Thyroid cancer: Controversy about over-diagnosis versus the perils of underdiagnosis

Abstract

In recent times, it has been reported that thyroid cancer is increasing.[1] Interestingly, this increase has been not restricted to any particular gender, age, or socioeconomic status. In the past decade, the use of ultrasound of the neck has become common. This has led to the increasing diagnosis of incidental thyroid nodules, or incidentalomas also called as 'a disease of modern technology'.[2] Another special situation is the widespread availability of positron emission tomography(PET), which has also resulted in the diagnosis of PET-detected thyroid incidentaloma, which poses another unique challenge to the treating physician. Therefore, it has been argued that the increase in diagnosis of thyroid cancer is attributable to detection of early, indolent cases, not from an actual increase in occurrence. Additionally, this rapid increase in the prevalence of thyroid cancers cannot be explained in the setting of stable underlying environmental risk factors and also the genetic changes leading to neoplasia are unlikely to happen very rapidly. The most dramatic report on this issue was published in the New England Journal of Medicine, which reported a remarkable increase in thyroid cancer diagnoses from the Republic of Korea.[3] The article highlights a popular concern in that country; as the incidence of thyroid cancer reportedly increased 15-fold between 1993 and 2011. Indeed the authors state that thyroid cancer is the most common cancer diagnosed in the Republic of Korea, with 40,000 cases diagnosed in the year 2011 alone! The most common type of thyroid cancer detected was papillary thyroid cancer. The authors attribute this to the wide-spread screening of people for thyroid cancer with a relatively cheap and noninvasive investigation, that is, ultrasonography (USG) thyroid as well as increased awareness of their population about diagnosis and treatment of cancers in early stages. At the same time, the report also stresses that despite the increase in prevalence, the mortality did not increase. This led those authors to suggest the possibility of over-diagnosis and to consider whether such an intensive screening thyroid cancer will indeed help in improving mortality, morbidity, quality of life, and overall outcome. This increasing concern about over-diagnosis has been addressed from other parts of the world. For example from Australia, where there was a rapid increase in the diagnosis of thyroid cancer. A study was carried out in Queensland, and the authors reported that the age-standardized incidence increased from 2.2/100,000 to 10.6/100,000 between 1982 and 2008. The increase was true for both early stage and advanced cancers, though the rise in incidence was higher for early-stage cancers.[4] Can it therefore be argued that this increase in early diagnosis rather than the late detection could be an advantage for the patients with thyroid cancer? Undoubtedly, thyroid cancer is best diagnosed early. In addition, with current advances in thyroid surgery and radioiodine therapy, the prognosis of thyroid cancer when appropriately treated is very good. Despite that, thyroid cancer surgery, especially, radical total thyroidectomy does result in complications like hoarseness of voice and hypoparathyroidism, not to mention permanent hypothyroidism. Hence, there is a distinct reason to be concerned about the benefits and risks of treatment of thyroid cancer. Little is understood about the true incidence and prevalence of thyroid cancer in India. Earlier, it was reported in India that the age-adjusted incidence rates of thyroid cancer per 100,000 are about 1 for males and 1.8 for females, and that the commonest type of thyroid cancer is papillary thyroid cancer, followed by follicular thyroid cancer.[56] The report about prevalence of thyroid malignancy in India comes from the eight city study that focused on the prevalence of thyroid dysfunction. About 0.1% of subjects from this study gave a history of thyroid malignancy.[7] As expected in a disease which is treated with a favorable outcome/survival, prevalence rates of present or past disease are higher than the incidence. More studies are needed from India, as both these reports have limitations. However, this clearly indicates that the problem of thyroid cancers in India (with an incident rate of 1-1.8 per 100,000) is grossly underestimated when compared to that in Australia (incidence 10.6/100,000 population) and Korea (incidence 70 per 100,000 population). Therefore, is it likely that in India, problem of thyroid cancer need not necessarily be that of over diagnosis but rather of under-diagnosis. Additionally, these clinical studies from Republic of Korea and Australia may not necessarily be applicable to the Indian settings. For example, it has been reported that the outcomes of treatment are poorer in iodine deficient regions due to higher prevalence of undifferentiated cancers in these areas.[8] Hence, the makers of clinical guidelines now have to walk a thin line that avoids over-diagnosis, at the same time avoids the perils of under-diagnosis. Rather than focusing on genetic preoperative diagnosis; especially in a country where it is difficult to even implement ultrasound-guided fine-needle aspiration cytology in all cases of thyroid nodules, it is important to generate an India-specific data of the present scenario. It is also prudent to develop a country-specific approach to the management of commonly encountered subsets of thyroid malignancy. The papillary thyroid microcarcinoma is for instance, a case in point. While thyroid lobectomy/hemithyroidectomy is advised in recommendations by American Thyroid Association for small, low-risk, isolated, intrathyroidal papillary carcinomas in the absence of cervical nodal metastases,[9] if a multifocal carcinoma is diagnosed, would that not require completion thyroidectomy?[10] On the other hand, given that some papillary thyroid microcarcinomas, especially those harboring mutations, could be more rapidly progressive, these lesions arguably need a more aggressive management approach. Preoperative genetic testing has been shown to be effective.[11] However, genetic testing being expensive, it can hardly be considered a routine option in a developing country like India. What then, is the correct diagnostic approach in India? Well, the obvious answer is that more data is required. A nationwide study on the clinical features and prognosis of thyroid cancer in India is important. A similar study has been carried out in chronic pancreatitis, another puzzling and mysterious disease; and this clarified many aspects of the disease among Indians.[12] Also, it is important to undertake population studies that ascertain the true incidence and prevalence of thyroid cancer in India. There have been past attempts to write consensus statements on management of thyroid nodules in India.[13] The future efforts to form guidelines to tackle the issue of thyroid malignancy should weigh the benefit of a favorable prognosis from early diagnosis and treatment with the risk of causing a physical, psychological, and financial burden from unnecessary screening. The time is ripe to take this work forward to the next level and to collaboratively work for the betterment of subjects affected with, or those at risk of thyroid cancers in India. Source of Support: Nil Conflict of Interest: None declared.