Update of the ADNEX risk model (ADNEX2) to diagnose ovarian cancer in surgically and conservatively managed patients with an adnexal mass: multicentre prospective cohort study

@misc{barrenada2026update,
  title = {{Update of the ADNEX risk model (ADNEX2) to diagnose ovarian cancer in surgically and conservatively managed patients with an adnexal mass: multicentre prospective cohort study}},
  author = {L. Barrenada and W. Froyman and J. Ceusters and C. Landolfo and L. Wynants and A. Ledger and P. Sladkevicius and A. C. Testa and C. Van Holsbeke and F. Buonomo and M. J. Kudla and R. Fruscio and D. Fischerova and D. Franchi and E. Epstein and V. Chiappa and F. P. Leone and J. Ensor and M. E. Coccia and S. Guerriero and J. L. Alcazar and F. Alves and L. Jokubkiene and F. Pozzati and F. Moro and F. Mascilini and C. Taliento and T. Bourne and L. Valentin and D. Timmerman and B. Van Calster},
  howpublished = {medRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.23.26365247},
  url = {https://www.medrxiv.org/content/10.64898/2026.10.23.26365247v1},
  note = {CC BY-NC},
}

TY  - UNPB
TI  - Update of the ADNEX risk model (ADNEX2) to diagnose ovarian cancer in surgically and conservatively managed patients with an adnexal mass: multicentre prospective cohort study
AU  - L. Barrenada
AU  - W. Froyman
AU  - J. Ceusters
AU  - C. Landolfo
AU  - L. Wynants
AU  - A. Ledger
AU  - P. Sladkevicius
AU  - A. C. Testa
AU  - C. Van Holsbeke
AU  - F. Buonomo
AU  - M. J. Kudla
AU  - R. Fruscio
AU  - D. Fischerova
AU  - D. Franchi
AU  - E. Epstein
AU  - V. Chiappa
AU  - F. P. Leone
AU  - J. Ensor
AU  - M. E. Coccia
AU  - S. Guerriero
AU  - J. L. Alcazar
AU  - F. Alves
AU  - L. Jokubkiene
AU  - F. Pozzati
AU  - F. Moro
AU  - F. Mascilini
AU  - C. Taliento
AU  - T. Bourne
AU  - L. Valentin
AU  - D. Timmerman
AU  - B. Van Calster
PY  - 2026
DA  - 2026/10/23
PB  - medRxiv
DO  - 10.64898/2026.10.23.26365247
UR  - https://www.medrxiv.org/content/10.64898/2026.10.23.26365247v1
AB  - ObjectiveThe ADNEX ultrasound-based prediction model estimates the probability that an adnexal mass is benign, borderline, stage I primary invasive, stage II-IV primary invasive, or secondary metastatic. ADNEX was developed on patients managed surgically. We aimed to update ADNEX to ADNEX2 using more recent data on both surgically and conservatively managed patients. ADNEX2 is designed for use in patients in whom the benign descriptors (BDs), a set of ultrasound profiles with an estimated risk of malignancy below 1%, do not apply.  DesignSecondary analysis of a multicentre prospective cohort study.  Setting17 oncology and non-oncology centres from 8 European countries.  ParticipantsPatients with a newly detected adnexal mass recruited between 2012 and 2016 who were managed surgically or conservatively with clinical and ultrasound follow-up.  InterventionsADNEX2 uses the same predictors as ADNEX (age, type of centre, lesion diameter, proportion of solid tissue, number of papillary projections, >10 cyst locules, ascites and acoustic shadows and CA125). Model updating involved logistic recalibration followed by Bayesian refitting. Validation was based on leave-one-centre-out cross-validation. ADNEX2 and ADNEX include CA125 but also work without CA125.  Main outcome measuresModel performance regarding discrimination (AUC), calibration (plots and observed:expected, O:E, ratio), and clinical utility (net benefit).  ResultsOf 6847 patients, 4625 (68%) had a benign tumour, 1710 (25%) had a malignant tumour, while tumour outcome was uncertain for 512 (7%) patients. BDs applied in 2190 (32%) patients, of whom 0.5% (95% CI, 0.2%-0.9%) had a malignancy. A two-step strategy using BDs followed by ADNEX2 had an AUC of 0.95 (0.94-0.96) to distinguish benign from malignant tumours. When evaluated on 4657 patients in whom BDs did not apply, ADNEX2 had an AUC of 0.93 (0.91-0.94). The two-step strategy with ADNEX2 was better calibrated than the two-step strategy with ADNEX (O:E ratio of 1.05 versus 1.14) and had marginally higher clinical utility. Not including available CA125 values in ADNEX2 reduced the ability to distinguish stage II-IV primary invasive tumours from other invasive malignancies.  ConclusionsADNEX2 is better calibrated than ADNEX. CA125 measurement is not crucial to estimate the risk of malignancy, but is recommended to estimate the risk of malignant subtypes.  Trial registration: clinicaltrials.gov NCT01698632.  What is already known on this topic- The IOTA ADNEX risk model is widely used to estimate the probability that an adnexal mass is benign or one of four malignant subtypes, and has been integrated into a two-step strategy following the application of ultrasound benign descriptors (BDs). - Like nearly all prediction models for adnexal masses, the original ADNEX model was developed exclusively using data from patients who underwent surgery (recruited between 1999 and 2012). This introduces selection bias when the model is used to determine who should be referred for specialized care. - Measuring serum CA125 is not essential for estimating overall malignancy risk, but is recommended when patients are referred to oncology centres to distinguish stage II-IV primary invasive cancer from stage I primary invasive cancer and secondary metastases.  What this study adds- ADNEX was updated to ADNEX2 using more recent multicentre data (IOTA5) including both surgically and conservatively managed patients with tumours to which benign descriptors did not apply. - ADNEX2 (used alone or in a two-step strategy after benign descriptors) maintains high discrimination (AUC 0.95 for two-step strategy with ADNEX2; 0.93 when benign descriptors do not apply), improves risk calibration compared with the original ADNEX model (O:E ratio 1.05 v 1.14), and offers marginally higher clinical utility.
ER  -