Management of papillary and follicular thyroid cancer
Authors: M K. Jones
Journal: Journal of the Royal Society of Medicine (2002)

Papillary and follicular thyroid cancers are well differentiated and slow growing, and have unique characteristics. Adjuvant treatments are thyroid hormone suppression and radioiodine (131I) therapy rather than chemotherapy and radiotherapy. Prognosis is generally excellent and is influenced by factors related to the patient, the disease and the therapy. Factors associated with a less favourable outcome are male sex, family history of papillary cancer, age >40 years, tumour diameter >4 cm, invasive or poorly differentiated tumour and lymph node or distant metastases1,2. 5-year survival rates in England and Scotland may be lower than in many European countries3, and audits suggest that variation in therapeutic effects is due to deficiencies in management4,5. Evidence from large randomized controlled trials is lacking because of the rarity, slow progression and good prognosis of these tumours, but retrospective clinical studies do shed light on controversial areas1,2. National guidelines under the auspices of the British Thyroid Association6 address these issues and recommend an aggressive, three-stage management approach for most patients, including total or near-total thyroidectomy, 131I ablation and thyroid hormone suppression therapy.

The first management stage for those with tumour diameters >1 cm includes total thyroidectomy with central node dissection and postoperative 131I ablation. (Most patients should have undergone fine-needle aspiration cytology for diagnosis and for planning of treatment.) The reason for additional 131I ablation is that, after surgery, most patients have thyroid remnants detectable on radioiodine scan. The treatment destroys residual thyroid tissue, including occult carcinoma, and facilitates subsequent detection of recurrent disease. Radioiodine ablation may be given four weeks after surgery, thyroid hormone treatment having been withheld postoperatively. A postablation scan is performed and, if uptake is discovered outside the thyroid bed, suggesting metastases, further therapy may be needed. Patients require thyroid hormone replacement, and the greater the suppression of thyroid stimulating hormone (TSH) the better the outcome7. Thyroxine is started on discharge from hospital and the dose is adjusted until serum TSH is <0.1 mu/L. Lobectomy followed by TSH suppression is considered only in low-risk patients with a unifocal non-invasive tumour ≤ 1 cm8.

After total thyroidectomy and 131I ablation the second management stage includes a diagnostic radioiodine scan and serum thyroglobulin estimation (after thyroxine withdrawal) at six months. (Thyroglobulin is produced by normal and neoplastic thyroid cells and its detection after total thyroid ablation suggests recurrent disease; monitoring is less sensitive when the patient is on thyroid hormone suppression because thyroglobulin production depends on TSH stimulation9.) If there is significant uptake in the neck, further 131I is administered and a post-treatment scan is performed. If there is no significant uptake in the neck, thyroxine is restarted and low-risk patients enter the third management stage.

The third stage involves long-term follow-up to detect recurrent disease. Mortality rate at 30 years is 8% but recurrence rate is 30%. Two-thirds of recurrences are in the first 10 years after treatment but one-third are later1. Follow-up methods include clinical examination, TSH monitoring to ensure adequate suppression, diagnostic scan and serum thyroglobulin measurement. If thyroglobulin becomes detectable in a patient taking thyroxine then thyroxine is withdrawn, a diagnostic scan is performed and the thyroglobulin measurement is repeated. In selected patients, recombinant human TSH administration avoids the need for thyroxine withdrawal10. Management of those with a negative scan but detectable thyroglobulin is controversial. The thyroglobulin level suggesting recurrent disease is not known and the particular value may be less important than the change in level with time and the risk category of the patient. If a false-positive thyroglobulin and a false-negative scan are ruled out, local recurrence is likely and initial investigation includes neck ultrasound (possibly with fine-needle aspiration cytology) and chest X-ray. If these investigations are negative, a non-contrast CT scan of the chest and bone scans are considered. Glucose is taken up by tumours, and fluoro-18-deoxyglucose positron emission tomography scanning may be useful. Over-enthusiastic investigation is clearly possible and observation may suffice if thyroglobulin levels do not rise progressively.

The most common causes of death are local recurrence and pulmonary metastases. Locally recurrent tumour is resected surgically with subsequent 131I therapy. Recurrences outside the neck are most frequently in lung but are also seen in bone. Patients whose metastases take up 131I are treated with radioiodine and the overall 10-year survival rate in those with distant metastases can be as high as 40%2.

Guidelines for the management of differentiated thyroid cancer in adults6 are comprehensive and lay great stress on the importance of aggressive early treatment. The management of medullary cell cancer of the thyroid is also covered. About 1000 new cases of thyroid cancer are reported in England and Wales each year11, so a district general hospital serving a population of 500 000 will assess only 10 per year. In view of the long-term risk of recurrent disease, many of these patients should be under scrupulous lifelong followup. The best results are likely to come from well coordinated specialist care by a multidisciplinary team.