Early Detection of Ovarian Cancer using the Risk of Ovarian Cancer Algorithm with Frequent CA125 Testing in Women at Increased Familial Risk - Combined Results from Two Screening Trials.
Early Detection of Ovarian Cancer using the Risk of Ovarian Cancer Algorithm with Frequent CA125 Testing in Women at Increased Familial Risk - Combined Results from Two Screening Trials.
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DOI：
10.1158/1078-0432.ccr-15-2750
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发表时间：
2017-07-15
期刊：
影响因子：
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通讯作者：
Lu KH
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作者：
Skates SJ;Greene MH;Buys SS;Mai PL;Brown P;Piedmonte M;Rodriguez G;Schorge JO;Sherman M;Daly MB;Rutherford T;Brewster WR;O'Malley DM;Partridge E;Boggess J;Drescher CW;Isaacs C;Berchuck A;Domchek S;Davidson SA;Edwards R;Elg SA;Wakeley K;Phillips KA;Armstrong D;Horowitz I;Fabian CJ;Walker J;Sluss PM;Welch W;Minasian L;Horick NK;Kasten CH;Nayfield S;Alberts D;Finkelstein DM;Lu KH
尽管疗效尚未得到证实，但具有家族性/遗传性卵巢癌风险的女性经常接受筛查。研究表明每个女性都有自己的 CA125 基线；高于此水平的显着增加可能比标准 6-12 个月 CA125>35U/mL 更早识别癌症。癌症遗传学网络和妇科肿瘤小组前瞻性试验的数据对 3,692 名具有明显乳腺癌/卵巢癌家族史或 BRCA1/2 突变的女性（13,080 个女性筛查年）进行了筛查，这些数据被结合起来评估一种新的筛查策略。具体来说，使用卵巢癌风险算法 (ROCA) 评估每三个月的血清 CA125，检测到每个受试者的基线显着增加，从而触发了经阴道超声检查。将特异性和 PPV 与一般人群筛查的水平（特异性 90%，PPV 10%）进行比较，并将检测阶段与历史高风险对照进行比较。超声转诊的特异性分别为 92% 和 90% (p=0.0001)，PPV 分别为 4.6% 和 10% (p>0.10)。 19 例恶性卵巢肿瘤中的 18 例（患病率 = 4，发病率 = 6，RRSO = 9）是通过筛查或降低风险的输卵管卵巢切除术 (RRSO) 检测到的。在事件病例中（最能反映长期筛查表现），3/6 的浸润性癌症为早期 (I/II)（50% 与 10% 历史 BRCA1 对照；p=0.016）。 9 例 RRSO 相关病例中有 6 例处于 I 期。ROCA 在 CA125 超过 35U/mL 之前标记了 3/6 (50%) 的事件病例。 9 名 0/I/II 期卵巢癌患者中有 8 名在最后一次随访时存活（中位时间 6 年）。对于有家族性/遗传性卵巢癌风险的筛查女性，与 CA125>35 U/mL q6/q12 个月相比，ROCA q3 个月在高特异性下具有更好的早期敏感性和较低但可能可接受的 PPV，因此需要进一步进行更大规模的队列评估。
Women at familial/genetic ovarian cancer risk often undergo screening despite unproven efficacy. Research suggests each woman has her own CA125 baseline; significant increases above this level may identify cancers earlier than standard 6–12 monthly CA125>35U/mL. Data from prospective Cancer Genetics Network and Gynecologic Oncology Group trials, which screened 3,692 women (13,080 woman-screening years) with a strong breast/ovarian cancer family history or BRCA1/2 mutations, were combined to assess a novel screening strategy. Specifically, serum CA125 q3 months, evaluated using a risk of ovarian cancer algorithm (ROCA), detected significant increases above each subject’s baseline, which triggered transvaginal ultrasound. Specificity and PPV were compared with levels derived from general population screening (specificity 90%, PPV 10%), and stage-at-detection was compared with historical high-risk controls. Specificity for ultrasound referral was 92% vs. 90% (p=0.0001), and PPV was 4.6% vs. 10% (p>0.10). Eighteen of 19 malignant ovarian neoplasms (prevalent=4, incident=6, RRSO=9) were detected via screening or risk-reducing salpingo-oophorectomy (RRSO). Amongst incident cases (which best reflect long-term screening performance), 3/6 invasive cancers were early-stage (I/II) (50% versus 10% historical BRCA1 controls; p=0.016). Six of 9 RRSO-related cases were stage I. ROCA flagged 3/6 (50%) incident cases before CA125 exceeded 35U/mL. Eight of 9 stages 0/I/II ovarian cancer patients were alive at last follow-up (median 6 years). For screened women at familial/genetic ovarian cancer risk, ROCA q3 months had better early-stage sensitivity at high specificity, and low yet possibly acceptable PPV compared with CA125>35 U/mL q6/q12 months, warranting further larger cohort evaluation.