Defining Recurrence in Metastatic RCC

Daniel J. George, MD: As for the question around switching therapies and disease progression, what really drives the decision to stop one therapy and move on to another is complex. There are multiple factors that weigh in to that, and these include factors that involve the patient. How well are they tolerating the therapy to factors that involve the tumor? How has the tumor responded initially? How is the tumor responding now? How is that tumor progressing? Is it progressing just in its existing tumor sites? Are there new sites? Is it a combination of both? These are all factors that we weigh in the decisions on therapy, and there’s probably no one right or wrong answer in any one case.

For me, as a treating physician for patients with metastatic renal cell carcinoma, I like to maximize the duration of that first-line therapy. And so, if I have a patient who has relatively asymptomatic disease growth of existing tumor lesions, I tend to keep them on treatment with that existing therapy, particularly if they’re tolerating it well. On the other hand, if they’ve had multiple dose reductions and interruptions, if they’re struggling to maintain quality of life on that therapy, that’s an indication for me, even with that slow progression, to consider a change in therapy.

On the other hand, if I have a patient that has a more rapid or more clinically significant disease progression, their cancer is starting to cause more symptoms. As in our case, more back pain associates specifically with disease progression in new spots in the spine or growth of existing spots in the spine. That, to me, is an indication to say, “OK, let’s switch therapies and let’s think about therapies that can work in that particular context, meaning can they palliate those symptoms?” Sometimes that might be a focal therapy, like adding more palliative radiation or a surgical resection of something that is causing a symptom that we’re concerned is immediately life-threatening, like a brain metastasis or pressure on the spinal cord. But it could also involve drugs that can shrink tumors, drugs that are known to shrink tumors and known to control growth, particularly when we’re seeing multiple areas involved. So, it’s not as amenable to say it’s a focal therapy of just one lesion.

Those are probably the factors, to me, that matter most: the tolerance in asymptomatic progression cases—the clinical progression in how to palliate that patient—in patients who have more aggressive multifocal disease progression.

Case Scenario 1: A 50-year old male with relapse of metastatic RCC

January 2014

• A 48-year old Caucasian man presented to his physician complaining of right upper quadrant discomfort and back pain
• CT scan of the abdomen and pelvis showed a large right renal mass with retroperitoneal adenopathy, largest node measuring 2.5 cm on right axis; metastatic lesion to T9, lytic
• The patient underwent cytoreductive nephrectomy, retroperitoneal node biopsy
• He was diagnosed with stage IV renal cell carcinoma, clear-cell histology, with metastases to bone and contralateral adrenal gland
• After radiation therapy to T8, he was then started on pazopanib 800 mg
• The first follow up scan showed a decrease in size of the adrenal lymph node
• The patient reported moderate diarrhea and mild fatigue which was controlled with antidiarrheal medication and rest
• He continues to do well with improved tolerance after dose adjustment to 600 mg

April 2016

• Imaging shows slow but steady progression in the adrenal lesion
• The patient complains of increasing back pain. He reports nausea and
• Pazopanib was discontinued and the patient was started on cabozantinib 60 mg