Diagnosis and Molecular Testing in Advanced RCC

Robert J. Motzer, MD:From his initial presentation, he originally presented with abdominal pain, which was found to be related to the diverticulitis. The metastatic kidney cancer was an incidental finding, which is now the most common way that kidney cancer is diagnosed. About 60% of patients at our center present with kidney cancer as an incidental finding.

One of the other features of this patient is the fact that in initial presentation he had a locally advanced disease, and with subsequent metastasis or relapse, within a year to 2 years. One of the problems, or the difficulties and challenges with this disease, is that there aren’t early warning signs for kidney cancer. So, about 25% of people will present with over metastasis at diagnosis, and another 30% of patients with localized disease will subsequently relapse. As a result, there’s a relatively large proportion of people diagnosed with kidney cancer that will ultimately need systemic therapy.

Good pathologic examination by pathologists is essential to type the kind of kidney cancer, to make sure it’s clear cell carcinoma. But beyond the morphology and the grade, there really isn’t any kind of standard biologic studies or biomarkers that are obtained on the kidney tumor that help us define treatment. There has been a high interest in studies for PD-L1 expression in kidney tumors, but for the most part they don’t exclude benefit with checkpoint inhibitors, and so they’re not used in standard management.

Transcript edited for clarity.

A Japanese-American Male With Recurrent RCC

November 2015

• At the age of 49, a Japanese-American man presented to the ER with abdominal pains
• CT of the abdomen and pelvis revealed diverticulitis with an incidental left renal mass (4.2 cm × 8.6 cm × 2.8 cm)
• SH: Marathon runner; nonsmoker; social drinker
• He underwent sigmoid colon resection; left radical nephrectomy
• Pathology; sigmoid colon pathology revealed diverticulitis; renal pathology revealed RCC, clear cell type
• Diagnosis: RCC stage PT2a
• KPS: 90
• Fuhrman Grade: 3/4

September 2017

• Follow-up CT showed residual soft tissue in the left nephrectomy bed, pulmonary lung metastasis, and an expansile lucent osseous lesion in the right pubic ramus
• Biopsy of one of the osseous lesions confirmed mRCC
• He began systemic therapy with sunitinib for 20 weeks and achieved stable disease and some shrinkage of the bone lesion
• KPS: 90
• MSKCC risk score: Intermediate

July 2018

• The patient now complains of left pelvic pain
• Imaging shows marked progression in retroperitoneal mass; new lung metastasis
• Laboratory values:
  • CBC: WBC - 7; Hgb - 12.6; Platelet - 190; ANC — 5.2;
  • CMP; Creatinine - 1.82 mg/dL; LFTs - WNL; Calcium - 9.2 mg/dL; LDH — WNL
• MSKCC risk score: Intermediate
• KPS: 80
• The patient was treated with palliative radiation therapy to bone metastasis
• He was then started on treatment with lenvatinib/everolimus