Mazzaferri E L, Kloos R T
Department of Internal Medicine, The Ohio State University, Columbus, USA.
Thyroid. 2000 Sep;10(9):767-78. doi: 10.1089/thy.2000.10.767.
Mortality rates from thyroid cancer have fallen significantly in recent decades, almost certainly as the result of earlier diagnosis and improved treatment of differentiated (papillary and follicular) thyroid cancer. Enhanced survival is likely a result of early diagnosis and therapy applied at a disease stage when treatment is most effective. In the United States and Europe, most patients at high risk for relapse and death from thyroid cancer are treated with total or near-total thyroidectomy and receive radioiodine ablation of residual normal or malignant thyroid tissue, followed by treatment with thyroid hormone, a strategy that cures more than 80% of patients. Still, some die of the disease and nearly 15% have local recurrences, while another 5% to 10% develop distant metastases. Over 50% of recurrences appear in the first five years, but distant metastases may surface years, and sometimes decades, after initial therapy. Much has been learned about risk stratification to predict recurrence and death from thyroid cancer but individual patients continue to have adverse outcomes not always foreseen by a low tumor stage. Follow-up must accordingly be meticulous and prolonged. The National Cancer Center Network (NCCN) has recently established consensus practice guidelines that give explicit advice about the diagnosis and management of benign and malignant thyroid tumors, including paradigms for long-term follow-up and the treatment of recurrent disease. The guidelines confirm that diagnostic scanning with 131I and measurement of serum thyroglobulin (Tg) levels are the mainstay of follow-up, offering the opportunity to detect recurrent or persistent cancer at very early stages. These guidelines advocate TSH-stimulated serum Tg measurements, done either during thyroid hormone withdrawal or stimulation with recombinant human TSH (rhTSH, Thyrogen), that often identify the presence of cancer well before diagnostic whole-body scanning or other imaging studies can spot the tumor, which offers the opportunity to treat recurrent disease at an early stage. The use of rhTSH adds a new dimension to long-term follow-up that avoids putting patients through the symptoms of hypothyroidism, and offers the opportunity to follow some patients with rhTSH-stimulated serum Tg levels without performing 131I whole-body scans. A multicenter international study has shown that serum Tg measurements alone are not as sensitive in the identification of patients with persistent or recurrent tumor as are rhTSH-stimulated serum Tg determinations. Although not yet approved for preparation of patients for 131I therapy, rhTSH has been used successfully in a compassionate use program for this purpose in a relatively large number of patients. Formal clinical investigations now planned to provide guidelines for the use of rhTSH for therapeutic 131I portend a new set of effective therapeutic paradigms for the management of differentiated thyroid cancer.
近几十年来，甲状腺癌的死亡率显著下降，几乎可以肯定这是分化型（乳头状和滤泡状）甲状腺癌早期诊断和治疗改善的结果。生存率提高可能是由于在疾病最有效的治疗阶段进行了早期诊断和治疗。在美国和欧洲，大多数有甲状腺癌复发和死亡高风险的患者接受全甲状腺切除术或近全甲状腺切除术，并接受放射性碘消融残留的正常或恶性甲状腺组织，随后进行甲状腺激素治疗，这种策略可治愈超过80%的患者。尽管如此，仍有一些患者死于该病，近15%的患者出现局部复发，另有5%至10%的患者发生远处转移。超过50%的复发发生在头五年，但远处转移可能在初始治疗后的数年甚至数十年后才出现。关于预测甲状腺癌复发和死亡的风险分层已经有了很多了解，但个别患者仍然会出现不良后果，而这些后果并不总是能通过低肿瘤分期预测到。因此，随访必须细致且持续时间长。美国国立综合癌症网络（NCCN）最近制定了共识实践指南，明确给出了关于良性和恶性甲状腺肿瘤诊断和管理的建议，包括长期随访和复发性疾病治疗的范例。这些指南确认，131I诊断性扫描和血清甲状腺球蛋白（Tg）水平测定是随访的主要手段，提供了在非常早期阶段检测复发或持续性癌症的机会。这些指南提倡在甲状腺激素撤药期间或用重组人促甲状腺激素（rhTSH，商品名Thyrogen）刺激后进行促甲状腺激素刺激的血清Tg测定，这通常能在诊断性全身扫描或其他影像学检查发现肿瘤之前就识别出癌症的存在，从而提供在早期阶段治疗复发性疾病的机会。rhTSH的使用为长期随访增添了新的维度，避免了让患者经历甲状腺功能减退的症状，并且提供了在不进行131I全身扫描的情况下通过rhTSH刺激的血清Tg水平对一些患者进行随访的机会。一项多中心国际研究表明，单独的血清Tg测定在识别持续性或复发性肿瘤患者方面不如rhTSH刺激的血清Tg测定敏感。尽管rhTSH尚未被批准用于为131I治疗准备患者，但它已在一个同情用药项目中成功用于此目的，涉及相当多的患者。目前计划进行的正式临床研究旨在为rhTSH用于治疗性131I提供指导，这预示着一套新的分化型甲状腺癌管理有效治疗范例。
