Use of CA125 and HE4 serum markers to predict ovarian cancer in elevated-risk women.

Publication Type:

Journal Article


Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (2014)


2014, May 2014, Public Health Sciences Division


Background. Serum markers are used prior to pelvic imaging to improve specificity and positive predictive value (PPV) of ovarian cancer multimodal screening strategies. Methods. We conducted a randomized controlled pilot trial to estimate surgical PPV of a "2 of 3 tests positive" screening rule, and to compare use of HE4 as a 1st-line (Arm 1) vs. a 2nd-line (Arm 2) screen, in women at high and elevated risk for EOC at five study sites. Semi-annual screening was offered to 208 women aged 25-80 with deleterious BRCA germ-line mutations, and to 834 women aged 35-80 with pedigrees suggesting inherited susceptibility. Annual screening was offered to 130 women aged 45-80 (Risk Group 3) with epidemiologic and serum marker risk factors. Rising marker levels were identified using the parametric empirical Bayes algorithm. Results. Both strategies yielded surgical PPV above 25%. Protocol-indicated surgery was performed in six women, identifying two ovarian malignancies and yielding a surgical PPV in both arms combined of 33% (95% CI: 4%-78%), 25% in Arm 1 and 50% in Arm 2. Surgical consultation was recommended for 37 women (26 in Arm 1, 11 in Arm 2). Based on 12 women with at least 2 of 3 tests positive (CA125, HE4 or imaging), an intent-to-treat analysis yielded PPV of 14% in Arm 1 and 20% in Arm 2. Conclusions. Positive screens were more frequent when HE4 was included in the primary screen. Impact. HE4 may be useful as a confirmatory screen when rising CA125 is used alone as a primary screen.