Renal Cell Carcinoma

Question 1

What is Fumarate hydratase def renal cell carcinoma, what is the genetic mutation and what cancers are they predisposed to?

Answer 1

This is a hereditary leiomyomatosis renal cell carcinoma syndrome. They can develop uterine and cutaneous leiomyomas and an aggressive form of RCC. It is auto dominant, the gene is Fumarate Hydratase on chr 1q43. You can also have a somatic form of this disease involving the same gene.

Question 2

Von Hippel Lindau Syndrome is assoc w/what gene and what is the mode of inheritance? Cancers they are pre-disposed to?

Answer 2

VHL gene on Chr 3p25. Clear cell carcinoma is greatly increased. Others: pheochromocytoma, hemangiomas, hemangioblastomas (brain, spinal cord, retina), pancreatic cancer, epididymal cysts, renal cysts.

Question 3

What is Birt Hogg Dube Syndrome?

Answer 3

Hereditary hair follicle tumors on face/neck. Higher risk of kidney tumors (chromophobe, oncocytoma, and clear cell), lung cysts (leads to spontaneous pneumo). BHD gene on Chr 17 and FLCN gene. Autosomal dominant.

Question 4

For stage 1 (T1a) what surgery is preferred? Tumor 4 cm or less
T1: less than and equal to 7
T2: greater than 7 up to 10cm
T3: tumor extends into major veins or perinephric tissue
T4: extends to adrenal gland

Answer 4

Partial nephrectomy, but you can also consider ablative techniques, surveillance, or radical nephrectomy

Question 5

For stage 1 (T1b) what surgery is preferred?

Answer 5

So here you can consider a partial or radical nephrectomy. Again active surveillance is an option as well as radical nephrectomy in select patients.

Question 6

For Stage II tumors (T2-7cm or more) what are the surgical options? What adjuvant tx is given? Stage II is T2,N0

Answer 6

You can do partial or radical nephrectomy. Adjuvant Pembro (Cat 1) for patients w/grade 4 tumors with clear cell histology +/-sarcomaotid or surveillance for those who don’t fit this. For non clear cell you just watch.

Question 7

For stage III tumors what are the surgical options? What is the adjuvant tx that is given? T3-tumor extends into major veins or perinephric tissue but not to adrenal gland or beyond gerotas fascia.

Answer 7

Most will need radical nephrectomy, but in select patients you can do a partial. Here for Stage III you give Pembro for every patient or you can do surveillance for clear cell only. For non-clear cell you just do surveillance.

Question 8

For stage IV tumors that are M0 what are the tx options here?

Answer 8

If they are resectable you do nephrectomy and then adjuvant Pembro for clear cell or you do surveillance. For non-clear cell you do observation. For those that aren’t you tx as metastatic dx

Question 9

Remember that for patients who have metastatic dx there is a role for nephrectomy and metastatecomy in those with oligometastatic dx. What are other tx options in this scenario?

Answer 9

First these patients should have favorable biology and have limited site disease. You can also do SBRT or ablative techniques. For those who do undergo complete metastatecomy you need to give adjuvant Pembro. So NCCN does list that you can do metastatectomy for patients with non clear cell histology (in addition to SBRT or ablative techniques).

Question 10

For favorable risk metastatic disease what are the Cat1 options?

Answer 10

Axitinib+Pembro, Cabozantinib+Nivo, Lenvatinib+Pembro. Ipi/Nivo is an option but is not a Cat 1 rec. You can also use Pazopainib or Sunitib if they are not a IO candidate.

Question 11

What is the first line tx options for poor/intermediate risk metastatic disease?

Answer 11

Cat 1 options: Ipi/Nivo, Cabo/Nivo, Pembro/Lenvatinib. Cabozantinib is a preferred option too but is not Cat 1.

Question 12

What are the options for 2nd line tx for metastatic RCC that is IO naive?

Answer 12

In addition to the IO options that you use in first line you can also do Nivo, Cabozantinib, and Everolimus/Lenvantinib

Question 13

What therapy can be used as 2nd line tx for metastatic dx that has progressed on IO therapy?

Answer 13

Axitinib, Belzutifan (only for those who received a VEGF/TKI), Cabozantinib, Everolimus/Lenvatinib, Tivozanib (only for patients who have 2 prior lines of tx).

Question 14

What are the tx options for non-papillary RCC?

Answer 14

Clinical trial, Cabozantinib, Cabozantinib+Nivo, Lenvatinib/Pembro

Question 15

What is tx for collecting duct tumors and renal medullary cancer?

Answer 15

Cisplatin/Gemcitabine, Carboplatin/Gemcitabine, Carboplatin/Paclitaxel

Question 16

What is the tx for leiomyomatosis assoc RCC?

Answer 16

Erlotinib+Bevacizumab

Question 17

Hereditary Renal cell papillary carcinoma involves mutation of what gene?

Answer 17

MET gene

Question 18

Know that Tuberous Sclerosis can be assoc with RCC and oncocytic tumors

Answer 18

Also assoc with renal cysts, angiomyolipomas, and clear cell carcinoma. TSC 1/2 is the gene mutation on chr 9 and 16 respectively. It is a tumor suppressor gene. It is auto dominant.