ASCO GU 2018: Current Role of Metastasectomy in Renal Cell Carcinoma

San Francisco, CA ( Dr. Leibovich discussed our current understanding of the utility of metastasectomy for metastatic renal cell carcinoma (mRCC). Beginning with a case with a common dilemma: A 56 year old with pT3aN0R0 RCC, who 3 years after surgery has a 2.3cm solitary pulmonary biopsy-proven clear cell renal cell carcinoma (ccRCC). He has a good performance status and is asymptomatic. What can you expect if you resect the nodule?

The EAU, ESMO, and NCCN guidelines all recommend metastasectomy for patients with a favorable risk profile. NCCN now uses the term “oligometastatic” in an effort to suggest that not only solitary metastases fall under this treatment paradigm. Our oldest data from Memorial Sloan Kettering originally demonstrated a 44% 5-yr OS for patients who had complete metastasectomy vs. 10-15% for those that didn’t. Since then, many other studies have found consistent survival benefits to receiving a complete metastasectomy; but of course, one could argue the strong role that patient selection plays in these findings.

As we learned from the many groundbreaking talks at GU ASCO 2018, the landscape for systemic treatment for mRCC is growing rapidly and with much better outcomes than we have enjoyed in the past. And while many of these agents (both TKIs and immune-oncologic (IO) agents) now have level 1 evidence for efficacy in mRCC, there is very little evidence for their role in combination with metastasectomy.

There are several potential rationales for performing a metastasectomy: Palliation, improving oncologic outcomes, or even attempting to delay or avoid systemic therapy that can be intolerable for some patients. In retrospective series, 61% of patients had only one site of metastatic disease, and those sites were usually resected if they were in lung, bone, lymph nodes, or the adrenal glands. Adrenal metastasectomy has the best 5–yr survival (60%). Though rare, pancreatic metastasectomy appears to also have a surprisingly high 5-yr OS (66%) if the lesion is isolated. 

Using the Leibovich mRCC risk criteria, multivariable analysis shows that complete metastasectomy confers a risk ratio of 0.5, which very significantly impacts the readout of the algorithm. Indeed, if the above patient was treated with metastasectomy, the algorithm would suggest he has a 5-year median survival; but if he did not have a complete metastasectomy, his survival would drop dramatically to 2 years. Previous work by Eggner et al. showed that in patients like our 56yo gentleman who is good-risk, metastasectomy is still beneficial (in fact, it appears to be beneficial in all risk groups). 

Dr. Leibovich discussed a multitude of other studies all pointing in the same direction: Metastasectomy offers improved PFS and OS to patients with oligometastatic disease.

Intriguingly, a recent prospective study assessing the role of an antitumor vaccine used in conjunction with metastasectomy found that the combination of surgery + vaccine improved survival even further than metastasectomy-alone. This is exciting data, because one can extrapolate the potential benefit of using combinations of metastasectomy with newer TKIs and IO agents to continue to expand the survival benefit of this procedure. 

Of course, surgery is surgery; and any surgery can come with complications. Meyer et al. published data on the complication rates after metastasectomy from different organs, showing that complications are neither uncommon nor insignificant. Hence, careful patient selection and appropriate informed consent is still key to achieving acceptable outcomes.

In conclusion, the role of metastasectomy for oligometastatic RCC has been cemented over several decades, with data consistently showing a survival benefit in patients who are treated with this option. However, minimal quality data exists to prove its efficacy. Well-selected patients can have durable DFS, and selection based on histology/grade, performance status, lab parameters, site of metastasis, metastatic burden, and interval to recurrence are all important variables to consider before moving to surgery.

As we learn more about the utility of IO agents, I believe that mRCC patient outcomes will continue to improve in general. However, I don’t expect to see the disappearance of metastasectomy as a standard treatment tool anytime soon.

Presented by: Bradley Leibovich, MD, Mayo Clinic 

Written by: Shreyas Joshi, MD, Fox Chase Cancer Center, Philadelphia, PA at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA