Differentiated thyroid cancer, the most common endocrine malignancy, can touch the lives of young and old individuals. It is generally associated with a normal lifespan whether it is completely eradicated or held in check with judicious medical interventions. Recent diagnostic imaging modalities—both for preventive health maintenance (eg, whole-body ultrasound screening offered free in several community settings) and for the diagnosis of other conditions (eg, PET scan performed for evaluation of nonendocrine malignancies)—further increase the likelihood of discovering incidental small malignant lesions in the thyroid gland.
While some of these incidentally discovered thyroid lesions will quickly prove to be of significant neoplastic consequence, they usually represent a “low-risk” situation. As Dr. Mazzaferri points out, these patients don’t want to hear that they are at a low risk of dying of this tumor; they want to be assured that they can be rendered free of disease. It is important to have a plan for these patients that is rational, validated, and effective without excessive complexity or morbidity. Dr. Mazzaferri’s comprehensive review addresses exactly this scenario of initial therapy for low-risk thyroid cancer so carefully and thoughtfully that it appears to leave very few areas of confusion and controversy.
But let us consider a hypothetical patient who has a small but larger than 1 cm papillary thyroid primary. A thorough neck ultrasound examination raises concern regarding metastatic deposits in cervical lymph nodes. The patient has a total thyroidectomy with bilateral level VI and ipsilateral level III and IV lymph node compartment dissection and a postoperative optimized thyroid remnant ablation with radioactive iodine. The thyroid dose is titrated to provide low normal thyroid-stimulating hormone (TSH) levels and there are no interfering thyroglobulin antibodies. With this background, our patient is retested 12 months later and has a benign-appearing postoperative ultrasound examination and a recombinant human thyrotropin- (Thyrogen [rhTSH])-stimulated thyroglobulin below 1 µg/L and is declared completely free of tumor. However, there are several caveats.
Patient Concerns and Perceptions
As Dr. Mazzaferri points out, many patients may not accept such extensive initial surgery if they perceive themselves to have low-risk disease. Furthermore, the preoperative ultrasound may not identify the presence of low-volume cervical lymph node tumor infiltration, and thus the patient may not even be asked to consider this operation. What if there are thyroglobulin antibodies rendering this measurement uninformative? What if the patient is trying to start a family or has a comorbidity that increases the risk of radioactive iodine toxicity and hence foregoes the radioactive iodine? Let us imagine that the tumor is 0.9 cm in size and optimal treatment recommendations include subtotal thyroid resection or even conservative surveillance.
All of these scenarios are plausible and relatively common, and of course they begin to create uncertainty if not confusion about the recommendations regarding optimal initial treatment of low-risk thyroid cancer. They are and will remain controversial because, understandably, health-care providers have varying philosophies—evidence-based guidelines notwithstanding. More importantly, there is significant variation in patient preferences regarding potential treatment-related risk and tolerance for uncertainty. Another important consideration relates to the possibility that, at the end of the proposed algorithm, the patients may have a false sense of security that they have been rendered “completely free of tumor.” This could lead to neglect of careful long-term surveillance for delayed reactivation of the disease.
Treating Papillary Thyroid Cancer as a Chronic Condition
Increasingly, we recognize that cancer should be viewed as a chronic condition. Papillary thyroid cancer serves as an excellent paradigm for this concept. While such low-risk patients may generally enjoy a normal lifespan, clinically meaningful recurrences are not uncommon and require management many years, even decades, after initial therapy. We have all learned not to say “If you have to have cancer this is the best kind to have” and to strongly urge regular, though not cumbersome, lifelong surveillance. In this setting, the patient would have serial evaluations with ultrasonography and thyroglobulin measurement allowing for the appreciation of nuances and changes that may alert us to disease reactivation and indicate a need for appropriate intervention.
One possibility for low-risk patients, therefore, might be to minimize potential treatment-related complications by limiting the extent of initial therapy and prospectively following carefully over time; in this manner we can identify the minority of such patients who harbor more virulent disease and provide them with more comprehensive management at that point. Hopefully, advances in molecular diagnostics may also permit more elegant stratification of risk during the initial preoperative diagnostic assessment, thus allowing us to hone in on this important subgroup of patients while permitting a more relaxed approach to the truly low-risk patients.
Ultimately, as so often and appropriately occurs in medical decision-making, one lucid, rational, evidence-based algorithm does not fit all—treatment recommendations have to be tailored to the individual patient’s characteristics. At the end of the day, then, we are left with some degree of uncertainty that I would prefer to view as “options” rather than “confusion and controversy.”
Financial Disclosure: The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.