The Changing Treatment Landscape and the Role of Surgery in RCC

Gennady Bratslavsky, MD, professor and chair of the Department of Urology and director of the Prostate Cancer Program at Upstate Medical University in Syracuse, New York

The role of surgery for renal cell carcinoma (RCC) and strategies used for treatment are ever evolving. As options for systemic therapies continually improve, many clinicians are opting to spare patients from undergoing procedures.

Gennady Bratslavsky, MD, professor and chair of the Department of Urology and director of the Prostate Cancer Program at Upstate Medical University in Syracuse, New York, recently hosted a presentation on the role of surgical in management in RCC at the 15th Annual Interdisciplinary Prostate Cancer Congress® and Other Genitourinary Malignancies, hosted by Physicians’ Education Resource®, LLC (PER®).

“I still think that there will be appropriately selected patients [for whom] surgery will remain the first and potentially the main type of treatment. We may even include metastasectomy [for some as] that has been used for years,” said Bratslavsky.

In an interview with CancerNetwork®, Bratslavsky spoke about what role surgery currently plays in RCC, new strategies on the horizon, and trials he is most excited to see read out.

What does the future hold for surgical management of RCC?

This is an evolving landscape. We are going to try to operate less on patients who we can avoid surgery, we’re going to try to prognosticate better and see who can be spared. The term intervention-free survival is something that will hopefully be used more and more. Some trials are being designed, for example, in a role for renal biopsy where type of surgery or timing of surgery may be affected.

The role of surgery for more advanced disease is also ever changing. Obviously, the dogma that every metastatic kidney cancer can be removed is wrong, [but] his can still render patients disease free and offer a durable long-term survival.

What adjuvant and neoadjuvant strategies for RCC are on the horizon?

The adjuvant [therapy] space is finally having some promise with the recently published KEYNOTE-564 trial [NCT03142334]. Adjuvant pembrolizumab [Keytruda] certainly [provides] an opportunity for us to expect and hope for disease-free survival [DFS]. Most of the adjuvant trials to date have not been more successful [than KEYNOTE-564]. Even in the S-TRAC [NCT00375674] trial of adjuvant [sunitnib; Sutent] utilization for a year after nephrectomy in patients with the kidney cancer that were found to be high risk, the presence of DFS never translated into overall survival [OS].

While KEYNOTE-564 is yet to mature—to demonstrate whether its use in the adjuvant setting would help with OS is yet to be determined—there is certainly quite a bit of hope that after 2 years of follow up, we’re starting to see a promise and a strong signal that this DFS may translate into OS, although this has yet to be seen. The recently completed PROSPER trial [NCT03055013] is bringing another opportunity for us to evaluate the role of immunotherapy in the neoadjuvant as well as the adjuvant setting for high-risk patients. There are many unanswered questions. Even if we identify an agent that is effective in improving DFS, we will always question the patients who would have not recurred and still would be subjected to therapy. There is still an ongoing need for better identification of these patients that are most likely to recur beyond our standard clinical variables that have been traditionally used in designing the trials for both neoadjuvant and an adjuvant therapy.

Are there any ongoing trials in RCC that you’re eager to see the results of?

Any research [conducted] has an enormous impact [on] the molecular subcategorization of renal neoplasms, the understanding of genetics, branched evolution, our ability to detect the circulating tumor DNA, and the numerous structures that still contain many of the genetic material and prognostic information. All of this has an enormous potential [for clinical impact].

We’re continuously learning about new pathways that may bring in more systemic options, with the biggest breakthrough [being] in our continued appreciation of how heterogeneous kidney cancer is as a disease, how heterogeneous the molecular characteristics are, and how heterogeneous the clinical course and the metastatic potential of each tumor is. These are not tumors that are created equal. They possess very different clinical behaviors and opportunities for targeted or immunotherapies. Research is strong.

Our lab at SUNY Upstate Medical University focuses on the role of molecular chaperones in identification of potential targets and how activity of chaperones can be modified. Our lab has been creating new avenues for therapeutics. Numerous centers and laboratories are doing a great job in identifying these new avenues into how this cancer can be targeted or identified, and even the identification of some biomarkers for better disease response. [There are many paths] that we’re trying to tackle from different angles.

Reference

Choueiri TK, Tomczak P, Park SH, et al. Adjuvant pembrolizumab after nephrectomy in renal-cell carcinoma. N Engl J Med. 2021;385(8):683-694. doi:10.1056/NEJMoa2106391