AVOIDING RAI FOR LOW RISK THYROID CANCER

Limited use of radioactive iodine (RAI) should be the strategy of choice in the treatment of low-risk differentiated thyroid cancer (DTC), as survival outcomes are excellent even without use of RAI, according to an expert single center's experience, which was published in the April issue of Thyroid.

"I always say that the best treatment for thyroid cancer is a good surgeon," Wendy Sacks, MD, from Cedars-Sinai Medical Center (CSMC), Los Angeles, California, told Medscape Medical News.

"We have…experienced surgeons at our institution who do an excellent job completely removing the cancer and involved lymph nodes, so additional RAI may not improve upon the surgical result," she added.

The new data, from the CSMC Thyroid Cancer Center, were reviewed to determine whether RAI treatment was given appropriately to a total of 444 patients with DTC who were treated at the center between 2009 and 2012.

Dr Sacks and colleagues also compared rates of RAI ablation at their institution with those from the US National Cancer Database (NCDB); they showed they were less likely to use RAI than the national average.

CSMC Thyroid Center Developed Own RAI Guidelines

The researchers explain that, for many years, it has been the standard of therapy in the United States to treat virtually all DTC patients with total thyroidectomy and RAI remnant ablation.

But the incidence of thyroid carcinomas has increased over the years, with the majority consisting of stage I disease and microscopic well-differentiated thyroid carcinomas. At the same time, "multiple studies have shown that RAI treatment for all tumor sizes has increased and particularly for low-risk thyroid cancers, such as stage I and II (without distant metastases)," they explain.

However, many trials "have shown that postoperative RAI ablation does not change an already excellent outcome for patients with low-risk thyroid cancers (stage I and II without distant metastases)," they point out.

Dr Sacks explained: "When it became evident several years ago that patients with low-risk thyroid cancer have excellent survival and recurrence-free survival whether they receive RAI or don't receive RAI, we wanted to guide our physicians to treat appropriately so that patients do not get a treatment that potentially can result in short-and long-term side effects."

Hence, the CSMC Thyroid Cancer Center, which was established in 2007, developed its own guidance on use of RAI, published in 2010, which was more stringent in terms of determining when to use RAI than the American Thyroid Association guidelines, last updated in 2009, which leave the decision on RAI use to the discretion of the treating physician.

Prudent Use of RAI for Low-Risk Patients

In the current study, all 444 patients had undergone total thyroidectomy at the CSMC Thyroid Cancer Center between the years 2009 and 2012, and all received RAI according to CSMC guidance.

Approximately 95% of the cohort had papillary thyroid cancer, and 65% had stage I disease. The mean follow-up was 0.8 years, with a range of 0 to 3.7 years.

Survival curves for patients with stages I to III DTC showed that those who did not receive RAI had 100% disease-free survival, which was actually a better outcome than those who had received RAI.

However, given that the total population with stage II and III disease was small, the difference between those with these stages of disease who did and did not receive RAI was not statistically significant, the investigators note.

A significantly increased incidence of recurrent disease was seen among stage I patients who received RAI, "indicating a probable selection bias, with patients having extensive lymph-node involvement," the authors observe.

CSMC physicians still use RAI for the treatment of thyroid cancer patients under the age of 45 with bulky lymphadenopathy, locally invasive disease, high-risk histology, or distant metastasis — all of whom fall in the staging categorization as stage I/II — but who are considered to be at intermediate to high risk for persistent or recurrent disease, they explain.

Only one patient with stage IV disease in the CSMC cohort did not receive RAI, so it was not possible to draw any conclusions about RAI use in stage IV DTC patients, they explain.

"Prudent use of RAI treatment should be considered for low-risk patients," they conclude.

Many Patients Being Overtreated with RAI Nationally 

The investigators also compared CSMC RAI treatment rates for DTC from 1998 to 2011 with data from the US NCDB: more than 100,000 patients nationally received RAI ablation during this period.

The analysis revealed that the national RAI rates for all stages of DTC in each year have consistently been over 50%, with an overall treatment rate of 57%.

Beginning in 2007, CSMC data show a significantly lower RAI ablation rate compared with the NCDB — ablation rates at CSMC among all thyroid cancer cases decreased from 50% in 2009 to 36% in 2012.

"This implies that many patients are being overtreated [nationally] because a majority of DTC patients are in the very-low- to low-risk category," the investigators suggest.

Because the numbers of patients with both stage II and III disease in the CSMC database were small, differences between CSMC and NCDB RAI rates in both of these groups of patients did not reach statistical significance.

Surgeon and Center Matters; Need for a Prospective Trial 

The authors also say that several studies have demonstrated that stage I patients who have surgery at facilities that focus on thyroid cancer have a much lower rate of RAI use compared with other institutions. "Such specialized facilities provide more surgeon training and have better surgical outcomes from total thyroidectomy, which resulted in less RAI use."

Endocrinologists practicing alongside surgeons with an expertise in thyroid surgeries "are also less likely to use RAI, in part because the likelihood of a substantial amount of residual thyroid tissue remaining is decreased," they observe.

With increased detection rates of DTC — the majority of them being low risk — there is a need for a prospective randomized trial evaluating the long-term effects of RAI on recurrence in DTC patients, the investigators urge.

Such a trial has now been initiated in France, where investigators will compare outcomes between monitoring alone for 5 years or the administration of 30 μCi of RAI with recombinant human thyroid-stimulating hormone in low-risk DTC patients followed by monitoring for 5 years.

"There is an argument that low-dose RAI…for remnant ablation confers very little risk for side effects, so if there is no downside to RAI, why not treat?" Dr Sacks explained.

"But recurrence-free survival outcomes have not yet been published, so we hope the ongoing prospective trial in [France] will answer this question."

The authors declared no relevant financial relationships.

Thyroid. 2015;25:377-385. Article