Testing and Management: Importance of early detection of recurrent disease

By Ernest L. Mazzaferri, MD MACP

Adjunct Professor off Medicine, University of Florida and Emiritus
Professor & Chairman of Internal Medicine
The Ohio State University

Thyroid cancer mortality rates in the United States have declined nearly 20% over the past 30 years.^[1] Papillary and follicular cancers (well-differentiated thyroid cancers [WDTC]) are the most common thyroid cancers, and have the best outcomes providing they are diagnosed early. Yet death from WDTC is still a concern. One large study of nearly 54,000 patients with thyroid cancer who underwent surgery in the United States between 1985 and 1995 found that papillary and follicular cancers—the two typically slow-growing cancers with the “best” prognosis—represented 70% of thyroid cancer deaths, and were especially dangerous when the tumor was advanced at the time of diagnosis.^[1;2] Overall, 10-year cancer mortality rates were about 7% for papillary and 15% for follicular thyroid cancer. ^[1]

In the past few decades, Thyroid cancer has been diagnosed earlier, providing an opportunity for treatment before the cancer has spread beyond the thyroid, and improving survival rates. Proper therapy—in most cases this means surgical removal of the tumor along with the entire thyroid gland, followed by radioactive iodine (I-131) ablation and thyroid hormone therapy—has the potential to reduce recurrence and mortality rates.

Recurrence rates and the need for follow-up

Although the long-term prognosis for survival with WDTC is generally quite good, tumor recurrence is common, affecting 20% to 35% of patients with the disease. Recurrence can occur any time, even decades after initial therapy. ^[1;2] Studies now show that many late cancer “recurrences” may actually be cases of persistent tumor that had fallen below our testing detection limits for as long as decades. ^[2]

Given the potential for this type of persistent “recurrence” and the percentage of thyroid cancer deaths caused by WDTC, there can be great risk associated with delay of diagnosis, even in recurrent thyroid cancers. We know that delaying the initial diagnosis of thyroid cancer longer than 1 year increases mortality rates significantly. The mortality risk worsens as the delay becomes longer, eventually imparting a risk comparable with that of advanced age. One study, based on regression modeling of 1510 patients without distant metastases at the time of initial therapy who had undergone surgery and I-131 therapy, found that the likelihood of death from WDTC was increased by multiple factors. ^[1] These included age of over 40 years, a tumor size of more than 1.0 cm, local tumor invasion or regional lymph node metastases, follicular histology, and a delay of therapy for more than 12 months and the extent of surgery and use of I-131 therapy. ^[1]

There are compelling reasons to believe that delay-related risks also exist with persistent, unrecognized thyroid cancers. For example, respiratory insufficiency due to pulmonary metastases is the most common cause of death from thyroid cancer. Additionally, tumor bulk of distant metastases ranks second only to patient age as a predictor of death from thyroid cancer. The longer the tumor remains, the greater its bulk. However, early diagnosis and treatment substantially enhance survival.

These facts lead us to two important possible conclusions: 1) that delay of diagnosis and treatment can be directly related to a higher mortality rate, and, conversely, 2) that early identification and treatment of recurrent and/or persistent WDTC can lower mortality rates. Meticulous initial therapy coupled with rigorous follow-up can have very favorable effects on patients with WDTC.

While there are no hard and fast rules governing how to schedule follow-up and evaluate for recurrence, clicking on the link below will allow you to download an algorithm that may help you choose a follow-up path for your patients in the months and years following initial treatment.

Download a graphic of follow-up algorithm (PDF).

Thyrogen in follow-up

Thyrogen^® (recombinant human thyroid stimulating hormone [rhTSH]) is an important diagnostic tool that can help identify cancer that persists or occurs after treatment. This drug facilitates the detection of remaining or recurrent disease while avoiding the need for hypothyroidism and its associated signs and symptoms. With Thyrogen, patients may be more likely to pursue follow-up studies, which may in turn facilitate an early identification of thyroid cancer. For more information, please see the important safety information below.

Summary

As with delaying the initial diagnosis, delaying the detection of persistent or recurrent thyroid cancer can increase mortality rates significantly. Mortality risk increases as the delay becomes longer. As discussed above, the tumor bulk of distant metastases ranks second only to a patient’s age as a predictor of death from thyroid cancer. Additionally, all therapeutic modalities seem to be more effective when the tumor bulk is smallest. In fact, the larger the tumor mass, the less likely that it will be ablated with I-131 therapy and the higher the mortality rate.

Given all of these facts, it follows that early detection and treatment are important goals in improving long-term outcome. To support these goals, any steps that can be safely taken to encourage patients to comply with—or even to seek out—a regular follow-up routine, like prescribing Thyrogen when appropriate rather than relying on withdrawal testing, should be taken.

For more information, please see the important safety information below.

References

1. Ries, LAG, Eisner MP, Kosary CL, et al. 2000 SEER cancer statistics review, 1973-1997. Bethesda, MD: National Cancer Institute.

2. Hundahl, SA, Fleming ID, Fremgen, AM, Mench, HR. 1998 A National Cancer Data Base Report on 53,856 cases of thyroid carcinoma treated in the US, 1985-1995. Cancer. 83:2638-2648.

About the Author

Ernest L. Mazzaferri, MD MACP

Dr. Mazzaferri is Adjunct Professor of Medicine at the University of Florida Gainesville, a Senior Research Scholar at the Health Outcomes and Policy Evaluation Center at The Ohio State University, and is an internationally recognized authority on thyroid cancer. He is emeritus professor of Internal Medicine and Physiology at The Ohio State University in Columbus, Ohio, where he served as chairman of the department of internal medicine for 15 years. He was formerly chief of endocrinology at Ohio State and was chairman of the department of medicine and acting dean at the University of Nevada. A Master of the American College of Physicians, and a member of many other organizations, including the Endocrine Society, the American Thyroid Association, and The American Clinical and Climatologic Association, Dr. Mazzaferri is the author of over 300 peer reviewed publications, editorials and review articles, and has authored two books and is the editor of several textbooks of endocrinology, including Endocrine Tumors. He is Editor-in-Chief of the Year Book of Endocrinology and editor of the endocrine section of the Year Book of Medicine. An international authority on thyroid cancer, Dr. Mazzaferri served on the Institute of Medicine Committee on Thyroid Cancer Screening, The National Academy of Sciences Committee on Exposure of the American People to I-131 from Nevada Atomic Bomb Tests, and the Institute of Medicine Committee on Health Effects Associated with Exposures Experienced during the Gulf War. He served as Chair of the Thyroid Cancer Guideline Committee of the National Cancer Center Network and as Chair of the Clinical Efficacy Assessment Committee of the American College of Physicians. He has been named in several publications as one of the best doctors in America. Dr. Mazzaferri received the prestigious Paul Starr Award from the American Thyroid Association in 1997 and the Distinguished Clinician's Award of the American College of Endocrinology in 2002.