SIU 2017: The Unmet Need in Locally Advanced RCC Treatment: Game Changers?

Lisbon, Portugal (UroToday.com) In this session, there were three well-respected Urologic Oncologists who were asked to talk about the single most important observation in the recent past. Each chose the area that they felt represented the most exciting discovery.

In this third and final Major Observation, Dr. Mulders discussed S-TRAC,1 the NEJM paper in which sunitinib was assessed in the adjuvant setting for patients with high-risk localized RCC treated with nephrectomy.

Patients who undergo major extirpative surgery for high grade localized or locally advanced RCC have a high risk of recurrence and outcomes similar to good-risk mRCC, but there are no good predictors for who develops those metastases. While there are numerous nomograms to risk stratify patients based on clinical charactertics (UISS, etc), these were utilized in the major adjuvant trials and have not demonstrated enough discriminatory value to show benefit of adjuvant therapy.

He briefly reviewed the history of adjuvant therapy trials for RCC, started with classic immunotherapy trials followed by the use of targeted therapy. He made some important points regarding the mode of action of targeted therapy – specifically as an angiogenesis inhibitor. Would it in principle work on micrometastatic disease?

Getting back to the S-TRAC study, it was the first positive trial for adjuvant therapy in this disease space. However, the ASSURE trial demonstrated no specific benefit in this same population.2 There are more trials reporting soon or ongoing. The pazopanib adjuvant study was also negative.

At this time, there is no recommended adjuvant therapy. However, there is indeed an unmet need for adjuvant therapy. Novel therapies such as immune checkpoint blockage may provide benefit that has not been convincingly seen with targeted therapy.

References:

1 Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy. N Engl J Med. 2016 Dec 8;375(23):2246-2254. Epub 2016 Oct 9. Ravaud A, et al.

2 Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial. Lancet. 2016 May 14;387(10032):2008-16. doi: 10.1016/S0140-6736(16)00559-6. Epub 2016 Mar 9.


Presented by: Peter Mulders

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 37th Congress of Société Internationale d’Urologie - October 19-22, 2017- Lisbon, Portugal
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