Thyroid cancer mortality in an aging population

Thyroid cancer is the fifth most common cancer diagnosed in women and accounts for more than 3 percent of all new cancer diagnoses.¹ Reports indicate thyroid cancer incidence is rising, not simply because of earlier detection, but also from a true increase in disease occurrence.² Fortunately, most patients diagnosed with thyroid cancer will survive. According to publicly available data from the Centers for Disease Control and Prevention, the annual mortality rate from thyroid cancer in the U.S. is constant at 0.5 per 100,000 population, but the number of thyroid cancer deaths is increasing.³ These trends likely reflect a growing population; however, this conclusion is based on incomplete evidence. Lim and colleagues recently identified a steady increase in incidence-based mortality for patients with thyroid cancer for nearly all histologic types and specifically for papillary thyroid cancer regardless of tumor stage or size at diagnosis.² The underlying cause for the observed trends in thyroid cancer mortality is unclear.

New staging technique

The American Joint Committee on Cancer Staging Manual, Eighth Edition, published in 2017 and implemented in 2018, significantly shifted differentiated thyroid cancer (DTC) staging.⁴ DTC includes papillary, follicular, and most Hürthle cell cancers that retain many of the cellular features of follicular thyroid cells. DTC staging in the 8th Edition better stratifies and separates the risk of cancer mortality among the stages.^5-8 Thyroid cancer staging is unique in its inclusion of patient age as a prognostic factor, although the relationship between age and mortality is poorly understood. Debate exists about the best way to incorporate age into the staging system, but most clinicians agree that it should be included.⁹ This newest edition shifted the age cutoff in DTC from 45 to 55, where now only those age 55 or older are eligible for stage III or IV disease depending on more typical pathologic features of disease. Other major changes include the removal of extrathyroidal extension as a determinate of tumor stage 3 (T3) disease and downgrading of regional lymph node involvement to stage II from higher stages in patients age 55 or older. Nevertheless, the long-standing mystery of how age affects mortality coupled with the recently identified increase in thyroid cancer mortality deserves further investigation.

The impact of age and an aging population

To revisit the impact of age on thyroid cancer mortality, we investigated trends in thyroid cancer cases and outcomes from the National Cancer Database (NCDB). Interestingly, most patients diagnosed with differentiated thyroid cancer are younger than 55 years old, but patients diagnosed with medullary or anaplastic thyroid cancer are more likely to be ages 55 and older (see Table 1). Yet even after adjusting for histology, sex, race, tumor/node/metastasis staging, and treatment, being age 55 or older is associated with worse survival rates (hazard ratio 4.3, 95 percent confidence interval 3.6–5.1) than patients ages 18–54. Although this association is nothing new, the population to which it is applied is constantly changing.

Table 1. Demographics of thyroid cancer patients in NCDB, 2004–2015

The U.S. population is not only growing, it is aging as well. Between 2010 and 2017, the proportion of the U.S. population ages 55 or older increased by 3.5 percent, from 25 percent to 28.5 (see Figure 1).¹⁰ Considering the U.S. population totals nearly 329 million, a modest 3.5 percent increase in the proportion of people ages 55 or older translates to about 11.5 million people. Taken together with the knowledge that older age predicts worse survival for patients with thyroid cancer, it makes sense that an aging population would experience an increase in thyroid cancer mortality.

Figure 1. Proportion of the U.S. Population Age 55 or Greater over Time

Clinical considerations

Although it is difficult to know if the aging population accounts for the entirety of the increase in thyroid cancer mortality, it certainly plays a role. Kazaure and colleagues explored the impact of patient age on thyroid cancer mortality and supported arguments showing that older age is associated with a shifting molecular profile of thyroid tumors and with an incomplete response to therapy. They propose that as we gain insight into the oncogenesis of thyroid cancer, we may better understand the relationship between age and mortality, and eventually be able to routinely personalize treatment approaches based on molecular and patient profiles.⁹ Until then, it is important to consider the age of the patient diagnosed with thyroid cancer and carefully weigh the risks of treatment against the risks of inadequately treated disease. As a national spotlight on overtreatment appropriately swings the pendulum toward more cautious and conservative approaches for most differentiated thyroid cancers, clinicians should guard against ignoring the fact that older age portends a greater risk of cancer mortality.

Age remains an important prognostic factor for thyroid cancer, but the relationship between age and thyroid cancer mortality is unclear. Incidence-based mortality for thyroid cancer is increasing, and it makes sense that our aging population is at least partially responsible, but more research into why thyroid cancer mortality is greater in older patients is imperative. Until we obtain a grasp on why thyroid cancer behaves differently based on the age of the patient, clinicians must consider their patient’s age when counseling them about the most appropriate treatment plan.

Acknowledgment

Statistical support for this article was provided by Bryan E. Palis, Senior Statistician, and Amanda E. Browner, Statistician, NCDB.

References

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