18th Meeting of the EAU Section of Oncological Urology (ESOU21)

ESOU 2021: Is Cytoreductive Nephrectomy Still Alive? When and Why?

(UroToday.com) The third renal cancer session at the 2021 European Association of Urology (EAU) Section of Oncological Urology (ESOU) Virtual Annual Meeting focused on the management of patients with advanced and metastatic disease. In this session, Dr. Axel Bex provided his perspective on the role of cytoreductive nephrectomy today, including both indications and rationale.

Dr. Bex began highlighting guideline recommendations from both the European Society of Medical Oncology (ESMO) and the EAU which emphasize that cytoreductive nephrectomy should not be considered the standard of care for patients with asymptomatic primary tumors who require systemic, on the basis of the CARMENA and SURTIME trials. However, the EAU guidelines recognize that patients with very low metastatic burden may be suitable for upfront cytoreductive nephrectomy following discussion at a multidisciplinary tumor board.

Notably, these studies were conducted in the era of tyrosine kinase-based targeted therapy. However, immune checkpoint-based therapy has become the standard of care for most patients with first-line metastatic renal cell carcinoma. Dr. Bex highlighted that the pivotal trials of immune checkpoint inhibition demonstrated the benefit of this approach in patients with the primary tumor in place. This, in Dr. Bex’s view, supports the idea that we can defer surgical resection in favor of systemic therapy as became the norm based on data from CARMENA and SURTIME.

He then presented a number of potential scenarios, highlighting the value in particular of the potential curative role of cytoreductive nephrectomy among patients who have a complete response at metastatic sites.

potential curative role of cytoreductive nephrectomy
Dr. Bex then highlighted the case of a gentleman with cT3a cN1 M1 who received nivolumab and ipilimumab who, despite good response, developed grade 3 colitis and required treatment adjustment. Thus, with a complete response at metastatic sites, cytoreductive nephrectomy offered the opportunity for a drug holiday. Notably, there was significant downstaging of the primary tumor.

Among patients receiving nivolumab and ipilimumab treated with the primary tumor in place, Dr. Bex highlighted that those who have good responses to the primary tumor also have generally good responses in their distal disease. Among these patients, those who have a complete response at distal sites were offered cytoreductive nephrectomy.

Moving forward, there are two planned Phase III trials assessing cytoreductive nephrectomy in the era of systemic therapy with immune checkpoint inhibitors, NORDIC-SUN and PROBE Trial. Each of these uses the former experimental arms from CARMENA and SURTIME, starting with systemic therapy.

While these trials are ongoing, Dr. Bex feels that there remains a role for cytoreductive nephrectomy, either upfront in patients with low volume disease for whom observation of the primary is being considered and in other patients in a deferred manner when a complete response is demonstrated at distant sites.

Presented by: Axel Bex, MD, PhD, Consultant Clinical Lead Specialist Centre for Kidney Cancer, The Royal Free London NHS Foundation Trust, Associate Professor UCL Division of Surgical and Interventional Science, London, United Kingdom

Written by: Christopher J.D. Wallis, MD, PhD, FRCSC, Instructor in Urology, Vanderbilt University Medical Center, Nashville, Tennessee, Twitter: @WallisCJD during the 18th Meeting of the EAU Section of Oncological Urology (ESOU21), January 29-31, 2021