Raue Friedhelm, Frank-Raue Karin
Endocrine Practice, Heidelberg, Germany.
Medical Faculty, University of Heidelberg, Heidelberg, Germany.
Recent Results Cancer Res. 2025;223:267-291. doi: 10.1007/978-3-031-80396-3_11.
After surgery, patients with MTC (medullary thyroid carcinoma) should be assessed for the presence of residual disease, the localization of metastases, and the identification of progressive disease. Postoperative staging is used to separate low-risk patients from high-risk patients with MTC. In addition to the TNM system, further histological staging with Ki67, mitotic count, tumor necrosis, and molecular analysis of somatic RET mutations is helpful for the stratification of patients in different prognostic categories. The number of lymph node metastases and involved compartments as well as postoperative Ctn (calcitonin) and CEA (carcinoembryonic antigen) levels should also be documented. Postoperative nonmeasurable Ctn levels are associated with a favorable outcome. In patients with basal serum Ctn levels less than 150 pg/ml following thyroidectomy, persistent or recurrent disease is almost always confined to lymph nodes in the neck. If the postoperative serum Ctn level exceeds 150 pg/ml, patients should be evaluated by imaging procedures, including neck and chest CT (computed tomography), contrast-enhanced MRI, US of the liver, bone scintigraphy, MRI of the bone and positron emission tomography (PET)/CT. One can estimate the growth rate of MTC metastases from sequential imaging studies using response evaluation criteria in solid tumors (RECIST) that document increases in tumor size over time and by measuring serum levels of Ctn or CEA over multiple time points to determine the tumor marker doubling time. One of the main challenges remains finding effective adjuvant and palliative options for patients with metastatic disease. Patients with persistent or recurrent MTC localized to the neck and slightly elevated Ctn levels following thyroidectomy might be candidates for neck reoperations depending on the extent of the tumor. Once metastases appear, the clinician must decide which patients require therapy, balancing the frequently slow rate of tumor progression associated with a good quality of life and suggesting active surveillance against the limited efficacy and potential toxicities of local and systemic therapies. Considering that metastatic MTC is incurable, the management goals are to provide locoregional disease control, palliate symptoms such as diarrhea, palliate symptomatic metastases causing pain or bone fractures, and control metastases that threaten life through bronchial obstruction or spinal cord compression. This can be achieved by palliative surgery, EBRT (external beam radiation therapy) or systemic therapy using multikinase inhibitors (MKIs) targeting RET or selective RET inhibitors requiring genetic testing prior to the initiation of therapy.
甲状腺髓样癌（MTC）患者术后应评估是否存在残留病灶、转移灶的定位以及疾病进展情况。术后分期用于区分MTC低风险患者和高风险患者。除TNM系统外，通过Ki67、有丝分裂计数、肿瘤坏死以及体细胞RET突变的分子分析进行进一步的组织学分期，有助于对不同预后类别的患者进行分层。还应记录淋巴结转移数量、受累分区以及术后降钙素（Ctn）和癌胚抗原（CEA）水平。术后不可测量的Ctn水平与良好预后相关。甲状腺切除术后基础血清Ctn水平低于150 pg/ml的患者，持续性或复发性疾病几乎总是局限于颈部淋巴结。如果术后血清Ctn水平超过150 pg/ml，应通过影像学检查对患者进行评估，包括颈部和胸部计算机断层扫描（CT）、增强磁共振成像（MRI）、肝脏超声、骨闪烁显像、骨骼MRI以及正电子发射断层扫描（PET）/CT。可以使用实体瘤疗效评价标准（RECIST）通过连续影像学研究评估MTC转移灶的生长速率，该标准记录肿瘤大小随时间的增加情况，并通过在多个时间点测量血清Ctn或CEA水平来确定肿瘤标志物倍增时间。主要挑战之一仍然是为转移性疾病患者找到有效的辅助和姑息治疗方案。甲状腺切除术后持续性或复发性MTC局限于颈部且Ctn水平略有升高的患者，根据肿瘤范围，可能是再次颈部手术的候选者。一旦出现转移，临床医生必须决定哪些患者需要治疗，权衡与良好生活质量相关的肿瘤进展通常较慢的情况，并建议进行积极监测，同时考虑局部和全身治疗的有限疗效及潜在毒性。鉴于转移性MTC无法治愈，管理目标是实现局部区域疾病控制，缓解腹泻等症状，缓解引起疼痛或骨折的有症状转移灶，并控制通过支气管阻塞或脊髓压迫威胁生命的转移灶。这可以通过姑息性手术、外照射放疗（EBRT）或使用靶向RET的多激酶抑制剂（MKI）或在治疗开始前需要进行基因检测的选择性RET抑制剂进行全身治疗来实现。
