ASCO GU 2020: Molecular Pathways and Management Options in Non-Clear Cell Renal Cell Carcinoma

Data from The Cancer Genome Atlas (TCGA) specific to papillary RCC shows that type 1 and type 2 papillary RCC show very different clinical outcomes, with type 2 papillary RCC patients having inferior survival. The surgical management of hereditary papillary renal carcinoma (HPRC)-associated renal carcinoma adheres to the “3 cm rule” in that surgery should be delayed until the diameter of the largest tumor reaches three cm. At that point, surgery should be nephron-sparing via enucleation of the mass(es).

Type 2 papillary RCC is characterized by SETD2 mutations, as well as increased expression of the NRF2-antioxidant pathway.¹ Furthermore, this disease entity is depicted by two distinct subgroups: TFE3 fusion RCC and fumarate hydratase-deficient RCC. TFE3 kidney cancer has genetic rearrangement of chromosome 1q21.2 + chromosome Xp11.1, forming t(X;1)(p11.2;q21.1). TFE3 kidney cancer only make of 2% of all renal tumors, however, make up 42% of RCCs in children and young adults. Dr. Linehan notes that the management of TFE3/TFEB renal cell carcinoma should not adhere to the 3-cm rule. For these patients, surgical management should not be delayed, should incorporate wide surgical margins and may require an open approach.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is characterized by cutaneous leiomyomas, uterine leiomyomas (fibroids) and renal cell carcinoma, often type 2 papillary histology. Similar to TFE3/TFEB tumors, these tumors should also not adhere to the 3-cm rule and surgical management should not be delayed. Furthermore, surgery should utilize wide surgical margins, should be done open, and the surgeon must be cognizant that these can be bilateral and multifocal. Dr. Linehan notes that an NCI led a Phase II trial among papillary RCC tested the combination of bevacizumab and erlotinib, finding an overall partial response rate of 44%, stable disease rate of 49% and median PFS of 12.8 months.