Which initial treatment is best for mRCC patients?

A retrospective observational study designed to identify whether cytoreductive nephrectomy or targeted therapy might be the optimal initial therapeutic approach to metastatic renal cell carcinoma adds to the argument in the literature advocating for a multimodal approach in appropriately selected patients.

Before applying the study’s findings to patient care, however, they need to be considered along with other current literature on this topic, said lead author Bimal Bhindi, MD, who was with Mayo Clinic, Rochester, MN at the time of the study. He is now at the Southern Alberta Institute of Urology, Calgary, Alberta.

“When the findings of our study are contextualized in the setting of recent randomized trials, including SURTIME and CARMENA, the take-home message is that intermediate- and poor-risk patients who require systemic therapy should be treated with it first,” he told Urology Times.

“Cytoreductive nephrectomy likely still has a role in selected cases, such as in patients with limited metastatic disease not requiring immediate systemic therapy and in patients showing a response to initial treatment with systemic therapy. More work is still needed, however, to precisely define which patients may benefit from surgery,” Dr. Bhindi added. The findings were published in the Journal of Urology (2018; 200:528–34).

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The study conducted by Dr. Bhindi and colleagues at Mayo Clinic was conceptualized around the time of the early reporting of results from SURTIME, a randomized trial investigating the sequencing of cytoreductive nephrectomy and targeted therapy with sunitinib (Sutent) for metastatic renal cell carcinoma.

“SURTIME found no difference between treatment groups in the primary endpoint analysis of progression-free survival at 28 weeks. Given that SURTIME did not reach accrual targets and closed prematurely, we sought to evaluate treatment sequencing in a retrospective observational study using a population of patients identified using the National Cancer Database,” Dr. Bhindi explained.

“The strengths of our study include its generalizability and statistical power because the population is derived from a large national data set. Unmeasured differences between groups that cannot be accounted for in a retrospective observational design and resulting in potential confounding is its main limitation.”

Continue to the next page for more.The retrospective observational study included 15,068 patients diagnosed with metastatic renal cell carcinoma between 2006 and 2013 who were treated with cytoreductive nephrectomy and/or targeted therapy. The total population was comprised of 6,731 patients (44.7%) who underwent initial cytoreductive nephrectomy and 8,337 patients treated initially with targeted therapy. Within 6 months among patients treated initially with cytoreductive nephrectomy, 48.0% had received targeted therapy and 15.3% had died. Only 4.7% of patients in the initial targeted therapy group had undergone cytoreductive nephrectomy within 6 months while 44.9% had died prior to cytoreductive nephrectomy within 6 months.

The outcomes analysis found that overall survival was significantly better in patients who received initial cytoreductive nephrectomy with or without targeted therapy than in the group receiving initial targeted therapy with or without cytoreductive nephrectomy (median 16.5 vs. 9.2 months, respectively; HR: 0.61, 95% CI: 0.59-0.64, p<.001). Further analyses, however, showed that a large part of the benefit seen in the initial cytoreductive nephrectomy group may have been attributable to the fact that compared with patients who received targeted therapy first, patients who underwent surgery first were more likely to receive multimodal therapy, Dr. Bhindi said.

Read: Phase III data point to new standard of care for mRCC

“In fact, overall survival among patients who underwent cytoreductive nephrectomy after initial targeted therapy was comparable to and maybe even slightly better than that of the initial cytoreductive nephrectomy group,” he noted.

In addition to SURTIME, recently reported results from the randomized phase III CARMENA trial showed non-inferior survival outcomes for patients treated with sunitinib alone compared with the group who underwent cytoreductive nephrectomy followed by sunitinib, whether considering the overall study population or the intermediate-risk and poor-risk groups who will require systemic therapy, Dr. Bhindi said.

“Notably, however, 17% of patients in the ‘sunitinib alone’ arm underwent deferred cytoreductive nephrectomy, and that suggests a potential ongoing role for multimodal therapy in a subset of patients,” said Dr. Bhindi. “It is also unknown if patients with limited metastatic disease who did not need systemic therapy, for example those who can be managed with cytoreductive nephrectomy followed by surveillance or metastasectomy, were included in the trial. These patients are well represented in the retrospective literature.”