Reviews & Analysis

Patients with advanced-stage ovarian cancer are widely believed to have a dismal prognosis; however, around 20% of women with this disease survive beyond 12 years after treatment and are effectively cured. In this Perspectives, Steven Narod presents the case that this proportion could be substantially increased through the combination of maximal debulking surgery and intraperitoneal chemotherapy.

Repurposing approved, non-anticancer drugs is an attractive strategy for patients with cancer. To date, successes in oncology drug repurposing have been limited, despite strong evidence supporting the use of many different drugs. A lack of financial incentives for drug developers and limited drug development experience within the non-profit sector are key reasons for this lack of success. The authors discuss these issues and offer solutions to seize this opportunity in the interest of patients and societies, globally.

Conducting high-quality prospective clinical trials in surgical oncology remains a challenge. The authors of this Perspectives examine some of the failures in published surgical oncology trials and discuss why they failed, and provide a critical assessment of the established prospective trial methodology in oncological practice and how these methods might be used more effectively in future evaluation of cancer-surgery practice.

Human papillomavirus (HPV)-screening technologies and HPV vaccination are revolutionizing the management of cancers related to this virus, in particular, cervical neoplasms. At present, however, the effectiveness of these modalities is not optimal, owing to the limited scope of HPV-vaccination and cervical screening programmes. In this Perspectives, an international panel of experts describes for the first time a new campaign, termed 'HPV-FASTER', which aims to broaden the use of HPV vaccination coupled with HPV testing to women aged up to 30 years, and in some settings up to 50 years, with the aim of accelerating the reduction in the incidence of HPV infections and cervical cancer. The authors describe the evidence supporting this approach and details on how it might be implemented, discuss the opportunities—particularly in low-resource settings—and challenges associated with the strategy, and highlight key research gaps that need to be addressed in future studies.

Stage IV gastric cancer is incurable and has a very poor prognosis. Although palliative chemotherapy remains the standard of care, increasing evidence indicates that palliative surgery can provide a prognostic and symptomatic benefit. This Perspectives summarizes the recent evidence underpinning the medical and surgical management of incurable gastric cancer, and provides evidence-based recommendations on treatment strategies and avenues for future research.

Response to first-line therapy is a primary determinant of outcome in patients with metastatic colorectal cancer (mCRC). In the past decade, the development of antiangiogenic and anti-EGFR biologic agents, doublet and triplet chemotherapy regimens, and combinations of these treatment modalities has created not only new first-line treatment options, but also new challenges for the management of this disease. In this Perspectives, these advances and the confusion surrounding their implications are discussed. The authors attempt to address some of the challenges in clinical decision-making and propose an algorithm for personalized allocation of first-line treatments in patients with mCRC.

Predictive biomarkers are invaluable for successful and cost-effective treatment of cancer, however, biomarker discovery is difficult and requires multiple independent studies to identify suitable predictors of efficacy. Clinical trials performed in the USA, Europe or Asia can offer unique opportunities for biomarker discovery and validation. In this Perspectives, the authors describe the current fragmented approach to biomarker discovery and validation, highlighting how collaborative engagement of the academic, regulatory and pharmaceutical communities can help address these issues.

Currently, most novel chemotherapies are initially tested in tumour cell lines and xenografts, which generally fail to reflect the full spectrum of tumour-specific mutations, and might explain the low success rates of experimental treatments. In this Perspectives, the mouse hospital co-clinical trial project is described, which enables treatments to be tested in mouse models that accurately reflect the tumour characteristics of individual patients.

A lack of clinical investigation, which has arguably become more pronounced in the past decade, currently hinders progress in cancer surgery research, and ultimately the treatment of patients with cancer. This Perspectives describes the major barriers to progress in surgical oncology, and how improvements might be made in this important, but often overlooked, aspect of cancer treatment.

Several guidelines propose the use of Ki67 expression to select which patients with early stage breast cancer and 1–3 positive nodes should not receive adjuvant chemotherapy. In this Perspective, the authors discuss why, in 2015, the oncologist should not rely on the use of this biomarker for decision-making in this patient population—owing to lack of analytical validity of Ki67 staining, its poor performance for prognostic purposes, and no strong evidence indicating that Ki67 staining predicts the efficacy of adjuvant chemotherapy.

Since February 2012, the FDA has identified widespread infiltration of counterfeit bevacizumab into the US drug-supply chain. This Perspectives uses this case study to highlight the continued lack of information, knowledge, and solutions necessary to protect patients against future breaches in the drug-supply network, as well as the need for collaborative efforts to enhanced surveillance for counterfeit medicines and improve communication of risk information.

The standard treatment for advanced-stage ovarian cancer is upfront cytoreductive surgery, and the extent of residual disease after surgery correlates with response to adjuvant therapy and disease outcomes. This Perspectives article provides an overview of the historical progression of primary cytoreduction and definitions of 'optimal' residual disease. In addition, approaches to personalizing surgical therapy and improving the quality of surgical care are discussed.

Surgery is the oldest oncological discipline and remains the cornerstone of treatment for most patients with cancer. However, the way surgery is used to treat cancer has evolved and outcomes continue to improve as a result of greater biological understanding, relentless technical innovation and a paradigm shift towards multimodal treatment. In this Perspectives, the authors discuss the developments in cancer surgery that have occurred over time and provide an overview of the key uses of surgery in the current era of multidisciplinary cancer care.

Numerous calls for improvement in the quality of follow-up care provided to cancer survivors, particularly survivors of childhood cancer have been issued by key health organizations in the USA; the Passport for Care (PFC) is a web-based support system for survivor care that was developed in response. In this Perspectives, key individuals involved in the development of this support tool for clinical decision making outline the programme, describe how it compares with similar guidance tools, and discuss the potential implications of the PFC for survivorship care. The challenges encountered and the lessons learned during development and deployment of the PFC are also highlighted.

Many cancers, particularly those that arise in childhood, have a hereditary component. In this Perspectives article, the authors provide their views on how the increased adoption of high-throughput DNA sequencing technologies, which produce vast genetic data that is not necessarily limited to known cancer-susceptibility loci, and cancer surveillance strategies are influencing the clinical management of familial cancer. Important ethical issues relating to genetic counselling and disclosure of genetic information on disease susceptibility are discussed, and strategies for approaching these ethical dilemmas are proposed.

Recent advances in multimodality imaging in cancer have involved the integration of multiple quantitative, functional measurements that provide a more-comprehensive characterization of tumours. In this Review, Yankeelov and colleagues discuss how, although some of these approaches still need some adjusting, they can already be applied informatively in clinical trials of cancer therapeutics using existing tools.

Patients with oligometastases who develop a small number of metastatic lesions might achieve long-term survival with the use of ablative surgery or stereotactic radiotherapy. More patients are receiving aggressive treatment for oligometastatic disease, yet long-term survival might not be due to the treatments themselves, but rather to the selection of patients with slow-growing indolent disease. The authors examine the key evidence supporting or refuting the existence of an oligometastatic state and its appropriate treatment.

Gene mutations and genomic aberrations are the basis of tumour development. Over the past decade, single-gene mutations and genomic profiling have been increasingly used in multidisciplinary consultations for risk-assessment and treatment planning for patients with cancer. In this Perspective, the authors discuss the direct and indirect influences of genomic profiling on surgical decision making, and analyse the limitations and unresolved issues of a genotypic-approach to the surgical management of cancer.

The current drug development procedures are far from optimal, owing to the continuous development of the health systems and the clinical research landscape. The European Organisation for Research and Treatment of Cancer proposes in this Perspective the use of collaborative molecular screening platforms (CMSPs) as a new approach for drug development. These CMSPs have the advantage of optimizing expertise of several partners and combining efforts alongside with cost-sharing models for efficient patient selection.

Tissue-preserving focal therapies that target individual cancer lesions rather than the whole prostate have emerged as potential interventions for localized prostate cancer. In this article, the Prostate Cancer RCT Consensus Group recommends the development of a cohort-embedded randomized controlled trial methodology to evaluate focal therapy use in men with clinically significant localized disease. The importance for a randomized controlled trial design to provide cost-efficient practice-changing data is highlighted.