title: Are rapidly growing cancers more lethal?
abstract: The view, that rapidly growing tumours are more likely than slow-growing tumours to metastasize and become lethal, has remained almost axiomatic for decades. Unaware of any solid evidence supporting this view, we undertook an exhaustive system-level analysis of intra- and intercellular signalling networks. This analysis indicated that rapid growth and metastasis are often different outcomes of complex integrated molecular events. Evidence from humans can be derived chiefly from screening interventions because interval cancers that surface clinically shortly after a negative screening test are, on average, more rapidly growing than cancers not detected by screening. We reviewed all available data limited to cancers of the breast, cervix and large bowel. The evidence from humans provides no support for the theory that rapidly growing cancers are more prone to metastasize. These findings indicate that the prevailing view should be reconsidered, as should the impact of length-biased sampling in cancer screening, and the findings provide no support for treating interval cancers more aggressively than non-interval cancers.
authors.affiliation: Clinical Effectiveness Research Group, Institute of Health and Society, University of Oslo, Oslo, Norway; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address: hadami@hsph.harvard.edu.
authors.forename: Hans-Olov
authors.initials: HO
authors.lastname: Adami
authors.affiliation: Department of Medical Chemistry, Semmelweis University, Budapest, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Csermely
authors.affiliation: Department of Medical Chemistry, Semmelweis University, Budapest, Hungary; Turbine Ltd., Budapest, Hungary.
authors.forename: Daniel V
authors.initials: DV
authors.lastname: Veres
authors.affiliation: Clinical Effectiveness Research Group, Institute of Health and Society, University of Oslo, Oslo, Norway; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Primary Care Research Unit, Vårdcentralen Värmlands Nysäter, Värmland County, Sweden.
authors.forename: Louise
authors.initials: L
authors.lastname: Emilsson
authors.affiliation: Clinical Effectiveness Research Group, Institute of Health and Society, University of Oslo, Oslo, Norway; Oslo University Hospital, Department of Transplantation Medicine and K. G. Jebsen Center for Colorectal Cancer Research, Oslo, Norway.
authors.forename: Magnus
authors.initials: M
authors.lastname: Løberg
authors.affiliation: Clinical Effectiveness Research Group, Institute of Health and Society, University of Oslo, Oslo, Norway; Oslo University Hospital, Department of Transplantation Medicine and K. G. Jebsen Center for Colorectal Cancer Research, Oslo, Norway.
authors.forename: Michael
authors.initials: M
authors.lastname: Bretthauer
authors.affiliation: Clinical Effectiveness Research Group, Institute of Health and Society, University of Oslo, Oslo, Norway; Oslo University Hospital, Department of Transplantation Medicine and K. G. Jebsen Center for Colorectal Cancer Research, Oslo, Norway.
authors.forename: Mette
authors.initials: M
authors.lastname: Kalager
mesh_terms: D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000401:mortality* / Q000473:pathology*; D011379:Prognosis
keywords: Breast cancer; Cancer stem-like cells; Cervical cancer; Colorectal cancer; Dormancy; Lethality; Metastasis; Signalling networks; Tumour growth