Differentiated Thyroid Cancer in People Aged 85 and Older Kastley Marvin, MD,* and Kourosh Parham, MD, PhD†

OBJECTIVES: To describe the characteristics and treatment patterns of differentiated thyroid cancer in older adults. DESIGN: Retrospective cohort study. SETTING: The National Cancer Institute Surveillance, Epidemiology, and End Results database. PARTICIPANTS: Individuals age 85 and older with a primary thyroid cancer diagnosis of papillary or follicular histology diagnosed between 1988 and 2007 (N = 424). MEASUREMENTS: Age, sex, histology, extent of disease, tumor size, treatment, type of surgery, cause of death, and length of survival. RESULTS: Tumor size and extent of disease were significantly related to cause of death (P = .02). Participants who did not have surgery were more likely to die of their thyroid cancer than of any other cause (P = .01), and whether a participant had surgery was significantly related to age (P = .002). Participants who had surgery had significantly longer survival than those who did not (P < .001). Type of surgery (P = .92) and adding radioactive iodine after surgery (P = .07) did not appear to influence length of survival. CONCLUSION: Although differentiated thyroid cancer is typically considered a relatively indolent disease, this is not the case in older adults. Surgery appears to reduce the likelihood of death from thyroid cancer in this population and confers a survival benefit. Type of surgery and adding radioactive iodine therapy do not seem to improve the survival benefit of surgical management. J Am Geriatr Soc 63:932–937, 2015.

Key words: thyroid cancer; treatment; surgery; thyroidectomy

From the *School of Medicine, University of Connecticut; and †Division of Otolaryngology—Head and Neck Surgery, Department of Surgery, University of Connecticut Health Center, Farmington, Connecticut. Address correspondence to Kourosh Parham, Division of Otolaryngology —Head and Neck Surgery, Department of Surgery, University of Connecticut Health Center, Farmington, CT 06030. E-mail: [email protected] DOI: 10.1111/jgs.13397

JAGS 63:932–937, 2015 © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society

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hyroid cancer is the most common endocrine malignancy, and its incidence is increasing, from 4.9 per 100,000 in 1975 to 14.3 per 100,000 in 2009.1 Differentiated thyroid cancer (DTC) typically progresses slowly and has a highly favorable prognosis, with an overall survival rate at 10 years of 80% to 95%. The slow progression is typified in the reports of incidental thyroid cancer found in cadavers with an unrelated cause of death.2 Nevertheless, some reports suggest that tumor characteristics and clinical courses are more aggressive in older adults diagnosed with thyroid cancer.3,4 Ten-year relative survival for individuals with papillary thyroid carcinoma has been reported to be 0.99 in individuals younger than 20 and decrease to 0.86 in individuals aged 70 and older.5 Tumors tend to be larger, with more extrathyroidal disease and distant metastases, in older adults.3,4,6 Age, primary tumor size, extrathyroidal invasion, and distant metastasis have been found to be significant prognostic indicators for cause-specific survival in DTC. Not only are tumors more advanced, but the mortality from cancer and the recurrence rate are also higher in older adults.4 In a populationbased study using the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database, 2.7% of participants with thyroid cancer as the first primary malignancy died of their disease. In individuals aged 75 and older, the 5-year incidence of death from thyroid cancer was 12.2%.7 From 2000 to 2050, the number of people aged 85 and older is projected to increase 350%. The proportion of the population aged 85 and older will increase from 1.6% in 2000 to 4.8% in 2050.8 One limitation of the current literature on DTC in older adults is the definition of “older.” The age varies in currently published studies, none of which is dedicated to addressing older adults. Although life expectancy is found to be significantly lower in individuals aged 60 and older with DTC, it is not affected in those younger than 45.9 The additional life expectancy of a 65-year-old in the United States in 2009 was 19.1 years, compared with an additional 4.6 years in someone who is 90 years old; grouping these individuals together when talking about the need for treatment obscures the known difference in life expectancy.10 It would follow that this is an important sector of the population to characterize.

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An important consideration is whether aggressive treatment of thyroid cancers diagnosed in the “old old,” with fewer remaining life-years, is preferred to conservative management. Treatment for DTC typically involves surgery, with its possible morbidity of recurrent laryngeal nerve injury and hypocalcemia; radioactive iodine (RAI) therapy, with its resulting side effects such as sialadenitis and xerostomia; and thyroid-stimulating hormone suppression, with its possible cardiac complications in older adults.11–13 The current study was designed to address the gap in the current literature by focusing on a segment of the population aged 85 and older. Population-level data were obtained from the SEER database. The specific aim of the study was to determine the characteristics of DTC and describe the treatment patterns in individuals aged 85 and older at diagnosis.

METHODS SEER is a publicly available database containing population-level information on cancer statistics. Characteristics of SEER are described elsewhere in detail.14 The SEER database was used to find individuals aged 85 to 115 at diagnosis with a single primary cancer that was thyroid cancer (C73.9) of papillary (International Classification of Diseases for Oncology, Third Edition (ICD-O3) codes 8050/3, 8260/3, 8341/3, 8342/3, 8343/3, 8344/3, 8340/3) or follicular (ICD-O-3 codes 8330/3, 8331/3, 8332/3, 8335/3) histology from 1988 through 2007. Because of improvements made to the database, including improved primary site reporting and extent of disease coding, data older than 1988 were not used. The 2007 upper cutoff was chosen based on the database publication date of 2010 because Centers for Disease Control and Prevention (CDC) life expectancy was 3 years or less for people aged 95 and older. The CDC National Vital Statistics Life Tables, 2009, were used to obtain the number of life years remaining based on current age.10 Individuals whose cancer was diagnosed according to autopsy or death certificate only were excluded. Individuals with missing data on surgical or radiologic treatment were then excluded. Tumor characteristics and treatment patterns were assessed. Histology included papillary and follicular types. Primary tumor size was divided into tumors 10 mm or less, 11 to 40 mm, and more than 40 mm in diameter. Extent of disease was defined as intrathyroidal (single or multiple tumors within the thyroid and extension into but not beyond the capsule), extrathyroidal (any extent of regional disease), and distant metastasis. Lymph node involvement, tumor grade, and staging of disease were not included because of incomplete data. Surgical management was divided into near total or total thyroidectomy, local excision or partial thyroidectomy, and none. Three individuals who received lymph node only surgery were excluded from analysis of management. Radiation treatment included radioactive isotopes, which were assumed to be RAI in the context of thyroid cancer. The institutional review board of the University of Connecticut determined this to be nonhuman subject research. Statistical analyses included chi-square tests for categorical variables, Wilcoxon rank sum test and Krusk-

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all–Wallace test for nonparametric length-of-survival data, and Kaplan–Meier log rank tests and Cox regression for survival modeling. The level of significance was set at .05.

RESULTS Four hundred fifty records identified, and after application of exclusion criteria, the final database consisted of 424 records. Age ranged from 85 to 101 (mean 87.9  3.2). For the purposes of statistical analysis, the sample was divided into four age groups: 85 (n = 117), 86 to 87 (n = 129), 88 to 90 (n = 98), and 91 and older (n = 80). This grouping was chosen to have a roughly comparable sample size in each group. Table 1 summarizes the characteristics of the sample.

Disease Characteristics Histology did not vary significantly according to age group (P = .21). Tumor size was significantly related to age, with more large tumors in the group aged 91 and older (P = .01). Most participants had intrathyroidal disease (n = 179, 42%), and 7% had distant metastasis at the time of diagnosis. Although there was no significant difference in the extent of disease according to age group (P = .29), significantly more participants aged 91 and older had greater extent of disease than those aged 85 to 90 (P = .03). Participant age was significantly related to having surgery, with fewer participants in the oldest age groups undergoing thyroid surgery (P = .002). Type of surgery did not vary according to age (P = .11). Cause of death was not significantly different according to age group (P = .23), although significantly more older (≥91) than younger (85–90) participants died of their thyroid cancer than of some other cause (P = .03). Twenty-seven percent of participants with papillary DTC died of their thyroid cancer, versus 39% of participants with follicular DTC (P = .03). Only 3% of participants with tumors 10 mm or less in diameter died from their thyroid cancer, whereas 22% of those with 11- to 40-mm tumors and 29% of those with tumors larger than 40 mm died from their thyroid cancer (P < .001). Examining cause of death according to extent of disease, 10% of participants with intrathyroidal tumors died of their thyroid cancer, and 39% of those with extrathyroidal disease and 70% with distant metastasis died of their thyroid cancer (P < .001). Twenty-two percent of participants who had surgery and 46% who did died of their thyroid cancer (P < .001). When dividing those with surgery into participants with surgery only and those with surgery and adjuvant RAI, 17% of participants with surgery only died of their thyroid cancer, and 21% of those with adjuvant RAI died of their thyroid cancer (P = .40). In terms of type of surgery, 21% of those who had a near total or total thyroidectomy and 20% of those who had local excision or partial thyroidectomy died of their thyroid cancer (P = .79).

Survival Characteristics Overall mean survival was 56.5 months (95% confidence interval (CI) = 50.9–62.2), and median survival was

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Table 1. Characteristics of Participants Aged 85 and Older with Differentiated Thyroid Cancer Characteristic

All, N = 424

85, n = 117

86–87, n = 129

88–90, n = 98

≥91, n = 80

P-Value

332 (78) 92 (22)

90 (77) 27 (23)

93 (72) 36 (28)

81 (83) 17 (17)

68 (85) 12 (15)

.10

347 (82) 77 (18)

101 (86) 16 (14)

99 (77) 30 (23)

83 (85) 15 (15)

64 (80) 16 (20)

.21

58 (14) 149 (35) 94 (22)

17 (15) 52 (44) 23 (20)

18 (14) 40 (31) 33 (26)

17 (17) 38 (39) 13 (13)

6 (8) 19 (24) 25 (31)

.01

179 (42) 132 (31) 30 (7)

56 (48) 35 (30) 7 (6)

56 (43) 37 (29) 8 (6)

42 (43) 27 (28) 7 (7)

25 (31) 33 (41) 8 (10)

.29

301 (71) 120 (28)

95 (81) 22 (19)

96 (74) 32 (25)

65 (66) 33 (34)

45 (56) 33 (41)

40 Extent of disease, n (%) Intrathyroidal Extrathyroidal Distant metastasis Treatment, n (%) Surgery No surgery Thyroidectomy, n (%) Local or partial Near total or total Adjuvant treatment, n (%) RAI after surgery Surgery only Cause of death, n (%) Thyroid cancer Other cause Alive

Values expressed as number (percent).

Table 2. Summary of Survival Statistics According to Disease Characteristics and Treatment Disease Characteristic and Treatment

Cause of death Dead from thyroid cancer Alive or dead from other cause Histology Papillary Follicular Tumor diameter, mm ≤10 11–40 >40 Extent of disease Intrathyroidal Extrathyroidal Distant metastasis Treatment Surgery No surgery Thyroidectomy Near total or total Partial Adjuvant treatment RAI after surgery Surgery only CI = confidence interval.

Kaplan–Meier Survival Curve Log Rank Test, P-Value

Hazard Ratio (95% CI)

11.0 (8–18) 66.0 (58–72)

Differentiated thyroid cancer in people aged 85 and older.

To describe the characteristics and treatment patterns of differentiated thyroid cancer in older adults...
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