Reoperation in metastasizing medullary thyroid carcinoma: Is a tumor stage-oriented approach justified?

doi:10.1016/S0039-6060(97)90217-8

Surgery

Volume 122, Issue 6, December 1997, Pages 1124-1131

https://doi.org/10.1016/S0039-6060(97)90217-8 Get rights and content

Abstract

Background. Lymph node metastases (LNM) are very often found in medullary thyroid carcinoma. After primary therapy, elevated levels of calcitonin are measurable in many patients. Because of the low sensitivity and specificity of diagnostic tools to detect micrometastases, the question remains whether an extended lymphadenectomy improves the chance of cure and whether this approach should be tumor stage oriented.

Methods. We analyzed the results of 36 patients with medullary thyroid carcinoma consecutively reoperated from 1988 to 1996, performing microdissection of all four locoregional lymph node compartments.

Results. Pathologic tumor stage (pT) category was classified as pT1, n = 3; pT2, n = 22; pT3, n = 6; and pT4, n = 5. LNM were found in 34 patients (94%). The cervicocentral compartment contained LNM in 85%, the cervicolateral compartments in 41% to 54%, and the upper mediastinum in 36%. Patients with different pT category did not differ in the rate of LNM. Ipsilateral cervicolateral LNM were found in 50% to 71% and contralateral cervicolateral LNM in 14% to 40%. Nine (35%) of 26 patients without distant metastases were biochemically cured. In 10 patients (38%) calcitonin level decreased more than 50%.

Conclusions. LNM were almost always (94%) found in patients who have elevated calcitonin levels after primary therapy. In patients without distant metastases, four-compartment lymphadenectomy gives a chance of cure in 35%. A tumor stage-oriented approach does not seem to be justified.

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The goal of lymphadenectomy for asymptomatic calcitonin elevations is the removal of microscopic metastatic nodal disease to prevent dissemination.7 However, a number of case series have shown that only a minority of patients actually achieve a biochemical cure following reoperative regional lymphadenectomy.9,11,12,21,22 In a recent series from Moley and colleagues,22 an improved ability to normalize postoperative serum calcitonin levels was found compared with an earlier series.21
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For the adequate planning of many reoperations, this information can be critical, sparing patients with occult MTC an odyssey through myriad institutions with continual imaging and further unnecessary operations. With the advent of the compartment-oriented microdissection technique, reoperations for MTC have become more effective in normalizing calcitonin levels.55,110–112 Suggestive of cure in the absence of distant metastases, the concept of biochemical normalization has gained much popularity as a key performance indicator against which the adequacy of the operation is gauged.
Thyroid cancer collectively encompasses a variety of tumors of disparate morphology and biology. With the exception of radio-iodine therapy for iodine-concentrating well-differentiated thyroid cancers, surgery is the foremost and generally sole effective treatment. Because the growth patterns of these tumors vary tremendously, there is a need to tailor the extent of dissection to the respective tumor entity, especially for less aggressive tumors. No international consensus exists about what precisely constitutes a ‘low-risk’ or ‘high-risk’ tumor. Established indications for less-than-total thyroidectomy include small (≤1 cm), unifocal, and non-metastatic papillary thyroid carcinomas (PTC), and minimally invasive follicular thyroid carcinomas (FTC; invasion of the tumor capsule only). Whether occult multifocal PTC and minimally invasive FTC with histopathological evidence of vascular invasion also fall into the ‘low-risk’ category remains unclear. For node-positive thyroid cancers, compartment-oriented microdissection is the gold standard of care, whereas the concept of prophylactic lymph-node dissection continues to arouse controversy. Most experts agree that routine lymph-node dissection is unnecessary for low-risk well-differentiated thyroid cancer (DTC). Because occult lymph-node metastases are frequent in high-risk PTC and medullary thyroid carcinoma, compartment-oriented microdissection helps prevent reoperations for ‘recurrences’ arising from residual nodes, sparing patients the excess morbidity from reoperations in the neck. Because of the looming epidemic of early forms of thyroid cancer, an international consensus is needed regarding (1) the definition of low- versus high-risk tumors; (2) classification of neck nodes; and (3) lymph-node dissection terminology.
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Surgeon philosophy in level of aggressiveness seems to influence the frequency of complications. Gimm and Dralle [16] report on 36 consecutive patients undergoing reoperation for MTC. The indication for reoperation in all patients was elevated calcitonin, with most patients also having imaging evidence of residual or recurrent regional disease.
The recommended initial treatment for locoregional recurrence of thyroid cancer is surgery. Of most value to the surgeon considering reoperation for thyroid cancer is the impact that such procedures have on patient survival; the data in this regard are limited. Also of great interest to the surgeon is morbidity associated with reoperation. Because these patients have already had a total or near total thyroidectomy, reoperation requires a surgical revisiting of an already operated bed; intuitively, one might predict a higher rate of complications owing to scar tissue. This article reviews the evidence regarding rates of various complications.
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In symptomatic patients, however, medullary thyroid cancers frequently are node-positive and more advanced. Clearance of lymph node metastases by systematic dissection may afford local control in the neck3,4-6,10,15-19 and mediastinum20 and may prevent tracheal and esophageal invasion owing to tumor penetration of the lymph node capsule.21 From a surgical perspective, it is important to distinguish between local disease, which may be surgically curable, and systemic disease, in which palliation is the ultimate goal of therapy.
The current American Joint Committee on Cancer/International Union Against Cancer classification designates cervical and mediastinal lymph nodes as regional lymph nodes. In a unilateral thyroid neoplasm, however, involvement of the contralateral cervical lymph node compartment or the mediastinal lymph node compartment, both of which have been designated “distant” lymph nodes, may serve as a surrogate parameter of distant metastases.
This institutional series consisted of 105 consecutive patients with medullary thyroid cancer who underwent systematic dissections of both distant lymph node compartments.
Thirty-eight patients had no distant lymph node metastasis, 36 patients had involvement of only 1, and 31 patients of both distant lymph node compartments. Significant associations (P < .001) were seen on univariate analysis between the number of involved “distant” lymph node compartments (none, one, or both) and extrathyroidal extension (3%, 33%, and 58%), the number of positive lymph nodes (means of 3, 13, and 33), and distant metastasis (8%, 36%, and 61%). In a multivariate logistic regression model, only involvement of one or both “distant” lymph node compartments (versus no distant lymph node metastasis) remained significantly related to distant metastasis in a dose-dependent fashion.
“Distant” lymph nodes in medullary thyroid cancer should be regarded as nonregional lymph nodes because their involvement is indicative of distant metastasis.

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^☆: Presented at the Eighteenth Annual Meeting of the American Association of Endocrine Surgeons, Baltimore, Md., April 6–8, 1997.

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Reoperation in metastasizing medullary thyroid carcinoma: Is a tumor stage-oriented approach justified?☆

Abstract

Surg Clin North Am

Medullary thyroid carcinoma: relationship of method of diagnosis to pathologic staging

Ann Surg

Long-term course of patients with persistent hypercalcitoninemia after apparent curative primary surgery for medullary thyroid carcinoma

Ann Surg

Compartment-oriented microdissection of regional lymph nodes in medullary thyroid carcinoma

Jpn J Surg

Medullary carcinoma of the thyroid: a study of clinical features and prognostic factors in 161 patients

Medicine

Prognostic factors in medullary thyroid carcinomas: survival in relation to age, sex, histology, immunocytochemistry, and DNA content

Cancer

Radioactive iodine in the treatment of medullary thyroid carcinoma of the thyroid

J Clin Endocrinol Metab

Kombinationstherapie von Adriamycin, Cisplatin und Vindesin beim C-Zell-Carcinom der Schilddrüse

Onkologie

Therapie des metastasierten medullären Schilddrüsenkarzinoms mit dem Somatostatinanalogon Octreotide

Med Klin

Medullary carcinoma of the thyroid: therapeutic strategy derived from fifteen years of experience

Surgery

Surgical management and follow-up of medullary thyroid carcinoma

J Surg Oncol