Treatment of Refractory Metastatic Renal Cell Carcinoma - Episode 3

Role of Cytoreductive Nephrectomy in mRCC

August 20, 2018

Thomas Hutson, DO, PharmD:Another area of change has been cytoreductive nephrectomy, which historically has been a standard of care in the management of this cancer. When one looks at the history of why we would do cytoreductive therapy knowing that almost all other cancers do not do this type of therapy in metastatic setting, it comes down to an understanding that cytokine-based treatments did not produce responses within the primary tumor site.

So, therefore, resection of the primary tumor, and then going on to interferon IL-2 made sense. This was coupled with single institution reports retrospectively of benefit to patients who received cytoreductive therapy going on to frontline therapy, as well as data from the large international consortium of several thousand patients showing that there was benefit in patients who received cytoreductive nephrectomy and went on to modern therapy such as the TKIs.

We’ve long awaited prospective data. Prospective data have finally been released, as a presidential presentation, which showed in the S-TRAC results that cytoreductive nephrectomy was noninferior to sunitinib therapy in intermediate-and poor-risk patients.

Now one could quickly look at this data and say, “Well intermediate and poor-risk, is this all the patients?” And I would say that it is the bulk of the patients. Twenty percent to 30% of patients that we see in clinic are in the good-risk category. In that setting, almost everyone would proceed forward with cytoreductive nephrectomy followed by frontline therapy if there was residual disease. However, in the intermediate- and poor-risk patients, those that are more symptomatic, such as the patient we’re discussing now, one gets pause as to whether cytoreductive nephrectomy is beneficial.

The S-TRAC trial shows that it’s noninferior, but it is not inferior or superior. So, therefore, we’re left with some feeling of comfort that cytoreductive nephrectomy was not harmful, but it’s not clear still who it ultimately benefits.

When I discuss this data set with surgeons in the United States, many of them do not feel that they’re going to change their practice. Already we are cautious in who we do cytoreductive nephrectomy for. So, in patients that are very symptomatic, we will often not do cytoreductive nephrectomy, and these are the same patients that have poor performance status; have large volume of tumor outside of the kidney. We would proceed directly into frontline therapy.

In patients who may be intermediate- or poor-risk but are not having a lot of symptoms from their cancer, and we believe that they would survive a surgery and be able to go on to frontline therapy, then we will proceed with cytoreductive therapy. The trial was beneficial in the sense that it provided data in support of cytoreductive nephrectomy, but it also provided data in support of sunitinib. We still have to individualize our choice of therapy to the patient that we are seeing in front of us.

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