First-Line Metastatic Renal Cell Carcinoma
History of Present Illness
A 59-year-old Caucasian man was diagnosed with metastatic clear cell renal carcinoma, International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate risk (2 points for <1 year to start systemic treatment and anemia).1
The patient presented with gross hematuria in March 2024. He was seen in urgent care and treated with antibiotics. The hematuria recurred and was evaluated by a urologist. He underwent a cystoscopy, which was negative.
Imaging
On April 18, 2024, the CT urogram showed a 17-cm left renal mass with renal vein tumor thrombus. There was loss of radiological plane between the pancreatic tail, as well as the descending colon tumor. It also showed a 4.7-cm right enhancing renal mass.
On May 20, 2024, the CT chest showed bilateral innumerable solid pulmonary nodules involving all lobes, which is highly concerning for metastatic disease. There was also a large centrally necrotic aortic-pulmonary window lymphadenopathy, compatible with nodal metastases. Additionally, there was a questionable enlarged left lower paraesophageal lymph node. The partially visualized abdomen redemonstrates a large left renal mass with surrounding numerous collaterals. There is an additional partially imaged right renal mass. Dr Smith, Urology, was consulted and the case was presented to the GU Medical Oncology clinic for review of the diagnosis and medical decision-making.
Review of Systems
- Constitutional: Denies fevers, chills, night sweats, weight loss, and weakness
- HEENT: No ocular or oral issues
- Cardiac: Denies chest pain, palpitations
- Respiratory: Denies dyspnea, coughing, wheezing, or hemoptysis
- GI: Denies vomiting, abdominal pain, diarrhea, hematemesis, melena or hematochezia
- GU: Denies hematuria, flank pain, suprapubic pain
- Musculoskeletal: Denies arthralgia, myalgia
- Skin: Denies skin rashes or wounds
- Neurologic: Denies headaches, dizziness, or focal weakness
- Psychiatric: Denies any confusion or changes to mood
- Endocrine: Denies heat/cold intolerance, polyuria, polydipsia, or polyphagia
- Hematologic: Denies adenopathy or ease of bruising
Allergies: No known allergies
Past Medical History
- Hypertension
- Hyperlipidemia
Medications
- Losartan
- Rosuvastatin
Past Surgical History
- None
Family History
- Paternal uncle with colorectal cancer
- Mother with diabetes, father with alcohol abuse
Physical Exam
- Karnofsky Performance Status: 100
- Constitutional: Oriented to person, place, and time. Well-developed and well-nourished
- HENT:
- Head: Normocephalic and atraumatic
- Eyes: EOM (extraocular muscles) are normal. Pupils are equal, round, and reactive to light
- Neck: Normal range of motion. Neck supple
- Cardiovascular: Normal rate, regular rhythm, normal heart sounds and intact distal pulses
- Pulmonary/Chest: Effort normal and breath sounds normal
- Abdominal: Soft. Bowel sounds are normal
- Genitourinary system: No hematuria, CVA tenderness
- Musculoskeletal: Normal range of motion
Final diagnosis
Left kidney, mass, core biopsies:
Renal cell carcinoma, clear cell type, with eosinophilic features
Impression
The patient was diagnosed with a locally advanced renal cell carcinoma on the left kidney with a tumor thrombus into the renal vein, a 4.7-cm enhancing right-sided renal mass, multiple bilateral pulmonary nodules, and large necrotic lymphadenopathy, all concerning for metastatic disease. The NCCN guidelines (2025) for treatment in stage IV disease recommend consideration of cytoreductive nephrectomy in select patients. This was not deemed to be a viable option to due extensive metastatic disease.
Genetic Testing
The NCCN recommends hereditary genetic testing for patients meeting certain criteria.* This patient was referred for testing due to bilateral/multifocal tumors. A hereditary mutation may drive treatment decisions. It is important for family members to assess their own risk and to take appropriate screening and preventative measures.
*For more information on criteria for further genetic risk evaluation, go to chrome- extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf
Plan
Recommend nivolumab 480 mg q 4 weeks/cabozantinib 40 mg daily to start as soon as authorized.
There are several therapies recommended for first-line metastatic RCC with varying levels of evidence. Head-to-head studies of these therapies are limited. Nivolumab and cabozantinib are a NCCN category I recommendation for poor/intermediate stage IV disease. A study found that the most common treatment-emergent adverse events of any grade associated with this drug combination are diarrhea (64%), palmar-plantar erythrodysesthesia (40%), hypertension (35%), hypothyroidism (34%), fatigue (32%), increased ALT (28%), decreased appetite (28%), and nausea (27%).4
Academic centers and research facilities may make regimen choices based on how the subsequent lines might line up with their clinical trials. The regimen is also chosen based on patient preference or need, such as a patient’s ability to get to the clinic, whether they need transportation, or the breadth of their insurance coverage. This patient denied financial difficulties or being dependent on someone else for transportation.
References
- IMDC. International mRCC Database Consortium. (2022, October 21). https://www.imdconline.com/
- Motzer RJ, Bacik J, Murphy BA, et al. Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 2002;20:289-296.
- Heng DY, Xie W, Regan MM, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: Results from a large, multicenter study. J Clin Oncol 2009;27:5794-5799.
- McGregor B, Mortazavi A, Cordes L, Salabao C, Vandlik S, Apolo AB. Management of adverse events associated with cabozantinib plus nivolumab in renal cell carcinoma: A review. Cancer Treat Rev. 2022;103:102333. doi:10.1016/j.ctrv.2021.102333
- National Comprehensive Cancer Network, NCCN Guidelines Kidney Cancer, Version 1.2025, chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf