Thyroid Cancer Guide

Treatment Recommendations for Thyroid Cancer

Streamlined responses to therapy assessment in patients with intermediate-risk thyroid cancer

Thyroid cancer is the most common endocrine cancer. According to the American Cancer Society, about 52,890 new cases of thyroid cancer are anticipated for 2020, including 2180 deaths.

Thyroid carcinoma biopsy in microscopy by Jxfzsy @iStock

Differentiated thyroid cancer 

Differentiated thyroid cancer (DTC) encompasses papillary, follicular and Hürthle cell cancer.

Papillary thyroid cancer

Papillary thyroid cancer is the most common type of thyroid cancer, accounting for about 70% to 80% of all thyroid cancers. DTC is associated with a favorable prognosis, including an 85% 10-year survival rate, with a 5- year survival rate for regional papillary thyroid cancer >99%.

Thyroid cancer treatments

Thyroid cancer is treated with surgery, radioactive iodine treatment, external beam radiation therapy and chemotherapy. Typically all (or most of) the thyroid gland is surgically removed and the patient is treated with thyroid hormone replacement therapy at a dose sufficient to prevent the growth of cancer cells while providing necessary thyroid hormone to the body. Routine follow-up can quickly identify any recurrence.

American Thyroid Association Guidelines

The 2015 American Thyroid Association guidelines recommend assessing response to therapy 1 to 2 years after initial therapy to determine long-term disease 

Thyroid carcinoma biopsy in microscopy by jxfzsy @iStock

recurrence; patients with good response to therapy were found to need less follow-up and did not require TSH suppression.

Methods of Assessment

This involves post-therapy whole-body scan (TxWBS), neck ultrasound (US), basal thyroglobulin (Tg), Tg antibodies (TgAB), and rhTSH stimulated Tg levels. Taken together, this information categorizes the patient’s response to therapy as excellent (basal Tg <0.2 ng/ml, normal TgAB levels and no structural evidence of disease on imaging), indeterminate, biochemical incomplete or structural incomplete.

Follow-Up Tests

Generally, US and basal Tg and TgAB tests are routinely performed during follow-up. The two approaches for Tg stimulation involve either rhTSH injection or thyroid hormone withdrawal (THW), both of which can be costly, time consuming, and affect both the patient and medical staff.

However, in an interview with EndocrineWeb, Eyal Robenshtok, MD, Endocrinology and Metabolism Institute and Head, Thyroid Cancer Service at the Bellinson Hospital and Davidoff Cancer Center in the Rabin Medical Center at   Tel Aviv University, noted that “while stimulation with rhTSH was routine for years, it carries significant cost and is pretty time consuming. If patients can be followed without stimulation, it saves the cost of rhTSH, saves 3 days of clinic visits for the patients (2 days for rhTSH injection and one day for blood tests) and the work for the physician related to the tests.”

Recombinant TSH (rhTSH)

Patients were exposed to prolonged periods of hypothyroidism as part of a treatment regimen after the introduction of radioiodine (RAI) treatment for well-differentiated thyroid cancer. Withdrawing TH elevates thyrotropin (TSH) which then stimulates the uptake of RAU in DTC cells and enhances RAI treatment efficacy. However, withdrawing TH causes iatrogenic hypothyroidism – with substantial consequences, including lethargy, constipation, myalgia, weakness, and mood disturbances. The introduction of recombinant human TSH (rhTSH) in the 1990s enabled elevation of serum TSH without requiring TH withdrawal and the associated symptomatic consequences. Nevertheless, there are questions regarding whether this process affords benefit and guidance as part of the regular 1-2 year follow-up.

Current Research

Consequently, Dr. Robenshtok and a group of researchers investigated whether Tg stimulation is essential for determining risk of recurrence 2 years after treatment.

“The current study was a result of everyday questions we have in clinical practice. We had patients who had ‘intermediate risk of recurrence’ (lymph node involvement of minimal extra-thyroidal extension) who had normal whole-body scans after radioiodine treatment, normal ultrasound (with very sensitive machines) and undetectable thyroglobulin levels. Although these patients had no evidence of disease, they were being subjected to rhTSH stimulation 1 to 2 years later. This despite evidence that even if Tg stimulation is abnormal, it often doesn’t alter treatment.”

Thyroidectomy and radioiodine therapy

This retrospective analysis of 120 patients classified as intermediate-risk of recurrence, as per the 2015 ATA stratification, compared the response to therapy assessment with versus without Tg stimulation. Adult patients were followed for an average of 7 years; as might be expected, 26% of them had persistent disease (14% biochemical and 12% structural), and there were no deaths from thyroid cancer during follow-up. All had initially been treated with total thyroidectomy and radioiodine therapy.

rhTSH stimulation

The study identified only 8 patients (7%) who were classified differently owing to rhTSH stimulation (either as excellent or indeterminate response); however, this finding had no effect on predictive value.

Tg stimulation

There was a very low risk of recurrence among those patients with a normal TxWBS after radioiodine treatment, normal US and undetectable basal TG.

Classification of response to therapy based on Tg stimulation was altered in only a very small percentage of patients, and the procedure provided minimal additional prognostic value. “Therefore, we suggest continued use of the response to therapy assessment tool, which is very effective in predicting clinical outcomes, using definition of excellent response to therapy based on basal Tg levels <0.2 ng/ml.”

Maria del Pilar Brito, MD, Director of the Thyroid Center at Mount Sinai Union Square, New York NY, readily agreed with the premise and the findings of the study, noting: “I’ve felt the same way about Tg stimulation beyond 1-2 years as this study has demonstrated. We don’t need to keep subjecting these patients to rhTSH each year.”

2015 ATA recommendations

She noted that the current practice, as described in the 2015 ATA recommendations, of whole-body scan, neck US, basal Tg and Tg antibodies, in the absence of any other areas for concern or suspicion, should be sufficient to provide a classification.

“Any time we increase the threshold for detection (via reduced testing), we move away from capturing an excess to having a smaller deficit on late detection; we move from higher sensitivity to higher specificity in practice.”

ATA recommendations for whole body scan

Further, noted Dr. Brito, “we can assess prognosis pretty successfully post-operatively and at one year with the ATA recommendations for whole body scan, US and basal Tg and TgAB; rhTSH  has not been demonstrated to be particularly helpful in identifying patients at risk for recurrence.”

2 years of follow-up after treatment for DTC

The study clearly demonstrated that for patients with no evidence of disease during the initial 2 years of follow-up after treatment for DTC, performing suppression of TSH is unnecessary and adds little prognostic information. Concluded Dr. Robenshtok, “While not including rhTSH in the follow-up of thyroid cancer patients might miss small disease remnants, …the clinical implications of these tiny remnants is small.”

The authors have no financial relationships relevant to this article to disclose.

There was no funding for this study.

Dr Brito has no financial relationships relevant to this study.

 

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