Eau 2018 survival analyses of patients with metastatic renal cancer treated with targeted therapy with or without cytoreductive nephrectomy database field definition

Copenhagen, denmark (urotoday.Com) in the cytokine era (1992-2005) addition of cytoreductive nephrectomy (CN) to cytokine therapy improved median survival from 7.8 months to 3.6 months in patients with metastatic renal cell cancer (mrcc). [1,2] the treatment for mrcc patients has changed drastically during recent years (figure 1). Two recent trials attempted to analyze the added benefit of CN to standard treatment of mrcc patients. These include the CARMENA study that had serious design issues and was closed after recruiting 456 patients, and the SURTIME study, that recruited 99 patients so far, and was negative for progression free survival (PFS).Targeted therapy

Due to significant difficulties in conducting prospective trials attempting to analyze the added benefit of CN to MRCC patients, we are only left with retrospective studies, and registry data.

A paper published in the journal of clinical oncology in 2016 tried to retrospectively analyze this question [1]. This was a retrospective analysis of the national cancer database (NCDB) in the US. Overall 15390 patients with mrcc treated with targeted therapy were analyzed. Two specific analyses were performed:

Figure 2 demonstrates the consort diagram of the study. The results showed a clear survival advantage in patients undergoing CN (17.1 vs. 7.7 months) (figure 3).Cytoreductive nephrectomy multivariable analysis also demonstrated that CN was a significant predictor of improved survival, with a hazard ratio of 0.49, p<0.001. The beneficial effect of CN increased with increasing survival time.

Aside from the obvious retrospective nature of the study with its associated selection bias, the major limitations include lack of data on the prognostic risk factors of the patients, including performance status, and lack of data on the type and duration of the lines of treatment patients received.

Whether this study helps us decide who should and who should not undergo CN is still debatable. Although this study demonstrates that CN has a benefit, in the real-world, CN is done less and less.Cytoreductive nephrectomy data from the SURTIME study demonstrates that the deferred CN approach appears to select out patients with inherent resistance to systemic therapy, who will probably not benefit the from the addition of CN.

In summary, younger male patients, with few comorbidities, with lower T and N stages, with better blood parameters, and better response to targeted therapy will probably benefit the most from CN. Patients who are good responders to targeted systemic therapy, with oligo-metastatic resectable disease, preferably in the lungs only, are the better patients to attempt a CN. CN is probably not very useful in patients with a life expectancy of less than 12 months, with +3-4 negative prognostic factors, who have bulky metastatic load, and who are non-responders to systemic therapy.Cytoreductive nephrectomy

Figure 3: clear advantage for cytoreductive nephrectomy in overall survival in the JCO paper assessing the effect of cytoreductive nephrectomy in metastatic RCC patients

Written by: hanan goldberg, MD, urologic oncology fellow (SUO), university of toronto, princess margaret cancer centre, twitter:@goldberghanan, at the 2018 european association of urology meeting EAU18, 16-20 march, 2018 copenhagen, denmark