Improved survival after cytoreductive nephrectomy for metastatic renal cell carcinoma in the contemporary immunotherapy era: An analysis of the National Cancer Database

Singla, Nirmish; Hutchinson, Ryan; Ghandour, Rashed; Freifeld, Yuval; Fang, Dong; Sagalowsky, Arthur I.; Lotan, Yair; Bagrodia, Aditya; Margulis, Vitaly; Hammers, Hans J.; Woldu, Solomon L.

doi:10.1016/j.urolonc.2020.02.029

Cited by 86 publications

(81 citation statements)

References 34 publications

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“…These findings were subsequently validated in a separate cohort of 121 patients with RCC receiving anti-PD-1 therapy. 82 96 In the largest retrospective study of ICB-treated patients to date, Singla et al 97 highlighted that patients receiving cytoreductive nephrectomy plus immune checkpoint blockade had improved survival compared with…”

Section: Gut Microbiomementioning

confidence: 99%

“…Retrospective studies have demonstrated progressive survival improvement for patients receiving cytoreductive nephrectomy across the cytokine, targeted, and IO eras 96 . In the largest retrospective study of ICB‐treated patients to date, Singla et al 97 highlighted that patients receiving cytoreductive nephrectomy plus immune checkpoint blockade had improved survival compared with ICB. An abstract of a prospective randomized single‐institution study of nivolumab alone, or in combination with either bevacizumab or ipilimumab before deferred cytoreductive nephrectomy reported comparable safety and excellent PFS 98 .…”

Section: Role Of Surgery In Advanced Rccmentioning

confidence: 99%

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Immune checkpoint blockade in renal cell carcinoma

Rappold

Silagy

Kotecha

et al. 2021

Journal of Surgical Oncology

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Immune checkpoint blockade (ICB) is the foundation of current first‐line therapies in patients with metastatic renal cell carcinoma (mRCC) with the potential for eliciting long‐lasting remissions. With the expanding arsenal of ICB‐based therapies, biomarkers of response are urgently needed to guide optimal therapeutic selection. We review the data behind ICB therapy in RCC, emerging biomarkers of response, and the evolving role of surgery in patients with mRCC.

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Section: Gut Microbiomementioning

confidence: 99%

Section: Role Of Surgery In Advanced Rccmentioning

confidence: 99%

Immune checkpoint blockade in renal cell carcinoma

Rappold

Silagy

Kotecha

et al. 2021

Journal of Surgical Oncology

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“…After a median follow-up of 14.7 months, the CN and IO group demonstrated superior OS compared to those receiving IO alone (not reached vs. 11.6 months; HR 0.23; P<0.001). Again, patients selected for CN may have had more favorable patient and tumor characteristics that contributed to their superior outcomes ( 48 ). Therefore, clinical trials are required to investigate the role of CN in the setting of IO therapy, as well as the sequencing of CN and IO systemic therapy ( Table 2 ).…”

Section: The Immune Checkpoint Inhibitor Period and Future Directionsmentioning

confidence: 99%

Cytoreductive nephrectomy for metastatic renal cell carcinoma, the ultimate urologic ‘Choosing Wisely’ campaign: a narrative review

Tabakin¹,

Stein²,

Anderson³

et al. 2020

Transl Cancer Res TCR

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In the early 2000s, cytoreductive nephrectomy in addition to systemic cytokines became standard of care for treating metastatic renal cell carcinoma. Since that time, the development of novel systemic targeted therapies and immuno-oncologic agents have challenged the utility of cytoreductive nephrectomy in clinical practice. In 2019, the controversial CARMENA study was published, providing the first level one evidence suggesting that cytoreductive nephrectomy combined with targeted therapy yielded no survival advantage over targeted therapy alone in intermediate and poor risk metastatic renal cell carcinoma patients. Later that year, the SURTIME trial demonstrated that patients undergoing targeted therapy with delayed nephrectomy maintained a survival advantage over those that underwent upfront cytoreductive nephrectomy followed by targeted therapy. Both of these studies underscored the importance of patient selection and timing of cytoreductive nephrectomy and systemic therapy. As new immuno-oncologic agents are trialed, particularly in combination, the role of cytoreductive nephrectomy will continue to be questioned. In this narrative review, we discuss the evolution of the role of cytoreductive nephrectomy in treating metastatic renal cell carcinoma through the context of the ever-changing landscape of targeted therapies and immuno-oncologic agents. We assess the evidence for cytoreductive nephrectomy with respect to patient factors, timing of surgery, and combination with other therapies.

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“…1,2 Although systemic first-line TKI therapy has changed clinical practice, [3][4][5][6][7][8] immediate CN remained among the possible treatment selections based on several retrospective or small studies. [9][10][11][12][13][14][15][16][17][18][19] However, the clinical implication of immediate CN remains inconclusive because a randomized controlled phase 3 noninferiority trial, CAR-MENA, demonstrated that sunitinib alone was not inferior to immediate CN followed by sunitinib, in terms of OS. 20 Conversely, the SURTIME randomized phase 2 trial that compared immediate CN followed by sunitinib versus three presurgical cycles of sunitinib followed by CN (deferred CN) reported significantly longer median OS in the deferred CN arm.…”

Section: Introductionmentioning

confidence: 99%

“…CN has been a standard treatment strategy for patients with primary mRCC based on two randomized studies that compared immediate CN plus interferon‐α versus interferon‐α alone, and demonstrated a survival benefit in those patients 1,2 . Although systemic first‐line TKI therapy has changed clinical practice, 3–8 immediate CN remained among the possible treatment selections based on several retrospective or small studies 9–19 . However, the clinical implication of immediate CN remains inconclusive because a randomized controlled phase 3 noninferiority trial, CARMENA, demonstrated that sunitinib alone was not inferior to immediate CN followed by sunitinib, in terms of OS 20 .…”

Section: Introductionmentioning

confidence: 99%

Impact of cytoreductive nephrectomy in patients with primary metastatic renal cell carcinoma receiving systemic tyrosine kinase inhibitor therapy: A multicenter retrospective study

et al. 2020

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To compare overall survival between patients with metastatic renal cell carcinoma treated by cytoreductive nephrectomy and those not treated by cytoreductive nephrectomy. Methods: We retrospectively evaluated 278 patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors between January 2008 and November 2019. Patients were divided into two groups: a cytoreductive nephrectomy group (immediate or deferred cytoreductive nephrectomy) and a group who received systemic tyrosine kinase inhibitor therapies alone without cytoreductive nephrectomy (control group). Overall survival comparisons were made in all patients in the control versus the cytoreductive nephrectomy group, the control versus the immediate cytoreductive nephrectomy group, the control versus the deferred cytoreductive nephrectomy group, and the deferred cytoreductive nephrectomy versus the immediate cytoreductive nephrectomy group. Analyses were weighted using the propensity scorebased inverse probability of treatment weighting method to adjust for group imbalances. Results: The median (range) age of the patients was 65 (59-73) years. Of the 278 patients, 132 and 146 were in the control group and the cytoreductive nephrectomy (immediate, n = 107 and deferred, n = 39) group, respectively. A significant difference was noted between the control and cytoreductive nephrectomy groups in age, clinical stage, International Metastatic Renal Cell Carcinoma Database Consortium risk factors, and the number of metastatic sites. Inverse probability of treatment weighting-adjusted Cox regression analysis showed a significant difference in overall survival between the control and the cytoreductive nephrectomy groups and between the control and the immediate or deferred cytoreductive nephrectomy groups. However, there was no significant difference in overall survival between the immediate and the deferred cytoreductive nephrectomy groups. Conclusions: Our findings suggest that metastatic renal cell carcinoma patients undergoing cytoreductive nephrectomy are more likely to have longer overall survival than those who receive tyrosine kinase inhibitor therapy only.

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Improved survival after cytoreductive nephrectomy for metastatic renal cell carcinoma in the contemporary immunotherapy era: An analysis of the National Cancer Database

Cited by 86 publications

References 34 publications

Immune checkpoint blockade in renal cell carcinoma

Immune checkpoint blockade in renal cell carcinoma

Cytoreductive nephrectomy for metastatic renal cell carcinoma, the ultimate urologic ‘Choosing Wisely’ campaign: a narrative review

Impact of cytoreductive nephrectomy in patients with primary metastatic renal cell carcinoma receiving systemic tyrosine kinase inhibitor therapy: A multicenter retrospective study

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