Population-based screening for cancer: hope and hype

Key Points Tumours within any organ site can have a spectrum of biological phenotypes, ranging from indolent to highly aggressive Screening for cancer is most likely to be beneficial when the target tumour type has a relatively uniform biology and a slower rate of progression Not all precursor lesions are on an obligate pathway towards invasive-cancer development Strategies for early detection of cancer must balance the benefits of mortality reduction (and reduction in invasive-disease incidence with screening for precancers) with the heterogeneity of the target disease and the consequent risk of overdiagnosis Screening can be viewed as a 'cascade' involving multiple steps, such as selection of individuals to be screened, administration of the screening test, workup of positive findings, and, ultimately, treatment Efforts are underway to individualize decision-making surrounding risk stratification, the modality and frequency of screening, and diagnostic and therapeutic interventions tailored to the biology of the detected tumour 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. Several important lessons have been learnt from our experiences in screening for various cancers. Screening programmes for cervical and colorectal cancers have had the greatest success, probably because these cancers are relatively homogenous, slow-growing, and have identifiable precursors that can be detected and removed; however, identifying the true obligate precursors of invasive disease remains a challenge. With regard to screening for breast cancer and for prostate cancer, which focus on early detection of invasive cancer, preferential detection of slower-growing, localized cancers has occurred, which has led to concerns about overdiagnosis and overtreatment; programmes for early detection of invasive lung cancers are emerging, and have faced similar challenges. A crucial consideration in screening for breast, prostate, and lung cancers is their remarkable phenotypic heterogeneity, ranging from indolent to highly aggressive. Efforts