State-of-the-art Lecture Immunotherapy: Impact from Surgeon’s Point of View
Dr. von Rundstedt made the important point that RCC is still very much a surgical disease, with 5-year overall survival (OS) probabilities of 65-85% for patients with pT2N0 RCC undergoing radical nephrectomy (RN), 47-68% for those with pT3aN0, and 43-72% for pT3b/cN0. However, the 5-year OS remains quite dismal for patients undergoing RN for pT4 tumors (28%). Surgery very much plays an integral role in high risk or advanced disease, including cytoreductive nephrectomy and metastasectomy, in addition to being part of a multimodal approach that may include neoadjuvant or adjuvant systemic therapy. Although the published literature for metastasectomy are not prospective nor standardly report use of systemic therapy agents, 57-65% of patients have single site metastasis and single lesion pulmonary metastasis have favorable outcomes with a median disease-free interval of 36 months.
We underestimate the natural history of pT3 RCC, according to Dr. von Rundstedt, since 56% of these patients are clinical T1/T2 and 26% will have disease recurrence after median follow-up of 14 months. This data provided much anticipation for the recently reported adjuvant systemic therapy trials, however the results of these trials have been somewhat underwhelming. The ASSURE trial (adjuvant sunitinib or sorafenib vs placebo) showed no difference in disease free survival (DFS), while S-TRAC (adjuvant sunitinib vs placebo) did show an improvement in DFS. Notably, 28% of patients had to discontinue treatment secondary to toxicity and OS endpoints have yet to mature. With regards to adjuvant immunotherapy, the Immotion Trial 010 is currently recruiting for 12 months of adjuvant atezolizumab vs placebo for all renal cancer histologies (≥pT1, any T and positive N). In the neoadjuvant setting, preliminary data from a Johns Hopkins series testing neoadjuvant nivolumab are encouraging from a safety standpoint as we await mature clinical outcome data. The Prosper Trial (neoadjuvant nivolumab vs immediate resection) is also underway.
Dr. von Rundstedt concludes that even in the immune therapy era, surgery remains the only chance at disease cure. There are exciting neoadjuvant immune therapy trials ongoing with an appropriate safety profile. This is an excellent opportunity for surgeons to get involved.
Speaker: Friedrich-Carl E. von Rundstedt, University Medical Center, Jena, Germany
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto
at the #EAU17 - March 24-28, 2017- London, England