EAU 2018: Surgical Safety of Immediate versus Deferred Cytoreductive Nephrectomy in Patients with Synchronous Metastatic Renal Cell Carcinoma - SURTIME

Copenhagen, Denmark (UroToday.com) Targeted therapy, including mTOR-inhibitors and tyrosine-kinase inhibitors, have drastically changed the landscape of the management of advanced renal cell carcinoma. Cytoreductive nephrectomy (CN) in the pre-targeted therapy era was the standard, but recent evidence suggests that a period of targeted therapy prior to CN may be an effective alternative approach to immediate CN. 

SURTIME, an European Organisation for Research and Treatment of Cancer (EORTC) randomized trial (30073), comparing sunitinib prior to CN vs. immediate CN, demonstrated that the sequence of CN and sunitinib did not affect progression free rate (PFR), though there may have been a signal suggesting survival benefit with deferred CN. Regardless, some of the cited concern anecdotally was that targeted therapy prior to CN may results in increased adverse events.

In this sub-analysis, the SURTIME Dr. Axel Bex reported surgical safety outcomes from both arms. Briefly, the study closed after 5.7 years due to poor accrual, at which point 99 patients had enrolled and median follow-up was 3.3 years. 

In the immediate CN arm, 46 of 50 patients had CN. In the deferred CN arm, 40 of 48 had post-sunitinib CN. Importantly, in the course of treatment with sunitinib, none of the primary tumors in the deferred arm became unresectable and only 2 patients had a sunitinib-related delay of CN > 2 weeks. 

AEs related to surgery (All grades and Grade 3-4) occurred in 52.2% (95% CI 36.1-63.9) and 28.2% (17.3-42.5) of patients in the immediate arm and 52.9% (30.7-60.2) and 27.5% (16.1-42.8) of patients in the deferred arm, respectively, although the number of intraoperative AEs were higher in the immediate arm. Postoperative AEs Clavien-Dindo ≥ 3, 30-day readmission/ prolonged hospitalization and in-hospital mortality were 6.5%, 13% and 4.3% in the immediate arm and 2.5%, 7.5% and 2.5% in the deferred arm, respectively. There were also no differences for surgery time, blood loss and hospitalization.

They also present reduction in tumor size related to pretreatment. The reduction in size ranged from 0-90% reduction! A small proportion of patients grew 0-20%. The authors attribute some of this reduction in size and reduction of neovascularization may have contributed to the lower adverse events in the pretreated group. 

It should be noted that this analysis is a secondary analysis for the study, and as such, it wasn’t powered for this analysis. Dr. Bex pointed this out in his oral presentation. However, despite that, based on pure numbers, the use of pre-CN targeted therapy is not associated with progression to unresectable disease, worse intra-operative outcomes or worse post-operative outcomes.

One of the audience members asked if they noted anecdotally if there was difficulty at the time of operation due to scarring/adhesions (based on anecdotal evidence from the neoadjuvant studies). However, Dr. Bex felt that the surgeries were in fact somewhat easier – and in some cases, he was able to perform laparoscopic nephrectomy (instead of open nephrectomy) or even complete a partial nephrectomy. 

Presented by: Axel Bex, The Netherlands Cancer Institute, Dept. of Urology, Amsterdam, Netherlands

Written by: Thenappan Chandrasekar, MD Clinical Fellow, University of Toronto, twitter: @tchandra_uromd at the 2018 European Association of Urology Meeting EAU18, 16-20 March, 2018 Copenhagen, Denmark

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