Diagnosing endometriosis: CA125 rules in, but not out

Endometriosis is a common estrogen-dependent disease that has a deleterious effect upon women's social functioning, emotional well-being, vitality, employment and relationships with medical practitioners. Diagnosis of endometriosis remains a challenge that is achieved by an invasive operative procedure, typically laparoscopy. Unfortunately, diagnostic delays of several years are common for women with endometriosis. For this reason, expert international panels report that identification of a clinically useful, non-invasive marker of endometriosis (Rogers et al. Reprod Sci 2013;20:483–99) or panel of markers remains an urgent unmet need. Many clinical markers have been examined for their potential predictive value in the diagnosis of endometriosis. Sadly, all lack adequate predictive value to be clinically useful (May et al. Hum Reprod 2011;17:637–53). In their study, Hirsch et al. (BJOG 2016;123:1761–8) describe a systematic review of the literature on the use of CA125 as a clinical marker of endometriosis. They report that CA125, with a cut-off of ≥ 30 units/ml, has a sensitivity and specificity of 0.52 and 0.93, respectively. From these results, they propose that CA125 can be used to ‘rule in’ the diagnosis of endometriosis but cannot be used to exclude such a diagnosis. Furthermore, it is suggested that a positive CA125 test result could be used to initiate treatment. Although presumptive treatment is reasonable, there is a down side, which is the cost to the patient that does not have endometriosis but is treated as if she does. Moreover, it is noted that, to ‘rule in’ the diagnosis of endometriosis, a clinical marker must have a sensitivity and specificity of ≥ 0.50 and ≥ 0.95, respectively (Nisenblat et al. Cochrane Database Syst Rev 2016;5:CD012179). The proposal put forward by Hirsch et al. therefore almost meets with this criterion. In contrast, to ‘rule out’ the diagnosis of endometriosis, Nisenblat et al. suggest a sensitivity of ≥ 0.95 and specificity of ≥ 0.50. Hence, based on the data from Hirsch et al., CA125 may have some value as a triage test to ‘rule in’ endometriosis. That endometriosis is a heterogeneous disease with multiple clinical presentations, lesion types and biochemical characteristics cannot be overstated. Therefore, moving forward, it may be necessary to evaluate CA125 together with other clinical markers to enhance the specificity of a ‘rule in’ test of endometriosis. Although no panel currently meets the Cochrane ‘rule in’ criteria, advances in the identification of clinical markers will have important implications for the more timely diagnosis of endometriosis, potentially obviating the need for surgical diagnosis. Novel clinical markers of endometriosis will not only have value as diagnostic tools but also have the potential to provide insight into patient response to treatment. Moreover, development of novel therapeutic interventions will be enhanced if clinical markers can reliably predict the presence or absence of disease without a surgical diagnosis of endometriosis. Full disclosure of interests available to view online as supporting information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.