Oncology and Therapy最新文献

Introduction: Muscle-invasive bladder cancer (MIBC) is an aggressive form of bladder cancer characterized by high rates of metastasis and recurrence. Given recent advances in the treatment landscape, real-world evidence on current treatment patterns and outcomes remains limited, particularly outside of the USA. This study aimed to describe characteristics, treatment patterns, and outcomes of patients with MIBC undergoing radical cystectomy (RC) in a contemporary real-world setting in Germany.

Methods: Adult patients with bladder cancer (BC) who underwent RC between October 2021 and June 2023 were identified from two German claims databases (AOK PLUS, GWQ). Patients with partial cystectomy, secondary malignant neoplasms, immunotherapies for metastatic disease prior to RC, radiotherapy, or in situ disease ≤ 6 months pre-RC were excluded. Patient characteristics and treatment patterns (neoadjuvant [NAT, ≤ 6 months pre-RC] and adjuvant periods [AT, ≤ 6 months post-RC]) were investigated in a descriptive analysis. Time to recurrence (from RC until end of follow-up [study period end: Dec 31, 2023]) was assessed as an exploratory outcome.

Results: The study sample included 319 patients from AOK PLUS (n = 243 male patients, n = 76 female patients; mean age 71.4 ± 9.7 years) and 273 patients from GWQ (n = 227 male patients, n = 46 female patients; mean age 68.6 ± 10.1 years). Surgery without NAT/AT was the most common treatment (75.9% AOK, 74.0% GWQ). NAT and AT therapy utilization was low (NAT: 12.5% AOK, 17.2% GWQ; AT: 12.5% AOK, 12.1% GWQ; NAT and AT: 0.9% AOK, 3.3% GWQ). The most common adjuvant therapies received were chemotherapy (8.5% AOK, 7.0% GWQ) followed by immunotherapy/nivolumab (3.8% AOK, 4.8% GWQ), while < 2.5% received radiotherapy. The 12- and 24-month recurrence-free survival rates were 76.5% and 67.2% (AOK) and 73.7% and 69.6% (GWQ), respectively.

Conclusion: The most prevalent treatment approach for MIBC was RC alone (in the absence of NAT or AT). The uptake of new therapeutic options, such as adjuvant nivolumab, in the real world was low, highlighting underutilization of available therapies.

The management of advanced prostate cancer has evolved significantly with the advent of androgen receptor-targeted agents (ARTAs) and docetaxel, which now form the cornerstone of first-line systemic therapy in advanced disease. However, as increasing numbers of patients progress after exposure to both an ARTA and docetaxel, optimal treatment sequencing in the post-ARTA, post-docetaxel metastatic castration-resistant prostate cancer (mCRPC) setting remains an area of clinical uncertainty, with limited comparative data to guide decisions. This narrative review synthesises the current evidence surrounding treatment strategies for mCRPC in this later-line setting. Available therapeutic options include radioligand therapy (e.g. lutetium-177-PSMA-617), cabazitaxel, PARP inhibitors (particularly for patients with DNA repair gene alterations), second-line ARTAs, further chemotherapy and immunotherapeutic approaches. However, direct head-to-head trials comparing these modalities are sparse, and much of the available data comes from retrospective or subgroup analyses, necessitating a nuanced interpretation of outcomes and limitations. Beyond efficacy, this article emphasises the critical role of practical and individualised considerations in therapy selection. These include toxicity profiles, patient comorbidities and preferences, biomarker-driven stratification (e.g. BRCA status, PSMA expression, sites of metastases), and health system factors such as drug availability and reimbursement policies, which may significantly influence access to optimal care. Finally, the review provides an overview of promising emerging therapies poised to expand the treatment landscape for mCRPC. These include bispecific T cell engagers, androgen receptor degraders, and antibody-drug conjugates, which are currently under investigation in clinical trials and may soon offer new avenues for treatment beyond traditional mechanisms.

Similar to other sub-Saharan regions, east African countries struggle to meet their overwhelming medical challenges, including a lack of well-trained doctors. New strategies for sub-speciality training are underway that may improve the workforce for head and neck surgeons and lessen the burden for patients with morbid and life-threatening diseases of this region. Detailing this approach is intended to encourage further training activity, increase global awareness, and create more intercontinental collaboration toward an improved skilled surgical workforce.

Urogenital cancers, including prostate, kidney, and bladder cancer, remain a significant clinical challenge due to their high incidence, molecular heterogeneity, and frequent resistance to standard therapies. Despite progress in genomic profiling and precision oncology, the translation of molecular data into effective therapeutic decisions remains limited by the lack of functional models capable of capturing tumor complexity. Patient-derived organoids (PDOs) have emerged as transformative tools in this context, offering the unique advantage of preserving the genetic, phenotypic, and functional features of individual tumors ex vivo. Beyond their well-established applications in drug screening and resistance studies, PDOs contribute to personalized treatment strategies by enabling functional molecular stratification, modeling tumor-microenvironment interactions, and predicting the efficacy of targeted and immunotherapeutic approaches. When integrated with liquid biopsy analyses, PDOs also allow real-time tracking of clonal evolution and can be repeatedly generated during the disease course, providing dynamic insights that guide longitudinal treatment decisions. As organoid biobanking and multi-omic integration advance, PDOs are poised to evolve into clinically actionable avatars that complement genomic profiling and help tailor therapeutic strategies for patients with urogenital cancers. Nevertheless, the clinical integration of PDOs still faces important barriers, including variability in culture protocols, incomplete representation of the native tumor microenvironment, and the time required for organoid establishment. Moreover, the predictive value of PDO-based drug screening-although promising-needs rigorous prospective validation in large patient cohorts. This review highlights the pivotal role of PDOs in bridging the gap between laboratory research and clinical oncology, emphasizing their application in guiding personalized therapeutic strategies. As organoid biobanking and genomic profiling expand, the integration of PDOs into precision oncology pipelines holds promise for reshaping the clinical management of urogenital malignancies and advancing toward truly individualized cancer treatment.

Introduction: Growing evidence suggests that increased matrix stiffness can significantly enhance the malignant characteristics of glioma cells. However, the mechanisms by which increased matrix stiffness regulates the tumorigenesis of glioma cells remain largely unknown. A growing number of studies show that carcinogenesis in various human cancers is linked to cell membrane glycoproteins and their corresponding receptors. Among these, synaptic vesicle glycoprotein 2 isoforms B (SV2B) has emerged as a transmembrane glycoprotein with significant functional implications. However, whether SV2B is involved in matrix-stiffness-mediated glioma tumorigenesis and its related mechanisms remains to be elucidated.

Methods: In this study, we aimed to investigate whether SV2B mediates the effects of matrix stiffness on the focal adhesion kinase (FAK)/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. To examine the expression of SV2B in patients with glioma, we analyzed data from bioinformatics databases. Furthermore, we assessed SV2B variation in glioma and its impact on overall survival. In vitro experiments included Western blot and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analyses to determine protein and messenger RNA (mRNA) expression in glioma cell lines. Cell viability and DNA replication capacity were evaluated using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and colony formation assays. Migration ability was assessed through Transwell and wound healing assays. Flow cytometry was employed to analyze apoptotic rates in glioma cells. Additionally, an orthotopic tumorigenesis model was established to investigate the in vivo effects of SV2B.

Results: Our results demonstrated low expression of SV2B in glioma tissues. Overexpression of SV2B was found to inhibit proliferation and migration and induce apoptosis of glioblastoma cells, while knockdown of SV2B promoted these processes. Furthermore, we observed that SV2B overexpression suppressed the epithelial-mesenchymal transition (EMT) process and inhibited the activation of the FAK/PI3K/AKT signaling pathway in glioma cells, with similar effects observed in vivo. Finally, we demonstrated that increased matrix stiffness can promote glioma tumor growth through FAK/PI3K/AKT pathway, while overexpression of SV2B can inhibit this effect.

Conclusions: Our study provides insights into the functional role of SV2B in matrix-stiffness-driven glioma progression, elucidating its molecular mechanisms and highlighting its potential as a therapeutic target.

The influence of social determinants of health (SDOH) on clinical outcomes for patients with cancer has become increasingly clear in recent years. This podcast, featuring a breast surgeon from the USA and a breast medical oncologist from Canada, provides updated definitions of SDOH, discusses the importance of assessing for SDOH-related barriers to optimal, equitable care for patients with metastatic breast cancer (mBC), and offers practical solutions that individual practices can implement. While this discussion is focused on the USA and Canada, SDOH factors are salient for healthcare providers around the world, irrespective of the healthcare systems deployed in their individual countries. Key SDOH that can impact care or outcomes for patients living with mBC are discussed by the hosts, including patient socioeconomic status, transportation logistics, health literacy, and social support. The importance of establishing trust between care provider and patient is also examined, especially for racial and ethnic minorities who have earned concerns and mistrust of healthcare systems. To aid practices in addressing SDOH-related barriers, various resources are identified, including free screening tools and support offered by patient advocacy and nonprofit organizations. Despite the scope of SDOH-related challenges, practices can collaborate to achieve progress toward equitable care for patients with mBC. Podcast Video (MP4 122704 kb).

In this plain language podcast, the authors discuss highlights from the American Urological Association (AUA) Annual Meeting 2025. These insights come from the perspective of an expert patient and physician, both of whom have experience and expertise in the field of bladder cancer. This podcast is intended to broaden the reach of complex data and insights from AUA 2025 to a broader audience, including non-specialists, helping enable better informed treatment decisions between patients and healthcare professionals. The authors introduce the current treatment landscape for patients and discuss four clinical trials focusing on patients with bacillus Calmette-Guérin (BCG)-naïve and BCG-unresponsive high-risk non-muscle invasive bladder cancer (HR-NMIBC). Three trials presenting novel treatment approaches and their impact on survival and disease progression are discussed: PD-1 inhibitors in combination with BCG, a first-in-use intravesical drug delivery system that targets treatment directly to the bladder, and a novel oncolytic tumor-directed therapy. Authors highlight the strengths and limitations of these novel mechanisms vs standard of care, including convenient and more accessible treatment, similar or more effective disease response, and safety profiles. Finally, a prospective observational trial comparing patient quality of life outcomes is discussed, highlighting the differences between patients receiving bladder preservation vs radical cystectomy, the current gold standard of treatment. Key data from AUA showcase the growing number of treatment options available to patients with BCG-naïve and BCG-unresponsive HR-NMIBC and present promising new agents and broader possibilities for existing agents. They also raise the continued need for a nuanced approach towards navigating bladder preservation and the importance of shared-decision-making and goals of care discussions between patients and their physicians when discussing care. Podcast (MP4 122704 kb).

Effective management of prostate cancer requires an approach that integrates oncological intent with careful consideration of coexisting comorbidities and functional reserve. This podcast explores how chronic health conditions, frailty and quality-of-life factors influence therapeutic choices across the disease continuum. In localised disease, long-term data demonstrating comparable survival between surgery, radiotherapy and active monitoring have reframed the rationale for radical intervention. Treatment decisions are now increasingly guided by competing health risks, anticipated life expectancy and patient preference. In advanced disease, treatment intensification with systemic combination therapy has extended survival but introduced new complexity. The cardiovascular, metabolic and cognitive toxicities of androgen deprivation therapy (ADT) necessitate individualised consideration of intermittent therapy or de-escalation for patients with substantial comorbidity. With the expanding use of triplet regimens in metastatic hormone-sensitive disease, assessing physiological rather than chronological age has become essential. The discussion further highlights the role of structured oncogeriatric assessment in optimising care. Tools such as the Rockwood Clinical Frailty Scale, G8 screening tool and comprehensive geriatric assessment (CGA) provide a systematic framework for evaluating frailty, polypharmacy, cognition and function, supporting balanced decisions about treatment escalation and supportive interventions. Collectively, the dialogue underscores a shift towards holistic, multidisciplinary decision-making that aligns cancer control with broader health, independence and wellbeing. Embedding frailty-informed assessment into prostate cancer pathways represents a necessary evolution towards truly personalised care. Podcast Video (MP4 314221 KB).

Introduction: The selective estrogen receptor degraders (SERD) have proven to be an effective treatment option for patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). The orally administered next-generation SERDs may be more tolerable and a preferred alternative to the intramuscularly (IM) administered fulvestrant. This study sought to identify patient and healthcare provider (HCP) perspectives on preferences, benefits, burdens, and ease of adherence of oral and IM endocrine therapy (ET).

Methods: Non-interventional, qualitative interviews were conducted in the USA, among adult patients with ER+ HER2- ABC and oncology HCPs. Eligible patients and HCPs had experience with both oral ET and fulvestrant within the past 3 years. One-on-one semi-structured interviews lasted up to 60 min.

Results: We interviewed 25 patients and 20 HCPs. The mean time from BC diagnosis was 12.6 years (standard deviation 8.4); 18 patients (72%) were currently receiving IM and 7 (28%) oral ET. Sixteen patients (64%) preferred oral ET, mainly owing to convenience (13/16, 81%), which was considered the main benefit (22/25, 88%); side effects were a common burden (18/25, 72%). Seven patients preferred IM ET, mainly owing to the monthly injection frequency (6/7, 85%). The primary benefit of IM ET was not having to remember daily dosing (12/22, 55%), and main burdens were injection pain (21/25, 84%) and travel to receive injection (14/22, 64%). Most patients (23/25, 92%) experienced ease of adherence to oral ET. HCPs perspectives were largely aligned to the patients' experiences.

Conclusion: Patients with ER+ HER2- ABC in this study preferred oral to IM ET owing to convenience, and disliked the pain associated with IM ET and travel to receive injections. Compared to IM fulvestrant, oral SERDs may offer an alternative with less burden on the lives of people living with cancer.