Background
Prostate specific antigen (PSA) testing can reduce prostate cancer mortality but may lead to overdiagnosis and overtreatment, particularly of low-risk disease. The increasing use of multiparametric MRI (mpMRI) aims to improve diagnostic accuracy and reduce unnecessary biopsies. With policy and practice recommendations for PSA testing and related referral pathways evolving, updated and policy?ready modelling is needed to quantify the benefits, harms, resource implications, and cost?effectiveness of contemporary pathways that incorporate mpMRI.
Objectives
To extend the Policy1?Prostate microsimulation for assessment of PSA testing strategies in Australia, with emphasis on mpMRI?integrated pathways, generating up?to?date estimates of benefits, harms, resource utilization, and cost?effectiveness.
Methods
Policy1?Prostate simulates PSA testing, downstream management, prostate cancer natural history, and survival in Australia (Caruana et al., 2024). We implemented two enhancements. First, we extended the natural history module to explicitly distinguish clinically significant (ISUP grade≥2) from clinically insignificant (ISUP grade<2) prostate cancer, enabling estimation of clinically meaningful detection, overdiagnosis, and downstream outcomes. Second, we added an mpMRI diagnostic module representing mpMRI performance within testing pathways. We conducted external validation at both trial and population levels: (i) trial?level validation against the Göteborg?2 trial for relative risks of diagnosis of clinically significant and clinically insignificant prostate cancer in intervention versus control arms (Hugosson et al., 2022); (ii) validation of prostate cancer mortality effects against the 23?year follow?up of ERSPC (mortality rate ratio comparing intervention with control) (Roobol et al., 2025); and (iii) reproduction of Australian prostate cancer incidence and mortality trends through 2021.
Results
Model predictions closely reproduced: (i) relative risks of diagnosis of clinically significant and clinically insignificant disease between intervention and control arms in Göteborg?2; (ii) the ERSPC 23?year mortality rate ratio under a range of feasible ‘contamination’ (i.e. control arm PSA testing) assumptions) (see Figure 1); and (iii) Australian incidence and mortality trends through 2021. Agreement with published evidence was good across all validation settings. The expanded framework enables evaluation of alternative testing intervals, mpMRI?based diagnostic pathways (including test?and?biopsy strategies), and downstream management approaches. Outputs encompass benefits (mortality reduction; detection of clinically significant disease), harms (overdiagnosis; excess biopsies and treatments), resource utilization (mpMRI and biopsy demand), and costs, supporting comparative effectiveness and cost?effectiveness analyses aligned to the Australian policy context.
Conclusion
Policy1?Prostate, now incorporating mpMRI and explicit stratification by clinical significance, shows good agreement with long?term international trial evidence and Australian epidemiological trends to 2021. The model is well positioned to assess benefits, harms, resource use, and cost?effectiveness of candidate recommendations for updated Australian PSA testing guidelines, particularly for pathways integrating mpMRI. These results can inform shared decision?making and directly support the ongoing guideline update process.
References
1. Caruana M, et al. Benefits and harms of prostate specific antigen testing according to Australian guidelines. Int J Cancer. 2024 Feb.
Methods
Policy1?Prostate simulates PSA testing, downstream management, prostate cancer natural history, and survival in Australia (Caruana et al., 2024). We implemented two enhancements. First, we extended the natural history module to explicitly distinguish clinically significant (ISUP grade≥2) from clinically insignificant (ISUP grade<2) prostate cancer, enabling estimation of clinically meaningful detection, overdiagnosis, and downstream outcomes. Second, we added an mpMRI diagnostic module representing mpMRI performance within testing pathways. We conducted external validation at both trial and population levels: (i) trial?level validation against the Göteborg?2 trial for relative risks of diagnosis of clinically significant and clinically insignificant prostate cancer in intervention versus control arms (Hugosson et al., 2022); (ii) validation of prostate cancer mortality effects against the 23?year follow?up of ERSPC (mortality rate ratio comparing intervention with control) (Roobol et al., 2025); and (iii) reproduction of Australian prostate cancer incidence and mortality trends through 2021.
Results
Model predictions closely reproduced: (i) relative risks of diagnosis of clinically significant and clinically insignificant disease between intervention and control arms in Göteborg?2; (ii) the ERSPC 23?year mortality rate ratio under a range of feasible ‘contamination’ (i.e. control arm PSA testing) assumptions) (see Figure 1); and (iii) Australian incidence and mortality trends through 2021. Agreement with published evidence was good across all validation settings. The expanded framework enables evaluation of alternative testing intervals, mpMRI?based diagnostic pathways (including test?and?biopsy strategies), and downstream management approaches. Outputs encompass benefits (mortality reduction; detection of clinically significant disease), harms (overdiagnosis; excess biopsies and treatments), resource utilization (mpMRI and biopsy demand), and costs, supporting comparative effectiveness and cost?effectiveness analyses aligned to the Australian policy context.
Conclusion
Policy1?Prostate, now incorporating mpMRI and explicit stratification by clinical significance, shows good agreement with long?term international trial evidence and Australian epidemiological trends to 2021. The model is well positioned to assess benefits, harms, resource use, and cost?effectiveness of candidate recommendations for updated Australian PSA testing guidelines, particularly for pathways integrating mpMRI. These results can inform shared decision?making and directly support the ongoing guideline update process.
References
1. Caruana M, et al. Benefits and harms of prostate specific antigen testing according to Australian guidelines. Int J Cancer. 2024 Feb.
2. Hugosson J, et al. Prostate Cancer Screening with PSA and MRI Followed by Targeted Biopsy Only. N Engl J Med. 2022 Dec.
3. Roobol MJ, et al. European Study of Prostate Cancer Screening - 23-Year Follow-up. N Engl J Med. 2025 Oct.
3. Roobol MJ, et al. European Study of Prostate Cancer Screening - 23-Year Follow-up. N Engl J Med. 2025 Oct.
Figure 1