Complete Surgical Metastasectomy Remains Critical Option in RCC

Bradley C. Leibovich, MD

Complete surgical metastasectomy can more than double the life expectancy for many patients with metastatic renal cell carcinoma (mRCC), according to the results of a meta-analysis of observational data published in The Journal of Urology.

This analysis looked at 8 published cohort studies with a reported total 2267 patients with mRCC. The median overall survival range for patients who underwent a complete surgical metastasectomy was 36.5 to 142 months compared to 8.4 to 27 months for those who received an incomplete surgical metastasectomy.

“When we pooled the data from these multiple studies, it appears that complete surgical removal of metastatic disease is very beneficial for patients,” said Bradley C. Leibovich, MD, an author on the trial.

OncLive: Please give an overview of this research.

In an interview with OncLive, Leibovich, a professor of Urology at Mayo Clinic, discussed the benefits of surgery and the need for more effective drug treatments for patients with mRCC.Leibovich: Many patients with kidney cancer have a tumor that is found when it is localized, meaning confined to the kidney. Surgery in those patients is curative the majority of the time without the need for any additional treatment. Some patients don't need surgery at all. However, a portion of patients have a disease that has already spread to other areas of the body.

Unlike other cancers, traditional chemotherapy drugs don't work for kidney cancer. The drugs that we have help extend a patient’s life but they don't usually cure the disease. These drugs are most beneficial at holding things steady or causing a tumor to shrink modestly and then holding it steady. Sooner or later, the cancer starts to outsmart these drugs and when that happens, we switch from drug to drug, but eventually, the patient is likely to succumb to the mRCC.

We have had about 10 drugs approved by the FDA since 2005. Prior to 2005, there was only 1 drug ever approved by the FDA, which was approved in 1992. Prior to 1992, there was nothing. Over the years, our group at Mayo Clinic have had an interest in removing the disease to the fullest extent possible in patients that have metastatic disease. We have seen that some of these patients are durably cured. Patients that aren’t cured seem to live much longer than patients who don't have surgery to remove all of their metastatic disease.

The problem is that it’s a very small subset of patients who can have all of their disease surgically removed. Therefore many kidney cancer experts would argue that we are simply operating on patients that are going to do well no matter how you treat them. If there is so little disease that you can feasibly surgically remove it all, nihlists would say that those patients are likely to do well with other options of treatment.

Over the years, there have been publications trying to address that concern by comparing patients who have had disease completely removed to those who have not and to adjust for other factors that might be significant in terms of those patients’ prognosis. When we adjust for disease factors to make a fair and balanced comparison, it seems like complete removal of metastatic disease is beneficial for patients with metastatic renal cell carcinoma.

The purpose of this research was to pool the data from multiple studies that have been done in this area and attempt to eliminate the bias that’s inherent in looking backwards over time rather than doing this as a prospective clinical trial. In fact, when we pooled the data from these multiple studies, it does still appear that complete surgical removal of metastatic disease is beneficial for patients.

What other challenges in RCC need to be addressed?

Our hope and expectation is that this paper will continue to keep people aware of the potential benefit of completely removing metastatic disease and to assure that doctors in the community who are using these new drugs don’t forget that surgical removal of metastatic sites is potentially additive to the drug treatment in extending survival.We would like more effective drug treatments. Around the globe, we are working hard to come up with better regimens to treat patients with these medications. There is additional work that needs to be done to determine if there are other ways to approach this problem.

Regarding the impact of surgery we need to determine if treating patients with drugs prior to complete surgical resection would work even better. Would giving a limited period of drug treatment after complete surgical resection make things better? Our data so far would indicate that it is not the case. We’ve been doing genetic analyses on these patients looking at the genetics of the primary tumor, and the metastatic disease to determine if we can better predict which patients will do well with these treatments, and which drugs to give if and when they do have recurrent disease after resection.

Are there currently any ongoing trials looking at those challenges?

Is there anything else you would like to highlight?

The challenges and need for additional work is seemingly endless.We have an ongoing trial of complete surgical resection with drug treatment afterwards. There are multiple trials of new drug therapies. We have a program now where we take out the metastatic disease and grow it in an animal model and test various drugs to determine the best form of treatment for the patient. I think the take-home message is, despite the fact that we have many new drugs for treating kidney cancer, they are unfortunately rarely curative. The data seem to indicate that surgical removal of disease remains an integral portion of providing those patients with maximum extension of life. We don’t want people to forget about the potential positive impact of surgery and the overall improvements that we’re making in the care of these patients.

Zaid HB, Parker WP, Safdar NS, et al. Outcomes following complete surgical metastasectomy for patients with metastatic renal cell carcinoma: a systematic review and meta-analysis. J Urol. 2017; 197(1):44-49. doi: 10.1016/j.juro.2016.07.079