Pediatric Renal Cell Carcinoma

Kiersten M. Craig; Dix P. Poppas; Ardavan Akhavan


Curr Opin Urol. 2019;29(5):500-504. 

In This Article


The predominance of MiTF tumors with TFE3 translocations gives a therapeutic target of the TFE3/mTOR pathway for medical management of RCC. Damayanti et al.[35] evaluated translocation RCC in a xenograft model and identified upregulation of the phospho-inositol-3 (PI3), AKT pathway. Inhibition of this pathway led to decreased cell proliferation.[36] Vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors target the PI3/AKT pathway, and have been shown to cause remission in some patients. Current COG studies are evaluating clinical efficacy in a randomized-controlled trial of axitinib or nivolumab monotherapy vs. combination therapy in patients with advanced translocation RCC.[37] Secondary outcomes include safety and characterization of clinical behavior of these tumors. Recruitment began in October of 2018 with target accrual of 87 patients. Follow-up is planned every 3 months for the first year, every 4 months for year 2, and every 6 months for years 3 and 4. Results of this study will help tailor optimal treatment strategies.

Unlike Wilm's tumor, nontranslocation tumor RCC is historically resistant to both chemotherapy and radiation therapy.[38] Patients with the aggressive renal medullary carcinoma variant in the COG study have been managed with either gemcitabine, platinum, or taxane regimens as well as immunotherapy, such as bortezumib.[2,39,40] Ambalavanan et al.[41] reviewed the literature for pediatric patients with RCC managed with medical management of RCC. Twenty patients received chemotherapy following an incorrect preoperative Wilm's tumor diagnosis. Although data is limited, complete response occurred following treatment with both sorafenib[42] and cabozantinib.[43] Sufficient data is lacking to warrant routine medical management of nontranslocation RCC in the pediatric population.