Introduction
Materials and methods
Patients
Ovarian cancers n (%) | Benign diseases n (%) | |
---|---|---|
162 | 251 | |
Age | ||
Median | 59.7 (24–90) | 35 (18–88) |
Range | ||
Hormonal status | ||
Premenopausal | 38 (23.5) | 214 (85.3) |
Postmenopausal | 124 (76.5) | 37 (14.7) |
Age interval | ||
W1 ( <20 YO) | – | 38 (15.1) |
W2 (21–30) | 3 (1.9) | 55 (21.9) |
W3 (31–40) | 7 (4.3) | 73 (29.1) |
W4 (41–50) | 28 (17.3) | 48 (19.1) |
W5 (51–60) | 47 (29) | 22 (8.8) |
W6 (61–70) | 43 (26.5) | 10 (4) |
W7 (71–80) | 25 (15.4) | 4 (1.6) |
W8 (>81) | 9 (5.6) | 1 (0.4) |
Ovarian cancer histopathology | NA | |
Serous | 132 (81.5) | NA |
Mucinous | 9 (5.6) | NA |
Clear cell | 8 (4.9) | NA |
Endometrioid | 13 (8) | NA |
Oarian cancer FIGO stage | NA | |
Stages I and II | 54 (33.3) | NA |
Stages III and IV | 105 (64.7) | NA |
Ovarian cancer grade | NA | |
Grade 1 | 34 (21) | NA |
Grade 2 | 54 (33.3) | NA |
Grade 3 | 74 (45.7) | NA |
Benign tumor histopathology | ||
Endometriosis | NA | 120 (47.8) |
Teratoma | NA | 43 (17.1) |
Follicular cysts | NA | 33 (13.1) |
Paraovarian cysts | NA | 26 (10.4) |
Hemorrhagic cysts | NA | 28 (11.6) |
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%ROMA = exp(PI)/[1-exp(PI)]*100,
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PI = A + W(HE4)*ln(HE4) + W(CA125)*ln (CA125),
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Below 20 years old: A = −12; W(HE4) = 2.38; W(CA125) = 0.063,
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From 21 to 30 years old: A = −11.44; W(HE4) = 2.19; W(CA125) = 0.158,
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From 31 to 40 years old: A = −10.88; W(HE4) = 2; W(CA125) = 0.254,
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From 41 to 50 years old: A = −10.32; W(HE4) = 1.81; W(CA125) = 0.349,
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From 51 to 60 years old: A = −9.77; W(HE4) = 1.61; W(CA125) = 0.445,
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From 61 to 70 years old: A = −9.21; W(HE4) = 1.42; W(CA125) = 0.541,
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From 71 to 80 years old: A = −8.65; W(HE4) = 1.23; W(CA125) = 0.636,
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Above 80 years old: A = −8.09; W(HE4) = 1.04; W(CA125) = 0.732.
Laboratory methods
Statistical analysis
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Sensitivity = TP/TP + FN
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Specificity = TN/FP + TN
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Positive predictive value (PPV) = TP/TP + FP
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Negative predictive value (NPV) = TN/FN + TN
Results
Patient, biomarker, and algorithm baseline characteristics
CA125 (U/ml) | HE4 (pmol/l) | ROMA (%) | ROMA P (%) | p (ROMA vs. ROMA P) | |||||
---|---|---|---|---|---|---|---|---|---|
Median | Range | Median | Range | Median | Range | Median | Range | ||
Ovarian cancer (all) | 397.5 | 9–7459.1 | 340.7 | 12–9264 | 90.3 | 0.5–100 | 91.46 | 1.33–99.9 | 0.8641 |
Serous | 421.1 | 9–7459.1 | 390.7 | 15–9264 | 91.9 | 0.5–100 | 92.5 | 1.3–99.9 | 0.7963 |
Mucinous | 58.8 | 11.3–600 | 69.2 | 15–538 | 30.1 | 6.2–95.8 | 27.2 | 1.9–96.1 | 0.9699 |
Clear cell | 389.9 | 95.8–1725.5 | 184.8 | 49.5–849.9 | 81.5 | 8.1–98.2 | 73.7 | 15.6–98.3 | 0.9581 |
Endometrioid | 00 | 41.5–2996.8 | 340.7 | 46.1–1235 | 94.6 | 21–99.3 | 93.2 | 2.5–99.4 | 0.9591 |
FIGO stages I and II | 130.3 | 9–2347 | 79 | 15–1235 | 35.3 | 0.5–99.3 | 33.6 | 1.3–99.3 | 0.8610 |
FIGO stages III and IV | 591 | 18–7459.1 | 593.75 | 20.7–9264 | 96.8 | 9–100 | 97.1 | 10.1–99.9 | 0.6691 |
Grade 1 | 68.2 | 9–459.7 | 70.8 | 15–414.3 | 20.5 | 0.5–93.9 | 23.1 | 1.3–93.8 | 0.9087 |
Grade 2 | 420.1 | 14–7459.1 | 289.3 | 20.7–9264 | 88.5 | 8.4–100 | 88.9 | 10.1–99.9 | 0.0114 |
Grade 3 | 535.1 | 11.2–5109.8 | 569.8 | 20.4–8160 | 96.7 | 1–100 | 96.4 | 2.98–99.9 | 0.8963 |
Benign diseases (all) | 22.5 | 3.2–502.7 | 46.7 | 17.8–206.5 | 6.7 | 0.7–87 | 8.29 | 1.15–85.2 | 0.0001 |
Endometriosis | 45.5 | 6.7–377 | 45.2 | 17.8–86.7 | 6.6 | 0.7–35.34 | 9.1 | 1.2–26.16 | 0.2295 |
Teratoma tumors | 15.5 | 6.3–51.9 | 46.6 | 26.3–724 | 6.48 | 1.65–17.9 | 6.76 | 1.87–17.6 | 0.2835 |
Follicular cysts | 14.5 | 3.2–88 | 55.3 | 24.2–206.5 | 8.76 | 1.6–65.7 | 9.9 | 1.6–67.8 | 0.4886 |
Paraovarian cysts | 13.7 | 4.1–52.7 | 48.6 | 36.4–186.8 | 7.5 | 3.7–87 | 7.9 | 3.8–85.2 | 0.7075 |
Hemorrhagic cysts | 15.4 | 5.5–274.8 | 44.3 | 24.8–95.7 | 5.7 | 1.7–31.6 | 6.5 | 3.2–30.9 | 0.6522 |
AGE interval | |||||||||
W1 ovarian cancer group | – | – | – | – | – | – | – | – | – |
W2 ovarian cancer group | 55.2 | 27–135.1 | 45.4 | 44.1–103.9 | 6.2 | 6–35 | 7.5 | 7.1–37.7 | 0.3827 |
W3 ovarian cancer group | 403.6 | 98.1–1252 | 95.4 | 15–464.8 | 31.5 | 0.5–95.5 | 43.6 | 1.3–95.6 | 0.3619 |
W4 ovarian cancer group | 265.4 | 14–4638.8 | 92.9 | 15–1500 | 34.7 | 0.5–99.7 | 44.7 | 1.3–99.4 | 0.7743 |
W5 ovarian cancer group | 500 | 9–5887 | 439.3 | 12–1655 | 96.4 | 4.5–99.7 | 96.3 | 1.9–99.8 | 0.7883 |
W6 ovarian cancer group | 233.3 | 9.8–7459.1 | 334.5 | 22–9264 | 90.9 | 6–100 | 91.6 | 5.2–99.9 | 0.9786 |
W7 ovarian cancer group | 839 | 21–5659 | 658.4 | 37–8160 | 97 | 25–100 | 97.2 | 23.8–99.9 | 0.7710 |
W8 ovarian cancer group | 777.5 | 66.9–3724 | 871.2 | 85.8–4940 | 97.7 | 55.1–100 | 97.9 | 55.1–99.9 | 1.0000 |
W1 benign group | 16 | 4.1–274.8 | 41.5 | 24.2–84.7 | 6.2 | 1.56–22.1 | 6.4 | 1.56–22.1 | 0.9420 |
W2 benign group | 28.1 | 7.7–377 | 45.5 | 26.3–80.4 | 5.4 | 1.65–20.3 | 6.2 | 1.87–22.7 | 0.0913 |
W3 benign group | 32.3 | 7.1–191.5 | 47.3 | 31.7–86.7 | 7 | 2.6–24.1 | 9.2 | 3.2–26.2 | 0.9529 |
W4 benign group | 21.6 | 5.5–168.8 | 44.5 | 17.8–74.2 | 6 | 0.7–17.6 | 8.9 | 1.15–21.3 | 0.0079 |
W5 benign group | 12.4 | 3.2–82.1 | 48.5 | 27.5–85.1 | 6.9 | 1.8–35.3 | 8.4 | 4.4–23.4 | 0.6641 |
W6 benign group | 15.9 | 6.7–79.8 | 63.8 | 47.1–206.5 | 14.3 | 6.7–65.7 | 14.1 | 6.6–67.8 | 0.6232 |
W7 benign group | 9.55 | 6.3–52.7 | 69.5 | 52–186 | 9.7 | 7.3–87 | 9.7 | 7.6–85.2 | 1.0000 |
ROC curve analysis
Tumor marker | ROC-AUC (95 % CI) | Comparison of ROC-AUC | ||
---|---|---|---|---|
ROMA P vs. CA125 p value | ROMA P vs. HE4 p value | ROMA P vs. ROMA p value | ||
All ovarian cancer vs. benign ovarian diseases | ||||
ROMA | 0.934 | 0.4222 | 0.0004 | 0.1411 |
ROMA P | 0.923 | |||
HE4 | 0.881 | |||
CA125 | 0.910 | |||
Advanced ovarian cancers vs. benign ovarian diseases | ||||
ROMA | 0.995 | 0.0205 | 0.0778 | 0.7725 |
ROMA P | 0.994 | |||
HE4 | 0.982 | |||
CA125 | 0.969 | |||
Not-advanced ovarian cancers vs. benign ovarian diseases | ||||
ROMA | 0.820 | 0.7623 | 0.0013 | 0.1531 |
ROMA P | 0.794 | |||
HE4 | 0.691 | |||
CA125 | 0.808 | |||
All ovarian cancers vs. benign ovarian diseases—premenopausal patients | ||||
ROMA | 0.812 | 0.3393 | 0.0242 | 0.2049 |
ROMA P | 0.829 | |||
HE4 | 0.779 | |||
CA125 | 0.876 | |||
All ovarian cancers vs. benign ovarian diseases—postmenopausal patients | ||||
ROMA | 0.945 | 0.4277 | 0.0022 | 0.0495 |
ROMA P | 0.935 | |||
HE4 | 0.888 | |||
CA125 | 0.947 |
Age interval | Tumor marker | ROC-AUC (95 % CI) | Comparison of ROC-AUC | ||
---|---|---|---|---|---|
ROMA P vs. CA125 p value | ROMA P vs. HE4 p value | ROMA P vs. ROMA p value | |||
W2 | ROMA | 0.755 | 0.3862 | 0.7901 | 0.6745 |
ROMA P | 0.745 | ||||
HE4 | 0.739 | ||||
CA125 | 0.673 | ||||
W3 | ROMA | 0.675 | 0.0946 | 0.2646 | 0.2545 |
ROMA P | 0.703 | ||||
HE4 | 0.669 | ||||
CA125 | 0.982 | ||||
W4 | ROMA | 0.863 | 0.9539 | 0.0673 | 0.6745 |
ROMA P | 0.872 | ||||
HE4 | 0.826 | ||||
CA125 | 0.868 | ||||
W5 | ROMA | 0.955 | 0.3405 | 0.0321 | 0.069 |
ROMA P | 0.926 | ||||
HE4 | 0.864 | ||||
CA125 | 0.956 | ||||
W6 | ROMA | 0.908 | 0.3528 | 0.1221 | 0.1468 |
ROMA P | 0.895 | ||||
HE4 | 0.869 | ||||
CA125 | 0.923 | ||||
W7 | ROMA | 0.96 | 0.3472 | 0.3881 | 1 |
ROMA P | 0.96 | ||||
HE4 | 0.93 | ||||
CA125 | 0.9 |
Sensitivity, specificity, PPV, and NPV
Ovarian cancer vs. benign ovarian diseases | Sensitivity (%) | Specificity (%) | PPV (%) | NPV(%) | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
All | PM | M | All | PM | M | All | PM | M | All | PM | M | |
ROMA | 88.1 | 75.7 | 91.9 | 84.9 | 92.5 | 89.2 | 87.6 | 63.6 | 96.6 | 92.4 | 95.7 | 76.7 |
ROMA P | 85 | 64.9 | 91.1 | 98 | 99.1 | 91.9 | 96.5 | 92.3 | 97.4 | 84.8 | 94.2 | 75.6 |