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Open research questions in Endometrial and Cervical Cancer Treatments

52 unresolved questions extracted from the limitations and future-work sections of 432 Endometrial and Cervical Cancer Treatments papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Objective: Little is known about patients with advanced ovarian cancer (AOC) who do not undergo cytoreductive surgery but receive maintenance therapy with poly (ADP-ribose) polymerase inhibitors (PARPis).

    Outcome of advanced ovarian cancer patients who do not undergo cytoreductive surgery in the era of PARP inhibitors maintenance therapy: a propensity score-based analysis · 2026 · DOI

  • 19,20 Limitations: The sample size is small, not all potential risk factors were included in the model, and future research should explore additional variables that may influence the occurrence of postoperative complications in this patient population.

    Development and validation of a nomogram prediction model for postoperative complications in elderly patients with endometrial cancer · 2026 · DOI

  • Molecular data, including assessments of recently recognized prognostic classifiers such as POLE mutations, p53 status, and mismatch repair deficiency (as introduced by The Cancer Genome Atlas, TCGA), were not available, which represents an important limitation given their emerging role in FIGO 2023 risk group stratification and their potential to modify the prognostic including impact of conventional pathological factors, LVSI(33). Similarly, the addition of chemotherapy in early-stage, high- intermediate-risk patients has yielded inconsistent results, with no clear survival benefit demonstrated in most studies.

    Prognostic determinants of survival in early-stage endometrial cancer: A retrospective analysis · 2026 · DOI

  • Whether inpatient admissions have concurrently shifted toward toxicity-like organ failure syndromes, with changing ICU use and rescue outcomes, remains unknown.

    Shifting drivers of hospitalization in endometrial cancer: Toxicity-like organ failure phenotypes in the modern treatment era. · 2026 · DOI

  • Ongoing research in endometrial cancer increasingly aims to refine the clinical utility of molecular classification and to identify novel therapeutic targets, including alternations in lipid metabolism [62, 63]. A major challenge remains the development of cost-effective surrogates for POLE muta- tion testing, which currently requires sequencing and access to specialized molecular laboratories - resources that remain limited in many clinical and diagnostic centers. Another promising avenue involves adapting the extent of surgical staging, particularly lymph node dissection, to the tumor’s molecular subtype, potentially improving prog- nostic precision and treatment outcomes [64]. Recent advances have also reshaped systemic therapy. The phase III RUBY trial demonstrated that adding dostar- limab to standard carboplatin–paclitaxel significantly improved progression-free and overall survival, estab- lishing chemoimmunotherapy as the standard of care for advanced or recurrent disease [65]. Similarly, the NRG- GY018/KEYNOTE-868 study demonstrated that pembro- lizumab combined with first-line chemotherapy improves progression-free survival in both dMMR and pMMR subgroups, underscoring the broad applicability of PD-1 blockade across molecular subtypes [66]. The DUO-E trial further established durvalumab, with or without olaparib, as an effective first-line strategy: durvalumab plus carbopla- tin–paclitaxel followed by durvalumab maintenance, with or without olaparib, yielded significant progression-free survival gains, with regulatory approval of durvalumab– olaparib maintenance in pMMR tumours and particularly pronounced benefit in p53-abnormal pMMR disease [67]. Beyond immunotherapy, the therapeutic landscape of endometrial cancer is being reshaped by antibody–drug conjugates (ADCs) and molecularly targeted agents. Early- phase data with trastuzumab deruxtecan and sacituzumab govitecan have shown clinically meaningful and durable responses in heavily pretreated, HER2- or TROP2-express- ing endometrial carcinomas, supporting ongoing phase II and phase III evaluation in this setting [68, 69]. Endocrine- targeted combinations have also demonstrated activity, as illustrated by the PALEO trial of letrozole plus palbociclib and phase II studies of abemaciclib with fulvestrant in hor- mone receptor–positive endometrioid subtypes [70], [71]. The PI3K/AKT pathway remains a critical molecular axis, with alpelisib and capivasertib showing promising activity Current Oncology Reports (2026) 28:62 1 3 62 Page 10 of 16 in genomically selected gynecologic cohorts [72]. Inhibi- tion of WEE1 kinase with adavosertib has produced antitu- mour activity in TP53-abnormal uterine serous carcinoma, supporting the broader rationale for targeting the DNA damage response (DDR) pathway [73]. Additional early- phase trials are investigating inhibitors of the PI3K/AKT/ mTOR signalling cascade, including sapanisertib, as well as DDR-targeted combinations designed to enhance sensi- tivity to PARP inhibition and immune checkpoint blockade [74]. Furthermore, next-generation ADCs directed against TROP2, FRα and HER2 are expanding therapeutic possi- bilities beyond traditional HER2-positive disease (Fucà et al. [75]). Parallel exploratory studies are focusing on epigenetic modulators and polo-like kinase (PLK) inhibition, along- side novel protein biomarkers. In particular, epigenetic alterations and overexpression of PLK4 have been impli- cated in aggressive clinicopathologic behaviour in endome- trial cancer, while emerging radiotheranostic work suggests that antigens such as MUC16 and CD24 may serve as both imaging and therapeutic targets [76, 77]. The results of pivotal phase III immunotherapy trials have already transformed clinical practice, establishing che- moimmunotherapy as the standard first-line approach for patients with advanced or recurrent endometrial cancer. The forthcoming implementation of ADC-based regimens and next-generation, biology-driven targeted therapies is antici- pated to further personalize systemic treatment and improve long-term outcomes for this challenging disease population [78].

    Decoding the 2023 FIGO Staging System in Endometrial Cancer: A Practical, Visually Guided Framework for Molecular Risk-Adapted Care Incorporating the 2025 Risk Group Update · 2026 · DOI

  • Based on the findings of this study, further multicenter research with a larger sample size is recommended to improve the generalizability of the results. Long-term follow-up studies should also be conducted to evaluate overall survival, progression-free survival, and late treatment-related toxicities. In addition, future studies should consider the inclusion of HPV-positive cases to better understand disease behavior and treatment outcomes in this subgroup.

    Comparison of outcomes and toxicities of concurrent chemo-radiation with weekly cisplatin versus weekly paclitaxel in locally advanced carcinoma cervix · 2026 · DOI

  • The study had limitations including non-randomized sampling with possible selection bias, a small sample size affecting outcome accuracy, and inability to assess HPV association due to limited testing facilities. CONCLUSION Concurrent chemoradiation with weekly paclitaxel was noninferior to weekly cisplatin in terms of treatment response. It can be used as an alternative in the treatment of locally advanced cervical carcinoma when cisplatin is contraindicated.

    Comparison of outcomes and toxicities of concurrent chemo-radiation with weekly cisplatin versus weekly paclitaxel in locally advanced carcinoma cervix · 2026 · DOI

  • Performance monitoring mechanisms, recalibration procedures, and quality assurance protocols for radiomics-AI models in cervical cancer radiotherapy are not embedded into routine clinical systems, preventing long-term validation of model stability and preventing identification of model drift.

    Radiomics and artificial intelligence in precision radiotherapy for cervical cancer: a narrative review · 2026 · DOI

  • Cost-effectiveness analysis and economic evaluation of radiomics-AI strategies for cervical cancer radiotherapy are rarely reported, leaving scalability and clinical implementation feasibility uncertain for institutional deployment.

    Radiomics and artificial intelligence in precision radiotherapy for cervical cancer: a narrative review · 2026 · DOI

  • Integration of radiomics-AI models with treatment planning systems in cervical cancer radiotherapy, inference time requirements within routine clinical workflows, regulatory requirements, data governance, model interpretability, and clinician trust mechanisms are rarely addressed in current literature.

    Radiomics and artificial intelligence in precision radiotherapy for cervical cancer: a narrative review · 2026 · DOI

  • Prospective clinical trials demonstrating whether radiomics-informed strategies for cervical cancer radiotherapy (supporting adaptive radiotherapy, dose modulation, intensified systemic treatment, or personalized surveillance) actually alter therapeutic management decisions and improve patient-centered outcomes are lacking.

    Radiomics and artificial intelligence in precision radiotherapy for cervical cancer: a narrative review · 2026 · DOI

  • Most published radiomics and AI models for cervical cancer precision radiotherapy remain at exploratory or early validation stages; evaluation in routine clinical settings is limited, indicating that technical feasibility has been demonstrated but full methodological readiness for clinical deployment has not been established.

    Radiomics and artificial intelligence in precision radiotherapy for cervical cancer: a narrative review · 2026 · DOI

  • Imaging protocols, preprocessing pipelines, feature extraction procedures, and validation strategies show substantial heterogeneity across radiomics studies in cervical cancer, fundamentally limiting cross-study comparability and preventing standardized benchmarking of radiomics-AI models.

    Radiomics and artificial intelligence in precision radiotherapy for cervical cancer: a narrative review · 2026 · DOI

  • Segmentation workflows and harmonization strategies in radiomics for cervical cancer radiotherapy are inconsistently reported across studies, leaving generalizability uncertain and preventing reliable assessment of external validity even in multicenter settings with similar imaging equipment.

    Radiomics and artificial intelligence in precision radiotherapy for cervical cancer: a narrative review · 2026 · DOI

  • Current radiation therapy planning systems such as Monaco lack automated registration algorithms, leading to temporal and spatial misalignment between ultrasound data and CT/MRI images.

    Impact of bladder volume precision control on setup errors and dosimetry in intensity-modulated radiation therapy for cervical cancer · 2026 · DOI

  • Extending the principle of bladder volume control to include multimodal stabilization could further reduce anatomical uncertainty and is a promising direction for next-level precision in pelvic radiotherapy.

    Impact of bladder volume precision control on setup errors and dosimetry in intensity-modulated radiation therapy for cervical cancer · 2026 · DOI

  • Concerning lymph node staging, firstly, there is a clear trend of expanding lymphadenectomy to the paraaortic area, followed by the sentinel node bio-psy introduction in the years 2018-2019, and finally, the complete transition to this method as the main staging procedure in 2021, when this examination was performed in 73% of surgeries, even with high-risk cancers limited to the uterus.

    Change in the trend of surgical treatment and staging of lymph nodes in endometrial cancer – results of the Oncogynecology Center, Department of Gynecology and Obstetrics, University Hospital Brnoand Masaryk University in the years 2012–2021 · 2022 · DOI

  • The so-called “sandwich” regimen of pelvic external beam radiation administered between cycles of Carboplatin/Paclitaxel (CT-RT-CT) is commonly used in clinical practice but has not been evaluated in randomized endometrial cancer trials.

    Adjuvant chemotherapy and radiation therapy with the “sandwich” method for endometrial cancer: an institutional analysis · 2021 · DOI

  • However, the optimal dose and schedule of concurrent cisplatin is not well defined, though widely accepted practice is the weekly schedule of 40 mg/m 2 for 5 weeks.

    Weekly vs. tri-weekly cisplatin based chemoradiation in carcinoma cervix: a prospective randomized study of toxicity and compliance · 2021 · DOI

  • CONCLUSION: Although there are no standard guidelines for management of FA carriers with malignancies and reports about chemo- or radiosensitivity in this population are scarce; patients with FA-A heterozygosity may have a high rate of complications from chemo/radiotherapy.

    Hypersensitivity to chemoradiation in FANCA carrier with cervical carcinoma—A case report and review of the literature · 2014 · DOI

  • Thus, whether a more powerful analysis would have de- tected an actual and clinically significant difference in DSS and DFS rates remains unclear.

    Long-Term Outcomes, Morbidity and Quality of Life in Node-Negative Early-Stage Vulvar Cancer: Sentinel Node Biopsy versus Inguinofemoral Lymphadenectomy · 2026 · DOI

  • OBJECTIVE: Pre-operative imaging has the potential to improve selection of surgical candidates in early-stage cervical cancer, but limited evidence exists on its association with post-operative adjuvant treatment.

    Pre-operative positron emission tomography scan is associated with lower rates of adjuvant treatment in surgically treated patients with cervical cancer: a 4C Working Group study. · 2026 · DOI

  • While this effectively mea- sures the reproducibility of the patient’s skeletal position, it does not account for potential changes in soft-tissue anatomy or tumor morphology (such as shrinkage) that may occur during the treatment course.

    Impact of bladder volume precision control on setup errors and dosimetry in intensity-modulated radiation therapy for cervical cancer · 2026 · DOI

  • Comprehensive management of tumor motion and deformation may require additional soft-tissue-based image guidance techniques beyond bony anatomy registration.

    Impact of bladder volume precision control on setup errors and dosimetry in intensity-modulated radiation therapy for cervical cancer · 2026 · DOI

  • Setup errors in this study were based on bony anatomy registration and do not account for potential changes in soft-tissue anatomy or tumor morphology such as shrinkage during the treatment course.

    Impact of bladder volume precision control on setup errors and dosimetry in intensity-modulated radiation therapy for cervical cancer · 2026 · DOI

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52 open questions have been extracted from the limitations and future-work passages of 432 Endometrial and Cervical Cancer Treatments 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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