Current Approaches to Primary Therapy for Papillary and Follicular Thyroid Cancer

Abstract

Papillary and follicular thyroid cancer, together referred to as differentiated thyroid cancer (DTC), is usually curable when discovered at an early stage. Its management, however, is often a challenge because there have been no prospective randomized trials of treatment and none are likely to be done, given its typically prolonged course and relative infrequency. Instead, clinicians rely on large patient cohort studies in which therapy has not been randomized, leading to some disagreement about management. Nonetheless, thyroid cancer mortality rates have fallen significantly (20%, P < 0.05) in the United States between 1973 and 1996 (1), almost certainly due to early diagnosis and effective treatment of DTC, which comprises 90% of thyroid cancers and 70% of the thyroid cancer deaths (2). The decline in mortality, however, occurred only in women (1), perhaps because they undergo routine medical examinations more than men, in whom thyroid cancer is typically discovered at an older age (1). DTC is more likely to be completely resected and ablated with iodine-131 (131I), an approach that has become more popular in the past several decades, when discovered at an early stage (3, 4). Much of the following discussion refers to treatment of DTC because the approach to treatment of papillary and follicular cancer is usually very similar. The annual incidence of thyroid cancer has risen nearly 50% since 1973, afflicting some 18,000 people and causing about 1,200 deaths in the United States in 1999 (1). Ten-year relative survival rates in a large cohort of United States patients with papillary and follicular cancer were, respectively, 93% and 85% (2). In 1,528 of our patients who were, as a group, slightly younger than those in the aforementioned study, 40-yr relative survival rates for papillary and follicular cancer, respectively, were 94% and 84% (P = 0.00011; Ref. 3). Patients with follicular cancer tend to be older with more advanced tumor stage at the time of diagnosis than those with papillary cancer. About half who die from thyroid cancer suffer a pulmonary death, either respiratory failure from pulmonary metastases or suffocation from airway compromise (5). In our cohort, 40-yr recurrence rates are about 35%, two thirds of which occurred within the first decade after initial therapy (Fig. 1A). These rates, including those for distant recurrence, are higher under age 20 and over 60 yr2 (Fig. 1B). Thirty-year cancer mortality rates were about 12% with local recurrence and 43% with distant recurrence (P = 0.001). Local disease comprised 68% of the recurrences in our study; among the 170 patients in whom the exact site of local recurrence was known, the 30-yr cancer mortality rate was twice as high with recurrence in the neck soft tissues (30%) compared with those in cervical lymph nodes or the contralateral thyroid (16%, P < 0.05). Distant metastases, mostly to the lungs, comprised 32% of the recurrences; after 40 yr of follow-up half have died of cancer. Tumor recurrence rates in 1528 patients after a median of 16.6 yr of follow-up. There were 359 recurrences (23.5% of patients). Local recurrence (n = 272, 17.8%) is cervical or mediastinal; distant recurrence (n = 114, 7.5%) is sites outside the neck. A, Number of patients with recurrences at 5-yr intervals; B, Cumulative percentage of recurrences, distant recurrences, and cancer deaths over 40 yr stratified by age at the time of initial therapy. Patients (n = 27) with both local and distant recurrences are shown as distant recurrence. [Mazzaferri, E. L., unpublished data; here and elsewhere the data are from a 1999 update and of a cohort in is to for tumor recurrence and mortality because is here that clinicians therapy and follow-up to of on DTC Ref. The first are patient age at and rates are among patients under age 40 yr (Fig. however, recurrence rates are high the first two of and after age 60 yr (Fig. DTC with about half the of women have about twice the of from and 3). of cancer recurrence and cancer from the for the diagnosis and treatment of thyroid cancer (3, of cancer recurrence and cancer from the for the diagnosis and treatment of thyroid cancer (3, on cancer recurrence, distant recurrence, and due to thyroid cancer in patients with distant metastases at the time of initial unpublished update of a patient cohort in stratified as than 40 yr 40 yr and older for cancer mortality and by decade for recurrences and distant metastases Tumor stratified from than to than is the of in patients with only in the thyroid and no of therapy with is treatment of patients with thyroid with or to treatment or more than on cancer recurrence, distant recurrence, and due to thyroid cancer in patients with distant metastases at the time of initial unpublished update of a patient cohort in stratified as than 40 yr 40 yr and older for cancer mortality and by decade for recurrences and distant metastases Tumor stratified from than to than is the of in patients with only in