Research Highlight |
Featured
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News & Views |
Lighting the torch: intratumoural T cell-to-stroma enrichment score as a predictor of immunotherapy response in urothelial carcinoma
T cell infiltration in the tumour microenvironment (TME) is a prerequisite for sustained antitumour immune responses. However, identifying predictive biomarkers that quantify T cell infiltration and the presence of proinflammatory TMEs associated with immune-checkpoint inhibitor (ICI) response for clinical implementation has proved challenging. Here, we highlight a study that validates a T cell-to-stroma enrichment score generated from RNA sequencing data as a novel biomarker for ICI response in patients with urothelial carcinoma.
- David H. Aggen
- & Jonathan E. Rosenberg
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News & Views |
Combination strategies for advanced-stage urothelial carcinoma: a paradigm shift
Durable responses with first-line platinum-based chemotherapy for advanced-stage urothelial carcinoma are rare, and patient outcomes are poor. Recently, CheckMate 901 became the first phase III trial to establish a significant overall survival benefit from a combined chemoimmunotherapy approach in this disease setting. Herein, we discuss key findings from CheckMate 901 and their implications in the context of a rapidly evolving treatment landscape.
- Nimira Alimohamed
- & Srikala S. Sridhar
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News & Views |
Combination neoadjuvant therapies are paving the way for bladder preservation to become the standard for selected patients
Neoadjuvant cisplatin-based combination chemotherapy followed by radical cystectomy with pelvic lymphadenectomy is the current standard therapy for cisplatin-eligible patients with muscle-invasive bladder cancer (MIBC). A phase II trial testing treatment intensification by adding the immune-checkpoint inhibitor nivolumab to chemotherapy has yielded promising complete response rates, which suggests that bladder-preserving treatment could become attainable in selected patients. This trial heralds a new era in demonstrating the feasibility of bladder preservation for selected patients with MIBC.
- Jakob Klemm
- , Ekaterina Laukhtina
- & Shahrokh F. Shariat
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Review Article |
Progress in systemic therapy for advanced-stage urothelial carcinoma
Patients with advanced-stage urothelial cancer (aUC) continue to have poor long-term survival outcomes. However, developments in the past 5 years, most notably the availability of maintenance therapy with the anti-PD-1 antibody avelumab, are beginning to change this issue. In this Review, the authors provide an overview of the treatment of patients with aUC, including considerations of the various promising new therapeutic modalities and how they might improve clinical outcomes.
- Rosa Nadal
- , Begoña P. Valderrama
- & Joaquim Bellmunt
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News & Views |
Harnessing potent therapies with care: enfortumab vedotin plus pembrolizumab for advanced-stage urothelial carcinoma
Following the recent FDA Accelerated Approval of enfortumab vedotin (EV) plus pembrolizumab for patients with advanced-stage urothelial carcinoma who are cisplatin-ineligible, herein we highlight key clinical outcomes with this combination based on results from Cohort K of the pivotal phase Ib/II EV-103 trial. We also discuss treatment sequencing, de-escalation strategies and toxicity management as EV–pembrolizumab becomes widely used in clinical practice.
- Pooja Ghatalia
- & Elizabeth R. Plimack
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Research Highlight |
First-line pembrolizumab plus lenvatinib is effective in non-clear-cell RCC
- Diana Romero
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News & Views |
A triple dose of optimism: an initial foray into triplet therapy in metastatic renal cell carcinoma
COSMIC-313 combines all of the approved drugs against actionable targets in renal cell carcinoma into one triplet regimen. Although this approach has greater clinical efficacy than one of the standard-of-care doublet therapies, toxicities can limit adequate drug administration and, thus, we argue that this regimen should not yet be adopted. We also discuss ongoing investigations of other triplet regimens.
- Kathryn E. Beckermann
- & Brian I. Rini
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Review Article |
Global trends in the epidemiology of bladder cancer: challenges for public health and clinical practice
Bladder cancer is among the ten most common cancers worldwide and therefore constitutes a substantial health-care burden. This Review summarizes the global trends in bladder cancer incidence and mortality, and describes the main risk factors associated with bladder cancer occurrence and outcomes. The implications, challenges and opportunities of these epidemiological trends for public health and clinical practice are also discussed.
- Lisa M. C. van Hoogstraten
- , Alina Vrieling
- & Lambertus A. Kiemeney
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Research Highlight |
Targeted biopsy reduces detection of clinically insignificant cancer
- Diana Romero
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News & Views |
Perioperative immunotherapy for renal cell carcinoma: looking beyond the data
The first phase III trial to test perioperative immune-checkpoint inhibitor therapy for high-risk renal cell carcinoma yielded highly promising results, leading to regulatory approvals of adjuvant pembrolizumab. However, subsequent phase III trials, including the IMmotion010 trial of adjuvant atezolizumab, did not demonstrate similar benefits. Although molecular biomarkers are urgently needed to better delineate responder subgroups, the unique design of each trial might partially explain some of the patterns identified.
- Chris Labaki
- & Toni K. Choueiri
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Review Article |
The emerging role of photoacoustic imaging in clinical oncology
Photoacoustic imaging is a novel imaging technique that provides scalably high levels of spatial resolution at rapid acquisition speed, without the need for radiation or exogenous contrast agents. In this Review, the authors describe the emerging role of this technology in the screening, diagnosis and management of patients with cancer, and provide an overview of the future implementation of this technology.
- Li Lin
- & Lihong V. Wang
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News & Views |
Prospective clinical deployment of machine learning in radiation oncology
Artificial intelligence and machine learning have the potential to make cancer care more accessible, efficient, cost-effective and personalized. However, meticulously planned prospective deployment strategies are required to validate the performance of these technologies in real-world clinical settings and overcome the human trust barrier.
- Issam El Naqa
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Review Article |
Beyond conventional immune-checkpoint inhibition — novel immunotherapies for renal cell carcinoma
Renal cell carcinomas (RCCs) are generally immunogenic, but only a subset of patients receiving currently approved immune-checkpoint inhibitors have long-term disease remission. In this Review, the authors provide a conceptual framework for developing novel immunotherapy approaches, including an overview of the most promising novel immune checkpoints and antigen-directed therapies, and highlighting the potential of these agents to further improve the outcomes in patients with RCC.
- David A. Braun
- , Ziad Bakouny
- & Toni K. Choueiri
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News & Views |
Methylation extends the reach of liquid biopsy in cancer detection
Measuring the methylation status of cell-free DNA (cfDNA) in plasma holds great potential for the early, noninvasive detection of cancer. Two recent papers published in Nature Medicine showcase the successful application of cfDNA methylation-based cancer detection to two highly challenging scenarios.
- Wenyuan Li
- & Xianghong Jasmine Zhou
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News & Views |
Olaparib for DNA repair-deficient prostate cancer — one for all, or all for one?
Mature results of the PROfound study demonstrate that the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib prolongs progression-free survival compared with second-generation hormonal therapies in men with metastatic castration-resistant prostate cancer harbouring BRCA1, BRCA2 or ATM mutations. However, a closer look at the efficacy of olaparib on a gene-by-gene basis suggests that its activity is most pronounced in BRCA2-mutant prostate cancers and might not be equally active in all homologous recombination repair-deficient cancers.
- Emmanuel S. Antonarakis
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Review Article |
Lineage plasticity in cancer: a shared pathway of therapeutic resistance
Lineage plasticity is a source of intratumoural heterogeneity and enables tumour adaptation to an adverse tumour microenvironment, eventually leading to therapeutic resistance. The authors of this Review provide an overview of the impact of lineage plasticity on cancer progression and therapy resistance, with a focus on neuroendocrine transformation in lung and prostate tumours, and discuss emerging management strategies and open questions in the field.
- Álvaro Quintanal-Villalonga
- , Joseph M. Chan
- & Charles M. Rudin
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Perspective |
All change in the prostate cancer diagnostic pathway
Advances in imaging and biomarker discovery have led to a revolution in prostate cancer diagnosis, and nontargeted prostate biopsies should become obsolete. The authors of this Perspective article describe the current diagnostic pathway and discuss how advances in prebiopsy multiparametric MRI and the discovery of novel tumour markers should lead to a new diagnostic pathway.
- Derek J. Lomas
- & Hashim U. Ahmed
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Review Article |
Cytoreductive treatment strategies for de novo metastatic prostate cancer
Systemic hormone therapies and chemotherapy are the cornerstones of treatment for patients with de novo metastatic prostate cancer, with a currently limited role for local treatments. Herein, the authors outline the pathobiological and immunological rationale for local cytoreductive treatment of the primary tumour and/or metastases in patients with this disease. They also review the preclinical and clinical evidence for the use of radical prostatectomy, prostate radiotherapy, minimally invasive ablative therapies, and metastasis-directed therapy (predominantly with stereotactic ablative radiotherapy) in this population.
- Martin J. Connor
- , Taimur T. Shah
- & Hashim U. Ahmed
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News & Views |
Continuing to improve outcomes of men with metastatic prostate cancer
In the TITAN and ENZAMET trials, unprecedented overall survival outcomes were observed in patients with metastatic castration-sensitive prostate cancer receiving an agent targeting the androgen receptor in addition to androgen-deprivation therapy early in the course of their disease. Herein, I discuss both trials in the context of other studies in this disease setting.
- Fred Saad