Preoperative CA125 Significantly Improves Risk Stratification in High-Grade Endometrial Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Cohort
2.2. Data Collection
2.3. Statistical Analysis
3. Results
3.1. Study Cohort
3.2. CA125 in Relation to Extra-Uterine Disease and LNM
3.3. Imaging in Relation to Extra-Uterine Disease and LNM
3.4. CA125 and CT Results in Relation to LNM
3.5. CA125 in Relation to Outcome
4. Discussion
4.1. Summary of Main Results
4.2. Results in the Context of Published Literature
4.3. Strengths and Weaknesses
4.4. Implications for Practice and Future Research
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Surgical LN Staging (n = 193) | No Surgical LN Staging (n = 140) | ||||||||
---|---|---|---|---|---|---|---|---|---|
Total (n = 193) | CA125 <35 U/mL (n = 125) | CA125 >35 U/mL (n = 68) | p Value | Total (n = 140) | CA125 <35 U/mL (n = 61) | CA125 >35 U/mL (n = 79) | p Value | ||
Age (years) | 66 (35–83) | 66 (35–83) | 66 (44–82) | 0.477 | 72 (48–93) | 74 (48–91) | 71 (51–93) | 0.234 | |
BMI (kg/m2) | 26.8 (17.6–56.0) | 26.8 (17.6–56.0) | 28.2 (18.0–42.6) | 0.750 | 28.2 (16.4–49.5) | 27.9 (19.5–47.8) | 29.1 (16.4–49.5) | 0.486 | |
Imaging modality | CT | 145 (86.3) | 94 (84.7) | 51 (89.5) | 0.393 | 69 (69.7) | 30 (55.6) | 39 (86.7) | <0.001 |
MRI | 10 (12.0) | 8 (15.4) | 2 (8.0) | 0.485 | 4 (16.0) | 3 (18.8) | 1 (11.1) | 1 | |
CT results | No extra-uterine disease | 101 (69.7) | 77 (81.9) | 24 (47.1) | <0.001 | 43 (62.3) | 22 (73.3) | 21 (53.8) | 0.052 |
Suspected LNM with or without suspected distant metastasis | 28 (19.3) | 9 (9.6) | 19 (37.3) | 11 (15.9) | 6 (20.0) | 5 (12.8) | |||
Suspected distant metastasis without suspected LNM | 5 (3.4) | 2 (2.1) | 3 (5.9) | 14 (20.3) | 2 (6.7) | 12 (30.8) | |||
Inconclusive | 11 (7.6) | 6 (6.4) | 5 (9.8) | 1 (1.4) | 0 (0.0) | 1 (2.6) | |||
FIGO stage a | IA | 69 (35.8) | 59 (47.2) | 10 (14.7) | <0.001 | 32 (22.5) | 25 (41.0) | 7 (8.9) | <0.001 |
IB | 40 (20.7) | 30 (24.0) | 10 (14.7) | 36 (25.7) | 22 (36.1) | 14 (17.7) | |||
II | 17 (8.8) | 10 (8.0) | 7 (10.3) | 10 (7.1) | 5 (8.2) | 5 (6.3) | |||
IIIA | 7 (3.6) | 5 (4.0) | 2 (2.9) | 12 (8.6) | 3 (4.9) | 9 (11.4) | |||
IIIB | 1 (0.5) | 1 (0.8) | 0 (0.0) | 5 (3.6) | 1 (1.6) | 4 (5.1) | |||
IIIC1-2 | 40 (20.7) | 17 (13.6) | 23 (33.8) | 3 (2.1) | 0 (0.0) | 3 (3.8) | |||
IVA | 1 (0.5) | 1(0.8) | 0 (0.0) | 7 (5.0) | 1 (1.6) | 6 (7.6) | |||
IVB | 18 (9.3) | 2 (1.6) | 16 (23.5) | 37 (25.0) | 4 (6.6) | 31 (39.2) | |||
Tumor grade a | 1 | 3 (1.6) | 0 (0.0) | 3 (4.4) | 0.020 | 6 (4.3) | 5 (8.3) | 1 (1.3) | 0.040 |
2 | 12 (6.2) | 10 (8.0) | 2 (2.9) | 4 (2.9) | 3 (5.0) | 1 (1.3) | |||
3 | 178 (92.2) | 115 (92.0) | 63 (92.6) | 129 (92.8) | 52 (86.7) | 77 (97.5) | |||
Total (n = 193) | CA125 <35 U/mL (n = 125) | CA125 >35 U/mL (n = 68) | p value | Total (n = 140) | CA125 <35 U/mL (n = 61) | CA125 >35 U/mL (n = 79) | p value | ||
Histology a | Endometrioid | 80 (41.5) | 54 (43.2) | 26 (38.2) | 0.480 | 56 (40.0) | 38 (62.3) | 18 (22.8) | <0.001 |
Serous | 89 (46.1) | 53 (42.4) | 36 (52.9) | 74 (52.9) | 19 (31.1) | 55 (69.6) | |||
Clear cell | 9 (4.7) | 7 (5.6) | 2 (2.9) | 1 (0.7) | 1 (1.6) | 0 (0.0) | |||
Other | 15 (7.8) | 11 (8.8) | 4 (5.9) | 9 (6.4) | 3 (4.9) | 6 (7.6) | |||
MI a | <50% | 94 (48.7) | 70 (56.0) | 24 (35.3) | 0.006 | 55 (41.7) | 30 (50.0) | 25 (34.7) | 0.076 |
=/>50% | 99 (51.3) | 55 (44.0) | 44 (64.7) | 77 (58.3) | 30 (50.0) | 47 (65.3) | |||
CI a | No | 143 (74.1) | 102 (83.6) | 41 (62.1) | <0.001 | 94 (71.8) | 47 (78.3) | 47 (66.2) | 0.124 |
Yes | 45 (23.3) | 20 (16.4) | 25 (37.9) | 37 (28.2) | 13 (21.7) | 24 (33.8) | |||
LVSI a | No | 110 (57.0) | 91 (72.8) | 19 (27.9) | <0.001 | 70 (52.6) | 39 (65.0) | 31 (42.5) | 0.010 |
Yes | 83 (43.0) | 34 (27.2) | 49 (72.1) | 63 (47.4) | 21 (35.0) | 42 (57.5) | |||
LNM b | No (N0) | 136 (70.5) | 107 (85.6) | 29 (42.6) | <0.001 | - | - | - | - |
Yes (N1) | 57 (29.5) | 18 (14.4) | 39 (57.4) | - | - | - | |||
Adjuvant therapy | Radiotherapy | 82 (42.5) | 60 (48.0) | 22 (32.4) | 0.006 | 59 (42.1) | 36 (59.0) | 23 (29.1) | <0.001 |
Chemotherapy | 60 (31.1) | 28 (22.4) | 32 (47.1) | 32 (22.9) | 4 (6.6) | 28 (35.4) | |||
Radio- and chemo-therapy | 10 (5.2) | 7 (5.6) | 3 (4.4) | 5 (3.6) | 2 (3.3) | 3 (3.8) | |||
No adjuvant therapy | 41 (21.2) | 30 (24.0) | 11 (16.2) | 44 (31.4) | 19 (31.1) | 25 (31.6) | |||
Radio-therapy | VBT | 36 (39.1) | 24 (35.8) | 12 (48.0) | 0.287 | 23 (35.9) | 15 (39.5) | 8 (30.8) | 0.476 |
EBRT ± VBT | 56 (60.9) | 43 (64.2) | 13 (52.0) | 41 (64.1) | 23 (60.5) | 18 (69.2) | |||
Follow up (months) | 39.0 (0–193) | 47.5 (0–193) | 33.8 (0–123) | 0.003 | 21.0 (0–132) | 36.0 (0–132) | 9.0 (0–83) | <0.001 | |
Recurrence | No | 120 (62.5) | 92 (74.2) | 28 (41.2) | <0.001 | 64 (46.0) | 41 (68.3) | 23 (29.1) | <0.001 |
Yes | 53 (27.6) | 27 (21.8) | 26 (38.2) | 40 (28.8) | 17 (28.3) | 23 (29.1) | |||
Progression | 19 (9.9) | 5 (4.0) | 14 (20.6) | 35 (25.2) | 2 (3.3) | 33 (41.8) | |||
Death | No | 125 (65.4) | 94 (75.8) | 31 (46.3) | <0.001 | 68 (49.6) | 43 (70.5) | 25 (32.9) | <0.001 |
Yes, caused by EC | 54 (28.3) | 23 (18.5) | 31 (46.3) | 56 (40.9) | 12 (19.7) | 44 (57.9) | |||
Yes, not caused by EC | 6 (3.1) | 5 (4.0) | 1 (1.5) | 8 (5.8) | 4 (6.6) | 4 (5.3) | |||
Yes, unknown cause | 6 (3.1) | 2 (1.6) | 4 (6.0) | 5 (3.6) | 2 (3.3) | 3 (3.9) |
Total (n) | Sensitivity % [95% CI] (n) | Specificity % [95% CI] (n) | PPV % [95% CI] (n) | NPV % [95% CI] (n) | ROC AUC (95% CI) | p Value | |||
---|---|---|---|---|---|---|---|---|---|
LNM | CA125 a | 193 | 68.4 [54.8–80.1] (39/57) | 78.7 [70.8–85.2] (107/136) | 57.4 [44.8–69.2] (39/68) | 85.6 [78.2–91.2] (107/125) | 0.721 (0.619–0.824) | <0.001 | |
CT b | 129 | 40.5 [24.8–7.9] (15/37) | 85.9 [77.1–92.3] (79/92) | 53.6 [33.9–72.5] (15/28) | 78.2 [68.9–85.8] (79/101) | 0.623 (0.520–0.744) | <0.001 | ||
CA125 <35 U/mL | CT b | 86 | 7.7 [0.0–36.0] (1/13) | 89.0 [79.5–95.2] (65/73) | 11.1 [0.0–48.3] (1/9) | 84.4 [74.4–91.7] (65/77) | 0.484 (0.316–0.652) | 1.000 | |
CA125 >35 U/mL | CT b | 43 | 58.3 [36.6–77.9] (14/24) | 73.7 [48.8–90.9] (14/19) | 73.7 [48.8–90.9] (14/19) | 58.3 [36.6–77.9] (14/24) | 0.660 (0.495–0.826) | 0.036 |
Univariate Analysis | Multivariate Analysis | |||||
---|---|---|---|---|---|---|
p Value | Adjusted OR | 95% CI | p Value | Adjusted OR | 95% CI | |
Age > 65 years * | 0.964 | 0.99 | 0.53–1.83 | - | - | - |
BMI >30 kg/m2 * | 0.790 | 0.91 | 0.46–1.81 | - | - | - |
NEEC histology | <0.001 | 3.75 | 1.82–7.70 | 0.028 | 3.72 | 1.16–11.95 |
CA125 > 35 U/mL | <0.001 | 7.99 | 4.00–15.99 | 0.003 | 6.25 | 1.85–21.09 |
CT with suspected LNM | 0.002 | 4.14 | 1.72–9.99 | 0.427 | 1.680 | 0.48–6.05 |
Deep myometrial involvement | <0.001 | 3.45 | 1.76 6.74 | 0.007 | 4.88 | 1.54–15.46 |
Cervical stromal involvement | 0.009 | 4.21 | 1.42–12.50 | 0.018 | 7.87 | 1.42–43.78 |
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Lombaers, M.S.; Cornel, K.M.C.; Visser, N.C.M.; Bulten, J.; Küsters-Vandevelde, H.V.N.; Amant, F.; Boll, D.; Bronsert, P.; Colas, E.; Geomini, P.M.A.J.; et al. Preoperative CA125 Significantly Improves Risk Stratification in High-Grade Endometrial Cancer. Cancers 2023, 15, 2605. https://doi.org/10.3390/cancers15092605
Lombaers MS, Cornel KMC, Visser NCM, Bulten J, Küsters-Vandevelde HVN, Amant F, Boll D, Bronsert P, Colas E, Geomini PMAJ, et al. Preoperative CA125 Significantly Improves Risk Stratification in High-Grade Endometrial Cancer. Cancers. 2023; 15(9):2605. https://doi.org/10.3390/cancers15092605
Chicago/Turabian StyleLombaers, Marike S., Karlijn M. C. Cornel, Nicole C. M. Visser, Johan Bulten, Heidi V. N. Küsters-Vandevelde, Frédéric Amant, Dorry Boll, Peter Bronsert, Eva Colas, Peggy M. A. J. Geomini, and et al. 2023. "Preoperative CA125 Significantly Improves Risk Stratification in High-Grade Endometrial Cancer" Cancers 15, no. 9: 2605. https://doi.org/10.3390/cancers15092605