Volume 13 Issue 9, September 2016

We believe that current controversies surrounding screening might be better approached by shifting the question from 'does screening work?' to 'for whom does screening work?' We propose a 'rule-out/rule-in' principle as an intellectual basis and starting point for screening. Finally, we advocate the 'equal management of equal risks' principle as an unifying framework for developing simplified and consistent screening guidelines and practice.

Annual thoracic CT screening is currently recommended for individuals deemed to be at high risk of developing lung cancer; however, Patz and co-workers now raise the very important question of choosing the optimal interval between screening exams, in order to balance the potential benefits and harms associated with each round of CT. Herein, we present important considerations for determining such intervals.

In a recent study, the addition of olaratumab to doxorubicin chemotherapy for patients with soft-tissue sarcoma resulted in prolongation of progression-free survival by only 2.5 months, but an overall survival benefit of 11.8 months; the large disparity between these outcomes raises important questions. We discuss these results in relation to those of other trials, and the implications for sarcoma therapy.

Patients with von Hippel–Lindau (VHL) disease are susceptible to a range of neoplasms. More than 50% of these patients suffer from a range of pancreatic lesions at some point in their lifetime, and the different types of lesions require different management approaches. In this Review, the authors describe the types of pancreatic lesions that are associated with VHL disease, and discuss the management of patients with different pancreatic manifestations; an overall patient-management algorithm is also presented.

Considerable hope, as well as a substantial degree of hype, has surrounded cancer-screening programmes, but current practices are suboptimal and are the subject of continued improvement efforts. In this Review, the authors discuss the experiences to date in screening for breast, cervical, colorectal, lung and prostate cancers, outline the lessons we have learned, and describe how this knowledge is informing improvements in cancer screening, with the hope they will eventually live up to the hype.

Reports of neoadjuvant therapeutic trials in breast cancer, particular those of dual-agent HER2 blockade, have described improved pathological complete response (pCR) rates and associations of this surrogate end point with prolonged survival; however, the same therapies have not been reported to improve survival in the adjuvant setting, or indeed long-term patient outcomes after neoadjuvant therapy. In this Review, the multiplex factors that might explain these apparent discrepancies, including study designs issues, and clinical and biological differences, are discussed.

The use of multigene panels for the assessment of cancer susceptibility is expanding rapidly in clinical practice. The appropriate management of individuals harbouring moderate-penetrance genetic variants in individuals referred for clinical testing is unclear. The authors of this Perspectives article provide a framework for clinical decision-making pending the development of a sufficient evidence base to document the clinical utility of the interventions for individuals with inherited moderate-penetrance gene mutations associated with an increased risk of cancer.