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Review
. 2015 Oct 13;10(10):e0139440.
doi: 10.1371/journal.pone.0139440. eCollection 2015.

Prevalence of Prostate Cancer Clinical States and Mortality in the United States: Estimates Using a Dynamic Progression Model

Howard I Scher  1 , Kirk Solo  2 , Jason Valant  2 , Mary B Todd  3 , Maneesha Mehra  3
Affiliations
Review

Prevalence of Prostate Cancer Clinical States and Mortality in the United States: Estimates Using a Dynamic Progression Model

Howard I Scher et al. PLoS One. .

Abstract

Objective: To identify patient populations most in need of treatment across the prostate cancer disease continuum, we developed a novel dynamic transition model based on risk of disease progression and mortality.

Design and outcome measurements: We modeled the flow of patient populations through eight prostate cancer clinical states (PCCS) that are characterized by the status of the primary tumor, presence of metastases, prior and current treatment, and testosterone levels. Simulations used published US incidence rates for each year from 1990. Progression and mortality rates were derived from published clinical trials, meta-analyses, and observational studies. Model outputs included the incidence, prevalence, and mortality for each PCCS. The impact of novel treatments was modeled in three distinct scenarios: metastatic castration-resistant prostate cancer (mCRPC), non-metastatic CRPC (nmCRPC), or both.

Results and limitations: The model estimated the prevalence of prostate cancer as 2,219,280 in the US in 2009 and 3,072,480 in 2020, and incidence of mCRPC as 36,100 and 42,970, respectively. All-cause mortality in prostate cancer was estimated at 168,290 in 2009 and 219,360 in 2020, with 20.5% and 19.5% of these deaths, respectively, occurring in men with mCRPC. The majority (86%) of incidence flow into mCRPC states was from the nmCRPC clinical state. In the scenario with novel interventions for nmCRPC states, the progression to mCRPC is reduced, thus decreasing mCRPC incidence by 12% in 2020, with a sustained decline in mCRPC mortality. A limitation of the model is that it does not estimate prostate cancer-specific mortality.

Conclusion: The model informs clinical trial design for prostate cancer by quantifying outcomes in PCCS, and demonstrates the impact of an effective therapy applied in an earlier clinical state of nmCRPC on the incidence of mCRPC morbidity and subsequent mortality.

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Conflict of interest statement

Competing Interests: MT and MM are employees of Janssen Global Services, whose company provided funding towards this study. KS and JV are employees of Lexidyne acting as consultants to Janssen. HS has received research funding from the Prostate Cancer Foundation as well as from Aragon, Bristol-Myers Squibb, Exelixis, Janssen Research & Development, Janssen Global Services, BIND Therapeutics, and Medivation; has acted as a compensated consultant/advisor to BIND Therapeutics, Dendreon, Endo/Orion Pharmaceuticals, Ferring Pharmaceuticals, Genentech, Novartis, Ortho Biotech Oncology Research & Development (now Janssen Research & Development; proceeds donated), Sanofi Aventis, and has acted as an uncompensated consultant/advisor to Aragon, Astellas, Astra Zeneca, Celgene, Endocyte, Exelixis, Foundation Medicine, Janssen, Johnson & Johnson Pharmaceutical Research & Development, Medivation, Millennium Pharmaceuticals, and Takeda Pharmaceutical Company, Pfizer. His institution, Memorial Sloan Kettering Cancer Center, has received research funding from the Prostate Cancer Foundation. There are no patents, products in development or marketed products related to this study to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Structure and results of the dynamic progression model depicting patient flow between the distinct prostate cancer clinical states in the base-case model from 1990 to 2009.
The model highlights movement to clinical states that have higher mortality rates. Improvement in progression-free survival of men in the nmCRPC scenario reduces the number of patients transitioning from nmCRPC into the mCRPC population, where mortality risk is highest and, as such, has a more permanent impact on mCRPC mortality. *Weighted averages of patents diagnosed with localized, locally advanced, and metastatic disease. **Localized disease or locally advanced disease. nmCRPC, non-metastatic castration-resistant prostate cancer; mCRPC, metastatic castration-resistant prostate cancer.
Fig 2
Fig 2. Impact of hypothetical novel treatment in 2015 for early-stage nmCRPC, mCRPC, and combined scenario. (A) mCRPC incidence, (B) mCRPC prevalence, and (C) mCRPC mortality.
The reduction in mCRPC incidence would lead to lower mCRPC prevalence and a sustained decline in mCRPC mortality. nmCRPC, non-metastatic castration-resistant prostate cancer; mCRPC, metastatic castration-resistant prostate cancer.
See this image and copyright information in PMC

References

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