Problem Persists: Overtreatment of Thyroid Cancer With RAI

Nancy A. Melville

July 18, 2019

About a quarter of all patients with low-risk thyroid cancer are still receiving radioactive iodine (RAI) therapy, despite recommendations against its use in the patient population.

The latest study to show this was published in the June issue of Surgical Oncology by Ambria S. Moten, MD, Department of Surgery, Temple University Hospital, Philadelphia, Pennsylvania, and colleagues.

Although the rate of RAI use in the study may seem high for a treatment that is generally not indicated, experts are quick to point out it is actually a bit of an improvement in the context of the previously widespread practice.

"I think the finding that 25% of low-risk patients received RAI during [the study's] timeframe is encouraging and probably is less than has been previously seen and published," said R. Michael Tuttle, MD, professor of medicine and clinical director of the Endocrinology Service at Memorial Sloan Kettering Cancer Center, New York City, commenting on the study for Medscape Medical News.

Nevertheless, "more awareness is needed and a better understanding of risk stratification so that clinicians and patients can feel comfortable that they are being appropriately selected for a more minimalistic management approach," said Tuttle, so that they "can still confidently expect a full productive life without disease specific mortality."

Tuttle was on the American Thyroid Association (ATA) Task Force in 2015 that issued new guidelines on thyroid nodules and differentiated thyroid cancer, as reported by Medscape Medical News.

Risk, but Little Benefit, From RAI Treatment in Low-Risk Thyroid Cancer

Traditionally, thyroid cancer has been treated by surgical resection of the thyroid followed by RAI treatment. RAI, taken orally, is concentrated in thyroid tissue and kills off any remaining thyroid cancer cells.

However, evidence in recent years has shown RAI to offer no added survival benefit in most low-risk patients.

"Low-risk thyroid cancer patients have a 5-year survival rate that is greater than 97%, whether they receive radioactive iodine ablation after appropriate surgery or not," says senior author Alliric Willis, MD, Department of Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.

So these patients will have no benefit from RAI, but this additional step adds to the treatment burden and introduces the potential for unnecessary additional health risks, such as the risk, although likely small, of secondary primary malignancies including leukemia and salivary gland cancer.

RAI also increases healthcare costs. A previous study that also highlighted overtreatment with RAI estimated the annual cost of this unnecessary treatment in patients with stage 1 thyroid cancer is approximately $9 million.

"This is really important when we're talking population health and managing the increasing cost of healthcare by more effectively and efficiently using our resources," says Willis.

Certain Groups of Patients More Likely to Be Overtreated

For their study, Moten and colleagues identified 32,229 patients with papillary thyroid cancer (PTC) diagnosed between 2011 and 2013 using nationally representative data from the Surveillance, Epidemiology, and End Results (SEER) program.

Just over half of patients (n = 17,286; 53.6%) met the criteria for being low-risk (stage T1 without metastasis).

However, 25% of this group had received treatment with RAI, contrary to ATA recommendations for most of these patients.  

The 2015 ATA guidelines, which are the most recent, specify that postsurgical RAI is not indicated for the management of patients with stage T1a thyroid cancers that have no lymph node involvement or distant metastases, and the treatment is not routinely indicated for the management of patients with T1b/T2 cancers that also have no lymph node involvement or distant metastases.

"Low-risk PTC patients were more likely to receive post-surgical RAI when not indicated under ATA guidelines if they were younger, male, Hispanic or Asian, or underwent extensive lymph node surgery," the authors comment.

They note their study covers a period (2011-2013) just before the publication of the 2015 ATA guidelines, but they add that the preceding guidelines, which came out in 2009, also did not recommend adjuvant RAI for T1a tumors, but recommended selective use of adjuvant RAI for T1b and T2 tumors.

"Thus, these particular patient groups appear to be over-treated with RAI according to both the current ATA guidelines and the preceding ATA guidelines," the authors note.

They add that previous studies have shown similar findings, with lower odds of RAI treatment observed in low-risk thyroid cancer among females, and more appropriate use of RAI seen among whites compared with Hispanics.

Willis hopes this latest study will raise awareness about overtreatment with RAI. 

"I think it will make people more mindful of following recommended guidelines with all patients so that we can give each patient the most effective treatment and get the best outcomes possible," he commented in a statement.

Patients Handed From One Specialist to Another

A key factor that can complicate decisions on use of RAI is the involvement of multiple clinicians — the endocrinologist, surgeon, and nuclear specialist, who may have different approaches, as detailed in a recent article by Medscape Medical News.

"The physician prescribing RAI is not usually the surgeon who is performing the operation, so they may not share a common plan," say Moten and colleagues.

Recognizing the patient groups most likely to receive unnecessary treatment is therefore a key step in preventing the problem, the authors assert.

"Identification of the type of patients at risk of receiving unnecessary RAI treatment will allow healthcare providers to be more aware of their practice patterns and consistently provide guideline-based care for optimal delivery of healthcare services," they say.

Some Exceptions for RAI in Low-Risk Cases

Tuttle noted that, according to the 2009 ATA guidelines, there are in fact some exceptions where RAI may be indicated even in low-risk patients, such as if there are nonpapillary thyroid cancer histologies, aggressive variants of papillary thyroid cancer, vascular invasion within the tumor, or nonspecific findings in the lungs.

"So the assumption that RAI is never indicated in T1a (with no lymph node involvement or distant metastases [N0Nx/M0Mx]) is probably too strict an interpretation of the 2009 guidelines," he explained.

"Nonetheless, my guess is that fewer than 5% of T1a/N0Nx/M0Mx would have a reasonable indication to consider RAI in my hands."

"So hopefully over time, we will see fewer low-risk PTC patients selected for routine use of RAI."

Tuttle also made the point that the risks of secondary cancers with RAI, though real, are quite low.

"I think the risk of getting a second malignancy after RAI is real and statistically significant in large cohorts followed for many years," he said.

"But the actual risk of an individual patient getting a second malignancy is very, very low."

When RAI is indicated, the benefit clearly outweighs the risk, but if not indicated, or indicated for marginal reasons, then any increase in secondary malignancies should be a concern, Tuttle said.

"But to be honest, the reason I don't routinely give RAI to low-risk patients is far more related to the lack of efficacy than to the risk of secondary malignancies."

RAI Use Rates Previously Over 50%

The previous study, which reported on the financial costs of RAI, published in Oncology, also detailed the prevalence of its use over time and showed that, back in 2004, RAI utilization rates were as high as 57.7% of patients, and by 2012, utilization was still as high as 45% in patients with stage 1 thyroid cancer and 71.4% in those with stage 2.

"We estimated there is an annual decline in RAI utilization by 1.7% per year," the authors conclude. 

"What was encouraging to see was that there was a downtrend in administrating RAI in this population over the study period, [and] this is likely a reflection of the increased understanding of RAI role in low-risk thyroid cancers," lead author Zaid Al-Qurayshi, MD, MPH, Department of Otolaryngology-Head & Neck Surgery, University of Iowa Hospitals and Clinics, and senior author Emad Kandil, MD, chief of the General, Endocrine and Oncological Surgery Division, Department of Surgery, Tulane University School of Medicine, New Orleans, Louisiana, told Medscape Medical News.

Wallner's study was supported by grants from the National Cancer Institute. The study authors, as well as Tuttle, Kandil, and Al-Qurayshi, have reported no relevant financial relationships.

Surg Oncol. 2019;29:184-189. Abstract

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