• Department of Obstetrics, Gynecology, and Women's Health, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA. Electronic address: kterada@ucera.org.
• Department of Obstetrics, Gynecology, and Women's Health, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.
• Biostatistics Core, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.

OBJECTIVE: To determine if an abnormal CA-125 level in a menopausal female without ovarian cancer is associated with an increase in mortality.

METHODS: The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Randomized Controlled (PLCO) Trial is a large multicenter prospective trial conducted by the National Cancer Institute (NCI). Over 78,000 healthy women aged 55-74 were randomized to a screening arm versus a usual medical care arm to evaluate the efficacy of screening in reducing mortality due to ovarian cancer. Women in the screening arm underwent annual screening for ovarian cancer with transvaginal ultrasound and CA-125 levels. There were 38,818 patients without ovarian cancer that had at least one CA-125 level drawn; 1201 (3.09%) had at least one abnormal level. The current study compares mortality in patients that had one or more abnormal CA-125 levels without ovarian cancer versus those with all normal levels.

RESULTS: Patients with one or more abnormal CA-125 levels, without ovarian cancer, had a significantly higher mortality than patients with all normal CA-125 levels in the PLCO screening trial (p<0.0001). This increased risk extended throughout the follow-up period. Analysis of cause of death listed on the death certificate showed an excess mortality attributable to lung cancer, digestive disease, and endocrine, nutritional, and metabolic disease.

CONCLUSION: Menopausal females with an elevated CA-125 and without ovarian cancer are exposed to an increased risk of premature mortality.