BACKGROUND Cancer of unknown primary (CUP) is defined as a primary metastatic malignancy, in which the primary tumor remains elusive in spite of a comprehensive diagnostic workup. The frequency and prognostic value of circulating tumor cells (CTCs), which are considered to be the source of metastasis, has not yet been systematically evaluated in CUP. METHODS A total of 110 patients with a confirmed diagnosis of CUP according to the European Society for Medical Oncology (ESMO) guidelines, who presented to our clinic between July 2021 and May 2023, provided blood samples for CTC quantification using CellSearch methodology. CTC counts were correlated with demographic, clinical, and molecular data generated by comprehensive genomic profiling of tumor tissue. RESULTS CTCs were detected in 26% of all patients at initial presentation to our department. The highest CTC frequency was observed among patients with unfavorable CUP (35.5%), while patients with single-site/oligometastatic CUP harbored the lowest CTC frequency (11.4%). No statistically significant association between CTC positivity and the number of affected organs (P = 0.478) or disease burden (P = 0.120) was found. High CTC levels (≥5 CTCs/7.5 mL; 12/95 analyzed patients) predicted for adverse overall survival compared to negative or low CTC counts (6-months overall survival rate 90% vs 32%, log-rank P < 0.001; HR 5.43; 95% CI 2.23–13.2). CTC dynamics were also prognostic for overall survival by landmark analysis (log-rank P < 0.001, HR 10.2, 95% CI 1.95–52.9). CONCLUSIONS CTC frequency is a strong, independent predictor of survival in patients with CUP. CTC quantification provides a useful prognostic tool in the management of these patients.

中文翻译：

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原发灶不明的癌症中循环肿瘤细胞的频率和预后价值

背景原发性不明的癌症（CUP）被定义为原发性转移性恶性肿瘤，其中尽管进行了全面的诊断检查，但原发性肿瘤仍然难以捉摸。循环肿瘤细胞（CTC）被认为是转移的来源，但其频率和预后价值在 CUP 中尚未得到系统评估。方法 根据欧洲肿瘤内科学会 (ESMO) 指南，共有 110 名确诊为 CUP 的患者于 2021 年 7 月至 2023 年 5 月期间到我们诊所就诊，他们提供了血液样本，使用 CellSearch 方法进行 CTC 定量。CTC 计数与肿瘤组织综合基因组分析生成的人口统计、临床和分子数据相关。结果 初次就诊时，26% 的患者被检测到 CTC。不良 CUP 患者的 CTC 频率最高（35.5%），而单部位/寡转移 CUP 患者的 CTC 频率最低（11.4%）。未发现 CTC 阳性与受影响器官的数量 (P = 0.478) 或疾病负担 (P = 0.120) 之间存在统计学上的显着关联。与阴性或低 CTC 计数相比，高 CTC 水平（≥ 5 CTC/7.5 mL；12/95 分析患者）预测总体生存不良（6 个月总体生存率 90% vs 32%，对数秩 P < 0.001； HR 5.43；95% CI 2.23–13.2）。通过界标分析，CTC 动态也可预测总体生存（对数秩 P < 0.001，HR 10.2，95% CI 1.95-52.9）。结论 CTC 频率是 CUP 患者生存的一个强有力的、独立的预测因子。CTC 量化为这些患者的管理提供了有用的预后工具。