Treatment patterns of aging Americans with differentiated thyroid cancer

Authors


Abstract

BACKGROUND:

The incidence of differentiated thyroid cancer (DTC) increases with age. Total thyroidectomy, often followed by radioactive iodine (RAI), is recommended for patients who have tumors that measure ≥1 cm in greatest dimension. In the current study, the authors assessed the use of thyroidectomy and RAI among elderly patients with DTC and the effects on survival.

METHODS:

Adults aged ≥45 years with DTC ≥1 cm in the Surveillance, Epidemiology, and End Results database from 1988 to 2003 were included. Bivariate and multivariate analyses were used to measure associations between demographic, clinical, and pathologic characteristics and the likelihood of receiving treatment according to current practice guidelines.

RESULTS:

Of 8899 patients who were identified, 26% were ages 65 years to 79 years, and 5% were aged ≥80 years. Compared with younger patients, patients aged ≥ 65 years were more likely to have larger tumors, stage IV disease, extrathyroid extension, and nonpapillary histology. Elderly patients were less likely to undergo total thyroidectomy (74% vs 80%; P < .001) or to receive RAI (47% vs 54%; P < .001). These trends were most pronounced among those aged ≥80 years. Among the patients who did not undergo surgery, elderly patients did not report higher rates of contraindications to surgery. In multivariate analysis, the groups ages 65 years to 79 years and aged ≥80 years were associated with lower rates of total thyroidectomy (odds ratio, 0.77 and 0.43, respectively; P < .001) and RAI (odds ratio, 0.85 [P < .01] and 0.39 [P < .001], respectively). Among elderly patients, predictors of worse survival included no surgery (hazard ratio, 5.51; P < .001) and no RAI (hazard ratio, 1.36; P < .001).

CONCLUSIONS:

Elderly patients with DTC received less aggressive surgical and RAI treatment than younger patients despite having more advanced disease and the improved survival associated with these treatments among elderly patients. Long-term outcomes should be measured to determine the impact of this apparent discrepancy in care. Cancer 2010. © 2010 American Cancer Society.

The elderly are a steadily growing segment of the US population. In 2000, Americans aged ≥65 years constituted 12.4% of the population and are projected to increase to 20% by 2050. Americans aged ≥80 years constituted 3.3% of the population in 2000 and are projected to increase to 7.3% by 2050.1 In the United States, a patient who survives to age 70 years averages an additional 14 years of life, whereas a patient who survives to age 80 years averages an additional 8 years of life.2 The projected increase in the elderly population is expected to raise the total number of oncologic procedures by up to 51% by 2020.3

Thyroid carcinoma is the most common endocrine malignancy; >30,000 new cases are diagnosed annually in the United States, and they represent 1% of all US cancers.4 Between 1973 and 2002, the incidence of thyroid cancer increased approximately 240%, from 3.6 per 100,000 population to 8.7 per 100,000 population, although disease-specific mortality rates were stable (0.5 deaths per 100,000 population).5 There is also a direct association between older age and the incidence and malignant potential of thyroid nodules.4, 6, 7 Differentiated thyroid cancer (DTC), which includes papillary, follicular, and Hurthle cell subtypes, encompasses >90% of all thyroid cancers. Less than 10% of patients die of this disease. Most major guidelines, including those released by the American Thyroid Association (ATA) in 2006, have recommended near-total or total thyroidectomy as the initial procedure of choice for DTC, and radioiodine ablation (RAI) is added for patients who have functioning remnants in the thyroid bed or distant metastases.8 The applicability of these guidelines to elderly patients (aged ≥65 years) has not been studied. To our knowledge, this is the first population-based study addressing treatment patterns of surgery and RAI administration and their effects on survival among patients aged ≥65 years with DTC in the United States.

MATERIALS AND METHODS

Data Sources and Study Subject s

The Surveillance, Epidemiology, and End Results (SEER) database was used to identify individuals in the United States who were diagnosed with papillary thyroid cancer (International Classification of Diseases for Oncology [ICD-O] histology codes 8050/3, 8340/3, 8341/3, 8342/3, 8343/3, and 8344/3), follicular thyroid cancer (ICD-O histology codes 8330/3, 8331/3, 8332/3, 8335/3, and 8337/3), and Hurthle cell thyroid cancer (ICD-O histology code 8290/3) in 17 SEER regions between 1988 and 2003. The 17 SEER regions are Atlanta, Connecticut, Detroit, Hawaii, Iowa, New Mexico, San Francisco-Oakland, Seattle-Puget Sound, Utah, Los Angeles, San Jose-Monterey, Alaska, rural Georgia, greater California (excluding San Francisco/Los Angeles/San Jose), Kentucky, Louisiana, and New Jersey. Collectively, these regions represent approximately 26% of the total US population. The SEER population is comparable to the general US population with regard to poverty and education level, but it is more urban and has a greater proportion of foreign-born individuals.9

In the current retrospective cohort study, all patients who had histologically confirmed DTC were identified. Patients aged <45 years who were missing data regarding surgery and American Joint Committee on Cancer (AJCC) stage, and whose DTC diagnosis was established by “autopsy only” or ”death certificate only” were excluded. The registries collect data regarding patient demographics, primary tumor site, histology, stage at diagnosis, and first course of treatment (surgery and/or radiation therapy); all of these data were included in our analyses.

Associations between the demographic, clinical, and pathologic characteristics of patients and the likelihood of receiving surgical care or RAI were assessed. Independent demographic variables included age at diagnosis, sex, race/ethnicity (white, black, Asian/Pacific Islander, other), Hispanic origin, marital status at diagnosis, year of diagnosis (1988-1991, 1992-1995, 1996-1999, or 2000-2003), and geography (Northeast, Midwest, South, or West). Clinical variables included the number of primary tumors, surgical therapy (none, lobectomy/isthmusectomy, or total/near-total thyroidectomy), reason for no surgery (not recommended, contraindicated, or patient/guardian refusal), lymph node dissection (none, limited, modified radical, or radical lymph node dissection), and radiation therapy (none, radioactive isotopes, or other radiation). Data regarding lymph node dissection were available only from 1998 through 2002. We assumed that radioactive isotopes were RAI for all patients with thyroid cancer. Pathologic variables included disease stage at diagnosis, tumor size, tumor extension/capsular invasion, lymph node metastases (none, ipsilateral cervical, bilateral/contralateral/midline cervical, mediastinal, or distant), histology (papillary, follicular, or Hurthle cell), the number of regional lymph nodes examined, and the number of metastatic lymph nodes removed. Tumor stage was determined according to the TNM classification system sponsored by the AJCC (AJCC Staging Manual, sixth edition).10 For patients with DTC, different staging criteria are used for patients aged <45 years and patients aged ≥45 years, so patients aged <45 years were excluded from the current analysis. The 2006 ATA management guidelines for patients with thyroid nodules and DTC state that only nodules that measure >1 cm should be evaluated, because they have potential clinical significance.8 Therefore, we excluded patients who had DTC <1 cm.

With regard to appropriate surgery, the ATA guidelines state in Recommendation 26 that most patients who have thyroid cancer should undergo initial near-total or total thyroidectomy; whereas thyroid lobectomy alone may be sufficient for patients who have small, low-risk, isolated, intrathyroid papillary carcinomas without cervical lymph node metastases. According to Recommendation 27, patients who have papillary thyroid carcinoma and suspected Hurthle cell carcinoma should be considered for prophylactic central-compartment (level VI) lymph node dissection. With regard to RAI, Recommendation 32 recommends radioiodine ablation for patients with stage III and IV disease, for all patients with stage II disease aged <45 years, for most patients with stage II disease aged ≥45 years, and for selected patients with stage I disease, especially those who have with multifocal disease, lymph node metastases, extrathyroid or vascular invasion, and/or more aggressive histologies.8

Statistical Analysis

Bivariate analyses of the independent variables with our outcomes of interest were performed by using chi-square statistical analyses for categorical variables and analyses of variance for continuous variables. Multivariate logistic regression models with a backward elimination procedure were used to adjust for patient demographic, clinical, and pathologic characteristics. Survival was calculated as the time (in years) from diagnosis until death, last follow-up, or December 31, 2003, whichever came first. Because SEER does not report the cause of death for individual patients, overall mortality was used for the survival analysis. For the bivariate analysis, the Kaplan-Meier method and the log-rank test were used to identify significant prognostic factors. For the multivariate analysis, a Cox proportional hazards regression model was used for variables that were identified as significant in the bivariate analysis. The strength of association between each predictor variable and the outcome of interest was expressed as an odds ratio (OR) for the likelihood of receiving treatment or as a hazard ratio (HR) for survival, which is presented along with a 95% confidence interval. Data analyses and management were performed using SPSS version 16.0 (SPSS, Inc., Chicago, Ill). All tests were 2-sided, and statistical significance was set at a probability value (P) of ≤.05. This study was granted an exemption from Institutional Review Board approval at our institution, because SEER is a public database with no personal identifying information.

RESULTS

Summary Statistics

From 1988-2003, 43,657 adults were diagnosed with DTC; 24,044 patients (55%) were aged >45 years, including 11,394 patients who had tumors ≥1 cm. These patients were the focus of the current study. Of these, 10,896 patients (96%) had complete surgery data, and 9377 patients (83%) had staging information (tumor size, extension, or lymph node metastasis). In total, 8899 patients had complete surgery and staging data and were included in the analysis; 2271 patients (26%) were ages 65 years to 79 years, and 444 patients (5%) were aged ≥80 years (Table 1). There were no significant differences between patients who did or did not have complete surgery and staging data with respect to other demographic, clinical, or pathologic characteristics.

Table 1. Characteristics of Patients Aged ≥45 Years With Differentiated Thyroid Cancer ≥1 cm by Age Group: Surveillance, Epidemiology, and End Results, 1988-2003 (N = 8899)
CharacteristicPercentage of PatientsP
All PatientsAges 45-64 Years (n = 6184)Ages 65-79 Years (n = 2271)Aged ≥80 Years (n = 444)
  1. NS indicates not significant (P>.05); AJCC, American Joint Committee on Cancer; SD, standard deviation; NOS, not otherwise specified.

Demographic characteristics
 Women71736771<.001
 Race    NS
  White81818383 
  Black6756 
  Asian/Pacific Islander12121211 
  Other1101 
  Hispanic1112107<.01
 Married70746342<.001
 Year of diagnosis    NS
  1988-19918897 
  1992-199516161713 
  1996-199923232223 
  2000-200353535257 
 Geography    <.001
  Northeast16151716 
  Midwest14131618 
  South1112117 
  West59605759 
Clinical characteristics
 No. of primary malignancies    <.001
  183867575 
  215122019 
  ≥33256 
 Surgery    <.001
  None1115 
  Lobectomy/isthmusectomy21202328 
  Near-total/total thyroidectomy78807667 
  Reason for no surgery (n = 87)   NS 
   Contraindicated1572418 
  Lymphadenectomy (n = 4718)   <.001 
   None60586463 
   Limited36383127 
   Radical/modified radical44610 
 Radiation therapy    <.001
  None42414257 
  Radioisotopes52545034 
  Other radiation6589 
Pathologic characteristics
 AJCC stage    <.001
  I30332314 
  II26272523 
  III36343945 
  IV961419 
 Tumor size: Mean ± SD, cm3.0 ± 2.22.7 ± 1.93.3 ± 2.14.2 ± 5.1<.001
 Extrathyroid extension23193137<.001
 Lymph node metastases    NS
  None80817977 
  Ipsilateral cervical991010 
  Bilateral/contralateral/midcervical2222 
  Mediastinal2123 
  Regional, NOS7779 
  Distant0001 
 Histology    <.001
  Papillary79827366 
  Follicular13121618 
  Hurthle cell861116 
 ≥1 Examined lymph node38403533<.001
 ≥1 Positive lymph node45434956.001

Overall, 71% of the patients were women, 81% were white, 89% were non-Hispanic, and 70% were married. DTC was the only malignancy diagnosed in 83% of patients; 15% of patients had another primary malignancy, and 3% had >1 other primary malignancy. Thirty percent of tumors were stage I, 26% were stage II, 36% were stage III, and 9% were stage IV. The mean tumor size was 3.0 cm (range, 1.0-9.9 cm); and 23% of tumors extended beyond the thyroid capsule. Most tumors were papillary (79%); 13% were follicular, and 8% were Hurthle cell.

Near-total or total thyroidectomy was performed in 78% of patients; 21% underwent lobectomy, and no surgery was performed in 1%. Among the 87 patients who did not undergo surgery, surgery was contraindicated in 15%, was not recommended in 37%, was refused by the patient or guardian in 24%, and the reason for no surgery was unknown in 30%. Adjuvant radiation was administered to 58% of patients, including RAI to 52%.

Eighty-five percent of the patients in our cohort were still alive as of December 31, 2005. The mean survival after a diagnosis of DTC was 14.5 years (range, 0-17.9 years). Patients ages 45 years to 64 years had a 10-year survival rate of 88%, whereas patients ages 65 years to 79 years had a 10-year survival rate of 62%. Only 18% of patients aged ≥80 years survived 10 years after diagnosis.

Bivariate Analysis

Compared with younger patients, patients aged ≥65 years were more likely to be men (P < .001), non-Hispanic (P < .01), and from the Midwest (P < .001). Older patients also were more likely to have multiple primary tumors, advanced-stage disease, larger tumors, extrathyroid extension, and nonpapillary histology (all P < .001). Despite their more aggressive disease, older patients were less likely to undergo near-total/total thyroidectomy, to undergo lymphadenectomy, or to receive adjuvant radiation (all P < .001). These trends were pronounced among those aged ≥80 years.

Patients aged ≥65 years who underwent near-total/total thyroidectomy were more likely to have advanced-stage disease (P < .05) and nonpapillary histology (P < .001) compared with age-matched counterparts who underwent lobectomy or no surgery (Table 2). Patients aged ≥65 years who received RAI were more likely to have advanced-stage disease (P < .001), nonpapillary histology (P < .001), and Asian/Pacific Islander race (P < .001) compared with age-matched counterparts who did not receive RAI (Table 3). Survival was shorter for patients aged ≥80 years (P < .001), for patients who did not undergo surgery (P < .001), and for patients who did not receive RAI (P < .001) (Table 4).

Table 2. Surgical Intervention Among Elderly Patients (Aged ≥65 Years) With Differentiated Thyroid Cancer ≥1 cm: Surveillance, Epidemiology, and End Results, 1988-2003 (N = 2715)
VariableSurgery of Primary Site, %P
None (n = 51)Lobectomy/Isthmusectomy (n = 646)Near-Total/Total Thyroidectomy (n = 2018)
  1. NS indicates not significant (P>.05); AJCC, American Joint Committee on Cancer; SD, standard deviation; NOS, not otherwise specified.

Age, y   <.001
 65-7912376 
 ≥8052867 
Sex   NS
 Men22374 
 Women22474 
Race   NS
 White22475 
 Black32869 
 Asian/Pacific Islander12475 
 Other02179 
Hispanic origin   NS
 Hispanic22375 
 Non-Hispanic22474 
Marital status   NS
 Married22376 
 Not married32572 
Year of diagnosis   <.001
 1988-199104456 
 1992-199523464 
 1996-199922077 
 2000-200321979 
Geography   <.01
 Northeast32968 
 Midwest12376 
 South32572 
 West22276 
No. of primary malignancies
 122474NS
 222474 
 ≥332276 
Lymphadenectomy, n = 1428   <.001
 None32374 
 Limited11089 
 Radical/modified radical0991 
Radiation therapy   <.001
 None33562 
 Radioisotopes01486 
 Other radiation81577 
AJCC stage   <.001
 I12772 
 II12673 
 III12475 
 IV61778 
Tumor size: Mean ± SD, cm4.6 ± 2.63.7 ± 2.33.3 ± 3.0<.001
Tumor extension   <.001
 Intrathyroid12771 
 Extrathyroid31781 
Lymph node metastases   <.001
 None12672 
 Ipsilateral cervical11385 
 Bilateral/contralateral/midcervical61183 
 Mediastinal9784 
 Regional, NOS41977 
 Distant201070 
Histology   <.001
 Papillary22177 
 Follicular23266 
 Hurthle cell22970 
No. of examined lymph nodes: Mean ± SD0.9 ± 3.52.2 ± 7.1<.001
No. of positive lymph nodes: Mean ± SD0.2 ± 1.10.7 ± 2.5<.001
Table 3. Radioactive Iodine Administration Among Elderly Patients (Aged ≥65 Years) With Differentiated Thyroid Cancer ≥1 cm: Surveillance, Epidemiology, and End Results, 1988-2003 (N = 2,672)
VariableRadioisotopes, %P
No RAI, n = 1399RAI, n = 1237
  1. RAI indicates radioactive iodine; NS, not significant (P>.05); AJCC, American Joint Committee on Cancer; SD, standard deviation; NOS, not otherwise specified;

Age, y  <.001
 65-795050 
 ≥806634 
Sex  NS
 Men5248 
 Women5248 
Race  .001
 White5248 
 Black6634 
 Asian/Pacific Islander4555 
 Other5743 
Hispanic origin  NS
 Hispanic4753 
 Non-Hispanic5347 
Marital status  <.05
 Married5050 
 Not married5644 
Year of diagnosis  <.01
 1988-19916337 
 1992-19955248 
 1996-19994951 
 2000-20035248 
Geography  <.001
 Northeast7426 
 Midwest5248 
 South5248 
 West4654 
No. of primary malignanciesNS
 15248 
 25347 
 ≥35743 
Surgery  <.001
 None946 
 Lobectomy/isthmusectomy7228 
 Near-total/total thyroidectomy4555 
AJCC stage  <.001
 I6040 
 II5446 
 III5050 
 IV4654 
Tumor size: Mean ± SD, cm3.5 ± 2.23.4 ± 3.4NS
Tumor extension  <.001
 Intrathyroid5644 
 Extrathyroid4456 
Lymph node metastases  NS
 None5446 
 Ipsilateral cervical4357 
 Bilateral/contralateral/midcervical3961 
 Mediastinal4456 
 Regional, NOS5446 
 Distant5050 
Histology  <.001
 Papillary5050 
 Follicular5842 
 Hurthle cell5941 
No. of examined lymph nodes: Mean ± SD1.6 ± 5.72.2 ± 7.1<.01
No. of positive lymph nodes: Mean ± SD0.4 ± 1.80.7 ± 2.6.001
Table 4. Bivariate Analysis of Overall Survival Among Elderly Patients (Aged ≥65 Years) With Differentiated Thyroid Cancer ≥1 cm: Surveillance, Epidemiology, and End Results, 1988-2003 (N = 2715)
VariableHR (95% CI)P
  1. HR indicates hazard ratio; CI, confidence interval; NS, not significant (P > .05); AJCC, American Joint Committee on Cancer; NOS, not otherwise specified.

Age, y
 65-791Reference
 ≥802.87 (2.45-3.36)<.001
Sex
 Men1Reference
 Women0.76 (0.66-0.88)<.001
Race
 White1Reference
 Black1.10 (0.81-1.48)NS
 Asian/Pacific Islander1.06 (0.40-2.83)NS
 Other0.88 (0.70-1.09)NS
Hispanic origin
 Hispanic1Reference
 Non-Hispanic1.04 (0.82-1.31)NS
Marital status
 Married1Reference
 Not married1.33 (1.16-1.53)<.001
Year of diagnosis
 1988-19911Reference
 1992-19950.87 (0.70-1.07)NS
 1996-19990.90 (0.72-1.13)NS
 2000-20030.73 (0.58-0.93)<.01
Geography
 Northeast1Reference
 Midwest1.11 (0.88-1.41)NS
 South0.97 (0.72-1.33)NS
 West0.95 (0.78-1.17)NS
No. of primary malignancies
 11Reference
 21.51 (1.29-1.77)<.001
 ≥31.91 (1.48-2.47)<.001
Surgery
 None1Reference
 Lobectomy/isthmusectomy0.15 (0.11-0.21)<.001
 Near-total/total thyroidectomy0.15 (0.11-0.21)<.001
Radiation therapy
 None1Reference
 Radioisotopes0.79 (0.68-0.91)<.001
 Other radiation1.72 (1.38-2.15)<.001
AJCC stage
 I1Reference
 II1.19 (0.94-1.51)NS
 III1.63 (1.32-2.01)<.001
 IV3.06 (2.45-3.81)<.001
Tumor size1.92 (1.65-2.23)<.001
Tumor extension
 Intrathyroid1Reference
 Extrathyroid1.98 (1.73-2.28)<.001
Lymph node metastases
 None1Reference
 Ipsilateral cervical1.60 (1.30-1.97)<.001
 Bilateral/contralateral/midcervical2.46 (1.72-3.54)<.001
 Mediastinal2.91 (2.07-4.09)<.001
 Regional, NOS2.19 (1.74-2.75)<.001
 Distant3.36 (1.39-8.12)<.01
Histology
 Papillary1Reference
 Follicular1.14 (0.95-1.36)NS
 Hurthle cell1.16 (0.93-1.45)NS

Over time, the rates of near-total/total thyroidectomy and RAI increased for all age groups, but the rate of increase was lower for the elderly (Fig. 1). In particular, patients aged ≥80 years with DTC appear to undergo less surgery and receive RAI less often than younger patients with DTC, and the current gap in RAI use between the extreme elderly and younger patients is especially pronounced. Rates of near-total/total thyroidectomy and RAI are higher for patients who have more advanced-stage tumors, but elderly patients receive less aggressive treatment for every stage of DTC (Fig. 2). This observation is particularly pertinent for RAI treatment among patients aged ≥80 years.

Figure 1.

These charts illustrate the percentage of patients with differentiated thyroid cancer by year who (Top) underwent near-total/total thyroidectomy by year and (Bottom) received radioactive iodine.

Figure 2.

These charts illustrate the percentage of patients with differentiated thyroid cancer by disease stage who (Top) underwent near-total/total thyroidectomy and (Bottom) received radioactive iodine.

Multivariate Analysis

In multivariate regression analyses, patient characteristics that were associated with not undergoing total thyroidectomy included ages 65 years to 79 years (OR, 1.27; P < .001), age ≥80 years (OR, 2.32; P < .001), and stage IV disease (OR, 1.35; P < .05). Patient characteristics that were associated with not receiving RAI included ages 65 years to 79 years (OR, 1.16; P < .01), age ≥80 years (OR, 2.45; P < .001), stage IV disease (OR, 1.23; P < .05), and black race (OR, 1.25; P < .05).

Variables that were associated with overall survival on bivariate analysis among elderly patients aged ≥65 years were studied in a Cox proportional hazards regression model (Fig. 3). Age at diagnosis was a strong predictor of survival, because patients aged ≥80 years had a 2.53 times greater risk of dying than patients ages 65 years to 79 years. Among elderly patients, not undergoing surgery compared with undergoing total thyroidectomy was associated with a 4.19 times greater risk of dying, whereas not receiving RAI resulted in a 37% greater risk of dying. Stage III and IV disease also was associated with decreased survival (P < .001 for both).

Figure 3.

Factors associated with overall survival are illustrated for patients aged ≥65 years who have differentiated thyroid cancer. RAI indicates radioactive iodine.

DISCUSSION

This study demonstrated that, on a population level, elderly Americans aged ≥65 years with DTC ≥1 cm receive less aggressive treatment with near-total or total thyroidectomy and RAI than their younger counterparts. These trends were more pronounced among patients aged ≥80 years and persisted throughout the 16-year study period. This pattern of treatment among older patients occurred despite the more aggressive characteristics of their tumors, which tended to be larger and more advanced in stage with extrathyroid extension. Although the rates of near-total/total thyroidectomy and RAI were increased among patients with more advanced-stage tumors, the apparent disparity in treatment by age was most pronounced among patients with stage IV tumors. After adjustment for all demographic, clinical, and pathologic variables, older age was associated independently with a lower likelihood of undergoing near-total/total thyroidectomy and receiving RAI. In addition, worse survival rates among the elderly were associated with not undergoing surgery or receiving RAI, although the type of surgery did not affect survival.

Indications for near-total/total thyroidectomy and RAI in patients with DTC have remained controversial. Because of the generally good prognosis of DTC, prospective randomized trials of treatment with meaningful clinical endpoints, such as tumor recurrence, distant metastasis, or cancer-related death, have been difficult if not impossible to perform, because they would require a prohibitive number of randomized patients and length of follow-up to achieve sufficient power.11 Overall, retrospective analyses have indicated that total thyroidectomy with RAI and suppressive hormone therapy improves disease-free survival, reduces disease recurrence, eradicates intrathyroid cancer, and facilitates the use of whole-body iodine scans and thyroglobulin surveillance monitoring for recurrence.12-16 Therefore, major professional societies, such as the American Association of Clinical Endocrinologists, the American Association of Endocrine Surgeons, the National Comprehensive Cancer Network, and the ATA, have recommended near-total or total thyroidectomy as the initial procedure of choice for DTC and the addition of radioiodine ablation for patients who have functioning remnants in the thyroid bed or distant metastases.8, 17, 18 The ATA also suggests that age >45 years also may be a criterion for recommending near-total or total thyroidectomy because of higher recurrence rates in this age group.12, 19-21

Data are mixed about the safety of thyroid surgery in the elderly. Some small studies have indicated that patients aged >75 years can undergo thyroidectomy with the same low morbidity and mortality observed in younger patients.22-25 However, a population-level study demonstrated that clinical and economic outcomes for elderly patients who underwent thyroid surgery were considerably worse.26 This result may be attributable in part to the decreased access older patients appear to have to high-volume surgeons, despite the finding that high-volume surgeons perform operations with fewer complications and with shorter length of hospital stay.27

The key determinants of clinical outcomes in elderly patients with thyroid cancer are not well understood. Elderly patients may present with more advanced disease because of less active surveillance or timely workups of new complaints consistent with the presenting symptoms of thyroid cancer, such as dysphagia, dyspnea, or hoarseness. Our data demonstrate that older age is associated with more aggressive thyroid pathology, such as an increased prevalence of follicular histology, vascular invasion, and extracapsular extension.28 It is likely that elderly cancer patients also fare relatively poorly because of the comorbidities that tend to accrue with age, including illnesses, frailty, and functional impairments. The typical elderly oncology patient has at least 3 comorbid conditions, and the prevalence of these conditions increases with age.29 Patients with a greater burden of comorbidity may face a higher risk of noncancer-related death and hospitalization.30 Elderly patients with significant comorbidity also face a restricted choice of cancer treatment options; for example, the estimated perioperative risk of cardiac or pulmonary complications may outweigh the perceived benefit of thyroidectomy.

It has been demonstrated that older patients are treated with less aggressive medical, radiation, and surgical therapy in other types of cancer, which may contribute to worse outcomes. A study of stage II and III rectal cancer demonstrated that elderly patients were less likely to receive the standard-of-care combination of fluorouracil-based chemotherapy with radiation, despite the association of this therapy with improved survival for patients with stage III cancer.31 Numerous studies consistently have demonstrated a similar trend in stage I or II breast cancer: Older women were less likely to receive optimal local treatment with mastectomy or local excision, axillary dissection, and radiation therapy.32, 33 Women aged ≥65 years also were less likely to undergo surgical treatment for endometrial cancer than women ages 50 years to 64 years, although the age-adjusted hazard of death was reduced with surgical intervention.34 Similar results also have been reported for gastric and colon cancer.35, 36

The limitations of this study include those inherent to large administrative databases, including coding errors. The SEER database lacks information regarding frailty or comorbidity, which may play a substantial role in a patient's decision to undergo treatment. Two variables, “number of primary tumors” and “primary reason for no surgery,” were used as proxies but probably do not represent the full scope of comorbidity. Older patients were more likely to have an additional primary tumor other than DTC, but there was no significant difference among age groups with regard to the rates of contraindications cited as the primary reason for not undergoing surgery. SEER also lacks data regarding socioeconomic factors, including median household income and insurance status; it is reasonable to assume, however, that most patients aged ≥65 years would be insured through Medicare or a private health maintenance organization. Data on long-term outcomes, such as cause-specific survival, recurrence rates, reoperations, and repeat RAI treatment, are not available in SEER; therefore, the impact of the treatment differences observed on these outcomes cannot be measured.

In conclusion, our population-based analysis demonstrates that elderly patients with DTC are treated less aggressively with surgery and RAI than younger patients who have similar cancers despite the finding that elderly patients present with more advanced disease. Surgery and RAI were associated with improved overall survival among elderly patients. Future directions for research should include measuring long-term outcomes (specifically, rates of recurrence and quality of life) among elderly patients with DTC. Optimizing the treatment of these challenging patients will require improved access to high-volume providers in addition to the continued collaboration of endocrinologists, surgeons, internists, and geriatricians to collect the data required to inform evidence-based practice guidelines that are targeted to the unique circumstances of this rapidly growing segment of the American population.

CONFLICT OF INTEREST DISCLOSURES

Dr. Sosa is supported in part by a Dennis W. Jahnigen Career Development Scholars Award, sponsored by the American Geriatrics Society/John A. Hartford Foundation.

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