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Progression of Low-Risk Papillary Thyroid Microcarcinoma During Active Surveillance: Interim Analysis of a Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma in Korea.

ABSTRACT: Background: Active surveillance (AS) is an alternative to thyroidectomy for the management of low-risk papillary thyroid microcarcinoma (PTMC). However, prospective AS data collected from diverse populations are needed. Methods: This multicenter prospective cohort study enrolled patients from three referral hospitals in Korea. The participants were self-assigned into two groups, AS or immediate surgery. All patients underwent neck ultrasound every 6-12 months to monitor for disease progression. Progression under AS was evaluated by a criterion of tumor size increment by 3 mm in one dimension (3 mm), 2 mm in two dimensions (2 × 2 mm), new extrathyroidal extension (ETE), or new lymph node metastasis (LNM), and a composite outcome was defined using all four criteria. Results: A total of 1177 eligible patients with PTMC (919 female, 78.1%) with a median age of 48 years (range 19-87) were enrolled; 755 (64.1%) patients chose AS and 422 (35.9%) underwent surgery. Among 755 patients under AS, 706 (female 537, 76.1%) underwent at least two ultrasound examinations and were analyzed. Over a follow-up period of 41.4 months (standard deviation, 16.0), 163 AS patients (23.1%) underwent surgery. Progression defined by the composite outcome was observed in 9.6% (68/706) of patients, and the 2- and 5-year progression estimates were 5.3% and 14.2%, respectively. The observed progression rates were 5.8% (41/706) and 5.4% (38/706) as defined by tumor size enlargement by 3 mm and 2 × 2 mm, respectively, and 1.3% (9/706) and 0.4% (3/706) for new LNM and ETE, respectively. No distant metastases developed during AS. In multivariate logistic regression analysis examining variables associated with progression under AS, age at diagnosis <30 years (odds ratio [OR], 2.86; 95% confidence interval [CI], 1.10 - 7.45), male sex (OR, 2.48; 95% CI, 1.47 - 4.20), and tumor size ≥6 mm (OR, 1.89; 95% CI, 1.09 - 3.27) were independently significant. Conclusions: The progression of low-risk PTMC during AS in the Korean population was low, but slightly higher than previously reported in other populations. Risk factors for disease progression under AS include younger age, male sex, and larger tumor size. Clinical trial registration: Clinicaltrials.gov NCT02938702.

SUBMITTER: Lee EK

PROVIDER: S-EPMC9700369 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Progression of Low-Risk Papillary Thyroid Microcarcinoma During Active Surveillance: Interim Analysis of a Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma in Korea.

Lee Eun Kyung EK Moon Jae Hoon JH Hwangbo Yul Y Ryu Chang Hwan CH Cho Sun Wook SW Choi June Young JY Chung Eun-Jae EJ Jeong Woo-Jin WJ Jung Yuh-Seog YS Ryu Junsun J Kim Su-Jin SJ Kim Min Joo MJ Kim Yeo Koon YK Lee Chang Yoon CY Lee Ji Ye JY Yu Hyeong Won HW Hah Jeong Hun JH Lee Kyu Eun KE Lee You Jin YJ Park Sue K SK Park Do Joon DJ Kim Ji-Hoon JH Park Young Joo YJ

Thyroid : official journal of the American Thyroid Association 20221101 11

Background: Active surveillance (AS) is an alternative to thyroidectomy for the management of low-risk papillary thyroid microcarcinoma (PTMC). However, prospective AS data collected from diverse populations are needed. Methods: This multicenter prospective cohort study enrolled patients from three referral hospitals in Korea. The participants were self-assigned into two groups, AS or immediate surgery. All patients underwent neck ultrasound every 6-12 months to monit ...[more]

PMID: 36205563

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Project description:It remains controversial whether patients with papillary thyroid microcarcinoma (PTMC) benefit from total thyroidectomy (TT) or thyroid lobectomy (TL). We aimed to investigate the impact of extent of surgery on the prognosis of patients with unilateral PTMC. Patients were obtained from the Surveillance, Epidemiology, and End Results database from 2004 to 2015. Cancer-specific survival (CSS) and overall survival (OS) were evaluated by Cox regression and Kaplan-Meier curves with propensity score matching. Of 31167 PTMC patients enrolled, 22.2% and 77.8% of which underwent TL and TT, respectively. Patients with TT were more likely to be younger, females, present tumors of multifocality, extrathyroidal extension, cervical lymph node metastasis (CLNM), distant metastasis, and receive radioactive iodine (RAI) compared with those receiving TL. The multivariate Cox regression model showed that TT was not associated with an improved CSS and OS compared with TL with hazard ratio (HR) and 95% confidence interval (CI) of 0.53 (0.25-1.12) and 0.86 (0.72-1.04), respectively. In addition, the Kaplan-Meier curves further confirmed the similar survival between TL and TT after propensity score matching. The subgroup analysis showed that TT was associated with better CSS for patients < 55 years, those with tumors of gross extrathyroidal extension, CLNM (N1b), and cases not receiving RAI with HR 95% CI of 0.13 (0.02-0.81), 0.12 (0.02-0.66), 0.11 (0.02-0.64) and 0.36 (0.13-0.90), respectively. TT predicted a trend of better OS for patients with N1b and distant metastasis after adjustment. In addition, TT was associated with better CSS than TL for patients with risk factors like N1b combined with gross extrathyroidal extension, and/or multifocality after matching. In conclusion, TL may be enough for low-risk PTMC patients. TT may improve the prognosis of unilateral PTMC patients with 2 or more risk clinicopathologic factors like CLNM, multifocality, extrathyroidal extension and a younger age compared with TL.

Project description:Biomechanical factors play an important role in tumor distribution, epithelial-mesenchymal transition (EMT), invasion and other important processes. Despite fewer reports investigating biomechanical function in papillary thyroid carcinoma (PTC), a large number of PTC cases are located close to the trachea and the majority of advanced cases of PTC have been associated with invasion of the trachea. However, the effect of trachea stiffness on PTC distribution and growth remains unknown. To clarify this issue, two types of PTC cells (TPC-1 and KTC-1) were seeded on a substrate with different stiffness to observe cell proliferation and movement. To identify the effect of trachea stiffness on the thyroid, two thyroid lobes (left and right) were evenly divided into interior (close to the trachea) and lateral (away from the trachea) parts, based on the vertical line between the trachea and thyroid lateral margin with different von Mises stress values. As PTC originates from papillary thyroid microcarcinoma (PTMC) with a maximum diameter of <1 cm, the present study selected PTMC as the study subject to reflect initial PTC distribution in the thyroid. The association between the percentage of PTMC distribution in different parts of the thyroid and von Mises stress values was analyzed. Both PTC cells exhibited stronger proliferation and mobility on the stiff substrate compared with that on the soft substrate. Furthermore, the results of finite element analysis revealed that the von Mises stress values of the interior parts of the trachea were notably higher compared with that in the lateral parts. PTMC distribution in the interior trachea was notably greater compared with that in the lateral section. There was also an observed association between von Mises stress values and PTMC distribution. In addition, the results of RNA-sequencing and reverse transcription-quantitative PCR demonstrated that three biomechanical genes were overexpressed in PTMC located in the interior section compared with that in adjacent normal tissue, and the related signaling pathways were also activated in these tissues. On the whole, these results indicated that trachea stiffness may supply a suitable biomechanical environment for PTMC growth, and the related biomechanical genes may serve as novel targets for PTMC diagnosis and prognostic estimation.

Project description:Background: Active surveillance is established as an alternative to surgery for papillary thyroid microcarcinomas, but inclusion criteria and mortality risk for pursuing a nonsurgical approach have not been clearly defined. To gauge the feasibility of expanding active surveillance thresholds, we investigated the effects of increasing size and age on disease-specific survival (DSS) in a large nonoperative thyroid cancer cohort, compared against a matched group of surgical patients. Methods: Papillary thyroid carcinoma patients staged T1-4N0M0 were identified in the Surveillance, Epidemiology, and End Results (SEER) database between 1975 and 2015, stratified by nonsurgical and surgical management. Propensity score matching was performed to adjust for imbalances in covariates. Multivariable models were constructed using restricted cubic splines to model nonlinear relationships of age and tumor size with DSS. Results: Overall, 1453 nonoperative patients and 54,718 surgical patients met the inclusion criteria. Collectively, increasing age and size after certain thresholds independently led to greater differences in DSS between nonsurgical and surgical patients. For younger ages (14-55 years), surgical approach compared with nonsurgical approach was not associated with any difference in the 10-year DSS among 0-4 cm cancers (99.8% vs. 100%, p = 0.470), 4.1-6 cm cancers (98.8% vs. 100%, p = 0.599), or >6 cm cancers (97.3% vs. 100%, p = 0.718). Older patients with larger tumors (>75 years, >6 cm) demonstrated the greatest difference in DSS (48.1% vs. 91.3%, p < 0.001). Similar results were found when applying propensity score matching. For age, restricted cubic spline plots showed minimal relative survival hazard in nonoperative cases beginning after age 60 years, with a change point illustrating acceleration in relative hazard beyond age 72 years. For size, relative survival hazard was observed after 2.0 cm and increased slowly with nodule growth up to an inflection point of 4.5 cm. Beyond this, mortality risk escalated with each additional year without plateau. Conclusions: Increasing age and size lead to progressively greater mortality risk without surgery, but only beyond certain thresholds. We define escalating gradients at which a nonsurgical approach may be deemed appropriate, and beyond which survival benefits from surgery become apparent. Such findings reconcile controversial observations regarding age and size in active surveillance and further reshape evolving treatment paradigms in thyroid cancer.

Dataset Information

Progression of Low-Risk Papillary Thyroid Microcarcinoma During Active Surveillance: Interim Analysis of a Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma in Korea.

Publications

Progression of Low-Risk Papillary Thyroid Microcarcinoma During Active Surveillance: Interim Analysis of a Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma in Korea.

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