A Triple-modality Approach to Adnexal Masses: Combining Sonography, Doppler, and Biomarkers for Ovarian Cancer Detection in Resource-limited Settings

Background: Ovarian cancer is the deadliest gynecologic malignancy, with 70% of cases diagnosed at an advanced stage in low-and middle-income countries (LMICs).Transvaginal sonography (TVS), Doppler interrogation, and inexpensive serum biomarkers-cancer antigen 125 (CA-125) and human epididymis protein 4 (HE4)-may offer an accessible diagnostic alternative.Objective: To determine the diagnostic accuracy of TVS morphology, color flow Doppler indices, and dual biomarkers, alone and combined, for differentiating benign from malignant adnexal masses.Materials and methods: In this single-center prospective cohort (January 2023-June 2024), consecutive symptomatic women aged 30-70 years with adnexal masses underwent TVS [International Ovarian Tumor Analysis (IOTA) Simple Rules], spectral Doppler (resistance index [RI] and pulsatility index [PI]), and serum CA-125 and HE4 assays.Histopathology was the reference standard.Diagnostic metrics, receiver operating characteristic (ROC) curves, and cost-effectiveness were analyzed.Results: Of 480 screened patients, 431 were included; malignancy prevalence was 45% (n = 194).TVS morphology yielded a sensitivity of 92.3% and a specificity of 75.6%.Adding an RI 35 U mL -¹ had a sensitivity of 78.1% and a specificity of 65.4%, whereas HE4 > 70 pmol L -¹ achieved 86.8 and 72.1%, respectively.The multimodal algorithm (TVS + RI < 0.4 + CA-125 + HE4) produced an area under the curve (AUC) of 0.91, a sensitivity of 90.4%, a specificity of 87.9%, and a negative predictive value of 92.0%.Conclusions: A tiered protocol beginning with TVS morphology, followed by Doppler RI and reflex HE4 and CA-125 testing, offers high diagnostic accuracy while remaining cost-feasible in LMICs.Implementation could expedite oncologic referral and improve survival.