Miriam E. Tucker

May 02, 2014

BOSTON — A new study from Japan lends support to the argument that most low-risk papillary thyroid cancer (PTC) patients don't need a total thyroidectomy and will do just as well with more conservative surgery.

Moreover, because there is no difference in survival, patients can be educated about the risks and benefits of both procedures and offered the choice, surgical resident Aya Ebina, MD, from the division of head and neck, Cancer Institute Hospital, Tokyo, Japan, said here at the American Association of Endocrine Surgeons (AAES) 2014 Annual Meeting.

"The favorable overall survival of low-risk patients, regardless of the extent of thyroidectomy, enables patients' autonomy in treatment-related decision-making," said Dr. Ebina.

She presented follow-up data from her institution, which in 2004 published its own novel risk-group classification system: Patients considered "high risk" are those who have distant metastasis; are 50 years or older with massive extrathyroidal invasion; or have large nodal metastasis of 3 cm or greater. All other PTC patients are considered low risk.

Since 2005, the Japanese group has treated all high-risk patients with total thyroidectomy (TT) plus radioactive iodine (RAI), while low-risk patients with unilateral PTC are given the option of either TT plus RAI or "less-than-total" thyroidectomy (LTT) — either lobectomy or subtotal thyroidectomy — along with routine central lymph-node dissection. (Patients with bilateral PTC are treated with TT/RAI.)

New Guidelines Due From American Thyroid Association Will Address Controversies

This contrasts with common practice in the United States and other Western countries, where, due primarily to concerns about possible remaining disease or recurrence, TT is typically performed as the initial surgery even for most low-risk patients. For example, the American Thyroid Association (ATA) in its most recent guidelines in 2009 recommends near-total or TT for all tumors greater than 1 cm.

The issue is controversial, however, and other studies have called the practice into question.

But new guidelines from the ATA, coming out soon, will "reflect the role of lobectomy much more," Ashok R. Shaha, MD, the Jatin P. Shah Chair in Head & Neck Surgery at Memorial Sloan-Kettering Cancer Center, New York, said during the question-and-answer period.

Dr. Shaha has served on several previous ATA guideline committees and has long advocated for more conservative surgery in low-risk PTC patients, which is the practice at his institution.

"We've shown again and again that the extent of surgery does not have any impact on the low-risk group on long-term survival, but it does have an impact on the quality of life of the patient. A patient with a total thyroidectomy at the age of 25 is going to live on medication for 75 years….If you leave half the thyroid behind, half of the patients won't need medication. The rest will live with thyroid medication but happily ever after," Dr. Shaha commented.

Patients' Choice; Survival the Same Regardless of Procedure

In the study presented by Dr. Ebina, a total of 1187 PTC patients underwent primary surgery between 1993 and 2010 at the Cancer Institute Hospital in Tokyo. They had a mean age of 54 years, and 76% were female. Eighteen percent (220) were deemed to be high risk, and 82% (967) low risk, according to the institution's classification system. The mean duration of follow-up was 8.3 years (range, 3–20).

Cause-specific survival at 10 years was 99% for the low-risk group, compared with 74% for the high-risk patients. Disease-free survival at 10 years was 88% vs 43%, respectively (P < .0001), Dr. Ebina reported.

Among 496 of the low-risk patients who were seen from 2005 onward, 82% chose LTT and only 3% choose TT. The other 15% left the decision up to the doctor.

A total of 122 low-risk patients ended up needing TT/RAI because they were found on ultrasound to have bilateral disease or coexisting Graves' disease. After 2005, 71% of the low-risk patients underwent lobectomy, 3% had subtotal thyroidectomy, and 24% had TT.

For the entire study period, 10-year cause-specific survival was 87% among the 791 low-risk patients who underwent LTT, compared with 91% for the TT group. That difference was not statistically significant (P = .61). Disease-free survival at 10 years was an identical 99% for both groups, Dr. Ebina reported.

Surgical complications were significantly more common with TT than with LTT, including hypothyroidism (100% vs 13%), transient hypoparathyroidism (41% vs 1%) and permanent hypoparathyroidism (7% vs 0.3%) (all P < .0001).

Predicting Recurrence: Risk Factors Play Important Role

Overall, recurrence rates were not significantly different between the low-risk LTT and TT groups. Recurrence in the remnant thyroid occurred in 4 patients (0.5%) in the LTT group vs none with TT (P = .34), lymph-node recurrence was 7% with LTT vs 6% with TT (P = .87), recurrence in the thyroid bed or other neck was 0.8% LTT vs 0% TT (P = .79), and at a distant site, 4% vs 3%, respectively (P = .45).

On multivariate analysis, predictors of both lymph-node and distant recurrence in the low-risk PTC patients included age 60 or greater, tumor size 3 cm or greater, and lymph node metastases of 2 cm or greater (all P < .0001). Massive extrathyroidal invasion was also a significant predictor of lymph-node recurrence (P = .04).

Distant recurrence-free survival at 10 years was 98% for both the 407 low-risk patients with none of those risk factors and the 413 with one of the risk factors.

However, it dropped to 70% for the 147 low-risk patients with 2 or more of the factors (P < .0001), suggesting that "low-risk patients possessing the risk factors for distant recurrence would be candidates for a prospective study investigating the advantages of TT followed by RAI," Dr. Ebina concluded.

Dr. Shaha endorsed that idea, commenting, "You have subclassified certain low-risk patients who are truly high risk….The clinical evaluation at the time of surgery will tell you what [condition] is a bad actor in the low-risk [group] and be more aggressive. Be more aggressive in aggressive cancers. You don't need to be aggressive in the low-risk group."

Dr. Ebina and Dr. Shaha have no relevant financial relationships.

American Association of Endocrine Surgeons (AAES) 2014 Annual Meeting; April 29, 2014; Boston, Massachusetts. Abstract 34.

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