Marital status, race/ethnicity, and outcomes in well-differentiated thyroid cancer in the elderly

Introduction

In the United States, it was estimated that 43,720 new cases of thyroid cancer were diagnosed in 2023, with 2,120 estimated deaths (1). Despite thyroid carcinoma having the highest 5-year survival rate of 98% from 2012–2018 compared to cancer arising from all other sites (1), the survival rate in well-differentiated thyroid carcinoma varies by several factors, including age, sex, tumor size, histologic grade and type, local invasion, multicentricity, and metastasis (2). Specifically, the relationship between mortality and increasing age has been observed in many studies (3-7). Because age has been shown to be an important prognostic factor in differentiated thyroid cancer management, it has subsequently been incorporated into scoring systems for thyroid cancer staging such as the American Joint Committee on Cancer (AJCC) 8th edition (8); the Metastasis, Age, Completeness of resection, Invasion, Size (MACIS) model (9); the Age, Grade, Extent, Size (AGES) score (10); and the Age, Metastasis, Extent, Size (AMES) score (11). For instance, in the widely used AJCC scoring system, the 7th edition ≥45 years of age cutoff was recently increased in the 8th edition to age ≥55 years of age (8). However, there has been controversy regarding integrating age into various scoring systems, with some studies suggesting a continuous scale rather than strict dichotomous categories (6,8,12).

While the appropriate incorporation of age when staging well-differentiated thyroid carcinoma is debated, the underlying reason for the association between increasing age and increased mortality is also unclear. A variety of theories have been proposed to explain why advanced age is associated with poor prognosis in thyroid carcinoma, including decreased radioactive iodine (RAI) responsiveness (13) and hormonal differences (4,14). Furthermore, older patients diagnosed with well-differentiated thyroid carcinoma are less likely to be referred for specialist surgical care (15), undergo a total thyroidectomy, or receive RAI despite having more advanced disease (16). Additionally, confounding this association could be related to the increased risk among older patients for reoccurrence (17) and complications associated with thyroidectomy (18), RAI (19), unplanned rehospitalization (20), and extended hospital stay (20).

Sociodemographic factors may play an additional role in the relationship between age and worsening prognosis in well-differentiated thyroid carcinoma. Despite the incidence of thyroid cancer increasing across all races and ethnicities (21), racial differences in adherence to thyroid cancer treatment recommendations and mortality have been well-documented. Black and Hispanic patients with well-differentiated thyroid carcinoma are more likely to present with advanced disease (22,23), with Black patients having the lowest survival rates compared to white patients and were less likely to receive appropriate care according to American Thyroid Association (ATA) guidelines (22,24,25). Furthermore, marital status’ role on stage at presentation and mortality in head and neck cancer treatment is well known (26-28), with unmarried patients more likely to present with metastatic disease, less likely to pursue definitive treatment, and more likely to have worse cancer-specific mortality than their married counterparts (29). For well-differentiated thyroid carcinoma, unmarried status has been shown to be associated with worse cancer-specific survival and undertreatment among patients ≥45 years of age (30).

In order to examine the impact of these independently established sociodemographic risk factors, we sought to analyze the interplay between age, race, and marital status in the treatment and prognosis for patients with well-differentiated thyroid carcinoma. Furthermore, with the most recent AJCC guidelines for well-differentiated thyroid carcinoma increasing the age cutoff to 55, combined with evidence favoring the implementation of a less dichotomous stratification of age into scoring systems, we utilized the age cutoffs 55–59, 60–64, 65–69, and 70+ years to better elucidate this relationship. We present this article in accordance with the STROBE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-113/rc).

Methods

Data

Data were collected from the Surveillance, Epidemiology, and End Results (SEER) dataset, a large, national tumor registry maintained by the National Cancer Institute (NCI, http://www.seer.cancer.gov/). We used the SEER9 incidence data to study outcomes for thyroid cancer diagnosed between January 1, 1988 to December 31, 2013. The analysis was limited to patients aged 55 years and older with a primary tumor of the thyroid gland, identified using an international classification of disease for oncology, third edition (ICD-O-3) code of C739 (thyroid gland) (31). We identified well-differentiated thyroid cancer using ICD-O-3 histology codes for papillary (8050, 8250, 8260, 8340, 8341, 8343, 8344, 8350) and follicular (8330, 8331, 8332, 8335) tumors. In addition, we only included the first primary tumors and excluded patients with prior or multiple cancer diagnoses. After excluding cases with missing treatment information, the final sample included 12,779 patients. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Outcomes and covariates

The primary outcome was disease-specific survival (DSS), which was defined using SEER cause-specific survival data. This variable identifies death from cancer only; deaths from other causes are censored. To better assess possible confounding factors related to the effect of marital status on thyroid cancer survival, we additionally analyzed overall survival (OS), defined as death from any cause, in a secondary analysis. The primary covariate of interest was marital status at time of diagnosis, classified as married, single, separated/divorced, widowed, and “other”. We also controlled for demographic characteristics, including age (55–59, 60–64, 65–69, and 70+ years of age), sex (male or female), and race/ethnicity (White non-Hispanic, Black non-Hispanic, Hispanic, Asian and “other”). Stratified analyses estimated the interaction between marital status and race/ethnicity. Disease stage was classified using SEER historic stage (local, regional, distant, and unstaged). Treatment was characterized by the type of surgery (none, local excision, lobectomy, subtotal thyroidectomy, total thyroidectomy) and type of radiation therapy (none, beam, RAI, “other”).

Statistical analysis

The statistical analysis was designed to determine whether there were significant differences in survival (both DSS and OS) by marital status across several demographic, disease, and treatment strata. We first compared patient, disease, and treatment characteristics across marital status categories using analysis of variance (ANOVA) for continuous characteristics and chi-squared tests for binary and categorical characteristics. Univariate survival analysis estimated five-year Kaplan-Meier survival curves by marital status across patient characteristics. Log-rank tests were used to determine whether survival differences by marital status were statistically significant. We performed a multivariable survival analysis using a Cox proportional hazards model that controlled for all other patient, disease, and treatment covariates. Results were summarized using hazard ratios. In addition, we fit Cox proportional hazards models stratified by race/ethnicity to estimate hazard ratios of DSS of marital status for each racial and ethnic group after controlling for covariates. All analyses were performed using Stata software (version 15, College Station, TX, USA). Statistical significance was defined as P<0.05.

Results

Demographic characteristics

In this sample of patients with thyroid cancer, 64.0% of patients were married, 8.6% were single, 8.7% were separated/divorced, 13.0% were widowed, and 5.8% had listed “other” for marital status. The majority of patients were White non-Hispanic (73.5%), while 6.3% were Black non-Hispanic, 7.0% were Hispanic, 10.2% were Asian, and 3.0% were listed as “other” race/ethnicity (Table 1). All patient characteristics differed significantly by race/ethnicity (P<0.05). Asian patients had the oldest average age of 65.1 years, followed by White non-Hispanic patients (65.0 years), Black non-Hispanic and Hispanic patients (64.8 years), and patients with a race/ethnicity of “other” (63.7 years; P=0.03). White non-Hispanic patients were most likely to be male (29.4%) than other racial and ethnic groups (P<0.001). Black non-Hispanic patients were least likely to be married (41.2%) and most likely to be single (20.1%) or separated/divorced (15.7%) than any other group (P<0.001). Hispanic patients were most likely to present with distant disease (7.3%) compared to other groups (P<0.001). White non-Hispanic patients were least likely to receive no surgery (2.7%) and Hispanic patients were most likely to total thyroidectomy (74.2%) compared to other groups (P<0.001). Black non-Hispanic patients were least likely to receive RAI (34.6%) and most likely to receive no external beam radiation therapy (61.2%) compared to other groups (P<0.001).

Marital status

In a multivariable analysis, widowed patients had a hazard of mortality of DSS that was 1.3 times greater than married patients (P=0.007; Table 2). There was no significant difference in DSS among patients whose marital status was listed as single (P=0.20), separated/divorced (P=0.37), or “other” (P=0.49) compared to their married counterparts.

Age

DSS was longest for patients 55–59 years of age, followed by 60–64, 65–69, and then 70+ years of age. Patients who were in the age group of 70+ years had a hazard of mortality of DSS that was 3.6 times greater than patients in the age group of 55–59 years (P<0.001). Patients in the 60–64 years of age and 65–69 years of age groups had DSS hazards of mortality that were 1.4 times (P=0.01) and 2.2 times (P<0.001) greater than patients aged 55–59 years, respectively.

Sex

Female patients had significantly better DSS compared to male patients. Male patients had a hazard of mortality of DSS 1.4 times greater than female patients (P<0.001).

Race/ethnicity

After controlling for other covariates, race/ethnicity was not significantly associated with DSS. There were no significant differences in hazards of mortality of DSS in those who indicated their race/ethnicity as Black non-Hispanic (P=0.44), Hispanic (P=0.20), Asian (P=0.07), and “other” (P=0.47) compared to patients with a race/ethnicity of White non-Hispanic.

Stage

Local stage disease had the best DSS, followed by regional, unstaged, and distant disease. Patients who had distant disease had a hazard of mortality of DSS 26.7 times greater than patients who had localized disease (P<0.001). Those who had regional or unstaged disease had a DSS hazard mortality that was 6.4 times (P<0.001) and 6.7 times (P<0.001) greater than patients with localized disease, respectively.

Surgery

Patients who received total thyroidectomy had the best DSS, with patients who received no surgery or local excision had a hazard of mortality of DSS 2.4 times (P<0.001) and 2.9 times (P<0.001) greater than patients who received total thyroidectomy, respectively. There were no significant differences in DSS in those who received a lobectomy (P=0.53) or subtotal thyroidectomy (P=0.054) compared to those who received a total thyroidectomy.

Radiation therapy

Patients who received no radiation therapy had the best DSS followed by patients who received RAI, “other” radiation, and then beam radiation. RAI, “other” radiation, and beam radiation had a hazard of mortality of DSS 1.3 times (P=0.006), 1.6 times (P=0.004), and 4.5 times (P<0.001) greater than patients who received no radiation therapy.

Kaplan-Meier analysis

As seen in Figure 1, in univariate analyses, marital status was not significantly associated with DSS among any of the age groups. For the 70+ years of age group, the widowed subgroup was estimated to have the worst DSS compared to other marital subgroups 20 months after diagnosis, but this was not statistically significant (P=0.16). For OS, while marital status was not significantly associated with OS among the two youngest age groups of 55–59 years of age (P=0.12) and 60–64 years of age (P=0.07), it was significantly associated with OS among patients aged 65–69 years (P=0.01) and 70+ years (P<0.001), with widowed patients exhibiting the poorest survival in the latter group (Figure 2).

Figure 1 Kaplan-Meier analysis of disease-specific survival by age and marital status. (A) Age 55–59 years. (B) Age 60–64 years. (C) Age 65–69 years. (D) Age 70+ years.

Figure 2 Kaplan-Meier analysis of overall survival by age and marital status. (A) Age 55–59 years. (B) Age 60–64 years. (C) Age 65–69 years. (D) Age 70+ years.

When stratified by sex, a similar relationship between marital status and DSS was found for both women (P<0.001) and men (P=0.004; Figure 3). When stratified by race/ethnicity, significantly worse DSS was found for widowed patients across White non-Hispanic (P<0.001) and Hispanic (P=0.009; Figure 4). There was no significant difference in DSS for those who indicated their race/ethnicity as Black non-Hispanic (P=0.47), Asian (P=0.19), or “other” (P=0.34).

Figure 3 Kaplan-Meier analysis of disease specific survival by sex and marital status. (A) Women. (B) Men.

Figure 4 Kaplan-Meier analysis of disease-specific survival by race/ethnicity and marital status. (A) White non-Hispanic. (B) Black non-Hispanic. (C) Hispanic. (D) Asian. (E) Other.

Stratified Cox proportional hazards models

As seen in Figure 5, when stratifying the White non-Hispanic group by marital status, widowed patients had worse DSS than their married counterparts. Additionally, with this same stratification, Asian patients who indicated their marital status as “other” had worse DSS than their married counterparts. When stratifying the Black non-Hispanic, and Hispanic groups by marital status, there were no significant differences in DSS compared to their married counterparts.

Figure 5 Cox proportional hazards models of disease-specific survival (A) and overall survival (B) by race/ethnicity and marital status.

When stratifying the Black non-Hispanic group by marital status, widowed patients had worse OS than their married counterparts (Figure 5). In the stratified analysis of White non-Hispanic patients by marital status, there was significantly worse OS among single, separated/divorced, widowed, and “other” groups compared to their married counterparts. In the stratified analysis of patient’s who indicated their race/ethnicity as Asian, separated/divorced patients had worse OS than their married counterparts. In the stratified analysis of patients who indicated their race/ethnicity as “other”, single and widowed patients had worse OS than their married counterparts.

Discussion

To better understand the relationship between age, marital status, race, DSS, and OS in older patients with well-differentiated thyroid carcinoma, we stratified age into groups of 55–59, 60–64, 65–69, and 70+ years of age. Widowed marital status, increasing age (60–65, 65–69, 70+ years), male sex, distant stage, local excision, and beam radiation were all related to worse DSS when compared to patients who were married, younger (55–59 years), female, presented with local stage, and underwent a total thyroidectomy without radiation. No significant differences in DSS were found between age groups when stratified by marital status. When comparing OS, age groups 65–69 years and 70+ years were significantly associated with marital status, with widowed individuals, notably in the 70+ years group, having worse OS than their marital counterparts. When stratifying patients based on marital status with married patients as the reference group, significant differences in DSS by marital status were found in patients who were male, female, White non-Hispanic, and Hispanic with the widowed groups having the worst DSS. Using Cox proportional hazards models to directly compare DSS within marital groups when stratified by race/ethnicity, White non-Hispanic widowed patients had worse DSS than their marital counterparts. However, when comparing OS, widowed marital status had significantly worse OS for both White non-Hispanic and Black non-Hispanic groups compared to their married counterparts.

Our study confirms the relationship between increasing age and lower survival demonstrated in previous studies (3-7). However, our study assessed this association across multiple age categories of 55–59, 60–64, 65–69, and 70+ years rather than the dichotomous cutoffs used by previous studies (3-7). Furthermore, we stratified these distinct age groups by marital status, but none of age groups had a significant relationship with DSS based on marital status. Previous studies have suggested that patients with medullary (32,33), anaplastic (34), and follicular (35) thyroid carcinoma tended to have better survival or prognosis if they were married. Furthermore, Shi et al. [2016] showed that widowed individuals with differentiated thyroid carcinoma had a significant survival disadvantage in all their sex and age subgroups tested (30). This relationship is not consistent across all studies, with Johnston et al. [2012] finding that mortality outcomes are not significantly influenced by marital status after 50 years of age (36). However, this study did not stratify patients age beyond those greater than 50 years while also grouping patients who were divorced, separated, or widowed as “previously married” (36). Our study, with age and marital status stratifications, demonstrates further complexity of this well-studied relationship. While we did not find a significant relationship between age and DSS among marital groups, we did find significant differences in OS by marital status in age groups 65–69 and 70+ years with worse OS in widowed individuals compared to other marital counterparts in the 70+ years of age cohort. These discrepant findings between OS but not DSS amongst this 70+ years of age cohort when stratified by marital status could be explained by a multitude of factors related to psychosocial support (37), socioeconomic status (38), and habitual behaviors (39,40). Future studies should incorporate these factors when assessing the effects of age and marital status on DSS in patients with well-differentiated thyroid cancer to further elucidate this complex relationship.

When directly comparing DSS in patients with well-differentiated thyroid carcinoma within marital groups when stratified by race/ethnicity, we found worse DSS in White non-Hispanic widowed patients compared to their married counterparts. However, both White non-Hispanic and Black non-Hispanic widowed patients had significantly worse OS compared to their married counterparts. These discrepant OS and DSS results, mainly with Black non-Hispanic widowed patients could imply that several other confounding factors could be negatively impacting their survival. Previous studies indicate that Black patients are more likely to present with advanced disease (22,23), have overall lower survival rates (24,41,42), and are less likely to receive aggressive treatment (23) or treatment according to ATA guidelines (25,43). However, recent studies have contradicted these findings, indicating that there were no significant differences in DSS (44), appropriate radiation (45,46), or surgical (46) treatment between Black and non-Black patients. However, Luff et al. [2022] and Brown et al. [2010] did not look specifically at treatment for well-differentiated thyroid carcinoma (44,46). Furthermore, while Ginzberg et al. [2023] assessed patients with well-differentiated thyroid carcinoma, they did not specifically assess older populations (45). The underlying reasons behind these racial and ethnic discrepancies are undoubtedly multifaceted, with a complex interplay between health system, physician, and patient factors (47). While system-specific factors related to health insurance, socioeconomic status, and utilization of academic centers likely play a role (47), the physician-patient relationship is also a factor, as Black patients have been shown to be less likely to discuss thyroid cancer care with a surgeon (48). A study by Radhakrishnan et al. [2022] found that primary care physicians had the greatest exposure to minority populations with thyroid cancer when compared to other physician specialties (48). Providing resources to equip primary care physicians in thyroid cancer management, as well as increasing the referral base for these patients to endocrine surgeons, could help address disparities in thyroid cancer care for racial/ethnic minorities.

These findings should be interpreted with the understanding of the limitations of our study. Our patient cohort had limited racial/ethnic diversity with the majority of the cohort being white, non-Hispanic patients. It is important to note that SEER database only captures marital status at the time of diagnosis and would not account for any marital status changes after that (30). For the marital groups studied, this could question the validity of survival outcomes and associations with different variables studied if marital status changes after diagnosis. The SEER database did not allow us to assess patient- vs. physician-decision making regarding pursuing surgical or radiation treatment. Finally, the SEER database does not allow us to assess whether surgical or radiation therapy was deferred by the doctor or the patient.

Conclusions

Overall, our study confirms that in patients with well-differentiated thyroid carcinoma, advanced age is associated with increased mortality. Furthermore, we elucidated the unique role of marital and racial/ethnic status on survival. While this study provides further evidence for the unique role that sociodemographic factors play in mortality in patients with well-differentiated thyroid carcinoma, future research into the interplay between socioeconomic status, mental health, and social support on overall mortality should be conducted to better elucidate this complex relationship.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-113/rc

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-113/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-113/coif). D.G. serves as an unpaid editorial board member of Gland Surgery from March 2025 to February 2027. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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