Association of Tumor Size With Histologic and Clinical Outcomes Among Patients With Cytologically Indeterminate Thyroid Nodules

Abstract

<p class="first" id="d9130211e321">This study assesses the association of indeterminate thyroid nodule size among adults with histologic and clinical outcomes such as cancer rates and response to therapy in considering a surgical approach. </p><div class="section"> <a class="named-anchor" id="ab-ooi180042-1"> <!-- named anchor --> </a> <h5 class="section-title" id="d9130211e327">Question</h5> <p id="d9130211e329">Should tumor size determine the extent of surgery for cytologically indeterminate thyroid nodules? </p> </div><div class="section"> <a class="named-anchor" id="ab-ooi180042-2"> <!-- named anchor --> </a> <h5 class="section-title" id="d9130211e332">Findings</h5> <p id="d9130211e334">In this cohort study of 652 indeterminate thyroid nodules, more than 90% of indeterminate thyroid nodules were benign or low-risk malignant tumors for which a lobectomy would be sufficient initial treatment regardless of tumor size. Tumor size was not associated with cancer rates, cancer aggressiveness, or response to therapy. </p> </div><div class="section"> <a class="named-anchor" id="ab-ooi180042-3"> <!-- named anchor --> </a> <h5 class="section-title" id="d9130211e337">Meaning</h5> <p id="d9130211e339">In the absence of other indications for total thyroidectomy, this study suggests that the preferred surgical approach for cytologically indeterminate thyroid nodules is a thyroid lobectomy regardless of tumor size. </p> </div><div class="section"> <a class="named-anchor" id="ab-ooi180042-4"> <!-- named anchor --> </a> <h5 class="section-title" id="d9130211e343">Importance</h5> <p id="d9130211e345">Tens of thousands of unnecessary operations are performed each year for diagnostic purposes among patients with cytologically indeterminate thyroid nodules. Whereas a diagnostic lobectomy is recommended for most patients with solitary indeterminate thyroid nodules, a total thyroidectomy is preferred for nodules larger than 4 cm. </p> </div><div class="section"> <a class="named-anchor" id="ab-ooi180042-5"> <!-- named anchor --> </a> <h5 class="section-title" id="d9130211e348">Objective</h5> <p id="d9130211e350">To determine whether histologic or clinical outcomes of indeterminate thyroid nodules 4 cm or larger are worse than those for nodules smaller than 4 cm, thus justifying a more aggressive initial surgical approach. </p> </div><div class="section"> <a class="named-anchor" id="ab-ooi180042-6"> <!-- named anchor --> </a> <h5 class="section-title" id="d9130211e353">Design, Setting, and Participants</h5> <p id="d9130211e355">In this retrospective cohort study, 652 indeterminate thyroid nodules (546 nodules &lt;4 cm and 106 nodules ≥4 cm) with surgical follow-up were consecutively evaluated at an academic cancer center from October 1, 2008, through April 30, 2016. </p> </div><div class="section"> <a class="named-anchor" id="ab-ooi180042-7"> <!-- named anchor --> </a> <h5 class="section-title" id="d9130211e358">Exposure</h5> <p id="d9130211e360">Tumor size.</p> </div><div class="section"> <a class="named-anchor" id="ab-ooi180042-8"> <!-- named anchor --> </a> <h5 class="section-title" id="d9130211e363">Main Outcomes and Measures</h5> <p id="d9130211e365">Differences in cancer rates, rates of invasive features, cancer aggressiveness, and response to therapy between indeterminate thyroid nodules smaller than 4 cm and 4 cm or larger. </p> </div><div class="section"> <a class="named-anchor" id="ab-ooi180042-9"> <!-- named anchor --> </a> <h5 class="section-title" id="d9130211e368">Results</h5> <p id="d9130211e370">A total of 652 indeterminate thyroid nodules (546 nodules &lt;4 cm and 106 nodules ≥4 cm) from 589 patients (mean [SD] age, 53.1 [13.8] years; 453 [76.9%] female) were studied. No differences were found in the baseline characteristics of patients or nodules between the 2 size groups. Tumor size was not associated with the cancer rate as a categorical (140 of 546 [25.6%] for nodules &lt;4 cm and 33 of 106 [31.1%] for nodules ≥4 cm; effect size, 0.05; 95% CI, 0.002-0.12) or continuous (odds ratio [OR], 1.03; 95% CI, 0.92-1.15) variable. No association was found between nodule size and prevalence of extrathyroidal extension, positive margins, lymphovascular invasion, lymph node metastasis, or distant metastasis. Most malignant tumors were low risk in both size groups (70% in the nodules &lt;4 cm and 72% in the nodules ≥4 cm), and tumor size was not associated with tumor aggressiveness as a categorical (effect size, 0.10; 95% CI, 0.03-0.31) or continuous variable (OR for intermediate-risk cancer, 0.91; 95% CI, 0.72-1.14; OR for high-risk cancer, 1.43; 95% CI, 0.96-2.15). At the last follow-up visit, 88 of 105 patients (83.8%) with malignant tumors in the smaller than 4 cm group and 21 of 25 (84.0%) in the 4 cm or greater group had no evidence of disease, and tumor size was not associated with response to therapy (effect size, 0.13; 95% CI, 0.07-0.33). </p> </div><div class="section"> <a class="named-anchor" id="ab-ooi180042-10"> <!-- named anchor --> </a> <h5 class="section-title" id="d9130211e373">Conclusions and Relevance</h5> <p id="d9130211e375">Most indeterminate thyroid nodules are benign or low-risk malignant tumors regardless of tumor size. In the absence of other indications for total thyroidectomy, this study suggests that a thyroid lobectomy is sufficient initial treatment for most solitary cytologically indeterminate thyroid nodules independent of the tumor size. </p> </div>