Total Thyroidectomy With and Without Prophylactic Central Neck Lymph Node Dissection in People With Low-risk Papillary Thyroid Cancer

Background: \- Papillary thyroid cancer (PTC) often spreads to lymph nodes in the neck. This can be hard to detect. People often have lymph nodes removed anyway, and researchers want to study if this is a good idea. Objective: \- To compare the effectiveness of removing lymph nodes in the neck that show no evidence of cancer along with the thyroid, or removing only the thyroid. Eligibility: \- Adults age 18 and older with PTC or thyroid nodules suspicious for PTC, with no evidence that the disease has spread in the body. Design: * Participants will be screened with medical history, physical exam, blood tests, scans, and x-rays. * Participants will: * Answer questions. They may have a tumor biopsy. * Have a flexible laryngoscopy. A small tube will pass through the nose to the vocal cords. * Group 1: have surgery to remove the thyroid gland only. Lymph nodes in the neck will be removed if the cancer has spread. * Group 2: have surgery to remove the thyroid and lymph nodes in the neck. * At all post-surgery visits, participants will answer questions and have blood drawn. In addition: * 1 day: laryngoscopy. * 2 weeks: possible laryngoscopy. * 3 months: ultrasound of the thyroid and neck. * Discuss whether to try hormone treatment and/or radioactive iodine. * Possible diagnostic whole body radioiodine scan (WBS). Participants will swallow a capsule or liquid and lie under a camera. * 6 months: ultrasound and maybe laryngoscopy. * 1 year: diagnostic WBS and ultrasound. Participants may get thyroid stimulating hormone. * Participants will have annual follow-up visits for 10 years. They will have a physical exam, blood drawn, scans, and may complete a questionnaire.

Background: * Thyroid cancer is the most common endocrine malignancy and papillary thyroid cancer (PTC) accounts for more than 80% of thyroid cancer. * The incidence of thyroid cancer has risen over the past decades. * Central neck lymph node metastasis (LNM) is common in PTC and preoperative imaging studies do not identify all involved lymph nodes in the central neck. * It remains controversial if prophylactic central neck lymph node dissection (pCND) in patients with low-risk PTC results in lower rates of persistent/recurrent disease and higher complication rates as there has been no randomized controlled trial addressing these issues to date. * Serum thyroglobulin (Tg), especially when thyroid stimulating hormone (TSH)-stimulated, is a very sensitive and specific marker for persistent/recurrent PTC, in the absence of interfering anti-Tg antibodies. * Retrospective studies have compared the postoperative TSH-stimulated Tg levels between those who underwent prophylactic central neck dissection (pCND) and those who did not with conflicting results. A randomized trial is needed. * Health-related quality of life (QOL) is a well-accepted tool to measure the outcome of cancer treatments. Short-form 36 (SF-36) version 2 (v2) questionnaire has been frequently used to evaluate the QOL in patients with thyroid cancer. There is no study evaluating the difference in QOL in patients with low-risk PTC undergoing total thyroidectomy (TT) with and without pCND. Objectives: -To determine and compare biochemical cure rates in patients with low-risk PTCs undergoing total thyroidectomy (TT) with and without pCND as measured by postoperative TSH-stimulated serum thyroglobulin (stim-Tg) at 3 months (prior to radioactive iodine treatment (RAI) treatment). Eligibility: * Patients greater than or equal to 18 years who have thyroid nodule(s) greater than or equal to 1 cm. but less than or equal to 4 cm. in size with either: * inconclusive thyroid cytology positive for B-Raf Proto-oncogene Serine/Threonine Kinase (BRAF) Valine 600 Glutamic Acid (V600E) mutation or rearranged in transformation/papillary thyroid carcinomas (RET/PTC) rearrangement or * cytologically suspicious for or consistent with PTC * Absence of extrathyroidal extension or lymphadenopathy suggesting metastatic PTC on physical examination and neck ultrasound. Design: * Prospective, single-blinded, randomized controlled clinical trial. * Cytology will be reviewed by Laboratory of Pathology, National Cancer Institute (NCI) or a pathology laboratory at the enrolling institution. Once patients provide written informed consent, they will receive routine history, physical, radiographic (neck ultrasonography (USG), and/or other indicated tests) examinations as well as blood tests. Preoperative fine needle aspiration for cytology and BRAFV600E mutation will be performed if participant has not had either test performed. * Preoperative assessment of QOL using standardized questionnaire (SF-36 v2) will be obtained within 30 days prior to surgery * Preoperative vocal cord assessment will be done by flexible laryngoscopy. * Participants will be randomized after clinical staging, including ultrasonography, to receive TT and pCND or TT alone and will be blinded from the result of randomization and treatment. Patients will remain blinded from treatment assignment for the duration of the study except for patients assigned to TT alone but found to have lymph node metastases as described below. * If participants in TT alone group are found to have lymph node metastasis at the time of the operation by frozen section analysis, a therapeutic central neck dissection (CND) will be performed. Participants will remain in the intention to treat (TT alone) group. TT patients will be informed if a therapeutic CND is indicated and as such the blind will be broken for these patients prior to study completion. * All participants will have intact parathyroid hormone (PTH), calcium and electrolytes checked preoperatively, in the morning after surgery, 2 weeks, and 6 months postoperatively. * Postoperative flexible laryngoscopy will be performed on postoperative day 1 (or postoperative day 2, if it cannot be performed on the first postoperative day) and 6 months postoperatively if vocal cord abnormality is found on postoperative day 1 * Postoperative assessment of QOL will be done on day 1, 2 weeks, 3 months and 6 months, 1, 5 and 10 years postoperatively. * Participants with postoperative hypoparathyroidism (low PTH and hypocalcemia) will be treated with calcium replacement with or without vitamin D analogue. Serum PTH and electrolytes will be monitored until resolved. * Stim-Tg will be checked at 3 months postoperatively (prior to RAI scan/ablation, if indicated) and at 1 year postoperatively or 1 year post-remnant ablation. 1 year stim-Tg evaluation will be performed in patients enrolled at the NIH but is optional in patients enrolled at non-NIH site(s) Unstimulated Tg, thyroid function tests, and anti-thyroglobulin antibodies will be checked annually for 10 years. * Soft tissue neck ultrasonography will be performed in all patients preoperatively and every year postoperatively for the first 10 years. * If biochemical evidence of tumor recurrence occurs, patients will undergo appropriate radiographic studies and/or nuclear scintigraphy. Tissue biopsy of suspicious lesion(s) will be performed if clinically indicated.