Summary of findings 1. Biomarkers evaluated as a diagnostic test for endometriosis.

Review question	What is the diagnostic accuracy of the urinary biomarkers in detecting pelvic endometriosis [peritoneal endometriosis, endometrioma, DIE]?
Importance	A simple and reliable non‐invasive test for endometriosis, with the potential to either replace syrgery or to triage patients in order to reduce surgery, would minimise surgical risk and reduce diagnostic delay
Patients	Reproductive‐aged women 1) with suspected endometriosis or 2) with persistent ovarian mass or 3) undergoing infertility workup or gynaecological laparoscopy
Settings	Hospitals (public or private of any level): outpatient clinics (general gynaecology, reproductive medicine, pelvic pain); research laboratories
Reference standard	Visualisation of endometriosis at surgery (laparoscopy or laparotomy) with or without histological confirmation
Study design	Cross sectional studies with a 'single‐gate' design (n = 4) or a 'two‐gate' design (n = 1); prospective enrolment; a single study could assess more than one test
Risk of bias	Overall judgement: Poor quality of most of the studies (no study had a 'low risk' assessment in all 4 domains)
	Patient selection bias: High risk ‐ 1 study; Unclear risk ‐ 4 studies; Low risk ‐ 0 studies
	Index test interpretation bias: High risk ‐ 5 studies; Unclear risk ‐ 0 studies; Low risk ‐ 0 studies
	Reference standard interpretation bias: High risk ‐ 0 studies; Unclear risk ‐ 1 study; Low risk ‐ 4 studies
	Flow and timing selection bias: High risk ‐ 1 study; Unclear risk ‐ 0 studies; Low risk ‐ 4 studies
Applicability concerns	Concerns regarding patient selection: High concern ‐ 3 studies; Unclear concern ‐ 0 studies; Low concern 2 studies Concerns regarding index test: High concern ‐ 0 studies; Unclear concern ‐ 0 studies; Low concern ‐ 5 studies Concerns regarding reference standard: High concern ‐ 0 studies; Unclear concern ‐ 0 studies; Low concern ‐ 5 studies
Biomarker		N of studies; N of women	Outcomes				Diagnostic estimates [95% CI]	Implications
			True positives (endometriosis)	False negatives (incorrectly classified as disease‐free)	True negatives (disease‐free)	False positives (incorrectly classified as endometriosis)
NNE (enolase I) cut‐off > 0.96 ng/mgCr		1; 59	22	17	14	6	Sensitivity 0.56 [0.40, 0.72] Specificity 0.70 [0.46, 0.88]	Insufficient evidence to draw meaningful conclusions
VDBP cut‐off > 87.83 ng/mgCr		1; 95	33	24	21	17	Sensitivity 0.58 [0.44, 0.71] Specificity 0.55 [0.38, 0.71]	Insufficient evidence to draw meaningful conclusions
CK 19 [CYFRA21‐1] cut‐off > 5.3 ng/ml		1; 98	7	56	33	2	Sensitivity 0.11 [0.05, 0.22] Specificity 0.94 [0.81, 0.99]	Insufficient evidence to draw meaningful conclusions
Proteome: peptide m/z 1824.3 Da cut‐off ≥ 29.34 au		1; 28	10	3	11	4	Sensitivity 0.77 [0.46, 0.95] Specificity 0.73 [0.45, 0.92]	Insufficient evidence to draw meaningful conclusions
Proteome: peptide m/z 1767.1 Da cut‐off ≥ 35.22 au		1; 27	9	3	13	2	Sensitivity 0.75 [0.43, 0.95] Specificity 0.87 [0.60, 0.98]	Insufficient evidence to draw meaningful conclusions
Proteome: peptide m/z 2052.3 Da cut‐off not reported		1; 122	50	10	43	19	Sensitivity 0.83 [0.71, 0.92] Specificity 0.69 [0.56, 0.80]	Insufficient evidence to draw meaningful conclusions
Proteome: peptide m/z 3393.9 Da cut‐off not reported		1; 122	51	9	44	18	Sensitivity 0.85 [0.73, 0.93] Specificity 0.71 [0.58, 0.82]	Insufficient evidence to draw meaningful conclusions
Proteome: peptide m/z 1579.2 Da [collagen alpha 6(IV) chain precursor] cut‐off not reported		1; 122	50	10	43	19	Sensitivity 0.83 [0.71, 0.92] Specificity 0.69 [0.56, 0.80]	Insufficient evidence to draw meaningful conclusions
Proteome: peptide m/z 891.6 Da [collagen alpha1 chain precursor] cut‐off not reported		1; 122	49	11	40	22	Sensitiviy 0.82 [0.70, 0.90] Specificity 0.65 [0.51, 0.76]	Insufficient evidence to draw meaningful conclusions
Proteome: 5 peptides m/z 1433.9 + 1599.4 + 2085.6 + 6798.0 + 3217.2 Da cut‐off not reported		1; 25	10	1	13	1	Sensitivity 0.91 [0.59, 1.00] Specificity 0.93 [0.66, 1.00]	Insufficient evidence to draw meaningful conclusions Approaches criteria for a replacement test or SnOUT/SpIN triage tests; further diagnostic test accuracy studies recommended