(UroToday.com) The landscape surrounding cytoreductive nephrectomy has been rapidly evolving over the last two decades in parallel to the growth of the immunotherapy armamentarium. During the kidney cancer session at the Society of Urologic Oncology (SUO, Dr. Jose Karam from MD Anderson Cancer Center presented a comprehensive look at this space and ways to improve the selection of patients for cytoreductive nephrectomy.
Dr. Karam started his talk by reviewing the history of cytoreductive nephrectomy and how it has evolved as advances have been made in the medical oncology field. Initial randomized controlled trials in the early 2000s demonstrated that upfront cytoreductive therapy for patients with metastatic or advanced renal cell carcinoma provided a survival benefit versus early cytokine-based therapy.
Given this evidence, cytoreductive nephrectomy became the standard of care. However, in mid-2010 more efficacious immunotherapies became available to patients prompting clinicians to reevaluate the continued role of cytoreductive nephrectomy. Early retrospective studies demonstrated a continued benefit to overall survival for patients undergoing surgery versus medication alone, however, the field recognized the need for higher-level evidence, and the CARMENA trial, Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma (CARMENA) was developed.
The CARMENA trial was a randomized controlled trial of sunitinib alone vs. surgery followed by sunitinib in 450 metastatic renal cell carcinoma (RCC) patients. The results demonstrated no benefit to the addition of surgery when patients were treated with sunitinib. This caused a radical shift in the treatment paradigm, with novel immunotherapies supplanting the role of surgery. However, Dr. Karam noted that post hoc and subgroup analyses did find that some patients still benefited from upfront cytoreductive nephrectomy. Given this and the conflicting results of retrospective studies clinicians have been slow to fully abandon upfront cytoreductive nephrectomy.
To that end, multiple researchers have sought to answer the question of whether we can better select patients for cytoreductive nephrectomy; looking at preoperative factors, pre-surgical therapy as a litmus test or biomarker, and genomics profiles. Multiple studies have shown that fit patents with less risk factors have improved survival with upfront cytoreductive therapy. This has led to the practice of using a trial of immunotherapy as a “litmus test” to establish whether a patient will benefit from surgery. Studies have shown that patients that progress while on therapy, regardless of the class of immunotherapy, have diminished overall survival (Figure1). Cancer genomics are actively being explored to develop new tools for identifying patients that would benefit from cytoreductive nephrectomy. While there are many promising studies, the technology is not quite ready for clinical application.
Given the complexity of this area, Dr. Karam finished by outlining his own clinical practice. This includes a multidisciplinary approach with patients being seen by both Urology and Medical Oncology prior to a joint conference, stressing the proper patient selection is key to successful cytoreductive nephrectomy, advocating that it still has a role for the appropriate patient.
Presented by: Jose A. Karam, MD, Associate Professor, Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
Written by: Adrien Bernstein, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Fox Chase Cancer Center, Philadelphia, PA, at the 21th Annual Meeting of the Society of Urologic Oncology (SUO), December 3-5, Virtual Conference