For many real-world patients with metastatic renal cell carcinoma (mRCC), undergoing cytoreductive nephrectomy (CN) prior to therapy with tyrosine kinase inhibitors (TKI) offers no better survival outcomes than receiving TKIs alone, new research confirms.

The previous CARMENA trial, the results of which were published in the New England Journal of Medicine in 2018, found no benefit associated with immediate CN in mRCC, but it enrolled a large percentage of patients with poor prognostic risk scores, a large primary tumor, and a large metastatic burden, who presumably benefit less from surgery.

For a real-world perspective, Michael Rink, MD, of the University Medical Center Hamburg-Eppendorf in Hamburg, Germany, and colleagues compared outcomes from 104 patients with mRCC treated with CN plus TKI and 158 treated with TKI only at their institution. Overall, 82% of patients had clear cell RCC and 6.9% had a sarcomatoid component. The most frequently used first-line therapy was sunitinib (66%), followed by sorafenib (20%) and pazopanib (10%), with a quarter of patients receiving 3 or more sequential TKI therapies.

Overall, the study found no significant differences in progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS) between the treatment groups, Dr Rink and his colleagues reported in Urologic Oncology. In subgroup analyses, however, CN was significantly associated with a 68% and 50% decreased risk of cancer-specific mortality in patients with sarcomatoid features and clear cell histology, respectively. Among patients with clear cell histology, CN was significantly associated with a 52% decreased risk of disease progression. The study found no superior survival by specific TKI treatment.


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“The potential advantage of CN in these patient groups may be attributed to a surgical tumor reduction of adverse histopathological features, that would otherwise potentially result in inferior oncological outcomes,” Dr Rink’s team wrote.

Individualized tailored decision-making will be of even greater importance in the growing treatment landscape of mRCC in the future, according to the investigators.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

References

Janisch F, Hillemacher T, Fuehner C, et al. The impact of cytoreductive nephrectomy on survival outcomes in patients treated with tyrosine kinase inhibitors for metastatic renal cell carcinoma in a real-world cohort. Urol Oncol. doi: 10.1016/j.urolonc.2020.04.033

Méjean A, Ravaud A, Thezenas S, et al. Sunitinib alone or after nephrectomy in metastatic renal-cell carcinoma. N Engl J Med. 2018;379:417-427.