Cesare Romagnolo1, Antonette E Leon2, Aline S C Fabricio3, Martina Taborelli4, Jerry Polesel5, Lino Del Pup6, Agostino Steffan7, Silvia Cervo8, Antonella Ravaggi9, Laura Zanotti10, Elisabetta Bandiera11, Franco E Odicino12, Novella Scattolo13, Elisa Squarcina14, Christine Papadakis15, Tiziano Maggino16, Massimo Gion17. 1. Unit of Gynecology and Obstetrics, G. Fracastoro Hospital, Via Circonvallazione 1, 37047 San Bonifacio, Verona (VR), Italy. Electronic address: cromagnolo@ulss20.verona.it. 2. Regional Center for Biomarkers, Department of Clinical Pathology, Azienda ULSS12 Veneziana, Regional Hospital, Campo SS Giovanni e Paolo 6777, 30122 Venice (VE), Italy. Electronic address: antonette.leon@ulss12.ve.it. 3. Experimental and Clinical Pharmacology Unit, CRO Aviano National Cancer Institute, IRCCS, Via Franco Gallini 2, 33081 Aviano (PN), Italy; Regional Center for Biomarkers, Department of Clinical Pathology, Azienda ULSS12 Veneziana, Regional Hospital, Campo SS Giovanni e Paolo 6777, 30122 Venice (VE), Italy. Electronic address: aline.fabricio@ulss12.ve.it. 4. Unit of Epidemiology and Biostatistics, CRO Aviano National Cancer Institute, IRCCS, via Franco Gallini 2, 33081 Aviano (PN), Italy. Electronic address: mtaborelli@cro.it. 5. Unit of Epidemiology and Biostatistics, CRO Aviano National Cancer Institute, IRCCS, via Franco Gallini 2, 33081 Aviano (PN), Italy. Electronic address: polesel@cro.it. 6. Division of Gynecological Oncology, CRO Aviano National Cancer Institute, IRCCS, Via Franco Gallini 2, 33081 Aviano (PN), Italy. Electronic address: ldelpup@cro.it. 7. CRO-Biobank, Clinical Cancer Pathology, CRO Aviano National Cancer Institute, IRCCS, Via Franco Gallini 2, 33081 Aviano (PN), Italy. Electronic address: asteffan@cro.it. 8. CRO-Biobank, Clinical Cancer Pathology, CRO Aviano National Cancer Institute, IRCCS, Via Franco Gallini 2, 33081 Aviano (PN), Italy. Electronic address: scervo@cro.it. 9. Division of Gynecologic Oncology, "Angelo Nocivelli" Institute of Molecular Medicine, University of Brescia, Spedali Civili 1, 25123 Brescia, (BS), Italy. Electronic address: antonella.ravaggi@unibs.it. 10. Division of Gynecologic Oncology, "Angelo Nocivelli" Institute of Molecular Medicine, University of Brescia, Spedali Civili 1, 25123 Brescia, (BS), Italy. Electronic address: laura.zanotti84@gmail.com. 11. Division of Gynecologic Oncology, "Angelo Nocivelli" Institute of Molecular Medicine, University of Brescia, Spedali Civili 1, 25123 Brescia, (BS), Italy. Electronic address: bandieraelisabetta@libero.it. 12. Division of Gynecologic Oncology, "Angelo Nocivelli" Institute of Molecular Medicine, University of Brescia, Spedali Civili 1, 25123 Brescia, (BS), Italy. Electronic address: odicino.franco@gmail.com. 13. Department of Clinical Pathology, G. Fracastoro Hospital, Via Circonvallazione 1, 37047 San Bonifacio, Verona (VR), Italy. Electronic address: novella.scattolo@ulss20.verona.it. 14. Istituto Oncologico Veneto (IOV), IRCCS, Via Gattamelata, 64, 35128 Padova (PD), Italy. Electronic address: elisa.squarcina@libero.it. 15. Unit of Obstetrics and Gynecology, Dell'Angelo Hospital, Via Paccagnella 11, 30174 Mestre (VE), Italy. Electronic address: christine.papadakis@ulss12.ve.it. 16. Unit of Obstetrics and Gynecology, Dell'Angelo Hospital, Via Paccagnella 11, 30174 Mestre (VE), Italy. Electronic address: tiziano.maggino@ulss12.ve.it. 17. Regional Center for Biomarkers, Department of Clinical Pathology, Azienda ULSS12 Veneziana, Regional Hospital, Campo SS Giovanni e Paolo 6777, 30122 Venice (VE), Italy. Electronic address: massimo.gion@ulss12.ve.it.
Abstract
OBJECTIVE: This multicenter study aims to evaluate HE4, CA125 and risk of ovarian malignancy algorithm (ROMA) performance in the differential diagnosis of epithelial ovarian cancer (EOC). METHODS: A total of 405 patients referred to gynecological oncologist with suspicious pelvic mass requiring a surgery for identification of EOC were consecutively enrolled; 387 patients satisfied inclusion criteria: 290 benign diseases; 15 borderline neoplasia and 82 tumors (73 EOC). RESULTS: Good diagnostic performance in discriminating benign from EOC patients was obtained for CA125, HE4 and ROMA when calculating optimal cut-off values: premenopause, specificity (SP) >86.6, sensitivity (SN) >82.6, area under the curves (AUC)≥0.894; postmenopause, SP>93.2, SN>82, AUC≥0.928. Fixing SP at 98%, performance indicators obtained for benign vs EOC patients were: premenopause, SN:65.2%, positive predictive value (+PV): 75%, positive likelihood ratio (+LR): 26.4 for CA125; SN:69.6%, +PV:76.2%, +LR:28.1 for HE4; SN:69.6%, +PV: 80%; +LR:35.1 for ROMA; postmenopause, SN:88%, +PV: 95.7%, +LR:38.7 for CA125; SN:78%, +PV:95.1%, +LR:34.3 for HE4; SN:88%, +PV:97.8%, +LR:77.4 for ROMA. When using routine cut-off thresholds, ROMA showed better well-balanced values of both SP and SN (premenopause, SN:87%, SP:86.1%; postmenopause, SN:90%; SP:94.3%). CONCLUSIONS: Overall, ROMA showed well balanced diagnostic performance to differentiate EOC from benign diseases. Meaningful differences of +PVs and +LRs between HE4 and CA125 suggest that the two markers may play at least in part different roles in EOC diagnosis, with HE4 seeming to be more efficient than CA125 in ruling in EOC patients in the disease group, also in early stages tumors, both in pre and postmenopause.
OBJECTIVE: This multicenter study aims to evaluate HE4, CA125 and risk of ovarian malignancy algorithm (ROMA) performance in the differential diagnosis of epithelial ovarian cancer (EOC). METHODS: A total of 405 patients referred to gynecological oncologist with suspicious pelvic mass requiring a surgery for identification of EOC were consecutively enrolled; 387 patients satisfied inclusion criteria: 290 benign diseases; 15 borderline neoplasia and 82 tumors (73 EOC). RESULTS: Good diagnostic performance in discriminating benign from EOC patients was obtained for CA125, HE4 and ROMA when calculating optimal cut-off values: premenopause, specificity (SP) >86.6, sensitivity (SN) >82.6, area under the curves (AUC)≥0.894; postmenopause, SP>93.2, SN>82, AUC≥0.928. Fixing SP at 98%, performance indicators obtained for benign vs EOC patients were: premenopause, SN:65.2%, positive predictive value (+PV): 75%, positive likelihood ratio (+LR): 26.4 for CA125; SN:69.6%, +PV:76.2%, +LR:28.1 for HE4; SN:69.6%, +PV: 80%; +LR:35.1 for ROMA; postmenopause, SN:88%, +PV: 95.7%, +LR:38.7 for CA125; SN:78%, +PV:95.1%, +LR:34.3 for HE4; SN:88%, +PV:97.8%, +LR:77.4 for ROMA. When using routine cut-off thresholds, ROMA showed better well-balanced values of both SP and SN (premenopause, SN:87%, SP:86.1%; postmenopause, SN:90%; SP:94.3%). CONCLUSIONS: Overall, ROMA showed well balanced diagnostic performance to differentiate EOC from benign diseases. Meaningful differences of +PVs and +LRs between HE4 and CA125 suggest that the two markers may play at least in part different roles in EOC diagnosis, with HE4 seeming to be more efficient than CA125 in ruling in EOC patients in the disease group, also in early stages tumors, both in pre and postmenopause.
Authors: Dirk Timmerman; François Planchamp; Tom Bourne; Chiara Landolfo; Andreas du Bois; Luis Chiva; David Cibula; Nicole Concin; Daniela Fischerova; Wouter Froyman; Guillermo Gallardo Madueño; Birthe Lemley; Annika Loft; Liliana Mereu; Philippe Morice; Denis Querleu; Antonia Carla Testa; Ignace Vergote; Vincent Vandecaveye; Giovanni Scambia; Christina Fotopoulou Journal: Int J Gynecol Cancer Date: 2021-06-10 Impact factor: 3.437