octubre 2019

Adjuvant Therapy in High-Risk Renal Cell Cancer: A Systematic Review and Meta-analysis

Riaz I, Faridi W, Husnain M, et al.
Mayo Clinic Proceedings, Volume 94, Issue 8, 1524 – 1534, August 2019
DOI: https://doi.org/10.1016/j.mayocp.2019.01.045

Abstract

Objective

To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating risk-benefit for adjuvant postoperative treatments in high-risk renal cell carcinoma by assessing reported disease-free survival (DFS), overall survival (OS), toxicity, and quality of life.

Methods

A literature search was performed in PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials to identify relevant RCTs (from database inception through May 15, 2018). The results of the ATLAS trial were published while writing this manuscript, and the manuscript was updated accordingly. A generic variance-weighted random effects model was used to derive estimates for efficacy and common adverse effects. Heterogeneity was assessed using the Cochran Q statistic and was quantified using the I2 test.

Results

Adjuvant therapy with tyrosine kinase inhibitors compared with placebo was observed to have a DFS hazard ratio [HR] of 0.92 (95% CI, 0.83-1.01) and an OS HR of 1.01 (95% CI, 0.89-1.15) (4 RCTs; 4417 patients). Analysis of DFS for sunitinib compared with placebo (n=1909) in the adjuvant setting detected an HR of 0.90 (95% CI, 0.67-1.19). Increased risk of grade 3 or 4 adverse events (relative risk [RR]=2.6; 95% CI, 2.28-2.97), diarrhea (RR=9.89; 95% CI, 4.22-23.14), fatigue (RR=3.11; 95% CI, 1.86-5.18), hypertension (RR=3.63; 95% CI, 2.99-4.41), and palmar/plantar dysesthesia (RR=2.70; 95% CI, 2.47-2.96) was observed.

Conclusion

Adjuvant vascular endothelial growth factor tyrosine kinase inhibitors in high-risk renal cell carcinoma did not improve OS or DFS, and there was a significant increased risk of toxicity in greater than half of the patients, leading to a decline in quality of life.

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Is cytoreductive nephrectomy relevant in the immunotherapy era?

Singla N, Ghandour R, Margulis V, et al.
Current Opinion in Urology. 29(5):526–530, September 2019
DOI: 10.1097/MOU.0000000000000659

Abstract

Purpose of review

The recent approval of immune checkpoint inhibitors (ICI) revolutionized the treatment paradigm for metastatic renal cell carcinoma (mRCC). However, the role of cytoreductive nephrectomy is not well defined in this setting. Here, we review the contemporary role and timing of cytoreductive nephrectomy for advanced RCC in the era of immunotherapy.

Recent findings

Evidence concerning combination systemic therapy and cytoreductive nephrectomy in the multimodal management of mRCC is primarily limited to studies conducted in the targeted therapy era. The oncologic role of cytoreductive nephrectomy in the setting of ICI remains largely undefined and is supported primarily by case reports. Nonetheless, patient selection for cytoreductive nephrectomy is paramount, and appropriate candidacy in the ICI era will likely be refined as increasing evidence emerges. Until then, a cautious balance between perceived oncologic benefit and risks of intervention must be exercised. Several trials are ongoing to help shed light on patient selection, technical feasibility, and optimal timing of cytoreductive nephrectomy in the immunotherapy era.

Summary

Although the role and timing for cytoreductive nephrectomy remain to be further elucidated in the immunotherapy era, patient selection remains critical for treatment planning. Further studies are urgently needed to better define the role of cytoreductive nephrectomy in this setting.

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The evolving role of cytoreductive nephrectomy in metastatic renal cell carcinoma

Graham J, Bhindi B, Heng D.
Current Opinion in Urology. 29(5):507–512, September 2019
DOI: 10.1097/MOU.0000000000000657

Abstract

Purpose of review

To review the evidence related to cytoreductive nephrectomy in metastatic renal cell carcinoma (mRCC) treated in the targeted therapy era, with a focus on observational studies and randomized trials.

Recent findings

A number of retrospective observational studies exploring the role of cytoreductive nephrectomy have been reported. These have suggested an association between cytoreductive nephrectomy and survival, with hazard ratio estimates ranging from 0.39 to 0.68 in favour of cytoreductive nephrectomy. In contrast, the CARMENA randomized trial demonstrated that sunitinib alone was noninferior to cytoreductive nephrectomy followed by sunitinib in intermediate-risk and poor-risk patients. The results of the SURTIME trial suggest that initial sunitinib followed by a deferred cytoreductive nephrectomy may also be a reasonable approach in select patients.

Summary

On the basis of the evidence to date, there is still a role for cytoreductive nephrectomy in the multimodality treatment of mRCC. Careful patient selection is of paramount importance and discussion in multidisciplinary tumour boards is encouraged. As the treatment landscape of mRCC continues to change, the role of cytoreductive nephrectomy in the modern immuno-oncology era will need to be explored.

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Rapid Deep Responses With Nivolumab Plus Ipilimumab in Papillary Renal Cell Carcinoma With Sarcomatoid Dedifferentiation

Schvartsman G, Carneiro A, Filippi R, et al
Clinical Genitourinary Cancer, August 2019
DOI: 10.1016/j.clgc.2019.05.023

Clinical Practice Points

First-line treatment with nivolumab and ipilimumab for intermediate and high-risk patients with meta- static renal cell carcinoma (RCC) is standard-of- care.

The United States Food and Drug Administration extended approval to all RCC histologies, despite enrollment of clear-cell RCC only.

Sarcomatoid and rhabdoid dedifferentiation is associ- ated with significantly worse prognosis and may lead to increased programmed death-ligand 1 upregulation.

We present the first 2 cases, to our knowledge, of papillary RCC with sarcomatoid dedifferentiation with rapid and deep responses to the ipilimumab and nivolumab combination.

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