Reviews & Analysis

Despite the achievement of locoregional control, a third of patients undergoing surgery for cancer will have disease recurrence. In this Review, the authors describe the potential to optimize the outcomes of patients with cancer by minimizing inflammation and activation of the sympathetic nervous system in the perioperative period, which is often achievable with simple and cost-effective changes in patient-management strategies.

Muscle-invasive bladder cancer (MIBC) is a heterogeneous disease for which treatment has, historically, lagged behind that of other solid tumour types. A more detailed understanding of the biology of individual tumours, and the identification of molecular features providing prognostic and predictive information is key to the application of personalized care for patients with MIBC. The publication of a study of 412 samples now provides such data.

In 2017, three groundbreaking immunotherapies for relapsed and/or refractory B-cell acute lymphoblastic leukaemia (ALL) were approved based on impressive outcomes observed in clinical trials. Additional breakthroughs included seminal research into ALL genomics and the importance of adherence to chemotherapy, which will have direct implications for clinical care.

Precision cancer medicine has the potential to dramatically improve the outcomes of patients with cancer; however, despite the precise nature of the therapies involved, generating reliable evidence of efficacy is often challenging. In this Perspective, the authors describe the challenges and potential solutions that might address the need for evidence in precision cancer medicine.

Data published in 2017 underscore the benefit of optimizing anti-HER2 therapy in early stage high-risk HER2-positive disease, and of capecitabine in patients with residual disease after optimal neoadjuvant therapy. In the advanced-stage setting, endocrine therapy combined with cyclin-dependent kinase 4/6 inhibitors, or olaparib could become the preferred option.

2017 saw the publication of clinical trial data and the approval of new treatment approaches for metastatic urothelial carcinoma. Pembrolizumab is now a well-established treatment for patients with disease progression after cisplatin, with high-level evidence supporting its superiority over second-line chemotherapy. For patients ineligible for cisplatin, atezolizumab and pembrolizumab provide meaningful clinical benefit as frontline therapies.

In 2017, results from phase III trials demonstrated the impressive safety and efficacy of adjuvant targeted and immune therapies in patients with resectable stage III–IV melanoma, and raised questions about the surgical management of patients with microscopic sentinel-lymph-node metastases. For patients with unresectable disease, new overall survival data added to the debate about the relative benefits of single-agent anti-PD-1 versus combined anti-PD-1 and anti-CTLA-4 immunotherapy.

2017 has been full of new discoveries that will influence the treatment of colorectal cancer. In the adjuvant setting, 3 months of chemotherapy might now be considered a new standard of care. Various other new treatments and promising biomarkers have also become available that will improve survival outcomes and the quality of life of many patients with metastatic disease.

In 2017, major advances in the treatment of non-small-cell lung cancer (NSCLC) continued to emanate from the fields of molecularly targeted therapy and immunotherapy. In the former, new drugs with improved efficacy and reduced toxicity entered the clinic; in the latter, immune-checkpoint inhibition proved efficacious after chemoradiotherapy for stage III disease, but had disparate results in the frontline treatment of stage IV disease.

Surgery remains the mainstay of treatment for patients with gliomas, independent of tumour grade, and maximal resection of the tumour is essential for long-term disease control. Herein, the authors discuss the current evidence on associations between the extent of glioma resection and clinical outcomes. They also describe the state-of-the-art surgical oncology approaches aimed at maximizing the extent of tumour resection while minimizing patient morbidity.

The receptor-tyrosine kinase RET has been identified as a potentially actionable driver of oncogenesis. Several multikinase inhibitors with activity against RET have been explored in the clinic, but have only modest efficacy in patients with thyroid cancers, mostly in those withRET mutations, or RET-rearranged lung cancers. Herein, the authors outline the aberrations in RET that contribute to tumorigenesis, review the current clinical data for inhibitors of this kinase, and discuss whether the limited clinical success achieved with these agents to date is attributable to the intractability of RET as a drug target or the lack of highly specific RET inhibitors.

The onset of acquired resistance to treatment is virtually inevitable in patients with solid tumours. In this Review, the authors describe the role of tumour heterogeneity in the development of acquired resistance, potential treatment strategies that take into account the heterogeneity of patient's tumours, and how a better understanding of tumour heterogeneity might improve the outcomes of patients.

Clinical trials are an essential aspect of drug development; however, in patients with non-castrate prostate cancer, the long natural history of the disease provides a major barrier to the introduction of new therapies. In this Review, the authors describe the potential of a novel, multi-arm, multistage, clinical trial project, with surrogate end points designed to fully reflect the effects of treatments, in transforming the treatment of patients with early stage prostate cancer, before the development of castration-resistant disease.

Cholangiocarcinoma, the second most common form of liver cancer after hepatocellular carcinoma, is a heterogeneous disease entity with a near-universal poor prognosis. Our understanding of the epidemiology and biology of cholangiocarcinoma is increasing, and importantly, potentially actionable molecular and immunological targets for novel therapies are increasingly being identified. Herein, the evolving developments in the epidemiology, pathogenesis, and management of cholangiocarcinoma are reviewed.

On 30^th August 2017, tisagenlecleucel became the first chimeric antigen receptor (CAR)-T-cell therapy to be approved by the FDA. This approval has important implications for health-care systems because the use of this promising treatment presents considerable logistical, toxicological, and financial challenges. Moreover, the high price tag of US$475,000 is questionable, considering the major role of US taxpayers in covering the development, delivery, and supportive-care costs of this treatment.

Radiomics is the high-throughput mining of quantitative image features from standard-of-care medical imaging to enable data to be extracted and applied within clinical-decision support systems. The process of radiomics is described and its pitfalls, challenges, opportunities, and capacity to improve clinical decision making. The radiomics field requires standardized evaluation of scientific findings and their clinical relevance. This review provides guidance for investigations to meet this urgent need in the field of radiomics.

In the past decade, the importance of patient-reported outcomes (PROs) as a key measure of the quality of care delivered to patients with cancer has been acknowledged. PROs were used in the context of research studies, but growing evidence indicates that the incorporation of electronic PRO (ePRO) assessments into standard health-care settings can improve the quality of care delivered to patients with cancer. The authors of this Review discuss aspects related to PROs such as measurements, implementation challenges, and outcome improvements associated with their use.

TP53, encoding the tumour-suppressor p53, is the most frequently mutated gene across all human cancers. Similar to other transcription factors, p53 has proved notoriously difficult to target therapeutically; to date, no p53-targeted therapies have entered the clinic. The diversity ofTP53 mutations, which can be categorized across a spectrum of different functional classes, is increasingly recognized as an additional challenge to developing p53-directed treatments. Herein, Kanaga Sabapathy and David Lane review this 'rainbow of p53 mutants', and discuss the implications for anticancer therapies targeting p53 or directed by TP53status.

Chimeric antigen receptor (CAR)-T-cell therapies are showing great promise in the treatment of cancer, particularly B-cell malignancies, but are associated with characteristic, potentially fatal toxicities, principally cytokine-release syndrome, CAR-T-cell-related encephalopathy syndrome, and haemophagocytic lymphohistiocytosis/macrophage-activation syndrome. Herein, the CAR-T-cell-therapy-associated TOXicity (CARTOX) Working Group, comprising multidisciplinary investigators from various institutions with clinical experience in the use of a range of CAR-T-cell platforms, review these acute toxicities and provide monitoring, grading, and management recommendations.

The development of therapeutic cancer vaccines has been pursued for many decades. Many vaccines can elicit immunity to tumour antigens, although their clinical efficacy remains modest. Recent results from two clinical trials highlight the potential of personalized vaccination strategies, made possible by high-throughput approaches to the identification of immunogenic tumour neoantigens. Thus, therapeutic cancer vaccines might soon move into the mainstream.