domingo, 12 de febrero de 2017

Early Detection of Ovarian Cancer using the Risk of Ovarian Cancer Algorithm with Frequent CA125 Testing in Women at Increased Familial Risk - Comb... - PubMed - NCBI

2017 Jan 31. pii: clincanres.2750.2015. doi: 10.1158/1078-0432.CCR-15-2750. [Epub ahead of print]

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.

Skates SJ1, Greene MH2, Buys SS3, Mai PL4, Brown PH5, Piedmonte M6, Rodriguez GC7, Schorge JO8, Sherman M9, Daly MB10, Rutherford TJ11, Brewster WR12, O'Malley DM13, Partridge EE14, Boggess J15, Drescher CW16, Isaacs C17, Berchuck A18, Domchek SM19, Davidson SA20, Edwards RP21, Elg SA22, Wakeley K23, Phillips KA24, Armstrong DK25, Horowitz IR26, Fabian CJ27, Walker J28, Sluss PM29, Welch WR30, Minasian L31, Horick N32, Kasten CH33, Nayfield S34, Alberts DS35, Finkelstein DM36, Lu K37.

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Abstract

PURPOSE:

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.

EXPERIMENTAL DESIGN:

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.

RESULTS:

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).

CONCLUSIONS:

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.