Goff BA et al. - An algorithm using symptom index (SI), CA-125, and HE4 was shown to predict cancer in women with pelvic masses. The triple screen has higher specificity and PPV than CA-125 alone, but similar sensitivity and NPV for predicting ovarian cancer.

Methods
218 women with pelvic masses referred to a gynecologic oncologic clinic had a triple screen consisting of a SI, CA-125 level, and a HE4 level.
The screeen was considered positive if at least 2 of the 3 markers were abnormal (positive SI, CA-125 greater than or equal to 35 U/mL, and HE4 greater than or equal to 140 pmol/L).

Results
66 patients had ovarian or fallopian tube cancer (97% epithelial), 124 had benign masses, 17 had borderline tumors, and 11 had metastatic disease. The SI, CA-125, and HE4 were positive in 87.9%, 74.2%, and 60.6% of ovarian cancer patients, respectively.
Of the 112 women with a positive SI 58 had ovarian cancer and 75 had non-benign masses.
By excluding borderline and metastatic cancers, the sensitivity of the triple screen was 79%, the specificity was 91%, the PPV was 83%, and the NPV was 89%.
CA-125 alone had a sensitivity, specificity, PPV, and NPV of 79%, 76%, 63%, and 87% respectively.
When only one of the three tests were abnormal, the sensitivity was 97%, but the specificity decreased to 50%.