Abstract
The revised recommendations for mammographic screening for clinically undetectable breast cancer recommended by the U.S. Preventive Services Task Force (1) have provoked a storm of controversy among physicians and the lay public. Similar recommendations limiting the use of prostate specific antigen (PSA) in screening for prostate cancer in older men were made last year (2). Although not nearly as controversial as the breast cancer screening recommendations, they are based on similar questions and concerns. It has always been assumed that the early detection of cancers and their treatment when they are smaller and presumably more curable provides significant benefit to our patients. This assumption is now being questioned. It is recognized that there are risks associated with routine screening. False-positive tests result in unnecessary biopsies; false-negatives can result in inappropriate complacency.
The most perplexing question raised by the revised screening guidelines is whether in fact there is value in identifying early cancers in certain populations. Once an early breast cancer is detected, it is almost always treated. Some of these cancers might never have progressed to clinically significant disease, even without treatment. In other patients, early detection and treatment fail to prevent progression, spread, and death from small but lethal cancers. It is very difficult to identify those patients in whom early intervention will make a difference. A similar logic states that men over 75 should not have PSA screening to detect asymptomatic prostate cancer because the morbidity of the treatment is a more serious problem than the natural course of this slow growing, common cancer.
We are faced with a similar dilemma in the treatment of well-differentiated thyroid cancer. The “Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer” (3) is a model for a well-written, thoughtful guideline whose recommendations are supported by evidence-based studies when available, or clearly noted to be based on the preponderance of expert opinion. These guidelines, however, fail to address the concerns expressed above. Recommendations 21 and 27 on the “preoperative evaluation and treatment of lateral cervical nodes” and Recommendations 49 and 50 on the “evaluation and treatment of lateral cervical nodes after initial therapy has been completed” assume that there is a benefit to identify and treat clinically occult lateral nodal metastases. There is little evidence to support this assumption. The observation that patients with positive nodes have a worse prognosis than those with negative nodes does not mean that removal of these nodes will result in improved cure rates. A modified neck dissection, even by an experienced surgeon, is a major operation with associated costs, complications, and long-term morbidity. Are all nodal metastases significant and do they all need to be treated? The authors of the guidelines allude to this question by recommending that “suspicious lymph nodes less that 5–8 mm may be followed without biopsy … ” and that larger nodes should be biopsied “if a positive result would change management” (italics added). What are the data that support this recommendation? We know that more than 50% of patients with papillary cancer may have positive nodes (4). Do we really believe that they all need neck dissections? As our diagnostic testing becomes more sensitive, we will ultimately be able to identify all these patients.
As endocrinologists and endocrine surgeons, we cannot continue to base our recommendations purely on the assumption that all thyroid cancers need to be treated. Perhaps, as was done with mammographic screening guidelines, we should not recommend screening for occult nodal metastases unless we can prove that there is a measurable benefit that outweighs the risks and costs of treating them when they are identified. We need to design and support the large multi-institutional studies needed to answer these questions. Should surgery only be performed for positive nodes above a certain size? Should surgery only be done if nodes are enlarging by objective criteria? Can absolute thyroglobulin levels or trends in the change in thyroglobulin levels be used in selecting patients who need a neck dissection? Should the status of molecular markers such as the BRAF mutation be used to select patients for more aggressive treatment? Is there any difference in survival, symptomatic recurrence, or morbidity in patients followed according to the guidelines compared with those followed only with suppressed thyroglobulin and physical exam? The American Thyroid Association (ATA) has performed a tremendous service by supporting the development of its guidelines. It needs to take the lead in developing the clinical research protocols needed to rationalize and individualize the treatment of thyroid cancer.