Survival Comparison of Incidentally Found versus Clinically Detected Thyroid Cancers: An Analysis of a Nationwide Cohort Study

Background The true benefit of thyroid cancer screening is incompletely understood. This study investigated the impact of ultrasound screening on thyroid cancer outcomes through a comparison with symptomatic thyroid cancer using data from a nationwide cohort study in Korea. Methods Cox regression analysis was performed to assess the hazard ratios (HRs) for all-cause and thyroid cancer-specific mortality. Considering the possible bias arising from age, sex, year of thyroid cancer registration, and confounding factors for mortality (including smoking/drinking status, diabetes, and hypertension), all analyses were conducted with stabilized inverse probability of treatment weighting (IPTW) according to the route of detection. Results Of 5,796 patients with thyroid cancer, 4,145 were included and 1,651 were excluded due to insufficient data. In comparison with the screening group, the clinical suspicion group was associated with large tumors (17.2±14.6 mm vs. 10.4±7.9 mm), advanced T stage (3–4) (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.09 to 1.41), extrathyroidal extension (OR, 1.16; 95% CI, 1.02 to 1.32), and advanced stage (III–IV) (OR, 1.16; 95% CI, 1.00 to 1.35). In IPTW-adjusted Cox regression analysis, the clinical suspicion group had significantly higher risks of all-cause mortality (HR, 1.43; 95% CI, 1.14 to 1.80) and thyroid cancer-specific mortality (HR, 3.07; 95% CI, 1.77 to 5.29). Mediation analysis showed that the presence of thyroid-specific symptoms was directly associated with a higher risk of cancer-specific mortality. Thyroid-specific symptoms also indirectly affected thyroid cancer-specific mortality, mediated by tumor size and advanced clinicopathologic status. Conclusion Our findings provide important evidence for the survival benefit of early detection of thyroid cancer compared to symptomatic thyroid cancer.

[1]  Maya B. Mathur,et al.  A brief primer on conducting regression-based causal mediation analysis. , 2023, Psychological trauma : theory, research, practice and policy.

[2]  C. Jung,et al.  Re-Increasing Trends in Thyroid Cancer Incidence after a Short Period of Decrease in Korea: Reigniting the Debate on Ultrasound Screening , 2022, Endocrinology and metabolism.

[3]  Tae Yong Kim,et al.  Recent Changes in the Incidence of Thyroid Cancer in Korea between 2005 and 2018: Analysis of Korean National Data , 2022, Endocrinology and metabolism.

[4]  C. la Vecchia,et al.  The epidemiological landscape of thyroid cancer worldwide: GLOBOCAN estimates for incidence and mortality rates in 2020. , 2022, The lancet. Diabetes & endocrinology.

[5]  U. Megwalu,et al.  Thyroid Cancer Incidence and Mortality Trends in the United States: 2000 - 2018. , 2022, Thyroid : official journal of the American Thyroid Association.

[6]  I. Shimon,et al.  Adverse Histological Features of Differentiated Thyroid Cancer are Commonly Found in Autopsy Studies: Implications for Treatment Guidelines. , 2021, Thyroid : official journal of the American Thyroid Association.

[7]  S. Balasubramanian,et al.  The Influence of Incidental Detection of Thyroid Nodule on Thyroid Cancer Risk and Prognosis - a Systematic Review , 2021, Clinical endocrinology.

[8]  J. Brito,et al.  Triggers of thyroid cancer diagnosis: a systematic review and meta-analysis , 2021, Endocrine.

[9]  Wangen Li,et al.  Incidence of microcarcinoma and non‐microcarcinoma in ultrasound‐found thyroid nodules , 2021, BMC Endocrine Disorders.

[10]  B. Jarzab,et al.  Early Diagnosis of Low-Risk Papillary Thyroid Cancer Results Rather in Overtreatment Than a Better Survival , 2020, Frontiers in Endocrinology.

[11]  Chao Zhang,et al.  Synergistic effect of clinicopathological factors on mortality risk in patients with differentiated thyroid cancer: An analysis using the SEER database. , 2020, Surgical oncology.

[12]  S. Vaccarella,et al.  Global trends in thyroid cancer incidence and the impact of overdiagnosis. , 2020, The lancet. Diabetes & endocrinology.

[13]  J. Brito,et al.  Long term declines of thyroid cancer mortality: an international age-period-cohort analysis. , 2020, Thyroid : official journal of the American Thyroid Association.

[14]  K. Choi,et al.  Association of screening by thyroid ultrasonography with mortality in thyroid cancer: a case-control study using data from two national surveys. , 2019, Thyroid : official journal of the American Thyroid Association.

[15]  Jung-Han Kim,et al.  Improved survival after early detection of asymptomatic distant metastasis in patients with thyroid cancer , 2019, Scientific Reports.

[16]  S. Roman,et al.  Geographic influences in the global rise of thyroid cancer , 2019, Nature Reviews Endocrinology.

[17]  S. Polat,et al.  A cancer of undetermined significance: Incidental thyroid carcinoma , 2018, Diagnostic cytopathology.

[18]  Sohee Park,et al.  National Epidemiologic Survey of Thyroid cancer (NEST) in Korea , 2018, Epidemiology and health.

[19]  Sun Wook Cho,et al.  Secular Trends for Diagnostic Motives and Environmental Risk Factors in Thyroid Cancer Using Questionnaire Survey , 2017 .

[20]  G. Ceresini,et al.  Causes of referral to the first endocrine visit of patients with thyroid carcinoma in a mildly iodine-deficient area , 2017, Endocrine.

[21]  Jett R. Brady,et al.  LOWER RATES OF RESIDUAL/RECURRENT DISEASE IN PATIENTS WITH INCIDENTALLY DISCOVERED THYROID CARCINOMA. , 2017, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[22]  J. Roh,et al.  Differences in the Recurrence and Survival of Patients with Symptomatic and Asymptomatic Papillary Thyroid Carcinoma: An Observational Study of 11,265 Person-Years of Follow-Up. , 2016, Thyroid : official journal of the American Thyroid Association.

[23]  M. LoPresti,et al.  Method of Detection of Well-Differentiated Thyroid Cancers in Obese and Non-Obese Patients , 2016, PloS one.

[24]  Elizabeth E Ward,et al.  Anthropometric Factors and Thyroid Cancer Risk by Histological Subtype: Pooled Analysis of 22 Prospective Studies. , 2016, Thyroid : official journal of the American Thyroid Association.

[25]  P. BritoJuan,et al.  The Impact of Subclinical Disease and Mechanism of Detection on the Rise in Thyroid Cancer Incidence: A Population-Based Study in Olmsted County, Minnesota During 1935 Through 2012 , 2015 .

[26]  M. Ward,et al.  Polybrominated diphenyl ethers and thyroid cancer risk in the Prostate, Colorectal, Lung, and Ovarian Cancer Screening Trial cohort. , 2015, American journal of epidemiology.

[27]  R. Nelson,et al.  Trends in Incidentally Identified Thyroid Cancers Over a Decade: A Retrospective Analysis of 2,090 Surgical Patients , 2014, World Journal of Surgery.

[28]  I. Reccia,et al.  Risk Factors for Nodal Metastasis and Recurrence Among Patients with Papillary Thyroid Microcarcinoma: Differences in Clinical Relevance Between Nonincidental and Incidental Tumors , 2009, World Journal of Surgery.

[29]  Y. Choi,et al.  Prevalence of Thyroid Cancer at a Medical Screening Center: Pathological Features of Screen-detected Thyroid Carcinomas , 2008, Yonsei medical journal.

[30]  J. Freeman,et al.  Management and outcome of recurrent well-differentiated thyroid carcinoma. , 2004, Archives of otolaryngology--head & neck surgery.

[31]  W. Chung,et al.  Ultrasonographic Mass Screening for Thyroid Carcinoma: A Study in Women Scheduled to Undergo a Breast Examination , 2001, Surgery Today.

[32]  V. Montori,et al.  The Impact of Subclinical Disease and Mechanism of Detection on the Rise in Thyroid Cancer Incidence: A Population-Based Study in Olmsted County, Minnesota During 1935 Through 2012. , 2015, Thyroid : official journal of the American Thyroid Association.

[33]  J. Higginson,et al.  International Agency for Research on Cancer. , 1968, WHO chronicle.