Case Studies in Thyroid Cancer - Episode 14

Case 2: RET+ MTC Disease Management

Dr Wirth reviews disease management considerations a 60-year-old man with RET+ metastatic medullary thyroid cancer.

Lori Wirth, MD: The patient did have 24-hour urinary fractionated catecholamines and metanephrines that were not elevated. We know that the patient does not have pheochromocytoma before going off to the operating room. A total thyroidectomy and central neck dissection were done. Pathology showed a 2-cm MTC [medullary thyroid cancer] arising from the isthmus with 2 of 5 positive central nodes. The largest was 1.8 cm. There was extranodal extension. The stage, the TNM [tumor, node, metastases] is at T2N1, and we haven’t done distant metastatic disease work-up yet. Molecular testing for germline alterations was negative for a RET germline mutation, so we know the patient does not have MEN2A [multiple endocrine neoplasia type 2A] or 2B [type 2B]. The performance status is 1. Then in follow-up, the patient’s calcitonin and CEA [carcinoembryonic antigen] levels 3 months after surgery are elevated at 110 pg/mL and 15 ng/mL, respectively.

Six months postoperatively the calcitonin and CEA levels are increasing; calcitonin is now 255 pg/mL, CEA is 29 ng/mL. The patient has a small node that’s popped up in the left neck. On CT scan, there are multiple cervical nodes and metastatic liver lesions that are now seen. The patient declined the offer of starting systemic therapy, so was maintained in follow-up. Twelve months later, the patient now has loose, watery stools 4 to 6 times a day, and on CT scan there is progression in the lymph nodes as well as in the liver. The calcitonin has jumped up to 1900 pg/mL, CEA is 119 ng/mL. You can calculate the calcitonin doubling time, we do this routinely in patients with MTC. If you google ATA [American Thyroid Association] calcitonin doubling time, you can get to a calcitonin and CEA calculator, so it’s easy to do. This patient’s calcitonin and CEA doubling times are 2.6 months and 3.6 months respectively. Marcia, are you starting to get nervous?

Marcia Brose, MD: Yes. I was going to say, I know the calcitonin doubling time is important, and I’ll say I use it for patients who have disease that’s a little more indolent than this to try to understand risk and maybe guide when I’m going to scan it, but you already had me at 12 months later, loose watery stools. I don’t think that calcitonin doubling time is going to mean anything at this point. This person is now symptomatic, and their disease by their biomarkers is going through the roof. I think I was already nervous when they turned it down at 6 months because they had metastatic liver lesions. I probably would have done everything in my power to try to encourage them do therapy at that point, but certainly I am now losing sleep.

Lori Wirth, MD: I agree wholeheartedly about the value of the tumor markers here. If the patient had much more stable disease without a large volume, was asymptomatic, and the calcitonin and CEA doubling times were each say 2.5 years, you’d be pretty reassured that they’re not going to get into trouble anytime soon.

Andrew Gianoukakis, MD: At that point with the [calcitonin level of] 255 [pg/mL], it’s over 150 [pg/mL]; the suggestion is in a follow-up with calcitonin of over 150 [pg/mL], you should look for distant disease if you hadn’t already discovered it and the liver lesions fit with that calcitonin of over 150 [pg/mL]. Then, as you mentioned, the patient is symptomatic. The doubling time is important as it’s related to mortality at 5 years and 10 years, with very low survival rates with thyroglobulin doubling times of less than 3 months, versus doubling times of over 2 years, where the survival at 5 and 10 years approaches nearly 100%.

This transcript has been edited for clarity.