Stage I and II Papillary and Follicular Thyroid Cancer
Surgery is the therapy of choice for all primary lesions. Surgical options include total thyroidectomy or lobectomy. The choice of procedure is influenced mainly by the age of the patient and the size of the nodule. Survival results may be similar; the difference between them lies in the rates of surgical complications and local recurrences.[1-7]
Standard treatment options:
This procedure is advocated because of the high incidence of multicentric involvement of both lobes of the gland and the possibility of dedifferentiation of any residual tumor to the anaplastic cell type.
From the National Cancer Center Data Base (NCDB) registry of 52,173 patients, 43,227 (82.9%) underwent total thyroidectomy, and 8,946 (17.1%) underwent lobectomy. For a papillary thyroid cancer measuring less than 1 cm, the extent of surgery did not impact recurrence or survival (P = .24 and P = .83, respectively). For tumors measuring 1 cm or larger, lobectomy resulted in higher risk of recurrence and death (P = .04 and P = .009, respectively). To minimize the influence of larger tumors, 1-cm to 2-cm lesions were examined separately; lobectomy again resulted in a higher risk of recurrence and death (P = .04 and P = .04, respectively). In this study, total thyroidectomy resulted in lower recurrence rates and improved survival for patients with papillary thyroid cancer measuring 1 cm or larger compared with lobectomy.[Level of evidence: 3iiA]
Furthermore, in a pattern of care study, using the NCDB registry from 1985 to 2003, 57,243 papillary thyroid cancer patients with tumors measuring 1 cm or larger underwent total thyroidectomy or lobectomy. Trends in the extent of surgery were examined for patients with papillary thyroid cancer over 2 decades. Logistic regression was used to identify factors that predict the use of total thyroidectomy compared with lobectomy. Use of total thyroidectomy increased from 70.8% in 1985 to 90.4% in 2003 (P < .0001). Patients treated at high-volume medical facilities or academic centers were more likely to undergo total thyroidectomy than were patients examined at low-volume medical facilities or community hospitals (P < .0001).[Level of evidence: 3i]
The objective of surgery is to completely remove the primary tumor, while minimizing treatment-related morbidity, and to guide postoperative treatment with radioactive iodine (RAI). The goal of RAI is to ablate the remnant thyroid tissue to improve the specificity of thyroglobulin assays, which allows the detection of persistent disease by follow-up whole-body scanning. For patients undergoing RAI, removal of all normal thyroid tissue is an important surgical objective. Additionally, for accurate long-term surveillance, RAI whole-body scanning and measurement of serum thyroglobulin are affected by residual, normal thyroid tissue, and in these situations, near total or total thyroidectomy is required. This approach facilitates follow-up thyroid scanning.
I131: Studies have shown that a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas. It may be given in addition to exogenous thyroid hormone but is not considered routine. Patients presenting with papillary thyroid microcarcinomas (tumors <10 mm) have an excellent prognosis when treated surgically, and additional therapy with I131 would not be expected to improve the prognosis.
Thyroid lobectomy alone may be sufficient treatment for small (<1 cm), low-risk, unifocal, intrathyroidal papillary carcinomas in the absence of prior head and neck irradiation or radiologically or clinically involved cervical nodal metastases. This procedure is associated with a lower incidence of complications, but approximately 5% to 10% of patients will have a recurrence in the thyroid following lobectomy. Patients younger than 45 years will have the longest follow-up period and the greatest opportunity for recurrence. Follicular thyroid cancer commonly metastasizes to lungs and bone; with a remnant lobe in place, use of I131 as ablative therapy is compromised. Abnormal regional lymph nodes should be biopsied at the time of surgery. Recognized nodal involvement should be removed at initial surgery, but selective node removal can be performed, and radical neck dissection is usually not required. This results in a decreased recurrence rate but has not been shown to improve survival.
Following the surgical procedure, patients should receive postoperative treatment with exogenous thyroid hormone in doses sufficient to suppress thyroid-stimulating hormone (TSH); studies have shown a decreased incidence of recurrence when TSH is suppressed.
I131: Studies have shown that a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas. For optimal treatment with RAI, total thyroidectomy is recommended with minimal thyroid remnant remaining. With a large thyroid remnant, a low thyroglobulin level cannot be achieved, which increases the chance of requiring multiple doses of RAI.
Consideration of RAI for remnant ablation is based on pathological risk features including:
- Evaluation of the size of the primary tumor.
- The presence of lymphovascular invasion.
- Capsule invasion.
- The number of involved lymph nodes.
RAI may be given with one of two methods of thyrotropin stimulation: withdrawal of thyroid hormone or recombinant human thyrotropin (rhTSH). Administered rhTSH maintains quality of life and reduces the radiation dose delivered to the body compared with thyroid hormone withdrawal. Patients presenting with papillary thyroid microcarcinomas (tumors <10 mm), which are considered to be very low risk, have an excellent prognosis when treated surgically, and additional therapy with I131 would not be expected to improve the prognosis.
The role of RAI in low-risk patients is not clear because disease-free survival (DFS) or overall survival (OS) benefits have not been demonstrated. One study reviewed 1,298 patients from the French Thyroid Cancer Registry. Patients were identified as having low-risk papillary or follicular cancer as they are defined by the American Thyroid Association and the European Thyroid Association criteria:
- Complete tumor resection.
- Multifocal pT1 <1 cm.
- pT1 >1 cm.
- pT2, pN0, pM0 (American Joint Committee on Cancer/Union Internationale Contre le Cancer [AJCC/UICC]) corresponds to stage I for patients younger than 45 years old.
- pT2, pN0, pM0 (AJCC/UICC) corresponds to stages 1 and 2 for patients older than 45 years old.
- pT1 and pT2 without lymph node dissection (Nx).
Of the 1,298 patients, 911 patients received RAI after surgery, and 387 patients did not receive RAI after surgery. Follow-up period was 10.3 years; in multivariate analyses, there were no differences in OS (P = .243) or DFS (P = .2659), according to RAI use.
Long-term complications of RAI using I131 include second malignancies, sialadenitis, and lacrimal and salivary gland dysfunction. Options for reducing the amount of radiation exposure by reducing the amount of RAI in each dose and also to give RAI in combination with rhTSH injections have been explored for low-risk thyroid cancer patients.
Two phase III, randomized, noninferiority studies of patients with low-risk thyroid cancer using a comparison of two thyrotropin-stimulation methods (thyroid hormone withdrawal or use of rhTSH) and two doses of radioiodine I131 1.1GBq [30mCi] and 3.7GBq [100mCi] using a 2 × 2 factorial design showed equivalent thyroid ablation rates between high and low dose I131 at 6 to 10 months after administration of I131.[15,16][Levels of evidence: 3iA and3iDii] However, differences in the inclusion criteria in one study  consisted of a low-risk, homogeneous cohort in which all of the patients underwent total thyroidectomy, and had pathological TNM stage pT1 ( ≤1 cm) and N1 or Nx, pT1 (>1–2cm) and any N stage, or pT2N0 without thyroid capsule extension/distant metastases. Complete thyroid ablation rate in this study was 92%. Patients undergoing thyroid hormone withdrawal had greater symptoms of hypothyroidism associated with deterioration in quality of life compared with the rhTSH group.
In the other study, patients with more advanced T stage (T1–T3, N0–1) and with less than a total thyroidectomy were included with a lower overall ablation rate of 85%. Neither study assessed the effect of low-dose RAI on long-term recurrences or survival. The studies also did not address whether RAI could be safely omitted in specific low-risk groups.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I papillary thyroid cancer, stage I follicular thyroid cancer, stage II papillary thyroid cancer and stage II follicular thyroid cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
- Carling T, Udelsman R: Thyroid tumors. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1457-72.
- Grant CS, Hay ID, Gough IR, et al.: Local recurrence in papillary thyroid carcinoma: is extent of surgical resection important? Surgery 104 (6): 954-62, 1988. [PUBMED Abstract]
- Cady B, Rossi R: An expanded view of risk-group definition in differentiated thyroid carcinoma. Surgery 104 (6): 947-53, 1988. [PUBMED Abstract]
- Mazzaferri EL, Jhiang SM: Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 97 (5): 418-28, 1994. [PUBMED Abstract]
- Staunton MD: Thyroid cancer: a multivariate analysis on influence of treatment on long-term survival. Eur J Surg Oncol 20 (6): 613-21, 1994. [PUBMED Abstract]
- Tollefsen HR, Shah JP, Huvos AG: Follicular carcinoma of the thyroid. Am J Surg 126 (4): 523-8, 1973. [PUBMED Abstract]
- Edis AJ: Surgical treatment for thyroid cancer. Surg Clin North Am 57 (3): 533-42, 1977. [PUBMED Abstract]
- Bilimoria KY, Bentrem DJ, Ko CY, et al.: Extent of surgery affects survival for papillary thyroid cancer. Ann Surg 246 (3): 375-81; discussion 381-4, 2007. [PUBMED Abstract]
- Bilimoria KY, Bentrem DJ, Linn JG, et al.: Utilization of total thyroidectomy for papillary thyroid cancer in the United States. Surgery 142 (6): 906-13; discussion 913.e1-2, 2007. [PUBMED Abstract]
- Beierwaltes WH, Rabbani R, Dmuchowski C, et al.: An analysis of "ablation of thyroid remnants" with I-131 in 511 patients from 1947-1984: experience at University of Michigan. J Nucl Med 25 (12): 1287-93, 1984. [PUBMED Abstract]
- Hay ID, Grant CS, van Heerden JA, et al.: Papillary thyroid microcarcinoma: a study of 535 cases observed in a 50-year period. Surgery 112 (6): 1139-46; discussion 1146-7, 1992. [PUBMED Abstract]
- Hay ID, Grant CS, Bergstralh EJ, et al.: Unilateral total lobectomy: is it sufficient surgical treatment for patients with AMES low-risk papillary thyroid carcinoma? Surgery 124 (6): 958-64; discussion 964-6, 1998. [PUBMED Abstract]
- Hänscheid H, Lassmann M, Luster M, et al.: Iodine biokinetics and dosimetry in radioiodine therapy of thyroid cancer: procedures and results of a prospective international controlled study of ablation after rhTSH or hormone withdrawal. J Nucl Med 47 (4): 648-54, 2006. [PUBMED Abstract]
- Schvartz C, Bonnetain F, Dabakuyo S, et al.: Impact on overall survival of radioactive iodine in low-risk differentiated thyroid cancer patients. J Clin Endocrinol Metab 97 (5): 1526-35, 2012. [PUBMED Abstract]
- Schlumberger M, Catargi B, Borget I, et al.: Strategies of radioiodine ablation in patients with low-risk thyroid cancer. N Engl J Med 366 (18): 1663-73, 2012. [PUBMED Abstract]
- Mallick U, Harmer C, Yap B, et al.: Ablation with low-dose radioiodine and thyrotropin alfa in thyroid cancer. N Engl J Med 366 (18): 1674-85, 2012. [PUBMED Abstract]