Risk for thyroid tumor growth declines with advancing age
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Advancing age may be associated with reduced risk for papillary thyroid tumor growth under active surveillance, according to findings published in JAMA Otolaryngology Head & Neck Surgery.
“Older individuals undergoing active surveillance of small, low-risk papillary thyroid cancer — particularly papillary microcarcinoma — may have a reduced risk for primary tumor growth that prompts surgery within a time frame of several years of follow-up, compared with younger patients,” study co-author Alexandra Koshkina, MD, MSc, clinical associate in the division of endocrinology, department of medicine, at Women’s College Hospital in Toronto, told Healio.
In a systematic review and meta-analysis, Koshkina and colleagues analyzed data from five studies consisting of adults undergoing active surveillance as primary management for low-risk papillary thyroid cancer (PTC), conducted through March 2019. Studies were conducted in Japan (n = 3), South Korea (n = 1) and the United States (n = 1).
“Active surveillance was defined as a structured program of clinical follow-up, including clinical assessments and neck imaging, in lieu of immediate surgery, in which there are prespecified disease progression criteria [that] would prompt a recommendation for surgery with curative intent,” Koshkina said. “In active surveillance studies, patients are also given an option to have surgery at any time point, even if the disease does not progress, if they prefer to do so. The patients in our review were all adults with PTC less than 2 cm in maximal diameter, where clinical disease was confined to the thyroid, meaning no metastatic disease nor extrathyroidal extension at diagnosis. Most of the patients included in the review had papillary microcarcinoma.”
Lower risk older than 40 years
Three studies included only microcarcinomas; two studies included tumors up to 2 cm in maximal diameter. The mean age of participants ranged from 51 to 55 years across four studies. The mean or median follow-up was at least 5 years in three studies and approximately 2 years in two studies.
In two studies with 1,619 participants, the pooled RR for tumor growth of 3 mm or more in maximal diameter among individuals aged 40 to 50 years compared with younger individuals was 0.51 when adjusted for confounders (95% CI, 0.29-0.89). Across four studies with 2,097 participants, the unadjusted RR for adults aged at least 40 years was 0.55 (95% CI, 0.36-0.82) compared with younger adults.
Among adults aged 40 to 45 years across four studies with 1,232 participants, the unadjusted RR for any tumor volume increase compared with younger adults was 0.65 (95% CI, 0.51-0.83). The pooled RR for incident nodal metastases among individuals aged at least 40 years across three studies with 1,806 participants was 0.22 (95% CI, 0.1-0.47); however, the risk did not rise to significance in a secondary analysis, which examined the pooled risk difference and was limited by a small number of events.
Researchers did not observe any thyroid cancer-related deaths or incident distant metastases.
“Older age was associated with a significantly reduced risk for tumor growth while under active surveillance compared with younger age, which was observed in respective pooled analyses examining maximal diameter increase — adjusted or unadjusted for other confounders — and tumor volume increase,” Koshkina said. “The risk of incident nodal disease under active surveillance was generally very low during the time frame studied, which may preclude meaningful interpretation of the results.”
Active surveillance option
Older individuals with small, low-risk papillary thyroid cancer, particularly papillary microcarcinoma without evidence of adverse features — nodal metastases, extrathyroidal extension or location adjacent to critical structures, such as the trachea and recurrent laryngeal nerve — may want to consider active surveillance as a disease management option, if available and feasible locally, according to study co-author David P. Goldstein, MD, MSc, associate professor in the department of head and neck surgery and otolaryngology at University Health Network and University of Toronto.
“However, given that the risks of nodal metastatic disease are relatively low, some fully informed younger individuals may also still choose to undergo active surveillance with the clear understanding of the necessity for close clinical/imaging follow-up,” Goldstein told Healio. “Our findings may inform counseling of patients about published disease outcomes relative to age, consistent with the recent recommendation of the American Association of Endocrine Surgeons.”
Co-author Anna M. Sawka, MD, PhD, associate professor in the division of endocrinology at University Health Network and University of Toronto, said one of the limitations of the review was the limited follow-up period and relatively low event rates for nodal metastatic disease.
“Longer-term prospective follow-up research is needed to fully understand the relationship between age of thyroid cancer diagnosis and risk of nodal metastatic disease at long-term follow-up,” Sawka told Healio. “Furthermore, molecular and translational research is needed to fully explain the findings. Our findings also need to be verified in larger cohorts of patients with papillary thyroid cancer whose primary tumors are greater than 1 cm in maximal diameter.” – by Regina Schaffer
For more information:
David P. Goldstein, MD, MSc, can be reached at david.goldstein@uhn.ca.
Alexandra Koshkina, MD, MSc, can be reached alexandrakoshkina@gmail.com.
Anna M. Sawka, MD, PhD, can be reached at sawkaam@yahoo.com.
Disclosures: The authors report no relevant financial disclosures.
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