Association between cytoreductive nephrectomy and survival among patients with metastatic renal cell carcinoma receiving modern therapies: a systematic review and meta-analysis examining effect modification according to systemic therapy approach

Hall, Mary E.; Bhindi, Bimal; Luckenbaugh, Amy N.; Laviana, Aaron A.; Moses, Kelvin A.; Satkunasivam, Raj; Rini, Brian I.; Klaassen, Zachary; Wallis, Christopher J.D.

doi:10.1007/s10552-021-01435-z

Cited by 8 publications

(4 citation statements)

References 13 publications

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“…The randomized CARMENA trial failed to demonstrate a positive effect of cytoreductive nephrectomy in mRCC patients treated with sunitinib [22]. Conversely, patients receiving nephrectomy in our cohort had a significantly better survival than patients retaining their primary renal tumor [12-month OS of 74.2% vs. 51.2%, respectively p < 0.0001] as other investigators recently reported with the use of immunotherapy in mRCC [23]. Whether selection bias or relevant biological mechanisms may cause such difference has still to be determined: randomized controlled trials such as the PROBE trial (NCT04510597) are ongoing.…”

Section: Discussionsupporting

confidence: 47%

Compassionate Use Program of Ipilimumab and Nivolumab in Intermediate or Poor Risk Metastatic Renal Cell Carcinoma: A Large Multicenter Italian Study

Basso

Paolieri

Rizzo

et al. 2022

Cancers

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This is a retrospective analysis on the safety and activity of compassionate Ipilimumab and Nivolumab (IPI-NIVO) administered to patients with metastatic Renal Cell Carcinoma (mRCC) with intermediate or poor International Metastatic RCC Database Consortium (IMDC) score as a first-line regimen. IPI was infused at 1 mg/kg in combination with Nivolumab 3 mg/kg every three weeks for four doses, followed by maintenance Nivolumab (240 or 480 mg flat dose every two or four weeks, respectively) until disease progression or unacceptable toxicity. A total of 324 patients started IPI-NIVO at 86 Italian centers. Median age was 62 years, 68.2% IMDC intermediate risk. Primary tumor had been removed in 65.1% of patients. Two hundred and twenty patients (67.9%) completed the four IPI-NIVO doses. Investigator-assessed overall response rate was 37.6% (2.8% complete). Twelve-month survival rate was 66.8%, median progression-free survival was 8.3 months. Grade 3 or 4 treatment-related adverse events occurred in 67 patients (26.9%). IMDC intermediate risk, nephrectomy, BMI ≥ 25 kg/m2, and steroid use for toxicities correlated with improved survival, while age < 70 years did not. IPI-NIVO combination is a feasible and effective regimen for the first-line treatment of intermediate-poor IMDC risk mRCC patients in routine clinical practice.

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Section: Discussionsupporting

confidence: 47%

Compassionate Use Program of Ipilimumab and Nivolumab in Intermediate or Poor Risk Metastatic Renal Cell Carcinoma: A Large Multicenter Italian Study

Basso

Paolieri

Rizzo

et al. 2022

Cancers

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“…In a recent systematic review and meta-analysis evaluating the association between cytoreductive nephrectomy and survival among patients with metastatic RCC receiving modern therapies, Hall et al demonstrated that there was a significant apparent benefit for cytoreductive nephrectomy and systemic therapy versus systemic therapy alone in patients receiving immunotherapy (pooled hazard ratio: 0.28, 95% CI 0.15–0.49, I 2 =21%) [17]. When these data were compared with older data evaluating the use of cytoreductive nephrectomy with only targeted therapy, a greater benefit of cytoreductive nephrectomy was seen in patients receiving immunotherapy ( P = 0.01).…”

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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“…All regimens have been shown to improve treatment efficacy and prognosis through randomized control trials (RCTs) (4)(5)(6)(7)(8). While the introduction of multiple effective systemic treatment options has been encouraging, nephrectomy as a treatment approach has been controversial (9)(10)(11)(12)(13)(14). A number of retrospective studies have demonstrated the benefit of upfront cytoreductive nephrectomy (CN) in mRCC treated with TKIs (9,10) and ICIs (11,12); however, several RCTs have shown negative data for upfront CN in mRCC treated with TKIs (13,14).…”

Section: Introductionmentioning

confidence: 99%

“…While the introduction of multiple effective systemic treatment options has been encouraging, nephrectomy as a treatment approach has been controversial (9)(10)(11)(12)(13)(14). A number of retrospective studies have demonstrated the benefit of upfront cytoreductive nephrectomy (CN) in mRCC treated with TKIs (9,10) and ICIs (11,12); however, several RCTs have shown negative data for upfront CN in mRCC treated with TKIs (13,14). It is important to clarify the association between treatment efficacy and surgical therapy to select the optimal systemic treatment regimen.…”

Section: Introductionmentioning

confidence: 99%

The impact of primary region resection on the therapeutic outcome of combination regimens for metastatic renal cell carcinoma

Teishima,

Hara,

Tobe

et al. 2023

Oncol Lett

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The present study aimed to clarify the relationship between the therapeutic outcome of combination regimens, including immune checkpoint inhibitors (ICIs) and/or tyrosine kinase inhibitors (TKIs), and cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC). The present study retrospectively assessed the association between treatment efficacy and prognosis with or without CN, and the timing of CN in 151 patients treated with combination regimens for mRCC who were categorized as intermediate/poor risk. The first-line regimens included the ICI-ICI and ICI-TKI regimens in 98 and 53 cases, respectively. In patients with recurrence after radical surgery (n=66), the 50% PFS times of the ICI-ICI and the ICI-TKI groups were 33.6 months and not reached (NR) (P=0.4032), respectively, and the 50% OS times were 53.7 months and NR (P=0.6886), respectively. Among the 38 patients with metastasis from the initial diagnosis who underwent upfront CN, the 50% PFS times of the ICI-ICI and the ICI-TKI groups were 10.5 and 8.2 months (P= 0.5806), respectively, and the 50% OS times were NR and 15.8 months (P=0.0587), respectively. Among the 51 patients who did not receive upfront CN, the 50% PFS time of the ICI-TKI group was significantly higher than that in the ICI-ICI group (4.1 months and NR, respectively; P=0.0210), and the 50% OS times were 29.8 months and NR (P=0.7343), respectively. In conclusion, according to the analysis of real-world data, good therapeutic efficacy can be achieved with any regimen in patients with recurrence after radical surgery. In addition, improved results could be achieved through treatment with ICI-TKI in patients without upfront CN.

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Association between cytoreductive nephrectomy and survival among patients with metastatic renal cell carcinoma receiving modern therapies: a systematic review and meta-analysis examining effect modification according to systemic therapy approach

Cited by 8 publications

References 13 publications

Compassionate Use Program of Ipilimumab and Nivolumab in Intermediate or Poor Risk Metastatic Renal Cell Carcinoma: A Large Multicenter Italian Study

Compassionate Use Program of Ipilimumab and Nivolumab in Intermediate or Poor Risk Metastatic Renal Cell Carcinoma: A Large Multicenter Italian Study

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

The impact of primary region resection on the therapeutic outcome of combination regimens for metastatic renal cell carcinoma

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