From the Guidelines
Chromophobe renal cell carcinoma patients should be treated with sunitinib as a first-line systemic treatment option, according to the most recent guidelines. This recommendation is based on the ESMO clinical practice guidelines for diagnosis, treatment, and follow-up of renal cell carcinoma, which suggest sunitinib as an option for chromophobe renal cell carcinoma 1.
Key Characteristics of Chromophobe Renal Cell Carcinoma
- Chromophobe renal cell carcinoma accounts for approximately 5% of all renal cell carcinomas
- Characterized by large, pale cells with prominent cell membranes
- Typically presents as a well-circumscribed, solid tumor with a light brown or tan color
- Generally has a better prognosis than clear cell renal cell carcinoma, with a lower rate of metastasis and higher survival rates
Treatment Options
- Surgical removal of the tumor through partial or radical nephrectomy is the primary treatment for localized disease
- Targeted therapies such as tyrosine kinase inhibitors (sunitinib, pazopanib) or mTOR inhibitors (everolimus) may be used for advanced or metastatic disease
- Sunitinib is recommended as a first-line systemic treatment option for chromophobe renal cell carcinoma 1
- Pazopanib and everolimus are also options, although the evidence for their efficacy specifically in chromophobe carcinoma is less robust than for clear cell carcinoma 1
Follow-up and Monitoring
- Regular follow-up imaging is essential after treatment to monitor for recurrence
- The distinct appearance of chromophobe cells under microscopy, showing a clear cytoplasm with a halo around the nucleus, is due to their high content of mitochondria and glycogen, which helps pathologists distinguish this subtype from other renal cancers.
Some patients with chromophobe RCC may benefit from mTOR inhibitors since mutation on chromosome 7 was shown to lead to a loss of the folliculin gene with upregulation of mTOR 1. However, the current recommendation prioritizes sunitinib as a first-line systemic treatment option 1.
From the Research
Definition and Characteristics of Chromophobe Renal Cell Carcinoma
- Chromophobe renal cell carcinoma (ChRCC) is a distinct subtype of renal cell carcinoma (RCC) with characteristic light microscopic, histochemical, and ultrastructural features 2.
- ChRCC is the second most common variant histology (non-clear cell) RCC, accounting for almost 5% of total RCC cases 3.
- It is characterized by chromosomal aneuploidy, TP53, PTEN, and mitochondrial gene mutations 4.
Clinical Course and Prognosis
- ChRCC typically has a favorable clinical course, with a better prognosis compared to clear cell RCC 2.
- Patients with ChRCC are associated with earlier stage tumors and longer overall survival compared to those with clear cell RCC 2.
- However, patients with metastatic ChRCC disease have a worse prognosis than those with advanced clear cell RCC 3.
Treatment Options
- There are no specific approved treatments for ChRCC, although some responses to tyrosine kinase and mTOR inhibitors have been observed 5.
- Sunitinib may be superior to everolimus and sorafenib in terms of objective response rate, but the optimum therapy for metastatic ChRCC is still missing 3.
- Immunotherapy has shown limited response in ChRCC, with only a few tumor responses observed with immune checkpoint inhibitors 3.
- Targetable pathways involving innate lymphoid cells/IL-15 and cysteine homeostasis/ferroptosis have recently been identified, offering potential new treatment options 5.
Current Research and Future Directions
- The therapeutic landscape of ChRCC is limited, with most treatments extrapolated from clear cell RCC or studies combining several forms of non-clear cell RCC subtypes 4.
- Ongoing clinical trials are investigating new treatment options for ChRCC, including targeted therapeutics and immunotherapy 4.
- Further research is needed to identify the best treatment for metastatic ChRCC, with a focus on high-quality studies and adequate sample sizes 3.