Reclassification as NIFTP Helps Reduce Over Treatment of Thyroid Cancer

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In an interview with Targeted Oncology, Yuri E. Nikiforov, MD, PhD, discussed what led to the reclassification of NIFTP and the incidence of thyroid cancer in patients.

Yuri E. Nikiforov, MD, PhD

Yuri E. Nikiforov, MD, PhD

The reclassification of encapsulated follicular variant of papillary thyroid cancer (EFVPTC) to noninvasive follicular thyroid neoplasm with papillary-like features (NIFTP) has positively impacted patients with this tumor by reducing financial costs, psychological burdens, and overtreatment, according to research.

In 2016, this new histology of the thyroid, NIFTP, became reportable to the field of thyroid cancer.1

“The reason for a classification was that we knew for many years that there is a group or a type of thyroid cancer that is extremely indolent. The patients do very well, and patients don't die of this disease. Yet, we were diagnosing it at an increasing rate. Patients were treated very aggressively. They were treated with the removal of the thyroid and given radioactive iodine. We felt that this is an overtreatment for these patients,” said Yuri E. Nikiforov, MD, PhD, in an interview with Targeted OncologyTM.

Prior to 2016, the tumor was a type of cancer known as EFVPTC where patients were typically treated with conventional thyroid cancer treatments. However, these tumors were deemed to be low-risk and experts found lobectomy to be a sufficient treatment.

Based on data from real cases across multiple countries around the world, this tumor was found to be indolent and low-grade, and a panel of experts renamed the tumor, NIFTP. With this reclassification, it is implied that more treatments and follow-up are not necessary.

“We now have molecular markers that can predict with high degree of confidence when we are dealing with these low-risk tumors, NIFTP or low-risk, and this may help us not over treat patients. If a diagnosis of NIFTP is rendered, no additional treatments are needed,” added Nikiforov, professor of pathology and vice chair of Department of Pathology at the University of Pittsburgh Medical Center, in an interview with Targeted OncologyTM.

In the interview, Nikiforov discussed what led to the reclassification of NIFTP and the incidence of thyroid cancer in patients.

Targeted Oncology: Can you discuss the reclassification of NIFTP?

Nikiforov: NIFTP, or non-invasive follicular thyroid neoplasms, respectively, like nuclear features, was introduced in 2016, so it has been slightly more than 5 years of this entity being part of the clinical practice. The reclassification happened in 2016. It was preceded by about 2 years of work of the international groups that I had privileged to organize and lead. The reason for a classification was that we knew for many years that there is a group or a type of thyroid cancer that is extremely indolent. The patients do very well, and patients don't die of this disease. Yet, we were diagnosing it at an increasing rate. Patients were treated very aggressively. They were treated with the removal of the thyroid and given radioactive iodine. We felt that this is an overtreatment for these patients.

The international group of physicians got together and looked at all the available information, and based on the data, it offered this data-driven reclassification of this cancer, and removed the word cancer, and called them as a non-cancerous or NIFTP. That in essence was needed in the field, and that was why this happened in 2016.

Can you discuss the incidence of this NIFTP?

The incidence varies. The initial publication suggested that around 45,000 patients worldwide will be affected with this loose term, cancer. There are different assessments of the incidence of this event. Some suggest between 5% and 10% of all thyroid cancers would be reclassified as non-cancer or NIFTP.

How do experts test and diagnose NIFTP?

For NIFTP, you need surgery. Surgery performed on the thyroid, frequently the removal of one lobe of the thyroid, which is called a lobectomy. And then at that time, patients get a diagnosis based on microscopic examination or a pathologist issued diagnosis. In the past, patients get a diagnosis of cancer and therefore, if it's a large nodule, the patient had to have the second surgery to remove the second lobe of thyroid and receive treatment with radioactive iodine. Now, when these tumors are histopathologically or microscopically diagnosed as non-cancerous, no further treatment is needed. There is no need for second surgery, there is no need for radioactive iodine, and there is not even a need for frequent surveillance that patients usually undergo.

What options are available for patients with NIFTP and what recommendations do you have for managing patients long-term?

There are still patients with thyroid cancer that undergo surgery. Depending on the size of the nodules they have, they may have treatment with radioactive iodine or not, and then they have suppression of thyroid TSH hormone on the levels of cancer, have [adverse events], and they are followed every 6 months to a year with the ultrasound and different imaging notice. When we diagnose NIFTP, all this is not needed. Patients require some surveillance by the endocrinologist on [primary care physician] maybe after 1 or 2 years and then pretty much no other surveillance or other treatments are required.

Can you discuss the over treatment of thyroid cancer and why the incidence has been increasing?

In the last 20-25 years, the incidence of thyroid cancer has been growing very fast. Mortality stays the same with just a minimal increase because we detected a lot of tumors that have very low malignant potential, or they have even no malignant potential, or they're very low. There are things we can do to not over treat patients. NIFTP in fact, is 1 of the ways how we can deescalate this treatment and minimize unneeded additional treatments and additional therapy for patients. Over the last several years, we started to see the trend for decreasing the incidence of thyroid cancer. Obviously it's difficult to be sure as it has complex factors, but we believe that both a decrease in medical surveillance, and NIFTP reclassification are factors that help us to start seeing a systematically decreasing incidence of thyroid cancer in the United States and all over the world.

What can you say about the molecular basis of NIFTP?

A big revolution in medicine, patient care, and in radiology is molecular testing. We are understanding molecular markers that can help us predict, even before surgery, if this is cancer or if this is NIFTP, non-cancerous, or low-risk or high-risk disease. NIFTP can be diagnosed only after removal of the part of the thyroid gland. We now have molecular markers that can predict with high degree of confidence when we are dealing with these low-risk tumors, NIFTP or low-risk, and this may help us not over treat patients. If a diagnosis of NIFTP is rendered, no additional treatments are needed.

What unmet needs still exist in this space?

We still need to diagnose better before we take patients for surgery. Even if you suspect that the nodule is cancerous or non-cancerous, we need to diagnose better if this is a low-risk disease or if this is more likely to be a high-risk disease because we can minimize surgical approaches, not remove the entire thyroid gland, and we can do a lobectomy to preserve the second lobe of the thyroid for the patient. [This means] no need for hormonal supplementation and a higher quality-of-life.

REFERENCE: Nikiforov YE, Seethala RR, Tallini G, et al. Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: a paradigm shift to reduce overtreatment of indolent tumors. JAMA Oncol. 2016;2(8):1023-1029. doi:10.1001/jamaoncol.2016.0386

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