Oncological Outcomes of Delayed Nephrectomy After Optimal Response to Immune Checkpoint Inhibitors for Metastatic Renal Cell Carcinoma

Pignot, G.; Thiery‐Vuillemin, Antoine; Albigès, Laurence; Walz, Jochen; Lang, Hervé; Balssa, L.; Parier, Bastien; Geoffrois, Lionnel; Bensalah, Karim; Schlürmann, Friederike; Ladoire, Sylvain; Bigot, Pierre; Borchiellini, Delphine; Cassuto, Ophélie; Thibault, Constance; Ingels, Alexandre; Saldana, Véronique; Roubaud, Guilhem; Bernhard, Jean-Christophe; Gravis, Gwénaëlle; Barthélémy, Philippe

doi:10.1016/j.euo.2022.07.002

Cited by 24 publications

(22 citation statements)

References 22 publications

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“…Pignot et al [5] also report a pathologic complete response (ypT0) in 16.7% of their patients, which is slightly higher than the ypT0 rates reported in other recent series [9,10]. This may reflect the duration and type of ICI regimen received, and it would be interesting to assess whether intraoperative inflammation and surgical difficulty correlate with pathologic response in the primary tumor.…”

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confidence: 81%

“…The encouraging oncologic efficacy of deferred CN after ICI in the series by Pignot et al [5] is worth highlighting, as this approach largely remains under-reported in the ICI era. At 24 mo, the authors found disease-free, progressionfree, and overall survival rates of 69.1%, 78.3%, and 86.1%, respectively.…”

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confidence: 93%

“…In this issue of European Urology Oncology, Pignot et al [5] present surgical and oncologic outcomes for 30 patients with mRCC treated with CN following a favorable systemic response to ICI. They report that delayed CN after ICI is feasible and demonstrates encouraging oncologic outcomes, with the potential to discontinue systemic therapy in a majority of patients.…”

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confidence: 99%

“…It is conceivable that the extent of inflammation observed may vary by the type and duration of systemic therapy received, which may account for these differences. These are quite variable in the study by Pignot et al, as their cohort exhibits considerable heterogeneity in prior lines of therapy, type of ICI regimen, duration of ICI (range 3-38 mo), number of ICI cycles (range 6-71), metastatic burden, and time elapsed between initiation of ICI and surgery [5]. Nevertheless, they raise important concerns, and thus the decision to pursue CNand the optimal time to operate-should follow a multidisciplinary discussion involving both surgeons and oncologists at experienced, high-volume centers.…”

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confidence: 99%

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A Swinging Pendulum: Bringing Back Cytoreductive Nephrectomy in the Era of Immune Checkpoint Inhibition

Pallauf

Ged²,

Singla³

2022

European Urology Oncology

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confidence: 81%

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confidence: 93%

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confidence: 99%

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confidence: 99%

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A Swinging Pendulum: Bringing Back Cytoreductive Nephrectomy in the Era of Immune Checkpoint Inhibition

Pallauf

Ged²,

Singla³

2022

European Urology Oncology

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“…Pignot et al [10], in another single-centre study, sought to evaluate the oncologic outcomes of patients who experienced a complete response or major partial response at metastatic sites and subsequently underwent a delayed cytoreductive nephrectomy. They included 30 patients, who were all diagnosed with synchronous metastatic disease, with multiple metastases.…”

Section: Role Of Cytoreductive Nephrectomy During the Targeted Therap...mentioning

confidence: 99%

The role of cytoreductive nephrectomy in the immuno-oncological therapy era

Magee

Helstrom

Kutikov

2023

Current Opinion in Urology

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Purpose of review Cytoreductive nephrectomy has had a variable role in the management of metastatic renal cell carcinoma (RCC) through the different systemic therapy eras. Initially felt to be beneficial with interferon, the utility of cytoreductive nephrectomy was called into question in the tyrosine kinase inhibitor (TKI) era. However, with the advent of immunotherapy for metastatic RCC, the role of cytoreductive nephrectomy continues to be debated. This study sought to evaluate the recent literature and discuss cytoreductive nephrectomy within the context of an improved systemic therapy era. Recent findings The literature that exists on the use of cytoreductive nephrectomy with immunotherapy is retrospective in nature and largely derived from large, institutional databases. Although smaller, single-institution articles exist and provide more granular data, issues concerning selection bias and unmeasured confounders persist. Overall, the available studies demonstrate that patient selection is paramount, and cytoreductive nephrectomy should be reserved for patients with no more than one risk factor, those requiring palliation of local symptoms and for those patients with stable, low volume disease or with a complete response following systemic therapy exposure. Summary The optimal use of cytoreductive nephrectomy in metastatic RCC remains unclear, but certain subgroups of patients, on evaluation of post hoc and retrospective data, seem to benefit from surgical intervention.

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Immune Checkpoint Inhibitor Therapy Before Nephrectomy for Locally Advanced and Metastatic Renal Cell Carcinoma

Ghoreifi,

Vaishampayan,

Yin

et al. 2024

JAMA Oncol

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ImportanceThe therapeutic landscape of advanced renal cell carcinoma (RCC) has rapidly evolved in the past 2 decades, with the advent of cytokines therapy followed by targeted therapies and novel immune checkpoint inhibitors (ICI). This article aims to review the current evidence and ongoing trials of neoadjuvant or prenephrectomy ICI therapy in patients with locally advanced and metastatic RCC.ObservationsA literature search was performed using the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and PubMed as well as relevant medical society meetings for English-language studies, articles, and abstracts published before January 31, 2023. Currently, level I evidence supports the use of ICI-based combination therapy as the first-line treatment of patients with metastatic RCC with the potential option of deferred nephrectomy in those who respond to treatment. Nevertheless, limited prospective data are available regarding the role and outcomes of nephrectomy (cytoreductive or consolidative) in conjunction with ICI therapy in both metastatic and locally advanced RCC. Although data from retrospective case series confirmed the feasibility and safety of deferred nephrectomy in this setting, the sequence of nephrectomy and whether it should be considered in patients with metastatic RCC is a common clinical dilemma. However, although neoadjuvant targeted therapy for nonmetastatic RCCs has been associated with some advantages yet not accepted as a standard, current data from a phase 3 randomized clinical trial failed to demonstrate the oncologic benefit of neoadjuvant nivolumab for locally advanced RCC.Conclusion and RelevanceThe findings of this review suggest that ICI-based combination therapy is the standard of care as the first-line treatment of patients with metastatic RCC. However, the role of neoadjuvant ICIs in locally advanced RCC is an active area of investigation. Deferred nephrectomy after ICI-based immunotherapy for metastatic RCC is feasible and safe yet should be performed in high-volume health centers by experienced surgeons. The multidisciplinary and careful approach is critical for treatment decisions.

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Oncological Outcomes of Delayed Nephrectomy After Optimal Response to Immune Checkpoint Inhibitors for Metastatic Renal Cell Carcinoma

Cited by 24 publications

References 22 publications

A Swinging Pendulum: Bringing Back Cytoreductive Nephrectomy in the Era of Immune Checkpoint Inhibition

A Swinging Pendulum: Bringing Back Cytoreductive Nephrectomy in the Era of Immune Checkpoint Inhibition

The role of cytoreductive nephrectomy in the immuno-oncological therapy era

Immune Checkpoint Inhibitor Therapy Before Nephrectomy for Locally Advanced and Metastatic Renal Cell Carcinoma

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