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Why are there different conclusions about thyroid cancer mortality?

In this month's edition of Head & Neck, La Barge et al analyze mortality due to thyroid cancer in the United States. Their motivation was to investigate why different conclusions had been reached about trends in thyroid cancer by two commonly cited papers. One paper asserted that US thyroid cancer mortality rates had not changed significantly over time, while the other reported mortality rates were increasing. LaBarge et al have now analyzed SEER mortality data for 1987 to 2017 and conclude there has been a 0.61% change annually in thyroid cancer mortality during the time period they examined. What gives—why the different results? A quick recap: the first paper to be published focused on the details of thyroid cancer incidence, they found a 290% increase in the incidence of thyroid cancer between 1975 and 2009. The authors reported mortality data from the National Center for Health Statistics (NCHS), noting minimal change over this time period. The second paper to be published focused on the details of thyroid cancer mortality and used mortality data as captured in SEER during 1992 to 2013. During their examined time period, they found mortality had increased 1.1% per year. The increase in mortality was significant for those who had advanced disease at the time of diagnosis, but not those who had localized or regional disease at the time of their diagnosis. Now we have this new paper with a somewhat different conclusion. Who is wrong and who is right? Nobody is wrong. First, the numbers of deaths due to thyroid cancer are very small relative to other types of cancer and causes of death. In 2018, SEER estimates that about 2180 people died of thyroid cancer across the United States. Figs. 1 and 2 in LaBarge et al's study show plainly the problem of trying to analyze small numbers: the trend lines are very jagged, indicating significant variation in estimates each year. This makes it very hard to get a handle on the trends. Depending on the time period you look at (each author group looked at different period), you may reach a different statistical conclusion. To get around this problem, the first paper that was published reported nationwide mortality, a somewhat coarse data source but useful for reporting general trends because the numbers available for analysis are largest. The second paper focused on mortality as captured in SEER, a more granular data source that is better for closely examining trends in specific groups of patients. Some important things to know about US mortality. The underlying data source used in the LaBarge, Davies and Lim all three papers was the same. The data that underlie both nationwide trend estimates (NCHS) and SEER-based estimates (SEER incidence-based mortality) are the same. It all comes from death certificates as provided to the National Center for Vital Statistics. The difference is that for people who died and whose cancer diagnosis was captured in SEER, we have the details of their histology, stage at diagnosis, and first course of treatment. Accurately classifying deaths is remarkably tricky. This problem has been recognized since the 1960's, when formal cancer registries were first envisioned. Research has sought to identify and understand the impact of case misclassifications on registry data accuracy. Case misclassification is especially problematic when the number of deaths available to analyze is very small, as is the case with thyroid cancer, which accounts for only about 0.4% of all cancer deaths annually in the United States. Every error in classification has an outsized effect on estimates. One commonly recognized source of misclassification in cancer deaths is the broad problem of attribution bias: once a person has a cancer diagnosis, their underlying cause of death may be attributed to it although they died of something else. This may be why observed mortality has been rising. More people have a thyroid cancer diagnosis than in the past. The way that SEER categorizes deaths due to cancer is also relevant. If a person captured in the SEER data had only one cancer diagnosis recorded, death from any cancer is attributed to the original cancer diagnosis. Howlader, who developed this system, explains: “the rationale is that if a cause of death is coded to another site it is likely a misclassification (eg, death from metastatic disease).” This system has been validated and works well for many cancer types, especially those that are more aggressive. It is unlikely, for example, that a person with liver cancer, which has a 5-year survival of about 24%, will move away from a SEER area, develop a Received: 23 November 2020 Accepted: 1 December 2020