March 2020

Management of Renal Masses and Localized Renal Cancer: Systematic Review and Meta-Analysis

Pierorazio PM, Johnson MH, Patel HD, et al.
J Urol. 2016 Oct;196(4):989-99.
DOI: 10.1016/j.juro.2016.04.081.

Abstract

Purpose

Several options exist for management of clinically localized renal masses suspicious for cancer, including active surveillance, thermal ablation and radical or partial nephrectomy. We summarize evidence on effectiveness and comparative effectiveness of these treatment approaches for patients with a renal mass suspicious for localized renal cell carcinoma.

Materials and methods

We searched MEDLINE®, Embase® and the Cochrane Central Register of Controlled Trials from January 1, 1997 through May 1, 2015. Paired investigators independently screened articles to identify controlled studies of management options or cohort studies of active surveillance, abstracted data sequentially and assessed risk of bias independently. Strength of evidence was graded by comparisons.

Results

The search identified 107 studies (majority T1, no active surveillance or thermal ablation stratified outcomes of T2 tumors). Cancer specific survival was excellent among all management strategies (median 5-year survival 95%). Local recurrence-free survival was inferior for thermal ablation with 1 treatment but reached equivalence to other modalities after multiple treatments. Overall survival rates were similar among management strategies and varied with age and comorbidity. End-stage renal disease rates were low for all strategies (0.4% to 2.8%). Radical nephrectomy was associated with the largest decrease in estimated glomerular filtration rate and highest incidence of chronic kidney disease. Thermal ablation offered the most favorable perioperative outcomes. Partial nephrectomy showed the highest rates of urological complications but overall rates of minor/major complications were similar among interventions. Strength of evidence was moderate, low and insufficient for 11, 22 and 30 domains, respectively.

Conclusions

Comparative studies demonstrated similar cancer specific survival across management strategies, with some differences in renal functional outcomes, perioperative outcomes and postoperative harms that should be considered when choosing a management strategy.

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A Pilot Study of Radiation Therapy in Combination With Pembrolizumab in Patients With Metastatic Renal Cell Cancer

Lin J, Song AJ, Hoffman-Censits J, et al.
Am J Clin Oncol. 2020 Feb;43(2):82-86.
DOI: 10.1097/COC.0000000000000636.

Abstract

Objectives

There is no study published regarding the benefit of radiation therapy (RT) in combination with immune checkpoint inhibitors (ICIs) for the treatment of metastatic renal cell cancer (mRCC). This report is part of an exploratory study aiming to determine the immunomodulatory activity of RT alone or in combination with pembrolizumab in solid tumors.

Materials and methods

mRCC patients were treated with a combination of RT (8 Gy×1 or 4 Gy×5) followed by pembrolizumab with or without lead-in dose of pembrolizumab. Treatment response was measured based on the modified Response Evaluation Criteria in Solid Tumors criteria. Adverse events were monitored and graded. Pre-RT and post-RT tumor biopsies were obtained to evaluate programmed death-ligand 1 expression. Immune markers from peripheral blood before, during, and after treatment were analyzed using flow cytometry.

Results

Twelve mRCC patients who progressed on prior antiangiogenic therapy were enrolled. Half had 2 lines of prior therapy. Two patients (16.7%) had partial responses and were on study for 12.4 and 14.5 months. Three patients had stable disease for a period ranging from 4.2 to 10.4 months, whereas 7 patients had progressive disease. Median progression-free survival was 8.6 months and median overall survival was 32.3 months. Three patients had grade ≥3 events (hyperglycemia, thrombocytopenia, transaminitis). Biopsied tissue programmed death-ligand 1 expression and tumor-infiltrating lymphocytes were numerically higher in responders comparing to nonresponders (Modified Proportion Score 45% vs. 30.45%; tumor-infiltrating lymphocytes odds ratio 4.92).

Conclusion

Combining RT with pembrolizumab in pretreated mRCC is well-tolerated and appears to have comparable efficacy with single-agent nivolumab.

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Impact of Patients’ Gender on Efficacy of Immunotherapy in Patients With Metastatic Kidney Cancer: A Systematic Review and Meta-analysis.

Hassler MR1, Abufaraj M2, Kimura S, et al.
Clin Genitourin Cancer. 2019 Sep 27.
DOI: 10.1016/j.clgc.2019.09.004.

Abstract

Recent meta-analyses on checkpoint inhibitors in cancer report conflicting data regarding the association of patient gender with inhibitor efficacy. In advanced kidney cancer, checkpoint inhibitors have shown improved outcomes in first- and second-line settings compared with standard of care, but the role of patient gender on treatment outcome is unclear. We aimed to assess the efficacy of immunotherapyaccording to patient gender in advanced kidney cancer. We performed a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search was performed using PubMed, Scopus, Web of Science, and The Cochrane Library to identify eligible studies published through February 16, 2019. Studies were included if they reported on the differential outcomes of male and female patients with metastatic kidney cancer receiving immunotherapy. Our outcomes of interest were overall survival (OS) or progression-free survival (PFS). Four randomized controlled trials comprising a total of 3664 patients (2715 males and 949 females) met our inclusion criteria. Both men and women with metastatickidney cancer had an OS and PFS advantage with immunotherapy compared with standard-of-care, but no statistically significant difference between the genders was observed (OS hazard ratio [HR] for men, 0.69; 95% confidence interval [CI], 0.59-0.8; P = .40; HR for women, 0.62; 95% CI, 0.48-0.81; P = .13; PFS HR for men, 0.7; 95% CI, 0.59-0.82; P = .24; HR for women, 0.68; 95% CI, 0.52-0.90; P = .105). In patients with advanced kidney cancer receiving checkpoint inhibitors, there seems to be no association of patient genderwith treatment outcome.

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Prognostic and predictive molecular biomarkers in metastatic renal cell carcinoma patients treatedwith immune checkpoint inhibitors: a systematic review

Rebuzzi SE, Perrone F, Bersanelli M, et al.
Expert Rev Mol Diagn. 2019 Oct 24:1-17.
DOI: 10.1080/14737159.2019.1680286.

Abstract

Introduction

In recent years, the treatment landscape of metastatic renal cell carcinoma (mRCC) has been improved using immune-checkpoint inhibitors (ICI). Nevertheless, the number of patients experiencing clinical benefit from immunotherapy is still limited, while others obtain more benefit from tyrosine kinase inhibitors (TKI). The identification of prognostic and predictive factors would be crucial to better select patients most likely to benefit from immunotherapy among the other potentially available therapeutic options.

Areas covered

This systematic review summarizes the current knowledge (2010–2019) on molecular prognostic and predictive biomarkers, assessed in peripheral blood and/or from tumor tissue, in mRCC patients treated with ICI.

Expert opinion

Among all the biomarkers analyzed, PD-L1 expression on tumor tissue is the most studied. It has an unfavorable prognostic role for patients treated with TKI, which seems to be overcome by ICI-based combinations. Nevertheless, no clear predictive role of immunotherapy efficacy has been observed for PD-L1 in mRCC. Emerging evidence regarding pro-angiogenic or pro-immunogenic genomic and transcriptomic signatures suggests a potential predictive role in patients treated with ICI-based combinations. The rationale for TKI-ICI combinations is based on tumor microenvironment and genomic background, which represent the target of these two main therapeutic options for mRCC.

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First-Line Systemic Therapy for Metastatic Clear-Cell Renal Cell Carcinoma: Critical Appraisal of Emerging Options

Loo V, Salgia M, Bergerot P, et al.
Target Oncol. 2019 Dec;14(6):639-645.
DOI: 10.1007/s11523-019-00676-y.

Abstract

Until recently, a dichotomy existed in the front-line approach of metastatic clear-cell renal cell carcinoma (mRCC). Specifically, patients received either targeted therapy or immunotherapy. Targeted therapy entailed use of agents blocking signaling through the vascular endothelial growth factor (VEGF) receptor, such as cabozantinib, sunitinib, or pazopanib. Immunotherapy entailed dual therapy with nivolumab and ipilimumab, both checkpoint inhibitors for intermediate/poor International Metastatic RCC Database Consortium (IMDC)-risk disease patients. Within the past year, two datasets have emerged that led to recent approvals of combined therapy with VEGF and checkpoint inhibitors. These regimens (axitinib with either avelumab or pembolizumab) are among several that have been or will be evaluated for patients with newly diagnosed mRCC. We aim to facilitate treatment decisions through this comprehensive and contextualized overview of recent datasets in this therapeutic space.

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