This narrative review examines the evolving treatment landscape for estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (mBC), with a primary focus on the role of ESR1 mutations (ESR1m) and their clinical implications, particularly the therapeutic role of elacestrant. The review synthesizes clinical trial data, real-world data, and molecular insights. It outlines how ESR1m drive endocrine resistance and influence therapeutic outcomes. A review of pivotal studies, including subgroup analyses from the EMERALD trial, highlights the efficacy and well-characterized safety profile of elacestrant in patients previously treated with endocrine therapy and cyclin-dependent kinase 4 and 6 inhibitors, particularly those with prolonged prior benefit from endocrine therapy + cyclin-dependent kinase 4 and 6 inhibitors, and shows consistency across demographic and molecular subsets. Additionally, the review discusses advances in biomarker-driven treatment sequencing, the impact of co-mutations such as PIK3CA mutations and ESR1m, and testing considerations to optimize precision medicine strategies. Real-world outcomes are evaluated in the context of clinical trial findings, demonstrating differences in treatment response and supporting recommendations for the routine assessment of ESR1m. The review aims to provide clinicians and researchers with a comprehensive and up-to-date perspective on the optimal integration of oral selective estrogen receptor degraders (SERD), particularly elacestrant, into individualized management algorithms for ER+/HER 2- mBC.
This symposium took place during the European Society for Medical Oncology (ESMO) Congress 2025 in Berlin, Germany. The aim of the symposium was to discuss strategic treatment sequencing and novel second-line and beyond (2L+) approaches for patients with oestrogen-receptor-positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced/metastatic breast cancer (a/mBC) after first-line (1L) treatment with endocrine therapy (ET) plus inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6i). Tiffany Traina from Memorial Sloan Kettering Cancer Center, New York, USA, described evolving standards in 2L+ ER+/HER2- mBC, including standard of care (SOC); primary and secondary endocrine resistance, emphasising that most patients with mBC will eventually develop resistance to ET; and ESMO guidelines for ER+/HER2- mBC, which are directed by endocrine sensitivity status and biomarkers. Sherko Kümmel from the Interdisciplinary Breast Unit, Kliniken Essen-Mitte, Germany, presented recommendations and strategies for treating ET-eligible patients after 1L ET plus CDK4/6i, including data from the EMERALD approval study with the selective oestrogen receptor degrader (SERD) elacestrant in patients with ESR1 mutations, and results for studies of the SERDs vepdegestrant, imlunestrant, and camizestrant. Frederik Marmé from University Hospital Mannheim and Medical Faculty Mannheim of Heidelberg University, Germany, discussed making biomarker-driven treatment decisions, including identifying mutations to drive therapeutic choices in mBC, the characteristics of ESR1 mutations, and the importance of timely ESR1 mutation testing at each progression during metastatic treatment, ideally by analysing circulating tumour DNA (ctDNA) from a liquid biopsy.
Globally, there are more than 650,000 newly diagnosed cases of bladder cancer annually, with up to approximately 80% of these cases being non-muscle invasive bladder cancer (NMIBC). Approximately 25% of NMIBC cases are classified as high risk. The current standard treatment for high-risk NMIBC is intravesical instillation of Bacillus Calmette-Guérin (BCG). Up to 40% of patients with high-risk NMIBC have disease recurrence or progression on this treatment. The standard of care for BCG-unresponsive high-risk NMIBC has traditionally been radical cystectomy; however, this is a complex, life-altering procedure that is associated with substantial morbidity, considerable impact on quality of life, and a 90-day post-surgery mortality rate of up to 8%. Many patients are ineligible for radical cystectomy or refuse this surgery. There is an unmet medical need for effective, bladder-sparing treatments for patients with BCG-unresponsive high-risk NMIBC who wish to preserve their bladder or are too frail for major surgery. For this article, EMJ conducted interviews in September 2025 with three key opinion leaders: Ashish Kamat from the Department of Urology, University of Texas, MD Anderson Cancer Center, Houston, USA; Joshua Meeks from the Department of Urology, Northwestern Medicine, Chicago, Illinois, USA; and Félix Guerrero-Ramos from the Department of Urology, Hospital Universitario 12 de Octubre, Madrid, Spain, to discuss recent developments in BCG-unresponsive NMIBC research. The experts discussed the diagnosis of patients with NMIBC with carcinoma in situ (CIS) with or without papillary disease, and current treatment approaches for BCG-unresponsive high-risk NMIBC. In addition, they looked at the complete response (CR) and duration of response (DOR) results in patients with BCG-unresponsive, high-risk NMIBC with CIS with or without papillary disease (Cohort 2) in the SunRISe-1 study. They also highlighted the importance of considering both CR and DOR to give a complete picture of overall clinical benefit. Following this, Kamat, Meeks, and Guerrero-Ramos described the safety profile of gemcitabine intravesical releasing system (Gem-iDRS) and quality-of-life data in Cohort 2 of the SunRISe-1 study. The next topic of discussion was the disease-free survival (DFS) rates in BCG-unresponsive high-risk papillary disease-only NMIBC (Cohort 4) in the SunRISe-1 study. Finally, the experts outlined the changing landscape and potential future developments in BCG-unresponsive NMIBC clinical practice and research in the context of the recent approval of the Gemcitabine Intravesical System (Gem-iDRS), as well as advances in diagnosis, treatment, and patient support they would like to see.
Aim: To provide practical recommendations to support the use of enfortumab vedotin combined with pembrolizumab (EV+P) for the first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma (mUC) eligible for platinum-based chemotherapy who present with comorbid conditions. Method: An international advisory panel of experts was convened to provide input into the development of these recommendations. The panel reviewed representative clinical scenarios involving patients with mUC and discussed available evidence, as well as their clinical experience, to determine key practical considerations before and during EV+P administration. Results: Key recommendations for patients with peripheral neuropathy, skin toxicities, diabetes/hyperglycaemia, impaired renal function, frailty, obesity, and ocular disorders were presented. EV+P is the standard-of-care first-line treatment for patients with unresectable or mUC who are eligible for platinum-based chemotherapy, and patients who meet its approved indication (per the Summary of Product Characteristics) should be able to have access to it without unnecessary clinical restrictions. The expert panel considered that clinicians must familiarise themselves with its safety considerations and adverse event management strategies, especially in potentially challenging scenarios such as its use in patients with baseline comorbidities. Best practice was regarded as initiating EV+P at the recommended starting dose, with dose modifications as required. Conclusion: Clinical judgment and shared decision-making are key to help optimise EV+P treatment, especially in patients with complex clinical profiles.
According to USA data, around 15% of patients with endometrial cancer (EC) have advanced disease at diagnosis, which is associated with poor survival rates and a high risk of recurrence. This symposium explored treatment strategies in advanced EC (aEC), focusing on the key role of immunotherapy in combination with targeted treatment such as the tyrosine kinase inhibitor (TKI), levatinib. Experts provided important real-world insights into treatment decision-making and the management of adverse events in order to optimise outcomes for patients.
Aggressive angiomyxoma (AA) is a rare, locally invasive, benign tumour that mostly affects women of reproductive age. Its occurrence during pregnancy is extremely rare and may delay diagnosis due to its painless, gradual growth and resemblance to common vulvovaginal lesions. The authors report a 23-year-old primigravida who presented in active labour with a large vulval mass. The mass had progressively enlarged during pregnancy, causing discomfort in daily activities. An emergency lower segment caesarean section was performed after excision of the 30x21x10 cm mass. Histology confirmed AA. Postoperative recovery was uneventful, and the patient was discharged with plans for long-term follow-up. This case emphasises the clinical importance of AA during pregnancy, its potential to mimic other vulval lesions, and the necessity for surgical management and histopathological diagnosis, along with close follow-up due to its high risk of local recurrence.
Lung cancer is one of the most common malignant tumours worldwide, with non-small cell lung cancer (NSCLC) accounting for the largest number of cases among both men and women. Poor patient prognosis due to therapeutic resistance remains a current issue, underscoring the need for a more comprehensive understanding of the underlying biology of the pathogenesis and progression mechanisms of NSCLC. Integrating multi-omics approaches, such as genomics, transcriptomics, proteomics, and metabolomics, has become crucial for studying the underlying biology of complex diseases like lung cancer. Applying these methods not only enhances knowledge of the mechanisms of lung cancer but also plays a pivotal role in identifying biomarkers and therapeutic targets for implementing personalised treatment plans. This review quantitatively analyses the predictive capability of integrated multi-omics models by synthesising findings from studies utilising clinical data (including survival outcomes and treatment response) with multi-omics technologies to pinpoint essential biomarkers and pathways associated with NSCLC. The author focused on comparing the reported predictive accuracy metrics of these models and the consistency of identified key biomarkers across different studies. The author highlights the importance of integrating multi-omics analyses in the development of targeted therapies, and offers a roadmap for future clinical applications, emphasising challenges in data integration and biomarker validation, alongside opportunities for novel clinical trial designs. This review aims to provide a comprehensive quantitative assessment of the current state of integrated multi-omics in NSCLC, ultimately informing the design of more effective personalised therapeutic strategies and future research directions.
Hepatocellular carcinoma (HCC) is the sixth leading cause of cancer-related mortality worldwide. Despite the availability of therapeutic options such as surgical resection, radiofrequency ablation, molecular-targeted agents, and liver transplantation, HCC shows a poor prognosis and limited responsiveness to conventional treatments. The tumour immune microenvironment (TME) influences key processes in HCC, including selection pressure on tumour cells, immune evasion, tumour evolution, treatment resistance, and recurrence. Among immune components within the TME, T cells, dominant among tumour-infiltrating lymphocytes (TIL), exert both suppressive and promotive effects on tumour growth. Thus, T cell-mediated immune responses are fundamental to cancer surveillance and elimination. Research highlights the crucial role of TILs in HCC prognosis, pathogenesis, and immunotherapy. Subpopulations such as Foxp3+ regulatory T cells, CD8+ cytotoxic T cells, and CD3+/CD4+ helper T cells show complex and often contrasting roles. However, the TME often induces T cell exhaustion or dysfunction, facilitating tumour progression and immune evasion. Understanding immune dysregulation is vital for improving anti-tumour immunity and refining T cell function. This review examines TIL subpopulation roles in HCC, emphasising their plasticity and therapeutic relevance. It also covers emerging T cell-based immunotherapies, especially TIL-based adoptive transfer and CAR-T cell therapy, both showing promise in preclinical and early clinical trials. These novel approaches offer new hope for enhancing immune-driven tumour eradication and improving HCC outcomes.
Introduction: Pinealoblastomas are rare, aggressive, Grade 4 tumours of the pineal gland, predominantly affecting children. Their occurrence in adults is exceedingly rare, posing significant diagnostic and therapeutic challenges due to the lack of standardised management protocols. Case Presentation: The authors present the case of a 23-year-old woman with a 3-month history of hearing loss. Brain MRI revealed a large (6.5×5 cm), unresectable pineal region tumour causing obstructive hydrocephalus. Biopsy confirmed the diagnosis of pinealoblastoma. Initial attempts at radiotherapy were precluded by severe agitation. A multidisciplinary team decision led to treatment with induction chemotherapy (cisplatin and etoposide) followed by craniospinal radiotherapy (54 Gy total dose) using the volumetric modulated arc therapy technique. Outcomes: The patient tolerated the treatment well, with significant improvement in her neuropsychiatric status. A post-therapeutic MRI at 3 months showed an 80% tumour regression (near-complete remission) and resolution of hydrocephalus. The patient made a full neurological recovery and successfully resumed her university studies. Conclusion: This case demonstrates that a sequential approach of induction chemotherapy followed by high-dose radiotherapy can be a highly effective strategy for managing unresectable pinealoblastoma in adults, leading to excellent oncological and functional outcomes. It underscores the need for adaptive, multidisciplinary management and highlights the potential of non-surgical modalities.
