Treatment of Refractory Metastatic Renal Cell Carcinoma - Episode 1

Case Review: Symptomatic Metastatic Renal Cell Cancer

August 20, 2018

Thomas Hutson, DO, PharmD:The case we’re going to discuss today is of a 70-year-old woman who presents with symptomatic disease and is found on CT scans to have a lesion in her right kidney, as well as both adrenal glands and a thyroid nodule. Undergoes a right radical nephrectomy with pathology, indicating a clear cell renal cell carcinoma. A resection of 1 adrenal lesion, RFA (radiofrequency ablation) of the other and is placed on sunitinib therapy as initial management of her cancer. She’s on that therapy for approximately 7 months, and then has progression of disease. So, we enter in at that point to discuss what would be the most appropriate second-line therapy in this patient with relatively small volume, although intermediate-risk, clear-cell renal cell cancer. The patient elected to receive second-line therapy, and the patient was placed on lenvatinib and everolimus.

This particular case is somewhat unique in the setting that it is an intermediate-risk based patient, just based upon risk factor analysis using either the Heng criteria, or the Motzer MSKCC criteria, in that the patient has had the presentation within 1 year of diagnosis of metastatic disease. This is a presentation synchronistically of metastatic disease, but the amount of disease outside of the kidney is small.

The doctors who were treating her elected to proceed with what amounted to metastasectomy with radiofrequency ablation of one lesion as well as surgical resection of the other but did not attempt surgical resection of the thyroid nodule. Some of us would have considered that to render the patient NED (no evidence of disease), and at that point we would have just monitored the patient with proactive surveillance CT scans every 3 months. However, given that the patient did have 1 area of disease; that being the nodule in the thyroid; the doctors elected to start the patient on sunitinib therapy.

Now when one looks at how the patient responded to sunitinib therapy, we have no information about the patient’s general tolerability of the medication or the dosing. The patient had some disease control obviously that lasted 7 months, but ultimately there was progression. When we look at the length of time the patient had benefit—ie 7 months—we would say that that falls within the range of what one would consider standard for an intermediate-risk RCC patient, based upon the years of data that we’ve collected of the use of sunitinib as a frontline therapy. I would not say that this patient was exquisitely sensitive to VEGF therapy, just that they had the average response to VEGF inhibitor therapy.

Also, looking at the sites of metastases, the presence of a solitary thyroid nodule, although not rare in kidney cancer, is certainly not the usual presentation where most patients will have multiple pulmonary nodules, lymph node metastases prior to the development of rarer target organ involvement such as the thyroid.

When one looks at the presentation of this patient and the identifiable characteristics that one has available to them at the time of diagnosis, this patient clearly falls within the intermediate-risk category, whether one applies the more modern Heng criteria, which is based in the targeted therapy era, or one uses one of the other criteria such as the Memorial Sloan Kettering criteria, and that’s predominantly based upon the synchronous presentation disease. The patient without a doubt has one risk factor.

We also want to gauge whether or not the patient is tolerating the disease burden well. This patient is already symptomatic with fatigue, weight loss, despite having relatively small volume of disease. So, that certainly weighs in and is certainly affecting the patient’s performance status, which is not ideal.

Transcript edited for clarity.


A 70-Year-Old African-American Woman with Metastatic RCC

December 2017

  • A 70-year-old African-American woman presented to her PCP with loss of appetite, fatigue, abdominal pains, and blood in her stool
  • CT of the chest, abdomen, & pelvis: distal esophageal thickening and appearance of a solid mass on the inferior pole of the right kidney (3.4 × 2.6 cm); well-defined hypodense nodules in the right lobe of the thyroid (2.1 × 2.8 cm) and bilateral adrenal glands
  • Biopsy of renal mass revealed neoplastic cells with clear cytoplasm arranged in nests and mitotic figures suggesting clear cell carcinoma
  • FNA from the thyroid nodule revealed neoplastic clear cells on cytology
  • IHC; PAX8+, CAIX+, TTF-1(-)
  • Diagnosis; right-sided renal cell carcinoma with clear cell histology; thyroid and bilateral adrenal metastasis (T4N0M1)
  • She underwent right radical nephrectomy, right adrenalectomy, and radiofrequency ablation of left adrenal metastasis
  • She was subsequently started on sunitinib and achieved a partial response within 3 months

June 2018

  • Seven months later, the patient reports having increased fatigue
  • MRI shows progression in both adrenal lesions
  • Therapy was changed to lenvatinib plus everolimus