Prostate cancer models overview
The CISNET prostate working group originated with investigators from Fred Hutchinson Cancer Research Center (PSAPC model) and the University of California Davis (SCANS model) in the year 2000. Beginning in 2005, investigators from Erasmus University Medical Center (MISCAN-PRO model) joined, and shortly afterwards investigators from University of California Davis moved to the University of Michigan.
The prostate models were originally developed to study the plausible roles of screening and changes in treatment on prostate cancer mortality (Etzioni et al., 2008, 2012). The models were also extended to reconcile widely disparate estimates of lead times and overdiagnosis associated with prostate-specific antigen (PSA) screening (Draisma et al., 2009), to compare natural histories and risks of cancer progression (Gulati et al., 2011), to examine contamination in the prostate section of the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial (Gulati et al., 2012), and to project expected disease trends under discontinued PSA screening (Gulati et al., 2014). Ongoing work is focused on assessing evidence of differential natural history in blacks and whites and reconciling effects of screening on mortality in the PLCO cancer screening trial and the European Randomized Study of Screening for Prostate Cancer (ERSPC).
Common structure and inputs
Each model contains the same basic components: (1) a natural history model, projecting latent onset and progression and clinical detection in the absence of screening and other-cause death; (2) a model for disease-specific and other-cause survival in the absence of screening; (3) a model for screening and, if PSA is explicitly modeled, for biopsy after screening; (4) a model for how screening impacts disease-specific survival; and (5) a model for how treatment impacts disease-specific survival.
Common inputs consist of disease incidence, prostate cancer screening patterns, and primary treatment trends in the US. The models also share estimates of disease-specific survival in the absence of screening and other-cause death rates from US life tables. Disease incidence is used primarily for calibration purposes. The calibration process is the process by which each model identifies natural history parameters that are most consistent with observed incidence. Calibrated CISNET prostate models have been applied to explain population trends in prostate cancer mortality (population models) and to project the outcomes of different screening and/or treatment interventions for policy development (cohort models).
The PSAPC and MISCAN-PRO models are microsimulation models that generate individual life histories composed of cancer natural history, screening, diagnosis, treatment, and survival events using computer algorithms and random draws from parametric statistical distributions. In contrast, the SCANS model is an analytic mathematical model that represents corresponding events in an integrated set of analytic probability models.
The PSAPC and MISCAN-PRO models assume that all prostate cancers begin in localized stage and can progress to distant metastases. The SCANS model does not specify stage at onset and requires only that stage does not regress during the window of detectability by screening.
The PSAPC model assumes that prostate cancers can be low or high grade at onset but cannot progress over time. The MISCAN-PRO model assumes that all prostate cancers begin in low grade and can progress over time. The SCANS model does not specify grade at onset and requires only that grade does not regress during the window of detectability by screening.
The PSAPC model generates PSA levels for each simulated individual at each screen. Simulated men with PSA > 4 ng/mL at a screen are referred to biopsy, compliance with biopsy referral depends on age and PSA level as observed in the PLCO cancer screening trial, and biopsy sensitivity increases with the dissemination of extended biopsy schemes over time. The MISCAN-PRO and SCANS models estimate an effective test sensitivity which combines the probability of a positive PSA test, receipt of biopsy, and sensitivity of the biopsy to detect latent cancer. The MISCAN-PRO model is currently being extended to simulate PSA levels at each screen.
All three models are designed to consider multiple mechanisms of screening benefit, including stage shift (i.e., that individuals whose cancers are detected by screening at an earlier stage and/or grade receive a corresponding improvement in cancer-specific survival) and cure rates (a fraction of individuals detected earlier by screening have their cancer death prevented by early detection; the cure rate may be constant across the population or may depend on lead time).
- Etzioni R, Tsodikov A, Mariotto A, Szabo A, Falcon S, Wegelin J, DiTommaso D, Karnofski K, Gulati R, Penson DF, Feuer E. Quantifying the role of PSA screening in the US prostate cancer mortality decline. Cancer Causes Control. 2008 Mar;19(2):175-81. [Abstract]
- Draisma G, Etzioni R, Tsodikov A, Mariotto A, Wever E, Gulati R, Feuer E, de Koning H. Lead time and overdiagnosis in prostate-specific antigen screening: importance of methods and context. J Natl Cancer Inst. 2009 Mar 18;101(6):374-83. [Abstract]
- Gulati R, Wever EM, Tsodikov A, Penson DF, Inoue LY, Katcher J, Lee SY, Heijnsdijk EA, Draisma G, de Koning HJ, Etzioni R. What if I don't treat my PSA-detected prostate cancer? Answers from three natural history models. Cancer Epidemiol Biomarkers Prev. 2011 May;20(5):740-50. [Abstract]
- Gulati R, Tsodikov A, Wever EM, Mariotto AB, Heijnsdijk EA, Katcher J, de Koning HJ, Etzioni R. The impact of PLCO control arm contamination on perceived PSA screening efficacy. Cancer Causes Control. 2012 Jun;23(6):827-35. [Abstract]
- Etzioni R, Gulati R, Tsodikov A, Wever EM, Penson DF, Heijnsdijk EA, Katcher J, Draisma G, Feuer EJ, de Koning HJ, Mariotto AB. The prostate cancer conundrum revisited: treatment changes and prostate cancer mortality declines. Cancer. 2012 Dec 1;118(23):5955-63. [Abstract]
- Gulati R, Tsodikov A, Etzioni R, Hunter-Merrill RA, Gore JL, Mariotto AB, Cooperberg MR, Expected population impacts of discontinued prostate-specific antigen screening, Cancer. 2014 Nov 15;120(22):3519-26. [Abstract]