Geißen Wiebke, Engels Svenja, Aust Paula, Schiffmann Jonas, Gerullis Holger, Wawroschek Friedhelm, Winter Alexander
University Hospital for Urology, Klinikum Oldenburg, School of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, Oldenburg, Germany.
Front Pharmacol. 2019 Oct 11;10:1123. doi: 10.3389/fphar.2019.01123. eCollection 2019.
Due to the high morbidity of extended lymph node dissection (eLND) and the low detection rate of limited lymph node dissection (LND), targeted sentinel lymph node dissection (sLND) was implemented in prostate cancer (PCa). Subsequently, nonradioactive sentinel lymph node (SLN) detection using magnetic resonance imaging (MRI) and a magnetometer after intraprostatic injection of superparamagnetic iron oxide nanoparticles (SPIONs) was successfully applied in PCa. To validate the reliability of this approach, considering the magnetic activity of SLNs or whether it is sufficient to dissect only the most active SLNs as shown in other tumor entities for radio-guided sLND, we analyzed magnetometer-guided sLND results in 218 high- and intermediate-risk PCa patients undergoing eLND as a reference standard. Using a sentinel nomogram to predict lymph node invasion (LNI), a risk range was determined up to which LND could be dispensed with or sLND only would be adequate. In total, 3,711 LNs were dissected, and 1,779 SLNs (median, 8) were identified. Among 78 LN-positive patients, there were 264 LN metastases (median, 2). sLND had a 96.79% diagnostic rate, 88.16% sensitivity, 98.59% specificity, 97.1% positive predictive value (PPV), 93.96% negative predictive value (NPV), 4.13% false-negative rate, and 0.92% additional diagnostic value (LN metastases only outside the eLND template). For intermediate-risk patients only, the sensitivity, specificity, PPV, and NPV were 100%. Magnetic activities of SLNs were heterogeneous regardless of metastasis. The accuracy of predicting the presence of metastases for each LN from the proportion of activity was only 57.3% in high- and 65% in intermediate-risk patients. Patients with LNI risk of less than 5% could have been spared LND, as no positive LNs were found in this group. For patients with an LNI risk between 5% and 20%, sLND-only would have been sufficient to detect almost all LN metastases; thus, eLND could be dispensed with in 36% of patients. In conclusion, SPION-guided sLND is a reliable alternative to eLND in intermediate-/high-risk PCa. No conclusions can be drawn from magnetic SLN activity regarding the presence of metastases. LND could be dispensed with according to a nomogram of predicted probability for LNI of 5% without losing any LN-positive patient. Patients with LNI risk between 5% and 20% could be spared eLND by performing sLND.
由于扩大淋巴结清扫术（eLND）发病率高且局限淋巴结清扫术（LND）检出率低，因此在前列腺癌（PCa）中实施了靶向前哨淋巴结清扫术（sLND）。随后，在前列腺内注射超顺磁性氧化铁纳米颗粒（SPIONs）后，利用磁共振成像（MRI）和磁力计进行非放射性前哨淋巴结（SLN）检测已成功应用于PCa。为验证该方法的可靠性，考虑到SLN的磁活性，以及是否像其他肿瘤实体的放射性引导sLND那样仅切除最活跃的SLN就足够了，我们分析了218例接受eLND的高危和中危PCa患者的磁力计引导sLND结果，并将其作为参考标准。使用前哨列线图预测淋巴结转移（LNI），确定了一个风险范围，在此范围内可以不进行LND或仅进行sLND就足够了。总共切除了3711个淋巴结，识别出1779个SLN（中位数为8个）。在78例淋巴结阳性患者中，有264处淋巴结转移（中位数为2处）。sLND的诊断率为96.79%，敏感性为88.16%，特异性为98.59%，阳性预测值（PPV）为97.1%，阴性预测值（NPV）为93.96%，假阴性率为4.13%，额外诊断价值为0.92%（仅在eLND模板外有淋巴结转移）。仅对于中危患者，敏感性、特异性、PPV和NPV均为100%。无论有无转移，SLN的磁活性都是异质性的。在高危患者中，根据活性比例预测每个淋巴结转移存在情况的准确率仅为57.3%，在中危患者中为65%。LNI风险低于5%的患者可以不进行LND，因为该组未发现阳性淋巴结。对于LNI风险在5%至20%之间的患者，仅进行sLND就足以检测几乎所有的淋巴结转移；因此，36%的患者可以不进行eLND。总之，在中/高危PCa中，SPION引导的sLND是eLND的可靠替代方法。从磁SLN活性无法得出关于转移存在与否的结论。根据预测LNI概率为5%的列线图可以不进行LND，而不会遗漏任何淋巴结阳性患者。LNI风险在5%至20%之间的患者通过进行sLND可以避免eLND。
