Hutson Dives Into Controversial Depths: When Is Nephrectomy Appropriate in RCC?

In patients with renal cell carcinoma (RCC), factors that determine whether a partial or full nephrectomy should be performed include tumor location and size, but efforts should be made to perform partial nephrectomies whenever possible to preserve kidney function, according to Thomas E. Hutson, DO, PharmD, FACP. Sometimes nephrectomy is not the best option for a patient, and that continues to be an area of active debate, Hutson added.

“In 2021, doing a partial nephrectomy would be considered a quality indicator. We want to ensure that the urologist is performing nephron-sparing surgeries when they can and that they do not shy away from them,” Hutson said. “A cytoreductive full nephrectomy is actually a very easy procedure, and it is more difficult to do a partial nephrectomy, but we should consider that if it can be done so that we can save kidney function for our patients.”

In an interview with OncLive® during a 2021 Institutional Perspectives in Cancer webinar on RCC, Hutson, the director of the Urologic Oncology Program and co-chair of the Urologic Cancer Research and Treatment Center at Baylor University Medical Center in Dallas, and a professor of medicine at Texas A&M College of Medicine, shared the case of a patient with RCC who presented with metastatic lymph node disease and detailed what factors should be taken into consideration when determining whether nephrectomy is appropriate.

OncLive®: Could you provide an overview of the second case that you shared during the program?

The second patient was a 48-year-old man, who is younger than the traditional median age [that we see with a] diagnosis of kidney cancer, which is essentially around [64 years] of age. He came into the clinic with symptoms of acute left flank pain and he had a history of intermittent urinary tract infections. On a workup of this, a CT scan revealed a renal tumor on the left side that measured about 7 cm in diameter. [He] also [had] pathologically-enlarged lymph nodes, not only around the kidney, but lymph nodes in the retroperitoneum that would be considered to be metastatic sites of disease.

Would a nephrectomy be considered for this patient?

In this situation, I would support doing a nephrectomy. However, we [would] do this to try to volume reduce the patient, even though we recognize that by going into the surgery we are going to leave disease behind. I mentioned there [he had] metastatic lymph nodes beyond the field of resection. If someone was able to fully resect the cancer—whether it is in the lymph nodes, the adrenal gland, or even in the liver—and the intention was to go in and do a complete resection, then I would absolutely support that. I would support doing a nephrectomy.

You have to take a step back and wonder whether nephrectomy is ultimately going to benefit [these patients]. We saw data from two phase 3 trials published a few years ago, the CARMENA [NCT00930033] and SURTIME [NCT01099423] trial, that suggested that we can do harm to patients if we proceed with aggressive cytoreductive nephrectomies in those settings. The other thing is that we recognize that our newer agents, our immunotherapy agents and our newer TKIs, will provide benefit even if the kidney is in place. That is where the controversy is today: defining who we should do nephrectomy on.

What factors do you consider when determining whether a radical or partial nephrectomy is optimal?

That is really a surgical decision, and it depends not only on the surgical skill, but on where the tumor is located in the kidney in relationship to the blood vessel supply. If the tumor is located in the poles of the kidney, then that is a cancer that can be handled by a partial nephrectomy. As tumors get larger in size, above 5 cm or 6 cm, or if they are located in the middle of the kidney, then sometimes all you can do is sacrifice the entire kidney.

This patient did undergo a radical nephrectomy and a lymphadenectomy was performed, so all the lymph nodes were removed; that put him in a surveillance category. Sometimes, community oncologists are asked by the urologist to give therapy in this setting with no evidence of disease remaining, and the current recommendation would be not to do that. We have no evidence that starting someone on therapy when we don't have visible evidence of cancer is of value, and we have nothing in that setting to follow to determine whether there's benefit. The recommendation would be to monitor patients with serial CT scans. Generally, in my practice, we are doing these every 3 months, and we are looking for evidence of disease recurrence.

Our patient presented with what would be metastatic lymph node disease, but he was amenable to complete surgical removal, and was placed into a category of no evidence of disease and high risk of recurrence. He was monitored expectantly and at 1 year of follow-up, he presented with multiple abdominal enlarged lymph nodes. In hindsight, he had micrometastatic disease outside of the surgical field. At the time of this recurrence, he had normal electrolytes, a good performance status, and he was felt to be in the favorable-risk classification by both the Memorial Sloan Kettering Cancer Center criteria and the International Metastatic RCC Database Consortium criteria, and the patient elected to start therapy.

Would you start therapy for this patient right away, or monitor them for a period of time?

We know that monitoring patients with metastatic disease can be appropriate in some situations, but it is becoming less so because we know that immunotherapy can work well in patients with small-volume disease. It is still worth considering in patients with very small disease. Sometimes, you can discuss monitoring those patients until there's more significant progression. In this patient, he did have abdominal disease and it was not small, so the patient and I elected to proceed with systemic therapy.

What option did you choose and why?

We are left to look at our National Comprehensive Cancer Network guidelines. In the favorable-risk category, immunotherapy-based regimens are listed; this includes axitinib [Inlyta]/pembrolizumab [Keytruda], axitinib/avelumab [Bavencio], and now, cabozantinib [Cabometyx]/nivolumab [Opdivo], as well as single-agent oral TKIs.

After discussing with the patient, he elected to go on axitinib/avelumab. He was on therapy for 3 cycles and started developing adverse effects [AEs], including hypertension, and an ACE inhibitor was started for that. His CT scans after his second cycle was done to assess for benefits and showed stable disease. At 6 months of follow-up, unfortunately, he had progression in his lymph nodes, with new metastatic lesions in his abdomen, and the largest size of disease as 2.7 cm. He [had] progression of disease earlier than we would have hoped with an immunotherapy/TKI [combination]. The question now becomes, do you continue on this therapy, or do you switch to a second-line treatment?

What factors to you consider when determining whether to stay on therapy or switch to another regimen?

The decision was based upon a of couple of different factors. We looked at the different agents, quality of life, performance status, the characteristics of disease, where it was located, and we ultimately thought it would be in the patient's best interest to proceed forward with a different therapy. We chose cabozantinib as a preferred second-line agent, and the patient's best response at 3 cycles of therapy was stable disease. The patient was able to stay on therapy and achieved a partial response. After 18 cycles of cabozantinib, he developed progression within his liver, so we had a progression-free interval of 18 months on second-line cabozantinib.

As far as AE management goes with cabozantinib, we want to monitor our patients frequently. Generally, we start off with every-2-to-3-week monitoring, and once we have established an understanding with the patient on what their AEs are going to be and they are comfortable, we back off into the frequency of maybe 6-to-8-week monitoring. We monitor for blood pressure, mouth sores, diarrhea, and hypertension. The biggest thing to do when starting an agent is to ensure that the patient understands the potential AEs and that you may need to lower the dose.