Cytoreductive nephrectomy ‘still plays a role’ for metastatic RCC
medwireNews: Cytoreductive nephrectomy (CN) continues to offer a significant overall survival (OS) benefit for carefully selected patients with metastatic renal cell carcinoma (RCC) in the era of immune checkpoint inhibitor (ICI) and targeted therapies (TT), a propensity score-based analysis indicates.
“In this large, retrospective, consecutive series of patients, we found that the benefit associated with cytoreductive nephrectomy seems to be similar across the immune checkpoint inhibitor and targeted therapy eras,” Ziad Bakouny, from Dana-Farber Cancer Institute in Boston, Massachusetts, USA, told delegates at the 2020 Genitourinary Cancers Symposium in San Francisco, California, USA.
“But, and I can’t stress this enough, patient selection remains key” regardless of first-line systemic treatment, he said, highlighting the recent recommendations from his colleagues Shaan Dudani and Daniel Heng who advised that upfront CN be considered only for patients with IMDC favorable- or intermediate-risk disease who are suitable for active surveillance, and patients for whom oligometastasectomy is feasible.
Deferred CN may be suitable for other patients, such as those with a strong response to systemic therapy, whereas CN should be “rarely” performed among patients with IMDC poor-risk disease, rapid progression, or a high disease burden, Bakouny said.
Bakouny explained that the recent “gold standard” results from the phase 3 CARMENA study showed that sunitinib alone is noninferior to CN plus sunitinib in patients who present with upfront metastatic disease.
But acknowledging that this trial focused on patients with poor- or intermediate-risk disease who may be less likely to derive a benefit from CN than their favorable-risk counterparts, the presenter and colleagues investigated the impact of the procedure in patients with metastatic RCC after the introduction of ICIs.
IMDC data were collated from 4639 patients attending one of 40 global centers between 2009 and 2019 who received either a first-line ICI regimen (n=437), usually consisting of two ICIs or an ICI plus a VEGF inhibitor, or were given a TT regimen (n=4202) using a tyrosine kinase inhibitor or mTOR inhibitor. Overall, 43.9% of the ICI cohort and 37.4% of the TT cohort did not undergo CN.
The researchers found that patients aged over 65 years were significantly less likely to undergo CN than other patients regardless of their first-line systemic regimen. This was also true for patients with versus without bone, brain or liver metastases and by increasing IMDC risk score.
Initial univariate analysis indicated that overall survival (OS) was higher with CN than without the procedure whether patients received a first-line ICI or TT regimen, with hazard ratios (HRs) for death of 0.44 and 0.48, respectively, after a corresponding median follow-up of 14.1 and 42.0 months.
And the OS benefit associated with CN regardless of first-line systemic regimen persisted both when using a classic multivariable model adjusting for age, histology, IMDC risk criteria and metastases, and when using an inverse probability of treatment weighting model which also accounted for favorable-risk patients being more likely to undergo CN than those with a poorer prognosis.
Nevertheless, Bakouny emphasized the limitations of the analysis, including the strong selection bias for CN even after correcting for known characteristics, the risk for unknown confounding factors, and the use of data only from large academic centers.
The ongoing NORDIC-SUN-Trial, PEARL, and CYTOSHRINK trials assessing use of deferred CN in patients undergoing treatment with nivolumab and ipilimumab alone or alongside radiotherapy will help provide more data on the use CN in the ICI era, he concluded.
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This independent news article was supported by an educational grant from Pfizer and Merck KGaA