Blood Biomarkers for the Non-Invasive Diagnosis of Endometriosis

Summary

A Cochrane review [Abstract] 1 included 141 studies with a total of 15 141 subjects evaluated 122 blood biomarkers. Included women were a selected population with a high frequency of endometriosis (10% to 85%), in which surgery was indicated. Laparoscopy is the gold standard diagnostic test for endometriosis. The predetermined criteria for a clinically useful blood test to replace diagnostic surgery were a sensitivity (Sn) of 0.94 and a specificity (Sp) of 0.79 to detect endometriosis. The criteria for triage tests were a sensitivity of 0.95 or over and a specificity of 0.50 or over, which 'rules out' the diagnosis with high accuracy if there is a negative test result (SnOUT test), or a sensitivity of 0.50 or over and a specificity of 0.95 or over, which 'rules in' the diagnosis with high accuracy if there is a positive result (SpIN test).

For anti-endometrial antibodies (4 studies, n=759) the mean Sn was 0.81 (95% CI 0.76 to 0.87) and Sp 0.75 (95% CI 0.46 to 1.00). For Interleukin-6, with a cut-off value of over 1.90 to 2.00 pg/ml (3 studies, n=309), Sn was 0.63 (95% CI 0.52 to 0.75) and Sp was 0.69 (95% CI 0.57 to 0.82). For CA-19.9, with a cut-off value of over 37.0 IU/ml (3 studies, n=330 women), Sn was 0.36 (95% CI 0.26 to 0.45) and Sp was 0.87 (95% CI 0.75 to 0.99).

Studies assessed CA-125 at different thresholds, demonstrating the following mean Sn and Sp for cut-off over 16.0 to 17.6 U/ml: 0.56 (95% CI 0.24, 0.88) and 0.91 (95% CI 0.75, 1.00); cut-off over 20.0 U/ml: 0.67 (95% CI 0.50 to 0.85) and 0.69 (95% CI 0.58 to 0.80); cut-off over 30.0 to 33.0 U/ml: 0.62 (95% CI 0.45 to 0.79) and 0.76 (95% CI 0.53 to 1.00); cut-off > 35.0 to 36.0 U/ml: 0.40 (95% CI 0.32 to 0.49) and 0.91 (95% CI 0.88 to 0.94).

A meta-analysis 2 assessing the diagnostic accuracy of serum CA 125 included 22 studies (16 cohort, 6 case-control) with 3626 participants. Bivariate hierarchical models were used to pool accuracy data of 14 studies (2920 participants) using CA 125 ≥ 30 units/ml. Pooled specificity was 93% (95% CI 89 to 95%) and sensitivity 52% (95% CI 38 to 66%). CA 125 was significantly more sensitive for the diagnosis of moderate or severe endometriosis compared with minimal disease (63%, 95% CI 47 to 77% versus 24%, 95%CI 19 to 32%, P-value = 0.001). The authors conclude that serum CA 125 could be used for a rule-in test for the diagnosis of women presenting with symptoms of endometriosis.