GU Oncology Peers Explore Early Therapy Approaches in Low-Volume mRCC

Chandler Park, MD

Medical Oncologist

Norton Cancer Institute

Advisory Dean/Clinical Professor

University of Louisville Medical School

Louisville, KY

DISCUSSION QUESTIONS

• What proportion of your patients with metastatic renal cell carcinoma (mRCC) have favorable-risk RCC with low-volume, indolent disease requiring only observation after left nephrectomy and adrenalectomy?

Chandler Park, MD: Approximately what proportion of your patients with metastatic RCC have favorable-risk disease like this?

Edmond Bendaly, MD: Not many in my practice, maybe 10% with indolent disease on diagnosis for years.

Park: Yes, that's what it’s like in my practice, maybe 5% to 10%. Typically, what ends up happening is if they end up with a spot in their lung 1.5 years later, it's likely they had metastatic disease at surgery. It was just too small to be seen on radiology and so this is not the typical presentation, but it does happen. Does anybody else have any favorable-risk patients in your practice [for] more than a year since you decided [to observe]?

Melhem Jabbour, MD: I have one; she has a lung metastasis, and she's been now 16 months still with no treatment. I've been watching her lung lesion because I have biopsy and I confirmed it, and she has vitiligo. So I said, “We’re going to watch you.” In her last CAT scan, the lesion was smaller. Because I confirmed by biopsy, I said I would watch her by CAT scan, and she's been doing [well]. As Dr Bendaly said, they don't usually come [without] either bulky disease or and brain metastases, but for this one I'm happy [to not give] treatment and I’ll be watching her.

Murtuza Rampurwala, MD: I had a patient who was diagnosed in 2000 with a radical nephrectomy a year later, with lung metastasis…and an abdominal metastasis [which were] resected, and then was put on a trial in 2002. They had adverse events a month later and left care. They showed up in the emergency department in 2017 with widespread metastatic RCC, exactly the same pathology from 16 years earlier. They received a year of nivolumab [Opdivo] at that time and had transaminitis with liver function tests in the 1000s range, came off slow prednisone taper, now has been off therapy for 6 years, and is doing well.

Anand Patel, MD: I’ve had a couple of people with nephrectomy bed occurrences with small nodularity. Urologists don't love to go back in. But in the couple cases I had on repeated scans, it was only there. One had an adrenalectomy with mild postoperative problems. Another had major complications and had splenectomy and major surgery.

Park: Those [stage T3 RCC cases] with renal pelvis invasions are very risky. You have these 3-cm masses in the kidney, and it goes into the renal pelvis. You're not thinking that it's going to recur, but that's a high-risk disease there…. But those are the things that I've seen show up later.

What about SBRT [stereotactic body radiotherapy] if they have a lung lesion? Does anybody use SBRT for these favorable-risk patients with 1 or 2 lesions, or even surgery?

Jabbour: I do. Why not?

Park: Yes, I do as well.

Mohamad K. Khasawneh, MD: I would if there is a single metastasis. I had a patient with a single rib lesion confirmed to be RCC; we removed that. If there is solitary metastasis, there are data to support that, though 50% of those patients tend to be in long-term remission if you do metastasectomy. The adjuvant pembrolizumab [Keytruda] trial did include some of those patients with resected M1 disease and considered them as high-risk patients.¹ You can also consider after resection of solitary metastases to give those patients adjuvant immunotherapy.

Park: Along that line, if you had a high-risk stage III, you decide to start adjuvant pembrolizumab based on KEYNOTE-564 [NCT03142334], and then they end up with 2 lesions in the lung, would you switch treatment? Would you do SBRT? Would you add cabozantinib [Cabometyx]?

Isoken Koko, MD: I would switch therapy.

Christos Kyriakopoulos, MD: I think it depends. Obviously, I would probably stop the pembrolizumab because the patient now has metastatic disease, so there is no point continuing adjuvant treatment, and then it depends on the size of the new tumor growth. If it's too small and it's not growing, and it's rather indolent, I might continue with observation. If it's growing, then I might try SBRT or something along those lines.

Park: That’s the reason I picked 2 [lesions]. If it's 3, I would switch, 100%. Two, maybe, if it's slow, maybe 6 months in, you do SBRT 1 time. If it happens again, you move over. Because then if they experience progression on pembrolizumab, you're not justified to do a CTLA-4 inhibitor there. You have to consider cabozantinib, and you can't continue with immune therapy. You're locked in with cabozantinib and maybe lenvatinib [Lenvima] plus everolimus there. It’s a tricky situation that all of us deal with in our practice, because it's not textbook.

_Reference:

_{1. Choueiri TK, Tomczak P, Park SH, et al; KEYNOTE-564 Investigators. Adjuvant pembrolizumab after nephrectomy in renal-cell carcinoma. N Engl J Med. 2021;385(8):683-694. doi:10.1056/NEJMoa2106391}