Cost-Effectiveness Analysis and Microsimulation of Serial Multiparametric Magnetic Resonance Imaging in Active Surveillance of Localized Prostate Cancer

Abstract

Purpose: Many localized prostate cancers will follow an indolent course. Management has shifted toward active surveillance (AS), yet an optimal regimen remains controversial especially regarding expensive multiparametric magnetic resonance imaging (MRI). We aimed to assess cost-effectiveness of MRI in AS protocols.

Materials and methods: A probabilistic microsimulation modeled individual patient trajectories for men diagnosed with low-risk cancer. We assessed no surveillance, up-front treatment (surgery or radiation), and scheduled AS protocols incorporating transrectal ultrasound-guided (TRUS) biopsy or MRI based regimens at serial intervals. Lifetime quality-adjusted life-years and costs adjusted to 2020 US$ were used to calculate expected net monetary benefit at $50,000/quality-adjusted life-year and incremental cost-effectiveness ratios. Uncertainty was assessed with probabilistic sensitivity analysis and linear regression metamodeling.

Results: Conservative management with AS outperformed up-front definitive treatment in a modeled cohort reflecting characteristics from a multi-institutional trial. Biopsy decision conditional on positive imaging (MRI triage) at 2-year intervals provided the highest expected net monetary benefit (incremental cost-effectiveness ratio $44,576). Biopsy after both positive and negative imaging (MRI pathway) and TRUS biopsy based regimens were not cost-effective. MRI triage resulted in fewer biopsies while reducing metastatic disease or cancer death. Results were sensitive to test performance and cost. MRI triage was the most likely cost-effective strategy on probabilistic sensitivity analysis.

Conclusions: For men with low-risk prostate cancer, our modeling demonstrated that AS with sequential MRI triage is more cost-effective than biopsy regardless of imaging, TRUS biopsy alone or immediate treatment. AS guidelines should specify the role of imaging, and prospective studies should be encouraged.

Keywords: cost-benefit analysis; multiparametric magnetic resonance imaging; prostatic neoplasms; watchful waiting.

Figure 1.

Microsimulation model schematic. Androgen deprivation therapy (ADT). The microsimulation model assessed men diagnosed with low-risk localized disease (observed GG1) and accounted for initial diagnostic misclassification (ie harboring unobserved GG ≥2). Men could experience disease progression, treatment if reclassified on surveillance (surgery or radiation for those under or over 70 years old, respectively) or die (including age-specific competing mortality). Surgery included a 0.1% perioperative mortality, and ADT increased annual all-cause mortality by 1%.17 Biochemical recurrence resulted in either maintenance ADT or 1 attempt at salvage therapy with chance of remission. Terminal cancer lasted maximum 6 months before cancer death.

Figure 2.

Cost-effectiveness plane. The base case analysis assessed cohorts of 500,000 patients with PASS trial characteristics using 10,000 parameter sets (Table 1). ICERs correspond to the inverse slope between points. The line represents the cost-effectiveness frontier consisting of nondominated strategies (Table 2), and a steeper slope represents more gain in QALYs per invested cost. yr, year.

Figure 3.

Probabilistic sensitivity analysis, cost-effectiveness acceptability curves by testing modality. The cost-effectiveness acceptability curve presents decision uncertainty as the probability each strategy is the most cost-effective, determined by the proportion of simulations selecting that strategy. Microsimulation models for the base case analysis were assessed with cohorts of 500,000 patients with PASS trial characteristics over 10,000 parameter sets (Table 1). Strategies are grouped by testing modality, and MRI triage based strategies were chosen most often at both $50,000 and $100,000 WTP thresholds (for greater detail, see supplementary Appendix S6, https://www.jurology.com). yr, year.

Figure 4.

Probabilistic 2-way sensitivity analysis of test performance and costs. Probabilistic sensitivity analysis was used to determine the incremental NMB between each strategy combination for 10,000 parameter set simulations of 500,000 individuals. Linear regression metamodeling was then used to determine thresholds and constraints for decisional change, and the preferred strategy (highest NMB) at each value within parameter ranges was identified. Ranges for the axes correspond to the uncertainty distributions of plausible parameter values used in the probabilistic analysis. A, test sensitivity ranges across confidence intervals presented in the source literature: TRUS biopsy 0.63 (0.19–0.93) derives from Drost et al and MRI 0.61 (0.46–0.74) from Hettiarachchi et al. B, costs range from 50% to 200% of Medicare reimbursement: TRUS biopsy $3,175 ($1,588–$6,350) and MRI $1,036 ($518–$2,072). yr, year.