To Screen or Not to Screen?
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Nobody would dispute that the early detection of cancer by appropriate screening is essential for treating cancer and decreasing cancer-related mortality and morbidity. However, there is some debate about what “appropriate screening” involves.
The incidence of thyroid cancer has risen rapidly in recent decades [1]. Although the main reason for this increased incidence has been the widespread ultrasound screening of thyroid nodules [2], it is also possible that unidentified factors, such as environmental pollution and the use of many chemicals in everyday life, might have contributed to the occurrence of thyroid cancer, and some researchers have suggested that a true increase in thyroid cancer has taken place [3].
Thyroid cancer is somewhat different from other cancers, insofar as its progression is relatively slow and the mortality rate is low. The very long course of thyroid cancer compared to other cancers has hindered long-term research evaluating the effects of early screening programs and interventions for cancer. The issues of postoperative care for thyroid cancer and morbidity after the treatment are also relevant for this reason [4].
In this issue of Endocrinology and Metabolism, four articles are published that aim to answer these key questions. Moon et al. [5,6] published two articles exploring whether early screening and intervention decrease mortality from thyroid cancer. Park et al. [7] investigated the side effects and complications of fine-needle aspiration cytology (FNAC) of thyroid nodules, in order to evaluate the benefits and harms of fine-needle aspiration (FNA) of thyroid nodules that are detected on ultrasound examinations. Joo et al. [8] scrutinized the role of ultrasonography in the risk stratification of thyroid nodules.
Based on these articles with recent clinical data, we can easily conclude that early screening and intervention for thyroid cancer are very useful for controlling disease, without significant side effects or morbidity. Articles published in the past and several guidelines, including the United States Preventive Services Taskforce (USPSTF), insisted that the early detection of thyroid cancer was unnecessary and even harmful, because it cannot decrease the mortality and morbidity of thyroid cancer and instead causes other problems due to FNAC or surgery [9]. However, the notion that early detection and intervention for thyroid cancer were unnecessary was based on old data (even decades old) that did not reflect recent developments in diagnostic tools and improvements in surgical techniques. Korean colleagues reported the progression of so-called low-risk papillary thyroid carcinoma during active surveillance and identified several risk factors, such as younger age, male sex, and larger tumor size [10].
An important issue in screening for thyroid cancer is the use of ultrasound screening. Many previous guidelines have recommended against ultrasound screening, instead suggesting palpation only. The underlying reason for opposing ultrasound screening is that the early detection of thyroid nodules results in unnecessary FNA, which may cause pain, bleeding, and infections, as well as incurring high medical expenses. The other basis of opposition to ultrasound screening is that the prognosis of thyroid cancers detected by physical examinations is excellent, as good as small thyroid cancers detected by ultrasound examinations [9]. If this notion is true, there would be little reason for the early detection of thyroid cancer using ultrasound. However, according to the article of Moon et al. [5], the early detection of thyroid cancer by ultrasound has benefits for reducing cancer mortality.
It should also be kept in mind that ultrasound is a very safe tool for examining body structures, and the use of ultrasound in medical practice has become increasingly popular. The Korean Association of Internal Medicine introduced a point-of-care ultrasound curriculum into the residency training program of internal medicine in 2017, and many countries have included ultrasound examinations in internal medicine training as well [11]. In the United States, incorporating ultrasound into medical students’ curriculum is recommended to help them improve their ability and confidence when learning and performing physical examinations [12]. Therefore, it is time to discuss a consensus for the next diagnostic steps based on ultrasound findings, rather than forbidding ultrasound examinations, since ultrasound is becoming an auxiliary tool for routine physical examinations. In the era of the wide use of ultrasound in medical practice, we should establish a standard protocol and guideline for the diagnostic workup of incidentally found thyroid nodules, rather than opposing or avoiding ultrasound screening of thyroid nodules. In this regard, many countries—including Korea—have proposed Thyroid Imaging Reporting and Data Systems (TIRADS) to evaluate thyroid nodules [13].
The active surveillance of papillary microcarcinoma has been widely adopted in various counties [14], including in Korea [15,16], in order to decrease surgical complications by conducting observations, while also minimizing mortality and morbidity by determining the proper time to perform surgery to prevent the spread of thyroid cancer outside the gland. Although more time will be needed to reach a final conclusion regarding the relevance of active surveillance, it is clear that many thyroid cancers grow very slowly, which justifies a delayed operation or even simple observation for small thyroid cancers.
With the accumulation of data obtained from active surveillance and the mortality and morbidity data of operated thyroid cancers, the recommendation of FNA according to the TIRADS has changed in the direction of a less aggressive approach. For the Korean TIRADS (K-TIRADS), the size criteria for FNA of indeterminate thyroid nodules (K-TIRADS 4) changed from 1 cm to 1–1.5 cm. The indication for FNA of K-TIRADS 3 nodules became 2 cm in the 2021 recommendation, instead of 1.5 cm in 2016. Furthermore, in the 2021 K-TIRADS recommendation, FNA is not indicated for K-TIRADS 2 nodules regardless of their size, but the 2016 recommendation advised FNA for K-TIRADS 2 nodules larger than 2 cm [17].
Several unanswered questions remain regarding the early detection and prevention of thyroid cancer, including the cost of active surveillance compared to early surgery, the complications of surgery, and the method of intervention (e.g., radiofrequency ablation). To answer these questions, many studies are being conducted by various groups. For example, a group of Korean researchers compared the costs of active surveillance and immediate surgery during a 10-year period [18].
Science and medicine progress with new evidence, and technology is improving as well. For thyroid nodules and cancers, with the recent evidence presented in this special issue of Endocrinology and Metabolism, our previous knowledge has changed and our approach and practice should be updated appropriately.
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CONFLICTS OF INTEREST
No potential conflict of interest relevant to this article was reported.