Cytoreductive nephrectomy (CN) in conjunction with immune checkpoint inhibitor (ICI) therapy for metastatic renal cell carcinoma (mRCC) is associated with significantly longer overall survival compared with ICI therapy alone, according to investigators.
Compared with patients who received ICI therapy alone, those treated with CN plus ICI therapy had a median overall survival of 56.3 months compared with 19.1 months for those treated with ICI therapy alone, a team led by Sarah P. Psutka, MD, MS, of the Fred Hutchinson Cancer Center at the University of Washington in Seattle, reported in Urologic Oncology. In adjusted analyses, the combination therapy arm had a significant 67% reduction in the risk for all-cause mortality compared with the monotherapy arm.
ICI therapy was used as first-line and second-line treatment in 28.1% and 17.4% of patients, respectively, and third-line or subsequent lines of therapy in 54.5% of patients. The investigators observed a survival benefit in patients who received an ICI in any line of therapy.
Dr Psutka and colleagues conducted a subgroup analysis of patients who received an ICI as first-line therapy. In this group, the median overall survival was not reached in patients who underwent CN compared with 14.9 months in those who received ICI therapy alone. On multivariable analysis, the addition of CN to ICI therapy was significantly associated with an 81% decreased risk of death compared with ICI therapy alone.
Addition of CN to treatment generated higher rates of complete response following first-line ICI therapy without higher rates of grade 3-4 adverse effects, according to investigators.
“Our data support the continued use of CN in carefully selected patients with mRCC undergoing treatment with contemporary immunotherapy,” Dr Psutka and colleagues concluded.
The study cohort consisted of 367 patients—232 who underwent CN and received ICI therapy and 135 who received ICI therapy alone. Survival had a median follow-up of 28.4 months. Of the patients undergoing CN, 202 (87%) underwent upfront CN and 30 (13%) deferred the surgery. The investigators found no significant differences in overall survival between patients who had upfront CN and deferred CN.
The authors acknowledged the study’s limitations. These include its retrospective design and observational nature “with the attendant impacts of selection bias, unmeasured confounding, and variation in institutional and provider practice patterns over time which may influence both the generalizability and impact the validity of the results.”
Another limitation was a lack of granular patient-level data and modest cohort size that prevented them from using propensity score matching techniques in their analysis, they noted.
Despite study limitations, the authors stated that their findings “add to the emerging literature regarding optimal management of patients with mRCC in contemporary practice. The speed at which immunotherapy has surpassed targeted treatment has left guidance regarding surgery for mRCC unclear,” the authors wrote. “Timely retrospective analyses offer crucial direction until knowledge gaps can be filled with large prospective clinical trials.”
Gross EE, Li M, Yin M, et al. A multicenter study assessing survival in patients with metastatic renal cell carcinoma receiving immune checkpoint inhibitor therapy with and without cytoreductive nephrectomy. Urol Oncol. Published online October 26, 2022. doi:10.1016/j.urolonc.2022.08.013