Department of Obstetrics and Gynecology, Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Department of Obstetrics and Gynecology, Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Gynecol Oncol. 2024 Feb;181:155-161. doi: 10.1016/j.ygyno.2023.12.021. Epub 2024 Jan 3.
To assess the prognostic value of human epididymis protein 4 (HE4) kinetics during and after neoadjuvant chemotherapy (NACT) cycles compared with cancer antigen 125 (CA-125), in predicting the surgical outcomes of interval debulking surgery (IDS) in patients with advanced-stage, high-grade serous ovarian cancer.
This retrospective cohort study was conducted at Severance Hospital in Seoul, South Korea and involved 123 women with high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who were diagnosed between April 2015 and July 2020. Three outcomes were considered: the chemotherapy response score (CRS) by omentum, residual disease after IDS, and recurrence. Other clinical, imaging, and biological parameters at baseline, during NACT cycles, and pre- and postoperative time were collected and analyzed.
We observed a substantial and gradual decrease in both CA-125 level (median from 1612 to 85.55 U/mL; p < 0.001) and HE4 level (514.7 to 87.7 pmol/L; p < 0.001) during NACT cycles, while pre-to-postoperative reduction was only significant for HE4 (median from 77.3 to 62.0 pmol/L (p < 0.001)). Of the total patients, 4.1% showed no response to NACT (chemoresistance) and 65.9% had a partial response. Residual disease was observed in 55 (44.7%) patients. Recurrence occurred in 90 patients (73.2%), with a median progression-free survival of 15.28 months. The percent reduction in CA-125 level- but not HE4 - during NACT was significantly associated with CRS (by omentum); the reduction in CA-125 during NACT cycles was higher when the CRS was found to be 3 and 2 (median = 96.4 [IQR = 8.3] and 93.7 [12.2] respectively) compared to score 1 (68.3 [34.1]), and the difference was statistically significant (p = 0.004). However, no significant association was observed between the percent reduction in CA-125 or HE4 levels during NACT and residual disease or recurrence. The normalization of HE4 - but not CA-125 - before surgery was predictive for surgery outcome; that is, an abnormal preop HE4 level was associated with a residual disease risk ratio of 2.72 (95% CI = 1.27-5.79).
Monitoring HE4 or CA-125 levels has low prognostic value in patients with advanced-stage, high-grade serous ovarian cancer who are treated with NACT followed by IDS. However, the preoperative level of the HE4 biomarker may be useful in identifying patients at higher risk for suboptimal cytoreductive surgery or who may require more extensive surgery. Further prospective studies are warranted to explore the prognostic utility of eventual combinations of clinical, radiological, and biological parameters, notably by using artificial intelligence-based models.
评估在接受新辅助化疗 (NACT) 期间和之后，人附睾蛋白 4 (HE4) 动力学与癌抗原 125 (CA-125) 相比，在预测高级别浆液性卵巢癌患者间隔减瘤手术 (IDS) 手术结果方面的预后价值。
这项回顾性队列研究在韩国首尔的 Severance 医院进行，共纳入 123 名被诊断为高级别浆液性上皮性卵巢癌、输卵管癌或原发性腹膜癌的患者，诊断时间为 2015 年 4 月至 2020 年 7 月。考虑了三种结局：网膜上的化疗反应评分 (CRS)、IDS 后残留疾病和复发。还收集和分析了基线、NACT 周期和术前及术后时间的其他临床、影像学和生物学参数。
我们观察到在 NACT 周期中，CA-125 水平（中位数从 1612 降至 85.55 U/mL；p < 0.001）和 HE4 水平（514.7 降至 87.7 pmol/L；p < 0.001）均有明显且逐渐下降，而术前至术后的降低仅对 HE4 有显著意义（中位数从 77.3 降至 62.0 pmol/L（p < 0.001））。在所有患者中，4.1%表现为对 NACT（耐药）无反应，65.9%有部分反应。55 例（44.7%）患者有残留疾病。90 例（73.2%）患者发生复发，无进展生存期中位数为 15.28 个月。NACT 期间 CA-125 水平的降低百分比——而非 HE4——与 CRS（通过网膜）显著相关；当 CRS 为 3 和 2 时（中位数分别为 96.4 [IQR=8.3] 和 93.7 [12.2]），NACT 期间 CA-125 水平的降低比 CRS 为 1 时（68.3 [34.1]）更高，差异具有统计学意义（p = 0.004）。然而，NACT 期间 CA-125 或 HE4 水平降低与残留疾病或复发之间没有显著相关性。HE4 在术前的正常化——而非 CA-125——对手术结果具有预测性；即术前 HE4 水平异常与残留疾病的风险比为 2.72（95%CI=1.27-5.79）。
监测高级别浆液性卵巢癌患者接受 NACT 后接受 IDS 治疗时的 CA-125 或 HE4 水平，预后价值较低。然而，HE4 生物标志物的术前水平可能有助于识别残留疾病风险较高或可能需要更广泛手术的患者。需要进一步的前瞻性研究来探讨临床、影像学和生物学参数的最终组合的预后实用性，特别是通过使用基于人工智能的模型。
