MELBOURNE – Measurement of the human epididymis protein 4 (HE4) tumor marker in women presenting with elevated cancer antigen 125 may improve the specificity of testing and help guide referral and management decisions, an investigator reported at the biennial meeting of the International Gynecologic Cancer Society.
Dr. Nithya Ratnavelu, subspeciality fellow at the Northern Gynaecological Oncology Centre in Gateshead, England, presented data from a prospective pilot study which showed the inclusion of HE4 measurement at the time of cancer antigen 125 (CA 125) measurement improved the specificity and positive predictive value of testing.
Bianca Nogrady/Frontline Medical News
Dr. Nithya Ratnavelu
The study involved 601 women presenting to primary care with vague abdominal symptoms, such as pelvic mass, abdominal pain, bloating, nausea, vomiting, or weight loss, who then had both their CA 125 and HE4 levels tested.
Women with abnormal CA 125 or HE4 were then referred for pelvic ultrasound, which identified two cases of ovarian cancer, both in postmenopausal women with elevated CA 125 and HE4.
The inclusion of HE4 at the time of CA 125 testing improved the specificity of testing from 95% with CA 125 alone to 98.6%, and the positive predictive value from 6.25% with CA 125 alone to 20% with the combined tests.
A total of fifty women presented with elevated HE4 levels, and ten of these also had abnormal CA 125. No cancers were found among the 40 women with elevated HE4 but normal CA 125, and doctors diagnosed one cecal tumor and one endometrial cancer in the 22 women with elevated CA 125 but normal HE4.
HE4 is a protease inhibitor that is overexpressed in certain histologies including ovarian, endometrial, respiratory, and renal cancers, Dr. Ratnavelu said, and was one of the more frequently investigated tumor markers in ovarian cancer.
While there were only two ovarian cancers found in the study, Dr. Ratnavelu said she had found the HE4 marker useful in her clinical practice.
“We have actually started using it clinically, and in a woman with maybe a slightly raised CA 125, with quite a small pelvic mass, to say instead of a big midline laparotomy, should we maybe just do laparoscopic surgery if your HE4 and ROMA score suggest it’s probably benign,” Dr. Ratnavelu said in an interview.
Another example she gave was of a premenopausal woman with bilateral ovarian cysts and a very high CA 125 but normal HE4, who turned out to have endometriosis rather than ovarian cancer.
“There is the potential here to aid management for community referrals,” Dr. Ratnavelu told the conference.
“Obviously, this is a pilot study, and to draw firm conclusions, further prospective multicenter studies are warranted.
In addition, a poster presented at the conference showed that an algorithm incorporating both HE4 and CA 125 measurements could be used to identify higher-risk patients with newly diagnosed endometrial cancer who were more likely to benefit from referral to specialist gynecologic oncologist services.
When they used cutoff points of a CA 125 greater than 35U/mL and/or an HE4 measurement greater than 111 pm, researchers found the odds of patients having deep myometrial invasion were 11.7 times higher among those with a positive test, compared with a negative test (95% confidence interval, 3.4-39.5; P < .001).
Similarly, patients who met those same cut-offs and had a high body mass index were 8.7 times more likely to require specialized treatment, compared with the negative population (95% CI, 3.7-20.5; P < .001), according to the retrospective cohort study in 200 patients surgically treated for endometrial cancer.
“Using an algorithm to triage higher-risk endometrial cancer patients to specialized centers could contribute to standardizing referral practices, optimizing the use of healthcare resources while improving oncologic outcomes, and overall quality of patient care,” wrote Dr. Eleftheria Kalogera and colleagues from the Mayo Clinic.
Dr. Ratnavelu declared travel expenses from Roche UK. There were no other conflicts of interest declared.