Study Supports Active Surveillance for Some Thyroid Cancer Patients

R. Michael Tuttle, MD

Results from an analysis of 3D tumor volume measurements shows papillary thyroid cancers (PTC) ≤1.5 cm grew slowly during a period of active surveillance, suggesting that surgery may not be necessary for all patients.¹

The findings from investigators at Memorial Sloan Kettering Cancer Center and the NYU Langone Medical Center support results from landmark Japanese studies that used the single binary endpoint of 3-mm of growth as the threshold for surgical intervention to establish the safety of active surveillance.

“[O]ur findings confirm that only 10% to 15% of small PTCs will increase in tumor diameter by 3 mm or more during the first 5 years of active surveillance and that an increase in tumor size is more likely in younger patients,” lead author R. Michael Tuttle, MD, Memorial Sloan Kettering Cancer Center, and co-investigators wrote.

“As the number of small, incidentally detected PTCs continues to increase, new approaches are needed to avoid overtreatment of tumors that would otherwise remain indolent and asymptomatic while identifying the small percentage of such tumors that will continue to grow. Because PTCs appear to follow predictable growth kinetics under active surveillance, serial measurements of tumor volume hold significant promise in triaging patients to observation versus surgery,” the researchers added.

A total of 291 patients with low-risk PTC were followed with active surveillance for a median of 25 months (range, 6-166). Eleven patients (3.8%) experienced tumor diameter growth ≥3 mm. The cumulative incidence of ≥3 mm tumor growth was 2.5% at 2 years and 12.1% at 5 years.

The cumulative incidence of volume increase >50% was 11.5% at 2 years and 24.8% at 5 years. Volume was stable in 229 patients, increased by more than 50% in 36 patients, and decreased by more than 50% in 19 patients. Volume change could not be determined in 7 patients. All tumors experiencing 3 mm growth also demonstrated a volume increase greater than 50%, with a mean increase of 178% (range, 96%-364%).

Risk category and younger age at diagnosis were independently associated with tumor growth. At 5 years, patients younger than 50 years at diagnosis were almost 7 times more likely to experience tumor growth compared with older patients (27.3% vs 4.6%; hazard ratio [HR], 4.5; 95% CI, 1.2-17.0; P = .03).

Similarly, younger age (HR, 0.97; 95% CI, 0.94-0.99; P = .01) and risk category (HR for inappropriate, 10.54; 95% CI, 2.39-46.53; P = .002) were independently associated with the likelihood of 50% volume growth.

Tumor size (<1.0 cm vs 1.0-1.5 cm) at baseline was not associated with an increase in either volume (HR, 0.93; 95% CI, 0.36-2.41) or diameter (HR, 1.94; 95% CI, 0.41-9.23).

Investigators found that tumors that increased in volume by >50% displayed classic exponential growth patterns, with a median doubling time of 2.2 years (range, 0.5-4.8; median r2 = 0.75; range, 0.42-0.99). Mean time to 50% volume increase was 22.9 months in these tumors.

Among the 11 tumors experiencing 3 mm or more diameter growth, the mean time to reach this threshold was 34.1 months. In all cases, a 50% increase in volume preceded the ≥3mm increase in tumor diameter by a median of 8.2 months (range, 3-46 months).

Writing in an accompanying editorial, Joseph Scharpf, MD, Head and Neck Institute, Cleveland Clinic Foundation, praised the study authors for their “excellent work that will benefit so many patients diagnosed with a cancer characterized as an epidemic of diagnosis rather than an epidemic of disease.”²

“In addition to supporting active surveillance in a population outside of Japan, the study has provided a very important template for patient selection,” Scharpf wrote. “It is interesting that nearly 80% of their study population were patients with a tumor size of 1.0 cm or less. Under the most current American Thyroid Association guidelines, there is a recommendation (recommendation 8) against fine-needle aspiration biopsy of thyroid nodules less than 1.0 cm. Therefore, this approach makes sense for this group of patients who perhaps should not have been diagnosed with thyroid cancer at this size level. It is anticipated that incidental detection of small PTCs will continue to increase, and it is imperative to continually explore new approaches to avoid potential overtreatment while still identifying tumors that would continue to grow.”

References

1. Tuttle RM, Fagin JA, Minkowitz G, et al. Natural history and tumor volume kinetics of papillary thyroid cancers during active surveillance [published online August 31, 2017]. JAMA Otolaryngol Head Neck Surg. doi:10.1001/jamaoto.2017.1442.
2. Scharpf J. Achieving active surveillance for thyroid cancer—not a euphemism for watching a ticking time bomb [published online August 31, 2017]. JAMA Otolaryngol Head Neck Surg. doi:10.1001/jamaoto.2017.1453.