr and 5-yr lung metastasis-free survival (LMFS), with assessment of discrimination and internal validation., Results and Limitations: Among 251 patients with IPN who underwent nephrectomy, 72 (29%) developed pulmonary metastases. Median follow-up for the cohort was 36.6 mo. Three-yr and 5-yr probability of LMFS for the overall cohort was 71% (95% confidence interval 65-77%) and 65% (95% confidence interval 57-72%), respectively. The nomogram developed included number and size of IPN along with postoperative pathological variables, and showed calibration with a concordance index (c-index) of 0.81 and a bootstrap corrected c-index of 0.78. Limitations include retrospective study with no external validation., Conclusions: We developed a nomogram to predict the individualized risk LMFS for patients who underwent nephrectomy for localized or locally advanced renal cell carcinoma., Patient Summary: We reviewed outcomes among kidney cancer patients who presented with small lung nodules and developed a clinical tool to predict risk of developing lung metastases., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Previous studies have shown a modest impact of tyrosine kinase inhibitors on primary renal tumors. Those studies were mostly retrospective or heterogeneous in their eligibility criteria with regard to histology, disease stage, duration of therapy, and time off therapy prior to surgery., Objective: To prospectively investigate the safety and efficacy of axitinib in downsizing tumors in patients with nonmetastatic biopsy-proven clear cell renal cell carcinoma (ccRCC)., Design, Setting, and Participants: This was a single-institution, single-arm phase 2 clinical trial. Patients with locally advanced nonmetastatic biopsy-proven ccRCC were eligible., Intervention: Patients received axitinib 5mg for up to 12 wk. Axitinib was continued until 36h prior to surgery. Patients underwent partial or radical nephrectomy after axitinib therapy., Outcome Measurements and Statistical Analysis: The primary outcome was objective response rate prior to surgery. Secondary outcomes included safety, tolerability, and quality of life. A dedicated radiologist independently reviewed all computed tomography scans to evaluate for response using Response Evaluation Criteria in Solid Tumors (RECIST)., Results and Limitations: A total of 24 patients were treated. Twenty-two patients continued axitinib for 12 wk; 1 patient continued axitinib for 11 wk and underwent surgery as planned. One patient stopped treatment at 7 wk due to adverse events (AEs). Median reduction of primary renal tumor diameter was 28.3%. Eleven patients experienced a partial response per RECIST; 13 had stable disease. There was no progression of disease while on axitinib. The most common AEs were hypertension, fatigue, oral mucositis, hypothyroidism, and hand-foot syndrome. Postoperatively, 2 grade 3 and 13 grade 2 complications were noted. No grade 4 or 5 complications occurred. Functional Assessment of Cancer Therapy-Kidney Specific Index-15 changed over time, with quality of life worsening while on therapy, but by week 19, it was not statistically different from screening. Limitations include single-arm design and small patient numbers., Conclusions: Axitinib was clinically active and reasonably well tolerated in the neoadjuvant setting in patients with locally advanced nonmetastatic ccRCC., Patient Summary: In this prospective clinical trial, we found that axitinib, when given prior to surgery, results in significant shrinking of kidney cancers. Larger studies are needed prior to further clinical use., Trial Registration: This clinical trial was registered with clinicaltrials.gov (NCT01263769)., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)