ESHRE workshop in Leuven 12 to 13 December 2024
There is no doubt that recent advances in sonographic imaging have allowed the diagnosis of endometriomas and deep endometriosis at anatomical locations with a degree of accuracy that was unfeasible a few years ago. Despite this, the diagnostic delay in endometriosis ranges from 5 to 12 years depending on the country.
In his presentation, Professor Vercellini from the University of Milan said the strongest risk factor for a diagnostic delay is early onset of the disease and of symptoms, most likely during adolescence. He stressed the importance of addressing this target group with educational material and initiatives to raise awareness, particularly among more vulnerable patients.
Data from recent studies show that endometriosis is highly prevalent among symptomatic girls and adolescents. The diagnostic delay is partly explained by the fact that doctors have wanted to avoid invasive procedures such as laparoscopy for surgical diagnosis in young people, despite this being considered the gold diagnostic standard until recently. Professor Vercellini said this was a particular issue in superficial peritoneal disease which cannot be identified with radiology.
However, a clinical diagnosis is possible, even in young women with pain symptoms associated with superficial peritoneal endometriosis. What doctors need to do is ask patients for their full medical history and that of their family; and carry out an accurate pelvic examination. A clinical diagnosis can be supported by a recently proposed algorithm and is sufficient for the start of empirical therapy (1).
In the second part of his talk, Professor Vercellini elaborated on the pros and cons of non-invasive diagnostic tests including the potential harms and opportunities. Stakeholders – including clinicians, scientists, the pharma sector and patients – often argue that there is a need to develop such a test, in particular for superficial peritoneal disease. Nevertheless, Professor Vercellini highlighted that if a test were available, its impact on the clinical management of the disease, the consequences at individual and community levels, and the financial aspects would have to be critically and meticulously considered.
One test is currently in the advanced translational research phase, not far off clinical implementation: the so-called saliva test for diagnosing endometriosis. Based on the presence of micro-RNAs in saliva, this test is commercially available and shows good performance based on initial investigations and one interim analysis from an ongoing multicentre study to confirm the external validity of the test (2).
Using the saliva test as an example, Professor Vercellini said that prior to the implementation of any diagnostic test, it is paramount that a consensus exists between experts in the event of abnormal test results. He described a scenario where a woman receives a positive test result but has no relevant symptoms. Should further care/surgery be offered to this woman? Another hypothetical case would be if there are obvious symptoms but the test is negative. Should this woman be excluded from further (surgical) care although she may be eligible for such care based on other clinical characteristics? Often, the impact of non-invasive tests on clinical practice is considerable such as the current saliva and other diagnostic tests developed for medical conditions other than endometriosis. But Professor Vercellini said their overall value, including cost-effectiveness, is often not evaluated sufficiently before they are marketed.
In addition, the saliva test can be purchased online in several countries. This direct-to-consumer way of offering a test is another major concern. Professor Vercellini said the fact a test can be purchased without medical prescription, and patients have already started presenting to gynaecologists and primary care with results in their hands (3), creates the risk that a diagnostic test is used for improper screening purposes. Inevitably, a screening test increases the prevalence of the disease and may lead to psychological burden which often creates unnecessary and increased anxiety among women.
Professor Vercellini supported his analysis with examples from other medical conditions, where direct-to-consumer tests have been used for a longer time and where this has raised significant concerns among experts who have highlighted the need to formulate strong position statements (4,5). Microbiome testing in gastroenterology, Covid-19, HIV, prostate health checks, thyroid function, and food sensitivity were among the tests referenced by Professor Vercellini.
In conclusion, the introduction of diagnostic tests should be preceded by proper evaluation of the consequences and the potential ability to improve clinical outcomes and patient care. A failure to do this can lead to the waste of individual and health care resources, and can even harm patients, due to overdiagnoses and consequently unnecessary treatments.
During his talk, Professor Vercellini did not focus on the technical/analytical validation of a potential diagnostic test. However, it is strongly recommended that test marketing takes place only after full technical and external validations; and following evidence-based assessment, preferably by means of a randomised controlled trial. Also, pressure from the various stakeholders is strong, as the marketing possibility of diagnostic tests is attractive and sales of various tests have surged in the last decades. In addition, patients want to get a diagnosis from their doctors and would welcome a diagnostic test for endometriosis. Therefore, regulatory bodies should control the whole process carefully, to allow a correct evaluation of these tools.
Professor Vercellini stressed that experts should not overemphasise the importance of identifying non-invasive biomarkers for a diagnostic test. A presumptive diagnosis of endometriosis can be made based on good family and personal medical history. And perhaps an effective way of using the available resources that has immediate impact on patient care is to allow doctors enough time to listen better to their patients and to provide adequate explanation and information during consultations.
References
1. Sanjay K Agarwal, Charles Chapron, Linda C Giudice, Marc R Laufer, Nicholas Leyland, Stacey A Missmer, Sukhbir S Singh, Hugh S Taylor. Clinical diagnosis of endometriosis: a call to action. Am J Obst Gynecol 2019 Apr;220(4):354.e1-354
2. Sofiane Bendifallah et al., Validation of a Salivary miRNA Signature of Endometriosis – Interim Data. NEJM Evid 2023 Jul;2(7):EVIDoa2200282
3. Simon M Scheck, Claire Henry, Nick Bedford, Jason Abbott, Michael Wynn-Williams, Anusch Yazdani, Simon McDowell. Non-invasive tests for endometriosis are here; how reliable are they, and what should we do with the results? Aust N Z J Obstet Gynaecol. 2024 Apr;64(2):168-170
4. Serena Porcari et al. International consensus statement on microbiome testing in clinical practice Lancet Gastroenterol Hepatol. 2024 Dec 5:S2468-1253(24)00311-X
5. Emma Grundtvig Gram, Tessa Copp, David F Ransohoff, Annette Plüddemann, Barnett S Kramer, Steven Woloshin, Patti Shih. Direct-to-consumer tests: emerging trends are cause for concern. BMJ 2024 BMJ. 2024 Dec 4;387:e080460
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