National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, Australia.
Australia New Zealand Gynecological Oncology Group, Camperdown, Australia.
J Clin Oncol. 2024 Apr 10;42(11):1301-1310. doi: 10.1200/JCO.23.01182. Epub 2024 Jan 12.
Cancer antigen-125 (CA-125) is recommended by treatment guidelines and widely used to diagnose ovarian cancer recurrence. The value of CA-125 as a surrogate for disease progression (PD) and its concordance with radiologic progression are unclear, particularly for women with platinum-sensitive relapsed ovarian cancer (PSROC) who have responded to chemotherapy and treated with maintenance poly(ADP-ribose) polymerase inhibitor (PARPi).
In this pooled analysis of four randomized trials of maintenance PARPi or placebo (Study 19, SOLO2, ARIEL3, and NOVA), we extracted data on CA-125 PD as defined by Gynecologic Cancer InterGroup criteria and RECIST v1.1. We evaluated the concordance between CA-125 and RECIST PD and reported on the negative predictive value (NPV) and positive predictive value (PPV).
Of 1,262 participants (n = 818 PARPi, n = 444 placebo), 403 (32%) had CA-125 PD, and of these, 366 had concordant RECIST PD (PPV, 91% [95% CI, 88 to 93]). However, of 859 (68%) without CA-125 PD, 382 also did not have RECIST PD (NPV, 44% [95% CI, 41 to 48]). Within the treatment arms, PPV remained high (PARPi, 91% [95% CI, 86 to 94]; placebo, 91% [95% CI, 86 to 95]) but NPV was lower on placebo (PARPi, 53% [95% CI, 49 to 57]; placebo, 25% [95% CI, 20 to 31]). Of 477 with RECIST-only PD, most (95%) had a normal CA-125 at the start of maintenance therapy and the majority (n = 304, 64%) had CA-125 that remained within normal range. Solid organ recurrence without peritoneal disease was more common in those with RECIST-only PD than in those with CA-125 and RECIST PD (36% 24%; < .001).
In patients with PSROC treated with maintenance PARPi, almost half with RECIST PD did not have CA-125 PD, challenging current guidelines. Periodic computed tomography imaging should be considered as part of surveillance, particularly in those with a normal CA-125 at the start of maintenance therapy and on treatment.
癌症抗原 125（CA-125）被治疗指南推荐用于诊断卵巢癌复发，应用广泛。CA-125 作为疾病进展（PD）替代标志物的价值及其与影像学进展的一致性尚不清楚，尤其是对于铂类敏感复发性卵巢癌（PSROC）患者，他们已经接受了化疗，并接受了维持性聚（ADP-核糖）聚合酶抑制剂（PARPi）治疗。
本研究对四项维持性 PARPi 或安慰剂治疗的随机试验（Study 19、SOLO2、ARIEL3 和 NOVA）进行了汇总分析，我们提取了根据妇科肿瘤学团体标准和 RECIST v1.1 定义的 CA-125 PD 数据。我们评估了 CA-125 和 RECIST PD 的一致性，并报告了阴性预测值（NPV）和阳性预测值（PPV）。
在 1262 名参与者（n = 818 例 PARPi，n = 444 例安慰剂）中，有 403 名（32%）出现 CA-125 PD，其中 366 名（PPV，91% [95%CI，88% 至 93%]）与 RECIST PD 一致。然而，在 859 名（68%）无 CA-125 PD 的患者中，有 382 名（NPV，44% [95%CI，41% 至 48%]）也没有 RECIST PD。在治疗组中，PPV 仍然很高（PARPi，91% [95%CI，86% 至 94%]；安慰剂，91% [95%CI，86% 至 95%]），但安慰剂的 NPV 较低（PARPi，53% [95%CI，49% 至 57%]；安慰剂，25% [95%CI，20% 至 31%]）。在 477 名仅有 RECIST PD 的患者中，大多数（95%）在维持治疗开始时 CA-125 正常，大多数（n = 304，64%）CA-125 仍在正常范围内。与有 CA-125 和 RECIST PD 的患者相比，仅有 RECIST PD 的患者中更常见无腹膜疾病的实体器官复发（36%比 24%；<.001）。
在接受 PARPi 维持治疗的 PSROC 患者中，几乎一半有 RECIST PD 的患者没有 CA-125 PD，这对当前指南提出了挑战。定期进行计算机断层扫描成像应作为监测的一部分，尤其是在开始维持治疗时 CA-125 正常且正在治疗中的患者。
