Early detection of recurrent disease
By Ernest L. Mazzaferri, MD MACP
Adjunct Professor of Medicine, University of Florida and Emiritus Professor & Chairman of Internal Medicine. The Ohio State University
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 Well Differentiated Thyroid Cancer (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. 
Given the potential for this type of persistent “recurrence” and the percentage of thyroid cancer deaths caused by WDTC, there can be a 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 WETC was increased by multiple factors.  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. 
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.
Thus, early identification of recurrent or persistent disease is important, yet patients are reluctant to go through frequent and rigorous cycles of follow-up. These cycles usually require hypothyroidism and its associated signs and symptoms; however, an elevated serum TSH level is an essential, which are key to a successful management of the identification of persistent disease.
As with delaying the initial diagnosis, delaying the detection of persistent or recurrent thyroid cancer can increase mortality rates significantly. Mortality risk increase 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 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 a regular follow-up routine should be taken.
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.