Cytoreductive nephrectomy may still remain standard for some with metastatic renal cell carcinoma
CHICAGO — The addition of cytoreductive nephrectomy to treatment with sunitinib malate did not provide a survival benefit for intermediate and poor-risk patients with metastatic renal cell carcinoma, according to results of the phase 3 CARMENA clinical trial presented at ASCO Annual Meeting.
However, as Terence Friedlander, MD, chief of hematology-oncology at Zuckerberg San Francisco General and associate director of the Helen Diller Family Comprehensive Cancer Center at Zuckerberg San Francisco General, told HemOnc Today, the results need to be viewed with caution.
“I think physicians have to be cautious of how we interpret the data,” he said. “I think that going forward, in intermediate and high-risk patients, that the standard-of-care is to start systemic therapy and consider nephrectomy. For the good-risk patients, I think the standard of care is not changed. I think we should still consider nephrectomy as a front-line therapy followed by systemic therapy.”
The major question in the field prior to CARMENA, was when a patient was newly diagnosed with kidney cancer, did they need their kidney removed, according to Friedlander.
Based on results from a study in the early 2000s from Robert C. Flanigan, MD, and colleagues, he said, the answer has been to remove the kidney, which has been applied across all patient groups.
“There has never been a study that has looked at high-volume or low-volume patients that tried to break apart those differences to look at who really needs cytoreductive nephrectomy,” he said. “The clinical reality is, there’s a big spectrum of how metastatic RCC patients present.”
For instance, some patients present with one or two small lung nodules and a big kidney mass, he said. While other times patients may present with the bulk of their cancer existing outside the kidney where they have mediastinal masses, lung or bone tumors, and maybe a moderate or large-sized kidney mass.
The goal of the study was to determine whether upfront cytoreductive nephrectomy adds a survival benefit and whether it should remain standard prior to initiation of sunitinib.
OS served as the study’s primary endpoint.
Researchers randomly assigned 450 patients (median age, 62 years) with synchronous metastatic renal cell carcinoma to cytoreductive nephrectomy followed by 50 mg sunitinib daily (n = 226) or 50 mg sunitinib alone (n = 224) for 6 weeks. Patients who underwent cytoreductive nephrectomy initiated sunitinib treatment 4 to 6 weeks postsurgery.
Researchers stratified patients based on Memorial Sloan Kettering Cancer Center (MSKCC) criteria. In the cytoreductive nephrectomy group, 55.6% were intermediate risk and 44.4% were poor risk, and in the sunitinib group, 58.5% were intermediate risk and 41.5% were poor risk.
When evaluated by MSKCC risk group, researchers observed no benefit with the addition of surgery for those with intermediate risk (19 months vs. 23.4 months; HR = 0.92; 95% CI, 0.68-1.24) or poor risk (10.2 months vs. 13.3 months; HR = 0.85; 0.62-1.17) disease.
“When the researchers reported the results, I was a little conflicted,” Friedlander said. “Because there was a fair amount of crossover in that some of the patients assigned to get sunitinib after nephrectomy never received sunitinib. It wasn’t a big number, but clearly those patients are going to do poorly and it’s going to look like nephrectomy doesn’t work.”
Additionally, as Friedlander noted, only 17% of patients within the sunitinib-only arm eventually went on to undergo the nephrectomy.
“It’s not that these patients should never get a nephrectomy, but maybe they should get systemic therapy and then if they have a nice response or stable disease then consider nephrectomy,” he said.
The results, according to Friedlander, demonstrated that there was no difference in long-term, clinically relevant outcomes.
Worried about the outcome
Friedlander said he was a little worried after hearing the presenter’s conclusion.
“[Arnaud Mejean, MD, PhD,] said that nephrectomy is no longer the standard of care for newly diagnosed RCC, but he should have said newly diagnosed intermediate and poor-risk RCC,” Friedlander said.
“What I worry about, and maybe this is overblown, but that trainees, community oncologists and urologists are all going to say, ‘OK, we shouldn’t be doing nephrectomies now.’”
He said he would argue that the standard of care for good-risk patients would be still to perform an upfront nephrectomy and then consider systemic therapy in the intermediate and poor-risk patients.
“The study results suggest that you don’t need to do a nephrectomy,” he said. “The researchers didn't completely account for all of the crossover, because the fact that the sunitinib monotherapy arm did undergo nephrectomies is going to muddy the results.” – by Ryan McDonald
Mejean A, et al. Abstract LBA3. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
Disclosures: Friedlander reports serving on an advisory board with Pfizer.