External validation of the O-RADS MRI risk stratification system and the clinicopathological characteristics of EOTs

The distributions of O-RADS MRI risk scores and clinicopathological characteristics among BeEOTs, BEOTs and MEOTs are shown in Table 1. Among 54 BeEOTs, a higher proportion were classified as O-RADS MRI 3 compared to O-RADS MRI 2 (66.67% vs. 29.63%), and O-RADS MRI scores of 4 and 5 each accounted for 1.85% (1/54). The risk stratification of BEOTs also ranged from O-RADS MRI 2 to 5. Of 104 BEOTs, 1 (0.96%), 53 (50.96%), 40 (38.46%), and 10 (9.62%) were classified as O-RADS MRI 2/3/4/5, respectively. 86.2% (175/203) MEOTs scored 4/5, whereas 13.8% (28/203) scored 3. No risk score of 2 was assigned to any of the MEOTs.

Table 1 O-RADS MRI scores and clinicopathological characteristics of 361 EOTs

68.52% (37/54) of BeEOTs and 82.69% (86/104) of BEOTs enrolled were premenopausal, whereas postmenopausal patients accounted for the majority of MEOTs (53.2%, 108/203). Serous, mucinous, serous-mucinous, and relatively rare endometrioid types were enrolled in BeEOTs and BEOTs. Serous (60.1%, 122/203), mucinous (7.39%, 15/203), endometrioid (13.79%, 28/203), clear cell (16.26%, 33/203), serous-mucinous (1.48%, 3/203) types were the main components of MEOTs. In addition, 1 malignant ovarian Brenner tumor and 1 ovarian carcinosarcoma were also enrolled into the MEOT group.

Of 203 MEOTs, 102 (50.25%) were in the early group (FIGO stage I-II), and 101 (49.75%) were in the advanced group (FIGO stage III-IV); the proportions of the two groups were nearly equal. Among MEOTs, the risk score of O-RADS MRI 5 was more prevalent in the advanced group (62.38%) whereas O-RADS MRI 4 was more prevalent in early group (61.76%), and the proportion of O-RADS MRI 3 in the early group was slightly higher than that in the advanced group (15.69% vs. 11.88%). Of 104 BEOTs, 87 (83.65%) were diagnosed at an early stage (FIGO stage I), whereas 17 (16.35%) were diagnosed at an advanced stage (FIGO stage II-IV).

Fig. 1

Flowchart of inclusion and exclusion

CA125 aids in screening MEOTs from EOTs with low-risk TICs in the O-RADS MRI 3 category

The MRI features of EOTs scored 3 and representative images of solid tissue with a low-risk TIC are shown in Table 2 and Supplementary Data 1, respectively. Only 1 (3.57%) of 28 MEOTs and 1 (1.89%) of 53 BEOTs assigned as O-RADS MRI 3 did not have solid tissue with a low-risk TIC. However, the prevalence of BeEOTs having solid tissue with a low-risk TIC in the O-RADS MRI 3 category was 16.67% (6/36), with a much lower rate than BEOTs and MEOTs (both P < 0.0001).

Table 2 MRI features of EOTs classified as O-RADS MRI 3

As shown in Table 3, among EOTs scored as O-RADS MRI 3, premenopausal MEOTs tended to have a higher ROMA index than premenopausal BEOTs did (P = 0.0012). However, no significant difference in the ROMA index was found between postmenopausal MEOTs and postmenopausal BEOTs (P = 0.3403). However, CA125 demonstrated a notable gradient variation among BeEOTs, BEOTs, and MEOTs classified as O-RADS MRI 3 (P = 0.0001). The AUC, cut-off value, sensitivity, and specificity of CA125 for distinguishing MEOTs from BeEOTs and BEOTs with a low-risk TIC were 0.7466, 60.39 U/ml, 70.37% and 80.7%, respectively (Supplementary Data 3).

Table 3 Differences in tumor biomarkers of EOTs among the O-RADS MRI 3, 4, and 5 categories

Among EOTs with a low-risk TIC but a CA125 level lower than 60.39 U/ml (subgroup 1), 87.5% (7/8) MEOTs were at FIGO stage I, and 12.5% (1/8) MEOT was at FIGO stage II, 62.5% (5/8) had normal CA125, HE4, and ROMA index levels (Table 4, Supplementary Data 2). 95% (38/40) BEOTs were at FIGO stage I. Among EOTs with a low-risk TIC and CA125 ≥ 60.39 U/ml in the O-RADS MRI 3 category (subgroup 2) (Table 4), no BeEOTs were included, 33.33% (4/12) BEOTs were at advanced FIGO stage (II-IV) and 63.16% (12/19) MEOTs were at advanced FIGO stage (III-IV).

Table 4 The distribution of FIGO stages in six subgroups of EOTs, stratified by O-RADS MRI, CA125 levels, or the ROMA indexThe ROMA index facilitates distinguishing between BEOTs and MEOTs of O-RADS MRI 4/5

48.08% BEOTs and 86.2% MEOTs were assigned a risk score of 4/5, but it remains challenging to distinguish them using O-RADS MRI system alone. The premenopausal ROMA index and CA125 level were both significantly higher in MEOTs than in BEOTs within the O-RADS MRI 4 and 5 categories (Table 3). The premenopausal ROMA index had a better application value than CA125 in distinguishing BEOTs and MEOTs in terms of sensitivity and specificity, although no meaningful distinctions were observed in the AUC (P = 0.2783), and the optimal cut-off value was 20.14% (Supplementary Data 3). Among premenopausal EOTs classified as O-RADS MRI 4/5 with a ROMA index below 20.14% (subgroup 3), 62.5% (10/16) and 25.0% (4/16) MEOTs were at FIGO stage I and II, respectively. 81.4% (35/43) BEOTs were at FIGO stage I-II. Two BeEOTs were also included in subgroup 3 (Table 4, Supplementary Data 2). Among premenopausal EOTs classified as O-RADS MRI 4/5 with a ROMA index higher than 20.14% (subgroup 4), 57.38% (35/61) MEOTs and 66.67% (2/3) BEOTs were at FIGO stage III, respectively. No BeEOTs were included in subgroup 4 (Table 4, Supplementary Data 2).

Considering the low incidence of postmenopausal BEOTs with O-RADS MRI 4/5, a ROMA index ≥ 29.9% (postmenopausal), representing a high risk for ovarian cancer in clinical practice, was selected as the cut-off value; the corresponding sensitivity and specificity were 82.47% and 100%, respectively. Among postmenopausal EOTs scoring 4/5 with a ROMA index below 29.9% (subgroup 5), 76.92% (10/13) and 7.69% (1/13) MEOTs were at FIGO stage I and II, respectively. All 4 BEOTs were at FIGO stage I, and no BeEOTs were included (Table 4, Supplementary Data 2). Among postmenopausal EOTs scoring 4/5 with a ROMA index higher than 29.9% (subgroup 6), 58.82% (50/85) MEOTs were at FIGO stage III-IV. No BeEOTs or BEOTs were included (Table 4, Supplementary Data 2).