Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen, 2100, Denmark.
Cluster for Molecular Imaging, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Sci Rep. 2024 Oct 30;14(1):26183. doi: 10.1038/s41598-024-77072-8.
Accurate initial staging of patients with breast cancer is essential for planning optimal treatment strategies. However, currently, no imaging modality is able to detect lymph node metastases preoperatively with sufficient reliability; therefore, the N status depends on the sentinel node procedure for ~ 70% of patients. In a prospective clinical trial of breast cancer patients, we compared head-to-head uPAR-PET/CT with current standard-of-care, ultrasound (US) and fine needle biopsy (FNB) as staging methods. Forty-nine patients (48 women and 1 man) with biopsy-proven early breast cancer underwent uPAR-PET/CT prior to surgery. All image data were analyzed by two separate teams, each consisting of a highly experienced certified specialist in nuclear medicine and a highly experienced certified specialist in radiology for visualization of primary tumor lesions and detection of lymph node and distant metastases. Histopathological assessment and verification of malignancy in the excised tissues (primary tumors and lymph nodes) were considered standard-of-truth. On a per patient basis, uPAR PET/CT demonstrated a sensitivity of 94% [CI: 83-99%] for detecting the primary tumor (both teams). For the detection of axillary lymph nodes the pooled sensitivity of uPAR PET/CT was 33.3% [CI: 16.5-54.0%], specificity 87.0% [CI: 66.4-97.2%] and accuracy 58.0% [CI: 43.2-71.8%]. In comparison, the standard-of-care preoperative clinical staging algorithm with US and FNB had a sensitivity of 41% [CI: 22-61%] and specificity of 100% [CI: 85-100%] for axillary lymph node metastases. We conclude that the results do not support the use of uPAR PET/CT for staging in breast cancer patients. However, the finding that 94% of primary tumors were uPAR-PET positive may be encouraging for pursuing uPAR theranostics in localized disease. Additionally, other potential applications, such as using uPAR-PET as a prognostic imaging biomarker of tumor aggressiveness, remain to be investigated.
准确的乳腺癌患者分期对于制定最佳治疗策略至关重要。然而，目前尚无任何影像学方法能够在术前以足够的可靠性检测淋巴结转移；因此，约 70%的患者的 N 分期依赖于前哨淋巴结活检。在一项乳腺癌患者的前瞻性临床试验中，我们对头对头的 uPAR-PET/CT 与当前的标准护理、超声（US）和细针活检（FNB）进行了比较，作为分期方法。49 名经活检证实患有早期乳腺癌的患者在手术前接受了 uPAR-PET/CT 检查。所有图像数据均由两个独立的团队进行分析，每个团队都由一位经验丰富的核医学认证专家和一位经验丰富的放射学认证专家组成，负责分析原发性肿瘤病变和检测淋巴结和远处转移。组织病理学评估和切除组织（原发性肿瘤和淋巴结）的恶性验证被认为是标准的真实情况。基于每位患者，uPAR PET/CT 在检测原发性肿瘤方面的灵敏度为 94%[CI：83-99%]（两个团队）。对于腋窝淋巴结的检测，uPAR PET/CT 的合并灵敏度为 33.3%[CI：16.5-54.0%]，特异性为 87.0%[CI：66.4-97.2%]，准确性为 58.0%[CI：43.2-71.8%]。相比之下，术前临床分期算法（包括 US 和 FNB）的灵敏度为 41%[CI：22-61%]，特异性为 100%[CI：85-100%]。我们得出的结论是，这些结果不支持将 uPAR PET/CT 用于乳腺癌患者的分期。然而，94%的原发性肿瘤为 uPAR-PET 阳性的发现可能令人鼓舞，因为在局部疾病中追求 uPAR 治疗学。此外，其他潜在的应用，如使用 uPAR-PET 作为肿瘤侵袭性的预后成像生物标志物，仍有待研究。
