External comparator cohort (ECC) studies with real-world data (RWD) may provide more reliable estimates of treatment differences compared to single-arm trials (SAT), yet they face limitations such as selection bias and data heterogeneity. This study assessed the perceived strength of evidence of ECC studies compared to SAT and randomized controlled studies (RCT). The study included healthcare professionals (HCP) from the European Hematology Association (EHA), the European Society for Medical Oncology (ESMO), and assessors from international regulatory agencies (RA). A conjoint analysis evaluated strength of evidence ratings for establishing an effect on OS for different hypothetical scenarios, based on different designs, RWD quality, and observed OS improvement, for a new cancer treatment for advanced disease and no effective treatments. Participants from HCP organizations rated RWD studies favorably (advantages outweigh disadvantages) more frequently (47.6%; n = 103) compared to RA participants (12.9%; n = 116). Compared to a SAT, a high-quality RWD ECC study showing a 1.5-month and 3-month OS improvement had 2.7 (95% CI: 1.9-3.8) and 14.7 (95% CI: 10.0-21.5) times higher odds of receiving a higher strength of evidence rating, respectively. The OR for RCT v. SAT was 36.4 (95% CI: 24.0-55.2) and 358.4 (95% CI: 217.3-591.3), respectively. Strength of evidence ratings were associated with maximum acceptable risk of severe or symptomatic toxicity. In conclusion, when evaluating the OS of new therapies, ECC studies with RWD, especially when based on high-quality RWD or demonstrating a larger OS benefit, were rated as more convincing than SAT without a formal control.

To identify randomised control trials (RCTs) of treatments (recommended by the National Comprehensive Cancer Network (NCCN), the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines and clinical expertise) for the second- or later-line treatment of advanced/metastatic gastric cancer. To determine the relative efficacy and safety of the treatments. RCTs were identified from a Rapid Literature Review and a published systematic review. Identified RCTs were subject to data-extraction and narrative review. Eligible RCTs were included in evidence networks to determine relative efficacy and safety of the treatments. In total, 44 RCTs (pertaining to eleven treatments), were identified for data-extraction and narrative review; 37 in the second-line setting, five in the second- and later-line setting and two in the third- and later-line setting. Evidence networks were feasible for the second-line treatments only. No statistically significant differences, across treatments, for key efficacy outcomes (overall-survival, progression-free survival), and additional outcome (objective-response rate) were identified. Pembrolizumab was associated with a statistically significant decreased risk of Grade ≥ 3 treatment-related adverse effects versus paclitaxel; no other significant differences, across treatments, were identified for this outcome. The appreciable number of RCTs identified indicates that the treatment landscape here is rapidly evolving. The introduction of novel treatments, in the second-line setting, has not had a statistically significant impact on key efficacy outcomes, and has had little impact on safety outcomes, versus more established treatments. There remains a need for novel treatments that will have a significant benefit on efficacy and safety outcomes.

Oncofertility, a multidisciplinary field that integrates oncology and reproductive medicine, is a vital component of comprehensive cancer care. This review compares fertility-related recommendations for adults with newly diagnosed cancer who are considering fertility preservation (FP) before treatment. Guidelines reviewed include the 2025 National Comprehensive Cancer Network (NCCN) Survivorship Guideline, 2025 ASCO Guideline on FP, 2022 Clinical Oncology Society of Australia (COSA) FP Guideline, and 2020 European Society for Medical Oncology (ESMO) Clinical Practice Guideline. Recent guidelines from NCCN, ASCO, COSA, and ESMO were reviewed and compared for recommendations on fertility risk discussions, female and male preservation methods, multidisciplinary care, future pregnancy, and contraception. All guidelines emphasize early, patient-centered discussions about fertility risks and preservation options before initiating cancer treatment. Embryo and oocyte cryopreservation are universally recommended as standard and effective FP methods for women. Ovarian tissue cryopreservation and ovarian transposition are recommended as alternative options. Sperm cryopreservation is strongly recommended, with ASCO and NCCN additionally supporting testicular sperm extraction for post-treatment FP. The use of gonadotropin-releasing hormone agonists is supported by COSA, ESMO, and NCCN in people with breast cancer at diagnosis, while ASCO limits its recommendation to adjunct use alongside established FP techniques. All guidelines highlight the importance of multidisciplinary care, including specialized oncofertility counseling and referrals to fertility and mental health specialists. Pregnancy after cancer treatment is generally considered safe across all guidelines, and only COSA and ESMO provide specific recommendations regarding contraception. There is a strong consensus on FP methods and the importance of early counseling. However, further high-quality research is necessary to strengthen the evidence base and improve guideline recommendations for fertility in people with cancer.

IntroductionDiabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS) are well-recognised acute complications of diabetes, but their presentation in patients with cancer—particularly as an initial manifestation—is poorly understood. ¹ Additionally, a small subset of rapidly progressive malignancies can present with metastatic disease in the absence of an identifiable primary tumour. These are classified as cancers of unknown primary origin (CUP), accounting for 3–5% of all cancers. ² Identifying CUP poses significant diagnostic and management challenges, especially in the acute care setting.²The European Society for Medical Oncology (ESMO) and the National Comprehensive Cancer Network (NCCN) recommend thorough physical examination, comprehensive laboratory testing, and whole-body imaging (CT and PET scans) for all patients with metastatic cancer of unknown primary (CUP).²Clinical CaseWe report a rare case of a 37-year-old woman with no known history of diabetes who presented to the emergency department with symptoms of vomiting, weight loss, and persistent headaches. Initial investigations revealed hyperglycaemia, ketonuria, and metabolic acidosis consistent with DKA. Neurological symptoms prompted an urgent CT head, which revealed multiple cerebral lesions with surrounding oedema. Subsequent MRI brain confirmed multiple ring-enhancing lesions suggestive of metastases. CT thorax/abdomen/pelvis and PET scan demonstrated widespread metastatic involvement including lungs, liver, and lymph nodes, but no identifiable primary tumour. Comprehensive infectious screening (including HIV, TB, and toxoplasmosis) and tumour markers (CEA, CA-125, CA 19-9, AFP, and beta-HCG) were unremarkable. An excisional biopsy of a cervical lymph node revealed poorly differentiated adenocarcinoma, consistent with a diagnosis of cancer of unknown primary (CUP).The patient’s DKA was promptly managed with insulin therapy and fluid resuscitation. Cerebral oedema was treated with high-dose dexamethasone. The case was discussed in a multidisciplinary team (MDT) meeting, and the patient was placed on CUP pathway. On follow-up, the malignancy remained of unknown origin, and the patient was referred for palliative oncological care.ConclusionThis case highlights the rare presentation of diabetic ketoacidosis as the initial symptom of an occult malignancy, specifically cancer of unknown primary origin. It underscores the importance of a comprehensive and multidisciplinary approach when atypical features accompany common endocrine emergencies. Clinicians should maintain a high index of suspicion and consider broader differentials when metabolic disturbances coexist with unexplained neurological or systemic signs.

Lung cancer biomarkers.

Addition of androgen-receptor pathway inhibitors to standard of care in metastatic hormone-sensitive prostate cancer: A systematic review and meta-analysis.

The evolving landscape of leptomeningeal metastases from NSCLC: an international, contemporary, multicenter cohort study.

Abstract Objective The European Society of Medical Oncology (ESMO) recommends a target haemoglobin (Hb) of 12 g/dL in patients receiving active cancer treatment. Untreated anaemia may impair treatment response and reduce survival. This study evaluated the identification and management of anaemia in patients with resectable oesophagogastric cancer at Oxford University Hospitals (OUH) and assessed whether anaemia contributed to delays in chemotherapy or surgery, aiming to identify areas for pathway improvement. Method A retrospective review was conducted over four months (September–December 2024), including 39 patients. Longitudinal data on Hb, MCV, and haematinics were collected at key milestones: referral, pre-neoadjuvant chemotherapy (pre-NAC), post-NAC, and pre-surgical assessment. Referrals and treatment for anaemia (oral/IV iron or transfusion) were reviewed by source, timing, and delivery mode (elective/emergency). Results At baseline, 18/39 (46%) patients were anaemic, and 11/39 (28%) met ESMO criteria for treatment. Of these, 8/11 (73%) received treatment (4 oral iron, 4 iron infusions). Prior to surgery, anaemia was present in 25/36 (69%), with 9/36 (25%) meeting treatment criteria. Of those, 5/9 (56%) did not receive treatment prior to surgery. Management was initiated by pre-op, oncology, and surgical teams. Three patients did not receive treatment due to limited capacity. One required emergency admission. No surgical delays occurred. Conclusions Anaemia is common and worsens during neoadjuvant chemotherapy for oesophagogastric cancer. Many patients remain untreated despite meeting ESMO criteria. Routine haematinics at defined milestones may prompt earlier intervention. A protocol-driven, MDT-embedded approach would help optimising treatment of anaemia prior to definitive surgery.

To compare and summarise the most up to date international guidelines and major recommendations for the management of small testicular masses (STMs). A systematic search was conducted in PubMed, EMBASE, Scopus, Google Scholar, and the Cochrane Library up to 1 November 2024. The latest editions of five international guidelines were included in the review: the European Association of Urology 2025; the National Comprehensive Cancer Network 2024; the American Urological Association 2023; the Canadian Urological Association 2022; and the European Society for Medical Oncology 2018. The Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool was applied by two authors (M.T. and G.F.) to assess the quality of these guidelines. Emerging evidence supports testis-sparing surgery (TSS) as a viable option for managing STMs, showing acceptable oncological outcomes and preservation of gonadal function in select patients. The shared indications for TSS include indeterminate STMs identified on ultrasonography with negative tumour markers, particularly in the case of a solitary testis or of bilateral tumours. Where intra-operative frozen section analysis is available, and confirms a benign lesion, a radical orchidectomy could be avoided. Consensus across guidelines favours TSS in suitable cases, balancing oncological control with functional outcomes and informed patient decisions.

Treatment for advanced non-small cell lung cancer (NSCLC) with activating mutations in HER2 relies on chemo-immunotherapy in the first-line setting, which fails to address the underlying human epidermal growth factor receptor 2 (HER2)-driven biology. This unmet need is fueling a shift toward HER2-targeted therapies for this patient population and for earlier lines of therapy. The European Society for Medical Oncology (ESMO) Congress 2025, held in Berlin, Germany, from October 17th–21st, included discussions of recent advances in the first-line treatment of HER2-mutant NSCLC. Among the highlights was the presentation of first-line data from the Beamion LUNG-1 Phase Ib expansion study evaluating zongertinib, an oral, HER2-selective tyrosine kinase inhibitor (TKI), in treatment-naive patients with advanced HER2-mutant NSCLC. The study demonstrated a confirmed objective response rate (ORR) of 77% by blinded independent central review (BICR), with a median time to response of 1.4 months. The study also demonstrated early signs of durability, with a 6-month duration of response (DoR) rate of 80% and a 6-month progression-free survival (PFS) rate of 79%. The safety profile of first-line zongertinib was manageable, with mostly low-grade treatment-related adverse events (TRAE) and a low incidence of interstitial lung disease (ILD)/pneumonitis (3%, both Grade 2). Additionally, ESMO 2025 featured data from SOHO-01, which evaluated another oral HER2 TKI, sevabertinib, in treatment-naive patients, further signaling a shift in the first-line treatment of HER2-mutant NSCLC from chemotherapy with or without immunotherapy to HER2-targeted therapies.

Data presented at the European Society for Medical Oncology (ESMO) Congress 2025 signal a potential shift in the management of early-stage human epidermal growth factor receptor 2 (HER2)-positive (HER2+) breast cancer. Results from the pivotal Phase III DESTINY-Breast05 and DESTINY-Breast11 trials suggest that trastuzumab deruxtecan (T-DXd) improves outcomes in curative-intent settings. The DESTINY-Breast05 trial demonstrated a statistically significant improvement in invasive disease-free survival (IDFS) with T-DXd compared to trastuzumab emtansine (T-DM1) in the adjuvant setting for patients with high-risk residual disease, reducing the risk of recurrence or death by 53%. This benefit was consistent across subgroups, and the safety profile of T-DXd was manageable. In DESTINY-Breast11, treatment with T-DXd followed by an anthracycline-free neoadjuvant regimen (paclitaxel, trastuzumab, and pertuzumab) resulted in a pathologic complete response (pCR) rate of 67.3%, with a more favorable safety profile than that of traditional anthracycline-containing therapy. These findings suggest a potential shift in treatment approaches for high-risk early-stage HER2+ breast cancer, with incorporation of antibody–drug conjugates (ADC) in pre- and post-operative settings to improve efficacy and tolerability compared to conventional chemotherapy backbones.

Inherited mutations in the BRCA1/BRCA2 genes significantly increase the risk of breast and ovarian cancer in women of reproductive age, posing a clinical and socioeconomic challenge due to loss of fertility during cancer treatment and preventive interventions. The expansion of genetic testing programs is shifting the focus to proactive management of reproductive potential, requiring the integration of oncology, reproductive medicine, and medical genetics. The novelty of this review lies in its comprehensive synthesis of data on the impact of treatment and prevention of BRCA-associated cancer on fertility and a critical assessment of the effectiveness of fertility preservation strategies. Purpose of the study . To summarize and analyze current advances, clinical guidelines, and unresolved issues related to preserving reproductive function in women carrying BRCA1/BRCA2 mutations. Materials and methods . A systematic search of PubMed/MEDLINE, Embase, the Cochrane Library, and Web of Science was performed, along with an analysis of international guidelines (ESHRE (European Society of Human Reproduction and Embryology), ASCO (American Society of Clinical Oncology), ASRM (American Society for Reproductive Medicine), NCCN (National Comprehensive Cancer Network), ESMO (European Society for Medical Oncology)). Keywords: “BRCA1,” “BRCA2,” “fertility preservation,” “oocyte cryopreservation,” “embryo cryopreservation,” “ovarian tissue cryopreservation,” “PGT-M,” “PARP inhibitors,” and “chemotherapy gonadotoxicity.”, in the period of 2005–2025. Studies with incomplete data, duplicates, reviews of low methodological quality, and case series with fewer than 10 observations were excluded. Priority was given to meta-analyses, RCTs, large cohorts, and consensus reports. Results. The included studies included cancer patients before and after treatment, BRCA carriers with and without prophylactic strategies, and IVF/ICSI cohorts with cryopreservation. Alkylating agents and taxanes have been shown to increase the risk of premature ovarian failure, while GnRH agonists partially reduce the risk of ovarian toxicity. The efficacy of oocyte and embryo cryopreservation in BRCA-positive women is comparable to the population-­based efficacy with optimized stimulation (GnRH antagonists, letrozole-­containing protocols). Ovarian tissue cryopreservation is applicable in urgently needed patients but requires oncoprotective assessment. PGT-M ensures the selection of mutation-free embryos. Multidisciplinary pathways improve the timelines of referrals and the completion rate of fertility preservation programs Conclusion. Early identification of BRCA-positive women and the integration of a gynecologic oncologist, reproductive specialist, and geneticist enable personalized strategy selection: gamete/embryo cryopreservation, ovarian tissue, pharmacoprotection, and PGT-M. Standardized stimulation protocols and therapy timing, long-term safety and fertility data, and economic access models are needed. Improvements in biotechnology and patient pathways improve reproductive outcomes and quality of life.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths worldwide, characterised by significant clinical heterogeneity and therapeutic complexity. The Barcelona Clinic Liver Cancer system has long been the primary framework for staging and treatment allocation; however, its 2025 update, while introducing important refinements, retains the structural limitations inherent to stage-based algorithms. Recent guidelines from international organisations - including the European Association for the Study of the Liver (2025), the European Society for Medical Oncology (2025), the American Association for the Study of Liver Diseases (2023), and various national bodies - have shifted towards flexible, patient-centred approaches that emphasise multidisciplinary tumour board decision making, feasibility assessment, and dynamic therapeutic adaptation. The multiparametric therapeutic hierarchy (MTH) has been introduced as an expert opinion framework to formalise this evolving approach. MTH maintains the prognostic value of staging while separating it from treatment decisions, replacing inflexible algorithms with a tri-axial model: an ordinal hierarchy of therapies ranked by survival benefit, a structured multiparametric feasibility assessment, and a converse therapeutic hierarchy allowing upward movement through curative-intent strategies over time. The model aligns with the conceptual and methodological directions of current guidelines, offering an auditable, adaptable, and ethically consistent decision-making tool for expert multidisciplinary teams. Although based on strong evidence supporting its conceptual foundations, MTH remains a “checklist” that requires prospective validation and additional detail with evidence-based parameters, including biomarkers, imaging criteria, patient-reported outcomes, and integration of artificial intelligence. By providing the conceptual basis for this Special Issue “The Multiparametric Therapeutic Hierarchy: A Multidisciplinary Approach to HCC Management”, MTH aims to support a coherent, multidisciplinary, and future-oriented framework for personalised management of HCC.

ESMO-ESTRO consensus statements on the safety of combining radiotherapy with CDK4/6, HER2, PARP, or mTOR inhibitors.

Review of the European Society for Medical Oncology (ESMO) Congress 2025

Gastrointestinal stromal tumors (GISTs) are the most common soft tissue sarcomas of the gastrointestinal tract, with most cases harboring oncogenic driver mutations in the KIT proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor α (PDGFRA). The advent of targeted therapy, notably the first tyrosine kinaseinhibitor (TKI) imatinib, has revolutionized the treatment landscape for GISTs. Recent advancements and emerging evidence in the diagnosis, treatment, and assessment of treatment response to TKIs in GISTs have led to updates to major clinical practice guidelines, including the latest guidelines from the Chinese Society of Clinical Oncology (CSCO, 2024), the US National Comprehensive Cancer Network (NCCN, version 1.2025), and the European Society for Medical Oncology (ESMO, 2022). Although these guidelines align on fundamental principles, some key differences in recommendations exist. This commentary highlights discrepancies in the recommendations for managing GISTs as outlined in these major guidelines. Based on emerging new evidence from recent studies, the authors propose recommendations to be considered for inclusion in future guideline updates to optimize management strategies and ultimately improve the outcomes of patients with GISTs.

1139P Asia-Pacific analysis of European Society for Medical Oncology (ESMO) study on availability, out of pocket costs (OPC) and accessibility of antineoplastics medicines

IntroductionIncluding drugs in the National Essential Medicines List is a complex process that considers population, budget, and socioeconomic factors. In Ecuador, these decisions rely on efficacy and safety data from existing studies without estimating the real impact and clinical benefit of the drugs. This study proposed a multicriteria model using minimal clinically important difference (MCID) values to evaluate oncologic drugs for inclusion.MethodsSafety and efficacy were assessed using MCID values for primary outcomes, incorporating measures such as overall survival (OS), disease-free survival (DFS), and complete remission, following the Magnitude of Clinical Benefit Scale (v1.1) of the European Society for Medical Oncology. Epidemiological and demographic data were obtained from the National Institute of Statistics and quality of life was evaluated using EuroQol-5D scores. Information on oncologic drugs and regulatory considerations was sourced from authoritative organizations. All parameters were systematically organized and weighted, ensuring the total criteria groups accounted for 100 percent.ResultsSeven criteria groups were established, each containing parameters evaluated on a scale from zero to five, designed to reward or penalize based on assessment goals. The groups were weighted from five to 30 percent to reflect their relative importance or impact on decision-making. The criteria and weights were as follows: (i) disease burden (30%); (ii) efficacy (30%); (iii) safety (15%); (iv) quality of life impact (5%); (v) availability and accessibility (5%); (vi) therapeutic alternatives and international recommendations (10%); and (vii) other important criteria (5%). Consequently, scores were weighted differently across groups.ConclusionsAccurately estimating the impact of oncologic drugs is critically important for public health. Implementing this multicriteria model will provide a more efficient, objective, and systematic framework for evaluating the inclusion, modification, or exclusion of oncologic drugs with respect to the National Essential Medicines List. This approach enhances decision-making processes and ensures the optimal selection of anti-cancer therapies, ultimately improving patient outcomes and resource allocation in Ecuador.

PROMENADE: pembrolizumab for early ER-low/HER2-negative breast cancer, real-world French cohort

ObjectivesAdvanced non-small cell lung cancer (NSCLC) treatment paradigms include prolonged systemic anti-cancer therapy (SACT) courses. Treatment breaks during significant life events may align with patients’ care goals but are poorly studied. We evaluated the temporal patterns of palliative SACT received by NSCLC patients during Christmas 2006–2023, a period during which treatment options increased.MethodsA retrospective, longitudinal study using electronic records examined palliative SACT for NSCLC in the month of December 2006–2023. It was conducted in a hospital designated as a European Society of Medical Oncology Designated Centre of Integrated Oncology and Palliative Care Services.ResultsIn December 2006–2023, 250 patients with NSCLC received palliative SACT with a mean age of 65.5 years (range: 36–94). Adenocarcinoma constituted 171 cases, and 188 patients were stage IV. During their last Christmas, 53% received palliative SACT (n = 133/250), 4% died within 30 days of treatment (n = 5/133) and 5% spent their last Christmas Eve/Day and/or Boxing Day admitted in hospital (n = 7/133). The proportion of those alive the following Christmas increased over the study period (p < 0.001).ConclusionsMost advanced NSCLC patients received palliative SACT during their last Christmas, reflecting the need for greater cognisance of goal-concordant care and for studies to provide an evidence basis for treatment breaks.