A Randomized Controlled Clinical Trial: No Clear Benefit to Prophylactic Central Neck Dissection in Patients With Clinically Node Negative Papillary Thyroid Cancer.

OBJECTIVE: The aim of this prospective randomized-controlled trial was to evaluate the risks/benefits of prophylactic central neck dissection (pCND) in patients with clinically node negative (cN0) papillary thyroid cancer (PTC). BACKGROUND: Microscopic lymph node involvement in patients with PTC is common, but the optimal management is unclear. METHODS: Sixty patients with cN0 PTC were randomized to a total thyroidectomy (TT) or a TT+ pCND. All patients received postoperative laryngoscopies and standardized radioiodine treatment. Thyroglobulin (Tg) levels and/or neck ultrasounds were performed at 6 weeks, 6 months, and 1 year. RESULTS: Tumors averaged 2.2 ±â€Š0.2 cm and 11.9% had extra-thyroidal extension. Thirty patients underwent a pCND and 27.6% had positive nodes (all ≤6 mm). Rates of postoperative PTH < 10 (33.3% vs 24.1%, P = 0.57) and transient nerve dysfunction (13.3% vs 10.3%, P = 1.00) were not significantly different between groups. Six weeks after surgery, both TT and TT + pCND were equally likely to achieve a Tg < 0.2 (54.5% vs 66.7%, P = 0.54) and/or a stimulated Tg (sTg) <1 (59.3% vs 64.0%, P = 0.78). At 1 year, rates of Tg < 0.2 (88.9% vs 90.0%, P = 1.00) and sTg < 1 (93.8% vs 92.3%, P = 1.00) remained similar between groups. Neck ultrasounds at 1 year were equally likely to be read as normal (85.7% in TT vs 85.1% in pCND, P = 1.00). CONCLUSIONS: cN0 PTC patients treated either with TT or TT + pCND had similar complication rates after surgery. Although microscopic nodes were discovered in 27.6% of pCND patients, oncologic outcomes were comparable at 1 year.

Performance of a Multigene Genomic Classifier in Thyroid Nodules With Indeterminate Cytology: A Prospective Blinded Multicenter Study.

Importance: Approximately 20% of fine-needle aspirations (FNA) of thyroid nodules have indeterminate cytology, most frequently Bethesda category III or IV. Diagnostic surgeries can be avoided for these patients if the nodules are reliably diagnosed as benign without surgery. Objective: To determine the diagnostic accuracy of a multigene classifier (GC) test (ThyroSeq v3) for cytologically indeterminate thyroid nodules. Design, Setting, and Participants: Prospective, blinded cohort study conducted at 10 medical centers, with 782 patients with 1013 nodules enrolled. Eligibility criteria were met in 256 patients with 286 nodules; central pathology review was performed on 274 nodules. Interventions: A total of 286 FNA samples from thyroid nodules underwent molecular analysis using the multigene GC (ThyroSeq v3). Main Outcomes and Measures: The primary outcome was diagnostic accuracy of the test for thyroid nodules with Bethesda III and IV cytology. The secondary outcome was prediction of cancer by specific genetic alterations in Bethesda III to V nodules. Results: Of the 286 cytologically indeterminate nodules, 206 (72%) were benign, 69 (24%) malignant, and 11 (4%) noninvasive follicular thyroid neoplasms with papillary-like nuclei (NIFTP). A total of 257 (90%) nodules (154 Bethesda III, 93 Bethesda IV, and 10 Bethesda V) had informative GC analysis, with 61% classified as negative and 39% as positive. In Bethesda III and IV nodules combined, the test demonstrated a 94% (95% CI, 86%-98%) sensitivity and 82% (95% CI, 75%-87%) specificity. With a cancer/NIFTP prevalence of 28%, the negative predictive value (NPV) was 97% (95% CI, 93%-99%) and the positive predictive value (PPV) was 66% (95% CI, 56%-75%). The observed 3% false-negative rate was similar to that of benign cytology, and the missed cancers were all low-risk tumors. Among nodules testing positive, specific groups of genetic alterations had cancer probabilities varying from 59% to 100%. Conclusions and Relevance: In this prospective, blinded, multicenter study, the multigene GC test demonstrated a high sensitivity/NPV and reasonably high specificity/PPV, which may obviate diagnostic surgery in up to 61% of patients with Bethesda III to IV indeterminate nodules, and up to 82% of all benign nodules with indeterminate cytology. Information on specific genetic alterations obtained from FNA may help inform individualized treatment of patients with a positive test result.

Preoperative ultrasonography findings predict the need for repeated surgery in papillary thyroid cancer.

OBJECTIVE: To determine the impact of neck ultrasonography in predicting papillary thyroid cancer persistence or recurrence. METHODS: Between March 2005 and March 2009, we identified patients with a preoperative diagnosis of papillary thyroid cancer. Exclusion criteria included no documented preoperative ultrasonography and initial surgery at an outside institution. Patients with positive preoperative ultrasonography were compared with patients who had negative preoperative ultrasonography by assessing rates of neck dissection, complications, disease persistence or recurrence, and the need for repeated surgery. RESULTS: Of 127 patients initially identified, 16 did not have preoperative ultrasonography and 4 did not have their initial surgery at our institution, leaving 107 patients in our cohort. Twenty-two patients had positive preoperative ultrasonography and 85 patients had negative preoperative ultrasonography. Patients with positive preoperative ultrasonography had a higher rate of repeated surgery than those with negative preoperative ultrasonography (27% vs 4.7%, P = .003). There was no difference in postoperative complication rates. No patients with negative preoperative ultrasonography and an ultrasound report stating specifically "no suspicious lymph nodes" required repeated surgery. CONCLUSIONS: Negative preoperative ultrasonography with specific lymph node evaluation predicts a low risk of needing early reoperation. Positive preoperative ultrasonography may be a marker for more aggressive disease and the best predictor of the need for additional surgery in the future.

In patients with thyroid cancer of follicular cell origin, a family history of nonmedullary thyroid cancer in one first-degree relative is associated with more aggressive disease.

BACKGROUND: About 5% of nonmedullary thyroid cancers (NMTCs) are familial. Most patients with a family history of thyroid cancer do not meet the definition of familial NMTC (FNMTC; two or more affected family members). The aim of this study was to determine whether patients with a family history of NMTC, but who do not meet the definition of FNMTC, have more aggressive disease. METHODS: A database of 1502 thyroidectomies was reviewed and 358 patients with NMTC who did not have a family history of benign thyroid disease and who underwent thyroidectomy from January 1994 to December 2008 were identified. These included 324 (90%) patients with papillary thyroid carcinoma (PTC), 24 (7%) with follicular thyroid cancer, and 10 (3%) with anaplastic or Hürthle cell carcinoma. Among them, those with and without a family history of NMTC in first-degree relatives were compared. Then patients with only one affected family member were compared with FNMTC patients. RESULTS: Thirty-seven (10%) patients had a family history of thyroid cancer, all to of which had PTC. Patients with a family history of NMTC had a similar tumor size than those without (2±0 vs. 2.1±0 cm, p=0.72) but they were significantly younger (43±3 vs. 49±1 years, p=0.04), and more likely to have multicentricity (48% vs. 22%, p=0.01), malignant lymph nodes (22% vs. 11%, p=0.02), and local invasion to surrounding tissues (5.4% vs. 0.6%, p=0.007). They also had a higher recurrence rate (24% vs. 12%, p=0.03) than patients without a family history. Interestingly, patients with only one affected family member were similar to FNMTC patients with respect to age (44±4 vs. 40±3 years, p=0.4), tumor size (2±0 vs. 1.9±0 cm, p=0.65), rate of multicentricity (44% vs. 52%, p=0.57), malignant lymph nodes (22% vs. 21%, p=0.93), local invasiveness (5.5% vs. 11%, p=0.59), and disease recurrence (28% vs. 21%, p=0.56). CONCLUSION: Patients with NMTC having a family history of thyroid cancer have more aggressive disease, regardless of whether they meet the current definition of FNMTC regarding number of affected family members. Therefore, any positive family history should be considered a risk factor for more aggressive thyroid carcinoma.