Active Surveillance for Low-Risk Thyroid Cancer: Lessons From Japan

Nancy A. Melville

May 23, 2018

The 20-year story of how a strategy of active surveillance of low-risk papillary thyroid microcarcinomas (PMCs) became accepted at a hospital in Japan, where the practice first gained recognition, has lessons for the rest of the world, say the researchers.

Active surveillance was initially proposed at Kuma Hospital in Kobe, and is now practiced by the majority of endocrinologists and surgeons at the institution, but acceptance took time, Ito Yasuhiro, MD, PhD, of the Department of Surgery, at Kuma Hospital, and colleagues explain in their article published in the April issue of Thyroid (2018;28:488-495).

"It is anticipated that this information will promote quicker acceptance of active surveillance at other hospitals in Japan and around the world," they note, adding that active surveillance as a management strategy is recommended by the Japan Association of Endocrine Surgeons/Japanese Society of Thyroid Surgery in their 2011 guidelines.

The American Thyroid Association also recommended this strategy of watchful waiting in 2015, but there is still reluctance to adopt the approach in the United States and elsewhere in the world, say the researchers.

Yet they believe, as evidence of the safety and superiority of active surveillance over immediate surgery continues to accumulate, "it is expected that the acceptance of this management option will occur more quickly and smoothly in other countries, thereby avoiding unnecessary surgery for this mostly indolent disease."

However, one US expert isn't so sure.

Joseph Scharpf, MD, Head and Neck Institute at the Cleveland Clinic Foundation, Ohio, told Medscape Medical News that a lack of confidence regarding very precise diagnostic markers to aid in active surveillance, as well as patient preference for surgery, may be holding back adoption of the practice.

Endocrinologists Initially Better at Active Surveillance Than Surgeons

Once identified as being cancerous, thyroid nodules have traditionally been treated with biopsy and immediate surgery, despite the fact that research increasingly shows low-risk PMCs commonly have an indolent clinical course, and even if the cancer does show signs of progression, there is still usually time for rescue surgery.

The Japanese researchers assessed trends in adopting an active surveillance strategy, including data on 4023 patients cytologically diagnosed with low-risk PMC at Kuma Hospital between 1993–2016.

When prominent surgeons first recommended active surveillance in 1993, there was no evidence on the safety and appropriateness of the practice and acceptance was low, at just 30% from 1993–1997, they explain.

In the two decades since, the frequency of active surveillance rose to 51% in 1998–2002, dipped a little to 42% in 2003–2006, and then soared to the "striking" heights of 88% in 2014–2016, they report.

Regarding the types of physicians looking after these patients, the researchers note that most cases of PMCs at the hospital were treated by surgeons prior to 2007, but were then treated by an increasing number of endocrinologists.

Use of active surveillance has been significantly higher among endocrinologists compared with surgeons (86% vs 58%; P < .0001).

The authors note that the difference could reflect higher-risk patients being referred to surgeons. "It is interesting that the frequency of active surveillance use by endocrinologists was much higher than that by the surgeons. This may be partially because endocrinologists often refer their PMC patients with concerning features to surgeons, and surgeons often recommended surgery for these cases."

The acceptance appears to have evened out, however, in the most recent time period evaluated in the study, 2014–2016, during which patients were assigned to active surveillance at a similar rate whether an endocrinologist or surgeon was the initial treatment contact.

The authors also note other important considerations in favor of active surveillance, including the possible risks of surgery, which though uncommon, can include permanent vocal cord paralysis and permanent hypoparathyroidism, even when performed by experienced surgeons.

Additionally, there is the cost. They point to a recent study indicating that the 10-year total cost of immediate surgery for PMC at Kuma Hospital in 2017 was as much as 4.1 times the 10-year total cost of active surveillance (Endocr J. 2017;64:59-64).

Reluctance to Adopt Active Surveillance Outside Japan Remains

Nevertheless, there is still reluctance to use active surveillance outside Japan, they say, pointing to an Australian study published in 2017 (Thyroid. 2017;27:661-671), which although small, showed clinicians still did not feel comfortable recommending active surveillance and questioned the strength of the evidence.

A larger study adding to the evidence, out of Memorial Sloan-Kettering Cancer Center, New York City, included nearly 300 patients with low risk papillary thyroid carcinoma (tumor diameter ≤ 1.5 cm) (JAMA Otolaryngol Head Neck Surg. 2017;143:1015-1020).

As previously reported by Medscape Medical News, use of 3-D measurement of tumor volume allowed for earlier identification of growth compared with ultrasonography in all cases in the study.

Growth in tumor diameter of 3 mm or more was observed in 3.8% of patients over a median of 25 months, with a cumulative incidence of 2.5% over 2 years and 12.1% over 5 years. Importantly, no regional or distant metastases developed during active surveillance.

Scharpf told Medscape Medical News that although the Memorial Sloan-Kettering experience offers important insights, acceptance of active surveillance in the United States is still far from that of Japan.

"I would say here at [the Cleveland Clinic] it's possibly lower than 5%" he noted.

"We do see larger nodules here, and that may be a factor, but I think in many cancer centers the acceptance is still very low."

A key factor in many of the decisions is simply patient preference, he noted.

"Some patients may not feel comfortable with just having observation. I frankly don't know if I had a biopsy-proven cancer if I would want to just have it observed," he confessed.

Another important barrier to confidence in active surveillance is the lack of more precise diagnostic markers. "We just don't have the molecular markers yet to personalize this approach to determine if a small lesion has the potential to turn into a larger aggressive lesion," he explained.

"Consequently, some of the low-risk nodules are looked at with rudimentary markers or metrics, like size, shape, and characteristics, but those don't give you a more in-depth look at the molecular level."

Finally, Scharpf noted that an important factor boosting the success of active surveillance in the Memorial Sloan-Kettering study was likely a high commitment and structure for the undertaking.

"At Memorial Sloan Kettering, you have a very strong team effort to watch these cancers, and a lot of hospitals don't currently have a team or protocol set up for doing this. It's something that has to be done with a lot of care."

The authors have reported no relevant financial relationships.

Thyroid. 2018;28:488-495. Full text

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