The Power Of Diagnosis For Thyroid Cancer Care
Dr Akira Miyauchi, the President and COO of Kuma Hospital – Thyroid Care Center of Excellence in Kobe, Japan, initiated a clinical trial in 1993 for patients diagnosed with low-risk thyroid papillary microcarcinomas. The experiment, which started the same year, allowed patients to choose between the immediate surgery (the agreed standard of treatment) or active disease surveillance. Dr Miyauchi addresses the findings of the 26-year analysis in this interview and how it affects the way doctors around the world treat low-risk thyroid papillary microcarcinomas.
In 1970, Dr Akira Miyauchi graduated from Japan’s Osaka University Medical School with a single-minded goal: To become a surgeon. Under Dr Shin-Ichiro Takai’s mentorship, Dr Miyauchi picked this speciality and spent the next 49 years, after earning his MD and PhD, distinguishing himself as a leading figure in the field of endocrine surgery. Today, he serves as Chairman of the Asian Association of Endocrine Surgeons and Chairman-Elect of the International Association of Endocrine Surgeons; in addition to presiding over Kuma Hospital in Kobe, Japan. But he’s most widely known these days for his ground-breaking work into the treatment of papillary thyroid cancer (PTC).
All About The Thyroid Disease[1]
An estimated 200 million people worldwide suffer from thyroid disease. Of this group, up to 60% are unaware of their condition. Usually, thyroid disease is diagnosed with tests evaluating three hormones: a thyroid-stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3). Usually, the TSH test, which assesses thyroid function, is given first, followed by an fT4 test if thyroid problems are suspected. Finally, an fT3 test assists in differentiating disease. If thyroid cancer is suspected, an MRI is performed and a fine needle aspiration (FNA) biopsy is conducted where appropriate.
After a PTC diagnosis, the standard recommended treatment was immediate surgery, even for small tumors which pose a limited risk. Studies by Dr Miyauchi, based on a 26-year clinical study at Kuma Hospital, challenged this practice by indicating that active surveillance is potentially the best course of action for patients with PTC tumours of less than one centimetre in size without lymph node metastasis or invasion of surrounding tissue.[2]
Dr Miyauchi’s study results were so convincing that in 2010, the Japanese guidelines for the management of thyroid tumours proposed active surveillance as an appropriate strategy for treating low-risk papillary thyroid cancer. Many associations followed suit in the following years including the American Thyroid Association (ATA). The revised Japanese Guidelines released in 2018 now suggest active surveillance of the thyroid’s low-risk papillary microcarcinoma. Work by Dr Miyauchi is particularly relevant as papillary thyroid cancer remains one of the world’s fastest-growing types of cancer.
Pioneering a Positive Trend
In Korea, rates of incidence of thyroid cancer increased by a factor of 15 from 1993 to 2011. Between 1975 and 2009, they nearly tripled across the United States. Despite this huge increase in the prevalence of thyroid cancer, disease mortality rates have remained relatively stable.[3],[4]
It’s not easy to explain such a difference, but Dr Miyauchi has a working theory. Through ultrasound with FNA to MRIs, CAT and PET scans, modern detection methods can recognize very small tumours that were undetectable 30 years ago. “I think the rising thyroid cancer rates are due to an increase in detection of small papillary thyroid cancer.”
Early detection is good for cancers that are aggressive, Dr Miyauchi said. Yet, premature or unnecessary surgery can have serious consequences like vocal cord paralysis for patients with indolent cancers such as small papillary thyroid cancer. Dr Miyauchi began looking at autopsy reports of patients who had died from causes other than thyroid cancer to determine whether his hypothesis had merit. He found small papillary thyroid cancer tumors greater than three millimetres in size in 2-6% of patients with an autopsy; a size that can be easily detected with ultrasound tests, although they had died from other causes.
“This shows that there is likely a high incidence of people in the general population who are living with small papillary thyroid cancer without any symptoms, and without knowing it,” Dr Miyauchi said. He began to question whether immediate surgical removal of small PTC tumors was always appropriate based on this information. Screening research at the Kagawa Cancer Examination Center performed by Dr Koji Takebe furthered his suspicions. Dr Takebe used ultrasound-guided fine-needle aspiration in the study to discover that 3.5% of subjects-otherwise healthy Japanese women with no symptoms of the disease-had small papillary cancer of the thyroid. “That number,” Dr Miyauchi said, “was more than 1,000 times higher than the prevalence of clinical thyroid cancer reported in Japanese women at that time.”
Life With Thyroid Cancer?
Why do so many people live normal, healthy lives, totally unaware that they have thyroid cancer? “I had a theory,” explained Dr Miyauchi, “that most small papillary thyroid cancer will remain small, and that only a small number of cases will ever show progression. The issue is, how can we identify the minority that shows progression? This method, consisting of close supervision without immediate surgery, would allow physicians time to determine whether or not they have an aggressive tumour. Such a “wait-and-see” approach would not harm patients because of the excessively small size of the tumours, according to Dr Miyauchi. If progression does occur, surgery can still be done without any lack of efficacy.
In 1993, Dr Miyauchi proposed a clinical trial at Kuma Hospital based on this hypothesis. The research began testing the active surveillance system later in that year. At the end of the study, Dr Miyauchi sought proof of his hypothesis. Just 8% of the patients involved in the study reported enlargement of the tumor by three millimetres or more. Metastasis of the lymph node was reported by only 3.4%.
“You may think lymph node metastasis appears to indicate a deficiency in active surveillance,” Dr Miyauchi said. “But it’s not.” That’s because a hemithyroidectomy in which one side of the thyroid is removed is the preferred surgical treatment for patients with small papillary thyroid cancer at present. “This treatment is unlikely to avoid metastasis of the lymph node in the lateral compartment, so in case of metastasis the patients still need a second operation.”
Pointing out that all the active surveillance patients in his study who developed metastasis of the lymph node were completely cured, Dr Miyauchi said, “I think one surgery is better than two.” Another major benefit of active surveillance is a lower complication risk. For patients undergoing immediate surgery, the rate of adverse events such as temporary or permanent vocal cord paralysis or chronic hypoparathyroidism was significantly higher. “So we believe that active surveillance is much safer for most patients than immediate surgery,” he said.[5]
Affordable Alternative
The ground-breaking study by Dr Miyauchi is a prime example of how diagnostics can lead to findings that drive superior patient outcomes, better informed clinical decisions, and substantially lower healthcare costs. Citing research carried out by Carrie Lubitz, Harvard Medical School’s Associate Professor of Surgery, Dr Miyauchi noted that the costs of well-differentiated care for cancer in the United States could double between 2013 and 2030.
Active surveillance is more economical than immediate surgery, which when factoring in post-operative treatment, is particularly expensive. “We found that immediate surgery was 4.1 times more costly than active surveillance,” said Dr Miyauchi. “I believe that active surveillance is much better for the individual patient and society as well.”[6]
Embracing active surveillance is only slowly catching up speed outside Japan. Even in the U.S, where the ATA has officially accepted active surveillance as an option to treat low-risk papillary thyroid cancer, health care officials are cautiously continuing. The ATA still does not actively advocate active supervision.
Nevertheless, Dr Miyauchi views the acceptance of active surveillance by the ATA as a significant step in its march toward acceptance by the mainstream. “They understand that this type of cancer can be an alternative to immediate surgery. Once those guidelines were written, many physicians worldwide became more interested in active surveillance.
Dr Miyauchi still expects an uphill fight. He understands that both doctors and patients are reluctant to embrace a ‘less is more’ approach to treatment especially when it comes to cancer. “Which is natural, there are still many hesitations,” he said. While, he will continue to use his Kuma Hospital platform to promote active surveillance, which he firmly believes is safer for patients, and better for the whole world. “The number one concern for me at the moment is to advocate the introduction of active surveillance in as many countries as possible”. [7]
Reference:
1. Thyroid Foundation of Canada website. 2018. About Thyroid Disease: https://thyroid.ca/thyroid-disease/
2. Ito, Y et al. 2018. Thyroid. Insights into the Management of Papillary Microcarcinoma of the Thyroid.: https://pubmed.ncbi.nlm.nih.gov/28629253/
3. Hyeong, S et al. 2014. New England Journal of Medicine. 371:1765-1767.: https://www.nejm.org/doi/full/10.1056/NEJMp1409841
4. Davies L, Welch HG. 2014. JAMA Otolaryngol Head Neck Surg. 140(4):317-22.: https://pubmed.ncbi.nlm.nih.gov/24557566/
5. Takebe K, Date M, Yamamoto Y et al. 1994. Mass screening for thyroid cancer with ultrasonography.: https://link.springer.com/article/10.1007/s00268-009-0303-0
6. Miyauchi A. 2016. Clinical Trials of Active Surveillance of Papillary Microcarcinoma of the Thyroid. World journal of surgery.: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746213/
7. Lubitz, CC et al. 2004. Cancer. 120(9) 1345-52.: https://www.scielo.br/pdf/aem/v63n5/2359-4292-aem-2359-3997000000168.pdf