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Open research questions in Ovarian cancer diagnosis and treatment

42 unresolved questions extracted from the limitations and future-work sections of 563 Ovarian cancer diagnosis and treatment papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Fertility preservation (FP) is important for patients who have not completed childbearing; however, the safety of oocyte and embryo banking remains unclear due to concerns for ovarian metastases.

    Incidence of Ovarian Metastases in Reproductive-Aged Women with Appendiceal Cancer: Implications for Fertility Preservation · 2026 · DOI

  • SET morphology has been associated with homologous recombination deficiency and BRCA1/2 mutations; however, its relationship with the immune microenvironment and progression-free survival (PFS) remains insufficiently understood.

    Prognostic Value of Morphological Characteristics and Immune Microenvironment in High-Grade Serous Cancer (HGSC) · 2026 · DOI

  • Third, no control group of other hypervascular ovarian tumours was included; therefore, the specificity, sensitivity, reproducibility, and diagnostic performance of the observed Doppler patterns could not be evaluated.

    Analysis of ultrasonic characteristics in 12 cases of ovarian Sertoli–Leydig cell tumour · 2026 · DOI

  • Tumor microstructure is closely associated with the ADC value (mm2/second), which serves as a potential imaging biomarker [27]. In this case series, the mean (range) ADC value of the solid components in 11 cases was 1.44 (1.08– 1.75) × 10–3 mm2/second on 1.5-T MRI. These findings This current study has several limitations. First, the pro- posed MRI-based morphological classification was based on a relatively small cohort of 11 cases from limited insti- tutional experience. Therefore, the reproducibility of the 9-type classification and its broader clinical applicability 1 3Abdominal Radiology Fig. 14 Solid lesion with central edema exhibiting a “renal cortico- medullary contrast-like” appearance. Clear cell carcinoma of the right ovary (pT1a) in a 56-year-old woman who presented with genital bleeding. The serum CA125 level was 30.1 U/mL. On T2-weighted imaging (T2WI) (a–c), the tumor exhibited a characteristic renal cor- ticomedullary pattern composed of a peripheral band-like structure (arrows) and a central geographic area (asterisks). Compared to the myometrium, the peripheral area appeared isointense to hyperin- tense on T2WI (a–c), isointense on unenhanced T1-weighted imag- ing (T1WI) (d), and hyperintense on contrast-enhanced T1WI (f). On the apparent diffusion coefficient (ADC) map (e), this peripheral area exhibited hypointensity, with a mean ADC value of 0.78 × 10–3 mm2/ second on 3.0-T magnetic resonance imaging. The central area (aster- isks) appeared hyperintense on T2WI (a–c), hypointense on T1WI (d), and hyperintense on the ADC map, without enhancement on contrast- enhanced T1WI (f). The resected specimen (g) indicated an entirely solid fibromatous lesion without evidence of endometriosis or adeno- fibroma. Histologically, the peripheral area (h) included cancer cells with eosinophilic to clear cytoplasm arranged in solid, papillary, or tubular structures, reinforced by fibrous stroma. Conversely, the cen- tral area (i) consisted of predominantly edematous stroma with mini- mal fibrosis and sparse cancer cell proliferation. A fibrothecoma-like stroma (open arrows) with sparse cancer cell proliferation (j) was iden- tified in the peripheral area, exhibiting hypointense regions on T2WI (c, g) remain uncertain. External validation in larger cohorts, pref- erably through multicenter studies, would be necessary to determine interobserver agreement, diagnostic performance, and generalizability across different MRI protocols, field strengths, and patient populations. Second, the absence of identifiable precursor lesions in several tumors may reflect either a biologically distinct indeterminate pathway or the overgrowth/obscuration of precursor lesions by advanced carcinoma. Therefore, further radiologic-pathologic and molecular studies are needed. In the present cohort, we con- sider the latter explanation more plausible, although this interpretation remains provisional and requires validation in future studies.

    MRI-based morphology of ovarian clear cell carcinomas · 2026 · DOI

  • CONCLUSIONS: In patients with HGSOC, AVB-001 is safe and effectively activates cytotoxic T cells, supporting further investigation of this locoregional immunotherapy.

    First-In-Human Trial of Encapsulated Cells Constitutively Expressing Localized IL-2 in Patients with High-Grade Serous Ovarian Carcinoma · 2026 · DOI

  • These findings position EGFR overexpression as a defining and targetable feature of NSMP LGSOC and support further preclinical validation of EGFR inhibitors as a treatment strategy for this understudied cancer subtype.

    Identifying therapeutic targets in low‐grade serous ovarian carcinomas with no specific molecular profile · 2026 · DOI

  • Data remains the paramount and essential element for the education of AI systems. Utilizing contemporary information processing technologies to exploit radiology report databases may enhance report search and retrieval, thereby assisting radiologists in diagnosis. There is a necessity to advocate for the establishment of interconnected networks that identify patient data globally and facilitate large-scale AI training tailored to diverse patient demographics, geographic regions, and diseases. Furthermore, we underscore the necessity for more diversified imaging libraries for uncommon malignancies, including OC. However, much of the literature is limited by common methodological current weaknesses, including retrospective study designs, small cohort sizes, lack of prospective validation, spectrum bias, variable label quality, segmentation variability, scanner and protocol heterogeneity, risk of data leakage, and inconsistent reporting of model calibration and clinical utility. These limitations highlight the need for more rigorous and standardized study designs to improve the reliability and generalizability of AI applications in oncology. In image-based diagnostic tasks, AI models have demonstrated performance comparable to, or exceeding, that of expert physicians. However, such evaluations often fail to account for the multidimensional information routinely considered by radiologists when interpreting complex examinations. Non-imaging patient attributes, including demographic characteristics, clinical history, and genetic or molecular data, provide critical contextual information that is not fully captured by image-only models and can substantially enhance predictive performance when appropriately integrated (90). The high performance of contemporary AI models is frequently accompanied by substantial algorithmic complexity, involving high-dimensional feature spaces and deep neural network architectures. As a result, the internal decision-making processes underlying image-based predictions are often difficult to interpret or explain, a limitation commonly referred to as the “black-box” problem (91). This lack of transparency presents a major barrier to clinical trust, regulatory approval, and routine implementation in oncological practice. Explainable artificial intelligence (XAI) has emerged as a promising solution to address these limitations by providing model interpretability alongside predictive accuracy. XAI techniques aim to elucidate the relative importance of input features, highlight salient image regions, and identify clinically meaningful variables that drive model outputs (92). Laios et al. (93) demonstrated the clinical utility of XAI by developing ensemble AI models capable of predicting outcomes following cytoreductive surgery for OC, while simultaneously revealing patient- and procedure-specific factors contributing to surgical risk. Subsequent work further extended this framework to predict surgical effort requirements using human-centered and clinically interpretable variables. Despite these advances, many radiomicsbased tools and imaging biomarker models discussed in this review continue to function as black-box systems, limiting their reliability and interpretability in real-world clinical settings.

    Applications of artificial intelligence and machine learning models in the prognosis and diagnosis of ovarian cancer · 2026 · DOI

  • Typical findings in adnexal torsion Ultrasonography Initial evaluation of all Widely available, (US) (first‑line) suspected cases, particularly in women of reproductive aged real‑time, no radiation, allows Doppler assessment and whirlpool sign visualization. Operator‑dependent; Enlarged ovary, limited by body habitus, bowel gas, or atypical ovarian position. peripheral follicles, stromal edema, free fluid, whirlpool sign.

    Ultrasonographic whirlpool sign in ovarian torsion with dual mature teratomas: A case report and literature review · 2026 · DOI

  • Acronym-based public health campaigns like BEAT may play a role in improving ovarian cancer symptom aware- ness through simplicity, memorability, and reaching a wide audience. Although BEAT is the most widely used tool for ovarian cancer symptom awareness in Ireland and the UK, and has been running since 2010, comparative stud- ies assessing BEAT’s effectiveness against non-acronym- based awareness campaigns in ovarian cancer are lacking, i.e., does a simple acronym like BEAT outperform detailed symptom lists or does it eclipse other key symptoms (e.g. fatigue)? Despite the long-standing existence of BEAT, it also remains unclear how the campaign has affected behav- iour or outcomes in practice. Measuring the effectiveness of symptom-based awareness campaigns is inherently chal- lenging, requiring large-scale surveys and longitudinal follow-up, which are costly and slow. Additional research, further than just symptom recall, is required to explore the impact of BEAT on stage at diagnosis, referral rates, and mortality rates to assess its true efficacy. Evaluating whether women with an ovarian cancer diagnosis recall awareness campaigns like BEAT, and whether clinicians themselves are familiar with the acronym, would also offer valuable insight into how effectively the campaign is reaching those it aims to influence. The evolution of BEAT presents an excit- ing frontier. Judging by other acronym-based campaigns (e.g. FAST), it has the potential to instigate meaningful change in the recognition of ovarian cancer symptoms in a timely manner. As BEAT spreads, it carries with it hope – that greater awareness can result in swifter action, and ulti- mately, to lives changed. Acknowledgements We thank all patient partners who contributed quotations and confirmed their approval of how these were presented in the manuscript. We also thank the Irish Network for Gynaecological Oncology (INGO) members, Ovacome, and OvaCare. Funding Open Access funding provided by the IReL Consortium. The first author Faye Lewis is funded by the North-South Research Pro- gramme administered by the Higher Education Authority on behalf of the Department of Further and Higher Education, Research, Innova- tion and Science and the Shared Island Fund (CLuB: The All-Ireland Cancer Liquid Biopsies Consortium https://www.clubcancer.ie). Data Availability The manuscript does not contain associated data. Competing Interests The authors declare no competing interests. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit h t t p : / / c r e a t i v e c o m m o n s . o r g / l i c e n s e s / b y / 4 . 0 / .

    Memorable Medicine: How the BEAT Campaign could Impact the Future of Ovarian Cancer · 2026 · DOI

  • This study has some limitations. ADC measurements are sensitive to ROI placement, sequence parameters, and scanner-specific factors, which may reduce repro- ducibility and contribute to inter-study variability [14, 19]. In addition, data from different MRI vendors were pooled without protocol harmonization, which may have affected the robustness of ADC-based thresholds. Although consensus reading was used, formal inter- observer agreement was not assessed. The exploratory nature of multiple diagnostic comparisons also increases the risk of type I error and statistical overinterpretation. Finally, validation in larger standardized multicenter cohorts is needed to confirm the generalizability of these findings.

    Adding apparent diffusion coefficient to the ovarian-adnexal reporting and data system MRI: a trade-off between sensitivity and specificity · 2026 · DOI

  • Semi-automated and manual CT segmentation approaches limit clinical applicability of radiomics models for adnexal mass classification. Fully automated segmentation using end-to-end deep learning architectures should be developed and validated to improve reproducibility and reduce operator dependence in clinical workflows.

    Diagnostic Performance of Computed Tomography-Based Machine Learning Models in the Classification of Adnexal Masses - A Systematic Review · 2026 · DOI

  • Current machine learning models for adnexal mass classification rely on radiomics features alone and do not systematically integrate clinical, genomic, and imaging data. Future hybrid clinicoradiomic-genomic models should be developed to enable individualized risk assessment and management stratification in gynecologic oncology.

    Diagnostic Performance of Computed Tomography-Based Machine Learning Models in the Classification of Adnexal Masses - A Systematic Review · 2026 · DOI

  • External validation of CT-based deep learning and radiomics models for adnexal mass classification has not been performed prospectively across different populations and scanner platforms. Studies must conduct scanner-agnostic external validation on independent datasets with varying CT equipment to ensure robustness before clinical application.

    Diagnostic Performance of Computed Tomography-Based Machine Learning Models in the Classification of Adnexal Masses - A Systematic Review · 2026 · DOI

  • The heterogeneity in CT image acquisition parameters, segmentation approaches (2D vs. 3D), and feature selection algorithms across studies prevents reliable comparison and meta-analysis of CT-based machine learning models for adnexal mass classification. Future studies must establish standardized CT acquisition protocols and radiomics pipelines to enable valid pooling of diagnostic performance data.

    Diagnostic Performance of Computed Tomography-Based Machine Learning Models in the Classification of Adnexal Masses - A Systematic Review · 2026 · DOI

  • Due to the rare pathology (less than 1 % of all tumors), insufficient information in the literature, lack of generalized recommendations and personal experience, doctors make many mistakes during the treatment of patients with struma ovary.

    Ectopic thyroid cancer in the ovary – unresolved issues of diagnosis and treatment of struma ovaria maligna · 2024 · DOI

  • Although this study provides insights into the immune landscape of HGSOC development and represents the largest available dataset of transcriptional and multiplexed imaging data of precancer, the sample size is still limited relative to the complexity of the disease and interpatient variability. Analysis of additional specimens will be needed to fully describe immune response across the HGSOC spectrum. In addition, 25% of STIC lesions associated with cancer have been reported to be dissemi- nated cancer cells, reflecting the complexity of studying HGSOC progression in clinical settings (12). Expanding the cohort to in- clude more STIC.I lesions would allow for the discovery of addi- tional mechanisms relevant to disease progression and improve the identification of markers linked to clinical outcomes, offer- ing a more complete understanding of HGSOC progression.

    Multimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma · 2024 · DOI

  • What do the results of this study add? The expression of NNMT in various ovarian neoplasms including serous cystadenomas, borderline tumours and serous carcinomas has not been studied and independently associated with poor survival, previously.

    Nicotinamide N-methyltransferase overexpression may be associated with poor prognosis in ovarian cancer · 2020 · DOI

  • Ovarian cancers, including both epithelial tumors and teratomas, have been associated with a spectrum of antibody-mediated neurological syndromes, although their clinical implications remain poorly defined.

    Paraneoplastic Neurological Syndromes in Ovarian Cancer: Case Report and Narrative Review for Diagnostic and Clinical Implications · 2026 · DOI

  • While complications were not observed in ovarian and peritoneal tumor biopsies in this study, isolated cases of complications occurred with trephine biopsies of other tumor localizations, suggesting need for further investigation of safety across different tumor types.

    CORE-NEEDLE BIOPSY UNDER ULTRASOUND GUIDANCE AS A METHOD OF HISTOLOGICAL VERIFICATION IN MALIGNANT OVARIAN NEOPLASMS · 2026 · DOI

  • Need to continue performing trephine biopsy under ultrasound guidance in ovarian tumors to obtain a larger patient sample for statistical comparison of efficacy and safety with diagnostic laparoscopy.

    CORE-NEEDLE BIOPSY UNDER ULTRASOUND GUIDANCE AS A METHOD OF HISTOLOGICAL VERIFICATION IN MALIGNANT OVARIAN NEOPLASMS · 2026 · DOI

  • Extracorporeal cystectomy and ovarian reconstruction require substantial technical expertise, involving a learning curve and a potential risk of cyst fluid leakage.

    Case Report: Minimally invasive management of torsion in a giant ovarian cyst in an obese child: a single-port approach combined with extracorporeal cystectomy · 2026 · DOI

  • This technique is best suited for lesions identified on imaging as low-risk, cystic, and well-defined, which introduces a certain degree of selection bias.

    Case Report: Minimally invasive management of torsion in a giant ovarian cyst in an obese child: a single-port approach combined with extracorporeal cystectomy · 2026 · DOI

  • Local infiltration anesthesia administered prior to umbilical puncture can partially alleviate postoperative discomfort and facilitate recovery, representing an area for further refinement in clinical practice.

    Case Report: Minimally invasive management of torsion in a giant ovarian cyst in an obese child: a single-port approach combined with extracorporeal cystectomy · 2026 · DOI

  • BACKGROUND: Haemostasis during ovarian cystectomy is reported to damage the ovarian reserve, but the comparative impacts of three haemostasis methods (bipolar energy, suture and haemostatic sealant) on ovarian reserve in patients with ovarian cysts are not well known.

    Impact of haemostasis methods during ovarian cystectomy on ovarian reserve: a pairwise and network meta-analysis · 2024 · DOI

  • However, before a presumptive diagnosis of a teratoma can be made, the suspect ovary, along with the rest of the reproductive tract, should be examined ultrasonographically on several occasions to confirm that the unusual structure maintains its appearance as a teratoma.

    Equine ovarian teratomas: Diagnostic challenges illustrated by case reports · 2021 · DOI

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42 open questions have been extracted from the limitations and future-work passages of 563 Ovarian cancer diagnosis and treatment papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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