Prognostic factors in mortality and morbidity in patients with differentiated thyroid cancer - Original Article

Ear, Nose & Throat Journal, Dec, 2002 by Robert L. Witt, Ann Marie McNamara

Abstract

We attempted to determine if women younger than 45 years of age who have isolated papillary thyroid cancer and whose tumors are smaller than 4 cm (T2N0M0) are at low risk for mortality and morbidity following thyroid lobectomy. To this end, we analyzed information on both women and men obtained from our review of the literature, and we integrated it with data compiled in the Delaware Cancer Registry. We performed a secondary analysis to determine if the risk of death and recurrence can be predicted on the basis of age, tumor size, sex, histology, and the type of operation. We found that among patients who had undergone either thyroid lobectomy or total thyroidectomy, mortality rates were 1.3% for those younger than 45 years of age and 15.6% for those 45 years and older (p<0.0001). With respect to tumor size, patients whose masses were smaller than 4 cm had significantly lower mortality (3.0%) and recurrence (11.1%) rates than did those whose tumors were 4 cm or larger (16.8 and 33.3%, respectively; p<0.0001). Other significant risk factors for death were male sex and the presence of follicular thyroid cancer (as opposed to papillary thyroid cancer). The risk of permanent hypocalcemia was significant among patients who had undergone total thyroidectomy, but not among those who had been treated with lobectomy. The subgroup of patients who had the lowest risk of mortality and morbidity was made up of women younger than 45 years who had a papillary thyroid tumor smaller than 4 cm that was limited to one lobe and who had undergone lobectomy. On the other hand, we found that lobectomy might carry a higher risk of recurrence (from a micrometastasis in the cervical lymph node) than does total thyroidectomy. Experienced surgeons whose rates of hypocalcemia and recurrent laryngeal nerve paralysis following total thyroidectomy are low offer their patients the unambiguous advantage of superior follow-up with thyroglobulin and radioactive iodine.

Introduction

Total thyroidectomy for papillary and follicular thyroid cancer is recommended for patients who are 45 years or older and for those who have large tumors, bilateral disease, and cervical or distant metastasis or other extrathyroidal spread. Conversely, few surgeons would argue that thyroid lobectomy is appropriate for patients younger than 45 years who have a tumor smaller than 1 cm (T1N0M0) that is limited clinically to one lobe. We set out to determine whether women younger than 45 years who have a papillary thyroid cancer smaller than 4 cm (T2N0M0) can be treated with thyroid lobectomy and experience low mortality and morbidity rates.

No prospective, randomized study has compared survival after total thyroidectomy, subtotal thyroidectomy, and thyroid lobectomy. Such an investigation would require decades of study and data accumulation. Because thyroid cancer deaths can occur decades after diagnosis, follow-up periods of 15 to 25 years are often necessary. (1,2) In conducting our study, we integrated data compiled in the Delaware Cancer Registry with information obtained through our own historical literature review. We analyzed mortality and recurrence rates as a function of age, tumor size, sex, histology, and the type of operation. We also determined the incidence of hypocalcemia and recurrent laryngeal nerve dysfunction according to the type of operation.

The literature is made up of widely divergent types of reports. (3,4) Narrative literature reviews describe series of studies, all of which have their particular strengths and weaknesses, that are discussed selectively and informally by one or more experts. A primary analysis contains original data, and a secondary analysis--such as the one we performed--contains a re-examination of previously published data. A meta-analysis is a statistical study of a collection of data obtained from many individual studies. Meta-analyses and quantitative retrospective analyses emphasize numbers over narrative, and they have greater statistical power than do other types of studies. Although meta-analyses are most useful when they include randomized, controlled trials, they have been used selectively in the otolaryngology literature to evaluate retrospective studies. (5)

Authors of numerous articles on differentiated thyroid cancer that appear in the endocrine and general surgery literature have advocated the use of total thyroidectomy, subtotal thyroidectomy, or lobectomy, depending on patient characteristics that predict survival and recurrence. However, the myriad classification systems in use make cross-comparisons difficult. In conducting searches of several databases covering the period from 1966 through 1998, we failed to find any meta-analysis or historical literature review that included data on all eight selected aspects of differentiated thyroid cancer that we wished to study; these eight aspects are mortality, recurrence, complications, age, tumor size, sex, histology, and type of operation.

In this article, we report our analysis of data obtained from published articles in which the authors advocated lobectomy (defined as lobectomy or thyroid isthmusectomy), subtotal thyroidectomy, or total thyroidectomy (either total or near-total) for differentiated thyroid carcinoma as well as data obtained from articles in which the authors took no stance on a preferred treatment. Discussions of prognostic factors and their influence on the management of differentiated thyroid cancer are sparse in the otolaryngology-head and neck surgery literature. Our analysis is unique in that no other article on prognostic factors in differentiated thyroid cancer included integrated data sets obtained from multiple studies and a state cancer registry.