Medullary Thyroid Cancer and vocal cord paralysis
Overview
Medullary thyroid cancer (MTC) is a rare form of thyroid cancer that affects only 3-5% of all thyroid cancer cases in the United States. While the prognosis for MTC is generally good, there is a chance of vocal cord paralysis (VCP) due to the involvement of the recurrent laryngeal nerve (RLN) preoperatively or nerve sacrifice during surgery. A newly published study has demonstrated the incidence of VCP in MTC and evaluated whether VCP impacts overall survival.
Medullary thyroid cancer (MTC) is a neuroendocrine tumor that is responsible for only around 3-5% of all thyroid cancers, yet causes 13% of all deaths related to thyroid cancer. The disease-specific survival rate for those with MTC is between 83-89%, although this drops to 36-51% for those with distant metastatic disease.
Furthermore, 70% of those presenting with a palpable thyroid nodule also have metastatic disease to the cervical lymph nodes, and 10% have distant metastases. These facts indicate the aggressive nature of MTC, which is reflected in the recommended treatment algorithm.
According to the American Thyroid Association (ATA) guidelines, MTC patients, even those with a negative neck ultrasound, should receive a total thyroidectomy and bilateral central neck dissection, as MTC is not responsive to iodine or radioactive iodine treatments like other well-differentiated thyroid cancers.
Methods
A review of the medical records of patients with medullary thyroid cancer (MTC) who were treated at Loyola University Medical Center between 2007 and 2021 was conducted. Details such as patient demographics, cancer diagnosis and treatment, laboratory values, and life expectancy were gathered for the review.
Two independent reviewers performed a chart review, excluding any patients under the age of 18, those without a diagnosis of MTC, those who had prophylactic surgery due to familial MTC syndromes, and those with incomplete data. Information on demographics, cancer diagnosis and treatment, laboratory and genetic testing, follow-up times, and survival data were collected, with all patients undergoing total thyroidectomy with bilateral central neck dissection.
Whether or not to perform lateral neck dissection was decided individually depending on the preoperative disease status, calcitonin level, and other factors that would influence prognosis. Summary statistics were provided for those with and without VCP, with counts and percentages used to summarize categorical variables and medians (Q1, Q3) used to summarize continuous variables. Kaplan–Meier curves were used to illustrate the time to VCP by stage and the time to death by VCP, with a Chi-square test and univariable Cox proportional hazard models used to test associations of patient characteristics with mortality. All analyses were conducted using SAS 9.4.
Results
In the study, 79 people participated, of which 47 (59.5%) were female. The mean age at diagnosis was 51.3 years old (standard deviation 13.58). Variants of uncertain significance in the VCP gene were found in 16.5% of patients. 71 patients were tracked for at least a year, with a median (quarter 1, quarter 3) of 7.2 (3.9, 11.0). People with VCP within one year were 7.2 times more likely to die compared to those without (95% confidence interval: 2.3, 22.7; p< 0.001).
Out of the 47 patients examined, 59.5% had lymph node metastases at the time of presentation, which was detected through preoperative imaging (ultrasound or CT scan) and then confirmed through pathology reports or in the final surgical specimen. 34% of these had isolated central compartment metastases, 29.8% had isolated lateral compartment metastases, and 36.2% had the disease in both the central and lateral compartments.
Data regarding the initial surgery was available for all but 2 patients, with 72 (93.5%) undergoing total thyroidectomy, and the remaining 5 (6.5%) undergoing lobectomy, partial thyroidectomy, or subtotal thyroidectomy. Additionally, 77.9% of the patients had bilateral central neck dissections, and 27 had lateral neck compartments addressed, 10 (13%) of whom had unilateral lateral neck dissections and 17 (22.1%) with bilateral lateral neck dissections.
Lastly, 7 (8.9%) of the patients had distant metastases at the time of presentation, with the most common locations being the liver (5 patients), followed by the lungs (4 patients) and bones (4 patients). In addition, 2 patients had metastatic disease to distant lymph nodes, and one patient had the disease in the adrenal gland.
Discussion
This study found that the incidence of vocal cord paralysis (VCP) in patients with medullary thyroid cancer (MTC) was 16.5%, higher than the rate of VCP after surgery for papillary thyroid cancer (PTC) which was 9.5%.
Vocal cord paralysis (VCP) is a common complication of medullary thyroid cancer (MTC). This is due to the location of the recurrent laryngeal nerve, which controls the vocal cords. This nerve runs close to the thyroid gland and may be affected by the spread of MTC to the neck or the treatment of the disease. VCP can cause hoarseness, difficulty speaking, and difficulty swallowing. Treatment for VCP may involve speech therapy, lifestyle modifications, and, in some cases, surgery.
Other studies have also noted a rate of permanent recurrent laryngeal nerve (RLN) palsy due to nerve sacrifice for oncologic clearance of 9%, and an additional 5% rate of temporary palsy. Van Beek et al. found a rate of 13.7% of at least transient RLN palsy in patients undergoing surgery for previously untreated MTC. The study had some limitations, such as 13 patients with RLN palsy being excluded from the final analysis due to missing data, and not all patients having information on pre or postoperative laryngoscopy, which may have caused the rate of RLN palsy to be underreported.
This highlights the importance of differentiating between permanent and temporary palsy when referring to vocal cord function. Kesby et al. emphasized the distinction between permanent palsy attributed to nerve sacrifice during surgery and temporary palsy thought to be secondary to nerve injury during surgery. Permanent palsy can have an impact on survival, whereas temporary palsy is not typically associated with such an effect.
Conclusion
The incidence of Medullary Thyroid Cancer (MTC) is increasing, and this research indicates that the occurrence of VCP is more likely to occur in MTC compared to other thyroid cancers. Furthermore, VCP has been found to have a statistically significant negative effect on survival.
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