TKI in Poor-Risk Advanced Renal Cell Carcinoma - Episode 1

Case Based Overview: Poor-Risk Advanced Renal Cell Carcinoma

February 7, 2020

Earle Burgess, MD:This patient is a 68-year-old male who presented with a 6-week history of painless gross hematuria. He has a past medical history of medically controlled hypertension and hypercholesterolemia. He tells us that he has been fatigued recently, has an approximate 10-pound weight loss. He’s able to meet his activities of daily living, but he’s unable to work due to fatigue. He tells us that he spends more than half the day, however, on his feet and active.

Laboratory assessment showed that he had a hemoglobin of 11.4 g/dL, a calcium level of 11.2 mg/dL. His hepatorenal function was normal. He had a normal lipid panel. He underwent imaging including a CT [computed tomography] of the chest, abdomen, and pelvis. This showed a large 8 cm renal mass, associated para-aortic lymphadenopathy, and lung metastasis.

The patient then underwent a cytoreductive nephrectomy and was found to have a pathologic T4 lesion that was consistent with clear cell renal cell carcinoma [RCC]. He was then initiated on treatment with ipilimumab and nivolumab for induction of 4 courses, after which he was found to have a partial response. He subsequently received 6 cycles of maintenance nivolumab followed by progression. At time of progression he was transitioned to cabozantinib monotherapy, 60 mg daily, which he continued for a total of 9 months followed by subsequent progression.

This patient is a typical presentation for someone with advanced kidney cancer presenting with poor-risk disease. Based on the available scoring systems that we commonly utilize he has a poor prognosis based on the following risk factors: his performance status, anemia, hypercalcemia, and the timing from diagnosis to need for treatment. Based on the IMDC [International Metastatic RCC Database Consortium] criteria he has a poor-risk status that confers an overall survival of approximately 8 months in the pre-immunotherapy era. For this reason, treatment is indicated.

We do know that for select patients, active surveillance is an appropriate consideration based primarily on a dataset published by Brian Rini, MD, and colleagues inThe Lancet Oncologya few years ago. In this study it was clear that an initial period of active surveillance is appropriate for select patients, and it does not appear to cause harm. However, patients who are most appropriate for active surveillance are those with good-risk status and a low metastatic burden.

In the particular case that we’ve discussed I do not think active surveillance is appropriate because he has a poor-risk status, therefore, a poorer prognosis, and a high metastatic burden.

Transcript edited for clarity.

Case: A 68-Year-Old Man With Poor-Risk RCC

A 68-year-old man presented with a 6-week history of painless intermittent hematuria, fatigue and a 7-lb weight loss.

H & P:

  • History of medically controlled hypertension and hypercholesterolemia
  • 30 pack/year smoking history, social alcohol use  
  • Thin, ill-appearing; able to meet activities of daily living but unable to work due to fatigue. He spends more than half the day active on his feet


  • CBC: Hb 11.4 g/dL, corrected Calcium,11.2 mg/dL, WBC, PLT, LFT all WNL
  • BP: 134/92
  • Lipid panel: WNL
  • U/A: gross hematuria


  • CT scan of the chest/abdomen/pelvis showed a left-sided 8.7 (I believe he said 8cm) cm renal mass, para-aortic lymph nodes, and pulmonary metastases


  • Underwent radical left nephrectomy; found to have Fuhrman grade 4 clear cell carcinoma without sarcomatoid features
  • IMDC risk-score: poor


  • Initiated treatment with ipilimumab 1mg/kg IV + nivolumab 3mg/kg IV q3w for 4 doses; achieved partial response; received maintenance nivolumab for 6 doses (q4w) followed by disease progression
  • Patient was switched to cabozantinib 60mg PO qDay