title: A model of the natural history of screen-detected prostate cancer, and the effect of radical treatment on overall survival.
abstract: The lead time and over-detection associated with prostate-specific antigen (PSA) screening, and generational improvements in all-cause mortality, make prostate cancer outcome studies from the pre-PSA era difficult to interpret in a contemporary setting. We developed a competing-risks hazard model to estimate the natural history of screen-detected prostate cancer, and the impact of radical treatment on overall survival. The model of hazard of mortality was fitted to clinical outcome data from the pre-PSA era, and the effects of screening, generational mortality improvements and radical treatment were incorporated. Sensitivities to the choice of baseline data and values of key parameters were assessed. Lead-time estimates in men diagnosed aged 55-59 years were 14.1, 9.3 and 5.0 years for men with Gleason scores <7, 7 and >7, respectively, assuming biennial screening with 100% attendance. Central estimates of 15-year prostate cancer mortality for conservative management of screen-detected prostate cancer ranged from 0 to 2% for Gleason scores <7, 9 to 31% for Gleason score 7 and 28-72% for Gleason scores >7. For men aged 55-59 years at diagnosis, the predicted absolute 15-year survival benefit from curative treatment was 0, 12 and 26% for men with Gleason scores <7, 7 and >7, respectively. Estimates of the survival benefit of radical treatment were relatively insensitive to values of key parameters. The case for curative treatment, rather than conservative management, of screen-detected localised prostate cancer is strongest in men with high-grade disease. This conclusion contrasts with current patterns of care.
authors.affiliation: Academic Unit of Radiotherapy and Oncology, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Downs Road, Sutton SM2 5PT, UK. chris.parker@rmh.nhs.uk
authors.forename: C
authors.initials: C
authors.lastname: Parker
authors.forename: D
authors.initials: D
authors.lastname: Muston
authors.forename: J
authors.initials: J
authors.lastname: Melia
authors.forename: S
authors.initials: S
authors.lastname: Moss
authors.forename: D
authors.initials: D
authors.lastname: Dearnaley
mesh_terms: D000368:Aged; D003198:Computer Simulation; D018450:Disease Progression; D018572:Disease-Free Survival; D042241:Early Diagnosis; D006801:Humans; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000401:mortality* / Q000601:surgery*; D019057:Quality-Adjusted Life Years; D018570:Risk Assessment; D015996:Survival Rate
chemical_list: D017430:Prostate-Specific Antigen