Age Should Not Drive Thyroid Cancer Staging

November 1, 2016
By: Samiha Khanna , Duke Health News

A study from the Duke Cancer Institute (DCI) finds a lack of statistical evidence to support the current practice of treating thyroid cancer patients under age 45 differently from those 45 and older.

The study, published Oct. 31 by the Journal of Clinical Oncology, found that in nearly 32,000 cases of papillary thyroid cancer, there was no specific age at which patients’ prognoses changed so significantly as to require age-based standards.

The data suggest doctors should evaluate patients of all ages using the same standards, including tumor size and lymph node involvement, to determine the stage and prognosis of the disease, said senior author Julie Ann Sosa, M.D., an endocrine surgeon and surgical oncologist at Duke.

The findings challenge current thyroid cancer staging guidelines from the American Joint Committee on Cancer (AJCC), as well as revised AJCC guidelines that were published this month and take effect in January.

“The bottom line is that a staging system based on age may not be the optimal way to assess a patient’s prognosis and guide their treatment,” said Sosa, who herself served on the AJCC panel to draft new guidelines, which convened before the new data were available.

“Our preliminary data show there is no dichotomy in outcome at any specific age,” Sosa said. “Regardless of whether patients are younger or older, the same things influence their survival. The implication is simple: we need to rethink and potentially revise the current staging system.”

Current AJCC guidelines split patients into two groups: those under 45, and those 45 and older. The older patients are evaluated on a four-tier system, in which a stage 1 diagnosis means the cancer is in its earliest phase and stage 4 indicates the cancer has spread to the lymph nodes or other parts of the body.

For patients under 45, the AJCC offers just two stages to encompass everything from a small, local tumor to cancer that has spread aggressively beyond the neck. Based on these standards, even metastatic cancer that has spread to lymph nodes throughout the neck in a 44-year-old patient is classified as stage 1, while in a patient just a year older, the same disease would be described as stage 4, with a more grave prognosis and potentially more aggressive treatment, Sosa said.

“In effect, current guidelines suggest patients under 45 have a brighter prognosis than older patients with the same disease, simply due to age,” said Sosa, who is also leader of the Endocrine Neoplasia Diseases Group at DCI and Duke Clinical Research Institute. “But the data that we examined at a national level do not reflect that.”

Rather, survival rates decreased gradually as patients got older, the researchers found, using a statistical model that accounted for factors including overall patient health and treatment received.

More than 98 percent of papillary thyroid cancer patients under age 60 survived 10 or more years after diagnosis, the study found. The researchers used data from 1998 to 2012 in the National Cancer Institute’s Surveillance, Epidemiology, and End Results registry.

“Thyroid cancer is a really important topic right now,” Sosa said. “It’s a cancer that tends to affect young and middle-aged people. It rarely proves fatal, and the overwhelming majority of patients live with the diagnosis the rest of their lives. The implication is that we could be under-staging our youngest patients, and if we are under-staging them, it means we are potentially undertreating them, not monitoring them closely enough, or potentially leaving them at greater risk for recurrence or even shortened survival.”

When revised AJCC guidelines take effect in January, they will continue to recommend separate guidelines based on age, but shifting the line to age 55. The revised guidelines used data based on models designed with the assumption that there is an age at which prognosis changes, the Duke authors said.

Duke’s statistical models took a step back, using models that were designed without the assumption that there is a known age at which there is a significant change in risk. Their results confirmed this, they said. 

“We used sophisticated approaches that flexibly looked for a change -- more than 10 different approaches -- and all found that there is no age at which risk significantly changes,” said study co-author Terry Hyslop, Ph.D., director of biostatistics at DCI. “What all the analyses showed was that risk increases evenly for each year of age, so we use a straight line to estimate that relationship.”  

The study authors say continued research on age-based standards should inform further AJCC revisions.

“This is just a first study,” Sosa said. “It’s important that this be replicated and potentially refined. We all need to have an open mind, and this should motivate us to be open to change and to potentially, significantly revise the framework for how we counsel patients.”

In addition to Sosa and Hyslop, study authors include Mohamed Abdelgadir Adam, MD; Samantha Thomas MS; Randall P. Scheri, MD; and Sanziana A. Roman MD

A grant from the Duke Cancer Institute supported this work. Sosa is a member of the Data Monitoring Committee of the Medullary Thyroid Cancer Consortium Registry supported by Novo Nordisk, GlaxoSmithKline, AstraZeneca and Eli Lilly. The other authors cited no competing financial interests.