Nonparallel patterns of calcitonin and carcinoembryonic antigen levels in the follow-up of medullary thyroid carcinoma

Abstract

Serum levels of calcitonin (CT) and carcinoembryonic antigen (CEA) were evaluated in a group of 41 patients with histologically proven medullary thyroid carcinoma (MCT) before and sequentially after treatment for a period up to 7 years. Before thyroidectomy, CT levels were high in all patients, and significantly more elevated when metastases were present. On the other hand, CEA levels were high in most but not all the patients, and they also were found more frequently to be elevated in patients with metastases. After treatment, most of the patients without metastases showed persistently normal basal and pentagastrin stimulated CT and CEA levels. In some patients either without or with local metastases, postoperative CT levels, although considerably reduced, remained persistently above normal limits, whereas CEA levels became completely normal. This pattern may be due to the persistence of minute occult foci of the tumor, not sufficient to produce measurable amounts of CEA, which is not synthesized by all tumor cells. Most of the patients with metastases at diagnosis, showed still elevated CT and CEA levels after treatment. In the nonprogressive cases both markers decreased after adjunctive treatment or remained unchanged. In patients with progressive disease, an increase of CEA levels in the absence of a parallel increase of CT levels, which even decreased, was often observed. In one patient with progressive disease high CEA levels were seen for the first time when liver metastases had occurred. These data seem to suggest that, even though CEA production is not recognizable in all patients with MCT, in the CEA positive cases CEA levels may follow a nonparallel pattern and may have a distinct diagnostic meaning with respect to CT levels. In some cases, particularly in advanced disease, CEA may be a more useful marker of poor prognosis.

Progression of medullary thyroid carcinoma: assessment with calcitonin and carcinoembryonic antigen doubling times

“…In the previous studies on the MTC patients, the trends in the calcitonin and CEA levels have been related to clinical kinetic parameters (7)(8)(9)(10)(11)(12)(13)(14), but no direct relationship with the progression rate assessed on repeated imaging modalities was reported. In the present study, the progressive or stable nature of the disease at an interval of 1 year was assessed using RECIST and this will permit decision on an objective basis of any therapeutic intervention, and to assess the effects of any therapy, in particular in the frame of early controlled trials; this will also permit less aggressive monitoring protocol in patients with long doubling times.…”

“…The calcitonin and CEA doubling times were discordant in 20% of patients, resulting in non-parallel trends, and progressive disease was observed in five out of the nine patients with either calcitonin doubling times longer than 24 months and shorter CEA doubling times, or with calcitonin doubling times shorter than 25 months and with CEA doubling times longer than 24 months. Therefore, as described previously (11,12), both the calcitonin and CEA doubling times should be determined and taken into account to predict the progression rate, as rapidly progressing tumors usually produce rapidly increasing amounts of both calcitonin and CEA, but also in a few cases relatively stable amounts of either calcitonin or CEA but increasing amounts of the other marker. It must be emphasized that even in patients with progressive disease, the doubling times of calcitonin and CEA were much longer than the doubling times of other markers in patients with cancers from other origins, but were similar to the PSA doubling time observed in patients with prostate carcinoma (28).…”

“…The trend of the calcitonin and CEA levels can be quantified by their doubling times (11)(12)(13)(14). Circulating calcitonin levels may vary by 30% or even more at short intervals of time.…”

Complementary Roles of 18F-DOPA PET/CT and 18F-FDG PET/CT in Medullary Thyroid Cancer

“…The primary treatment is total thyroidectomy, often including modified neck lymph node dissection. Follow-up is based on the tumor markers calcitonin and carcinoembryonic antigen (CEA) and neck ultrasonography (5). Persistent or increasing serum calcitonin and CEA levels imply residual or recurrent disease, but conventional imaging frequently remains negative.…”

Diagnostic Accuracy of 18F-FDG PET in Restaging Patients with Medullary Thyroid Carcinoma and Elevated Calcitonin Levels

“…Surgery remains the primary and only effective mode of treatment (5). Postsurgically, serum calcitonin is often used as a tumor marker whereby elevated calcitonin levels suggest residual, recurrent, or metastatic disease (3,(6)(7)(8). Ultrasound, CT, and MRI provide structural but no functional information.…”