Moving on to the second patient scenario of renal cell carcinoma, panelists reflect on the treatment pathway for favorable risk metastatic disease.
Hans Hammers, MD, PhD:This is a patient who also presented in 2017 with hematuria. He’s now 59 years old. He had a large tumor with tumor thrombus. He underwent a left radical nephrectomy, was a clear renal cell carcinoma high-grade, 10.5 cm in the largest dimension. He had no evidence of metastatic disease and essentially cruised along with just some small pulmonary nodules that were really small and really not suspicious at that time. And then in 2019, for the first time, we saw an increase in the right middle lobe in the chest, and a new right adrenal gland lung nodule that was suspected to be problematic. And then things essentially worsened on subsequent scans in early 2020 with some very mild changes in the chest. But now we also had a new 1 cm hyper-enhancing lesion in the distal pancreas, which was biopsied and was found to be positive for renal cell carcinoma. So again, this is a patient 2017 until 2020 when it’s clear that there was a significant problem with recurrent disease. In this patient, we offer systemic therapy, but we also consider focal therapy in some of those patients. He had pancreatic involvement, and Dr Garant can probably expand on that as well. So the decision was made to send them to stereotactic radiation, [and] radiate the pancreas and the adrenal lesion. A few months later, 1 of the lung nodes was enlarging and he received additional radiation to that. And with that, there was stability in radiographic findings. But unfortunately, roughly a year later, he clearly progressed in multiple disease sites. [There were] multiple pulmonary lung nodules as well as a new and enlarging hepatic as well as intermuscular lesions, new right renal and osseous lesions, as well as enlarged mesenteric lymph nodes and [a] suspicious lesion in the proximal stomach. He was started on systemic therapy with lenvatinib [Lenvima] and pembrolizumab [Keytruda]. So PD-1/TKI [tyrosine kinase inhibitor] regimen. He had some blood pressure issues that needed some [medication] adjustment and also some fatigue. He also had some dehydration for which he required additional counseling on when to take breaks and also maintain his hydration status. But imaging studies were very favorable essentially demonstrating response to therapy in all disease sites, and he continues essentially, on this particular regimen now for more than a year with a continued benefit. In March of this year, he had a complication, developed a rectal fistula that required surgical repair. And the decision was made to stop lenvatinib and continue on immunotherapy alone. So this is not an uncommon way to treat favorable-risk patients. Dr Garant, what do you think about this case and how does it fit into the practice or the treatment pattern that we often observe here at UT Southwestern [Medical Center]?
Aurelie Garant, MD: Absolutely. So this is a gentleman who had favorable-risk disease status post radical nephrectomy, and limited sites of progression, approximately a year and a half after surgery situated in 1 adrenal gland and the pancreas. These are patients who are good candidates for definitive intent of stereotactic ablative body radiotherapy. These are outpatient-based treatments, which require some pretty rigorous immobilization because the treatment accuracy is typically in the order of 5 mm or less. So we’re able to treat these with extreme amounts of accuracy in over classically 3 to 5 sessions. Although sometimes it can be done in only 1 outpatient-based treatment session. Historically, kidney cancer histology was felt to be radioresistant, but there have been some emerging studies which revealed that very brisk exposure to radiation over a few sessions actually leads to profound responses in patients. And so, in this case, I suspect that this patient probably got something along the lines of 3 to 5 fractions of treatment to those 2 sites. The main areas of concern from our perspective are the small bowel and the upper abdominal cavity. The bowel viscus is actually quite radio sensitive, so we plan carefully to avoid the small bowel when aiming at the pancreas and the adrenal area, and also very careful with the spinal cord. Other tissues in the vicinity are typically more resilient, including vessels. So I think that this was a good candidate for SBRT [stereotactic body radiation therapy]. It may have been done as a part of our prospective phase 2 trial at the time. And so, it seemed like a good scenario for that particular approach.
Hans Hammers, MD, PhD:And what does a surgeon think about patients like these? Obviously, probably not a patient that you would have sent for surgical resection. We often talk about oligometastatic disease to kind of try to figure out who are the best patients who would benefit from focal therapy, either surgery, surgical recurrence. Let’s say it was just, for example, an adrenal nodule surgery would have been something to be offered. Sometimes even we go after pancreatic lesions as well. How do you and Dr Garant, Dr Margulis, think about how do you define oligometastatic disease? And how do you select the best patients for this particular approach?
Vitaly Margulis, MD: For me, obviously this is a multifactorial decision. I think some of the factors that I’ve taken to the equation would be time from original surgery to reoccurrence in one of those sites. If it’s something within a year, certainly I’m less enthusiastic. How many sites were involved? In this case, you have pancreas, adrenal, lung, so I think the surgical approaches are less palatable just because of the morbidity associated with surgery. Certainly, this patient was 2 to 3 years after his initial nephrectomy, had a single site or even, for example, a growing tail of pancreas in adrenal site. Those could be addressed very effectively with surgery. We now have minimally invasive approaches to this. A patient could undergo easily a robotic adrenalectomy and distal pancreatectomy and essentially go home the next day. And so things like that. What is a prior surgical history? How hostile will be the abdomen? How much scar tissue would the surgeons have to deal with? Sometimes our radiotherapy colleagues may have some difficulties for abovementioned reasons. Proximity to the bowel, for example, so on and so forth, where surgical approaches may be more palatable. But to me, honestly, the clinical trajectory of the disease probably is one of the most important factors.
Hans Hammers, MD, PhD:Dr Garant, how do you guys define oligometastatic disease?
Aurelie Garant, MD: That is an excellent question. In our experience, typically 1, 2, or 3 metastases is an easy number to remember, especially in the IMDC [International Metastatic RCC Database Consortium] favorable-risk patients. In the extracranial setting, we’ll typically see that some will go up to 5 metastases. The intracranial scenarios are a little bit different and definitely a topic of further discussion and evolving discussion. But yes, I would say right now in the community, up to 5 lesions is typically broadly accepted as the oligometastatic paradigm. And also, we consider normal tissues around what we want to ablate in estimating our chances of success.
Hans Hammers, MD, PhD: Great. Very good.
Transcript edited for clarity.