Metastatic site impacts survival in targeted RCC treatment

By Eleanor McDermid, Senior medwireNews Reporter

Bone and liver metastases may have the heaviest impact on the survival of patients receiving targeted therapy for metastatic renal cell carcinoma, suggest data from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).

This is consistent with previous findings in patients treated with cytokines. The current study included 2027 patients who between them received eight different agents targeting vascular endothelial growth factor (VEGF) and the mammalian target of rapamycin (mTOR).

Overall, 34% of patients had bone metastases and 19% had liver metastases. These impacted on their survival, with median overall survival times of 14.9 versus 25.1 months for patients with and without bone metastases and 14.3 versus 22.2 months for those with and without liver metastases.

Both types of metastasis were independent predictors for mortality, with bone metastases raising the risk by 40%, liver metastases by 42%, and the two combined by 82%, relative to metastasis in other sites (primarily the lung). The mortality risk was especially high for patients with multiple bone or liver metastases; their median overall survival time was just 10.1 months.

Bone and liver metastasis was also associated with IMDC risk group, with bone metastasis affecting 27%, 33%, and 43% of patients in the favorable-, intermediate-, and poor-risk groups, respectively, while liver metastasis was present in 23% of the poor-risk group versus 17% of the favorable- and intermediate-risk groups.

Furthermore, adding bone and liver metastasis to the IMDC predictive model significantly improved its accuracy, report lead researcher Toni Choueiri (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) and colleagues in European Urology.

In an accompanying editorial, Guru Sonpavde (University of Alabama at Birmingham Comprehensive Cancer Center, USA) and co-authors note that metastases were not prospectively identified, which could have given more weight to symptomatic ones, and that data on the volume of disease were not available.

However, they say there is accumulating evidence that the site of metastasis relates to tumor biology, and believe it is “not too far-fetched to imagine the site of metastatic disease as a potential predictive factor for benefit from specific agents in the future.”

They add: “Understanding whether a specific effect against a specific site is due to the amplification of a given pathway in this site of disease would be of great value.”

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