Grant Number:	5U01CA199338-05 Interpret this number
Primary Investigator:	Etzioni, Ruth
Organization:	Fred Hutchinson Cancer Research Center
Project Title:	Modeling to Improve Prostate Cancer Outcomes Across Diverse Populations
Fiscal Year:	2019

 DESCRIPTION (provided by applicant): Prostate cancer is the most common cancer in men. In the US, 1 in 7 men will experience a prostate cancer diagnosis in his lifetime. Identifying ways to reduce the burden of prostate cancer is therefore a top research priority. Management of prostate cancer has changed dramatically since the advent and widespread dissemination of the PSA test. Since the early 1990s, prostate cancer mortality in the US has dropped by almost half. The CISNET Prostate Working Group (PWG) was formed to use disease modeling to explain these mortality trends. The CISNET PWG has developed three models of prostate cancer natural history, detection, and survival and calibrated them against US prostate cancer trends. Results indicate that both screening and treatment changes have reduced prostate cancer deaths. However, policies must be tailored to limit harms and costs associated with overdiagnosis and overtreatment. Different approaches for doing this have been proposed but cannot all be investigated in prospective studies. The objective of this application is to utilize and extend the CISNET PWG models to identify tailored and targeted intervention strategies that offer the most benefit while limiting harms and costs. We will determine whether we can improve screening further by using novel stratification approaches and also whether we can safely limit harms of overtreatment by judicious choices of primary and secondary therapies. These approaches will be applied in the US population and in international cancer control settings that may require modified strategies. We will provide decision makers with model access via online calculators with graphical user interfaces. Our specific aims are: Aim 1: Identify active surveillance strategies that minimize patient burden without increasing risks of progression to non-curable disease or death. Aim 2: Develop stratified approaches to prostate cancer screening that target high-risk men based on polygenic risk and baseline PSA at age 45. Aim 3: Model secondary treatment strategies, their impact, and implications for population prostate cancer control. Aim 4: Determine whether racial disparities in prostate cancer mortality can be reduced by using stratified screening and treatment strategies. Aim 5: Modularize models to evaluate cancer control programs in non-US populations and collaborate with investigators in the UK and the Caribbean to develop policies for their populations and resources. Aim 6: Develop online calculators to support patient-physician decisions and policymaker deliberations about PSA screening and treatment for localized prostate cancer. These aims are highly responsive to the funding opportunity announcement, addressing 6 of the 9 targeted priority areas. Our cumulative expertise in prostate modeling, our existing models, and our close ties with clinical experts who provide access to large, high-quality datasets for model validation and calibration position us well to uniquely contribute to the national and international dialogue about how best to address and control this most common cancer in men.




Lifetime Health and Economic Outcomes of Biparametric Magnetic Resonance Imaging as First-Line Screening for Prostate Cancer : A Decision Model Analysis.
Authors: Gulati R. , Jiao B. , Al-Faouri R. , Sharma V. , Kaul S. , Fleishman A. , Wymer K. , Boorjian S.A. , Olumi A.F. , Etzioni R. , et al. .
Source: Annals Of Internal Medicine, 2024-06-04 00:00:00.0; , .
EPub date: 2024-06-04 00:00:00.0.
PMID: 38830219
Related Citations

Racial disparities in prostate cancer mortality: a model-based decomposition of contributing factors.
Authors: Gulati R. , Nyame Y.A. , Lange J.M. , Shoag J.E. , Tsodikov A. , Etzioni R. .
Source: Journal Of The National Cancer Institute. Monographs, 2023-11-08 00:00:00.0; 2023(62), p. 212-218.
PMID: 37947332
Related Citations

Free PSA and Clinically Significant and Fatal Prostate Cancer in the PLCO Screening Trial.
Authors: Yim K. , Ma C. , Carlsson S. , Lilja H. , Mucci L. , Penney K. , Kibel A.S. , Eggener S. , Preston M.A. .
Source: The Journal Of Urology, 2023 Oct; 210(4), p. 630-638.
EPub date: 2023-06-29 00:00:00.0.
PMID: 37384841
Related Citations

Transcriptome-Wide Association Analysis Identifies Novel Candidate Susceptibility Genes for Prostate-Specific Antigen Levels in Men Without Prostate Cancer.
Authors: Chen D.M. , Dong R. , Kachuri L. , Hoffmann T. , Jiang Y. , Berndt S.I. , Shelley J.P. , Schaffer K.R. , Machiela M.J. , Freedman N.D. , et al. .
Source: Medrxiv : The Preprint Server For Health Sciences, 2023-05-05 00:00:00.0; , .
EPub date: 2023-05-05 00:00:00.0.
PMID: 37205487
Related Citations

Corrigendum to "Young Age on Starting Prostate-specific Antigen Testing Is Associated with a Greater Reduction in Prostate Cancer Mortality: 24-Year Follow-up of the Göteborg Randomized Population-based Prostate Cancer Screening Trial" [Eur Urol (2022)].
Authors: Carlsson S.V. , Godtman R.A. , Pihl C.G. , Vickers A. , Lilja H. , Hugosson J. , Månsson M. .
Source: European Urology, 2023 Mar; 83(3), p. e88.
EPub date: 2022-12-08 00:00:00.0.
PMID: 36503643
Related Citations

Estimating the Number of Men Living with Metastatic Prostate Cancer in the United States.
Authors: Devasia T.P. , Mariotto A.B. , Nyame Y.A. , Etzioni R. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2023-01-30 00:00:00.0; , .
EPub date: 2023-01-30 00:00:00.0.
PMID: 36716178
Related Citations

Young Age on Starting Prostate-specific Antigen Testing Is Associated with a Greater Reduction in Prostate Cancer Mortality: 24-Year Follow-up of the Göteborg Randomized Population-based Prostate Cancer Screening Trial.
Authors: Carlsson S.V. , Arnsrud Godtman R. , Pihl C.G. , Vickers A. , Lilja H. , Hugosson J. , Månsson M. .
Source: European Urology, 2022-11-02 00:00:00.0; , .
EPub date: 2022-11-02 00:00:00.0.
PMID: 36334968
Related Citations

Correction: Estimating patient health in prostate cancer treatment counseling.
Authors: Chesnut G.T. , Tin A.L. , Fleshner K.A. , Benfante N.E. , Vickers A.J. , Eastham J.A. , Sjoberg D.D. , Carlsson S.V. .
Source: Prostate Cancer And Prostatic Diseases, 2022-03-31 00:00:00.0; , .
EPub date: 2022-03-31 00:00:00.0.
PMID: 35361969
Related Citations

Estimating patient health in prostate cancer treatment counseling.
Authors: Chesnut G.T. , Tin A.L. , Fleshner K.A. , Benfante N.E. , Vickers A.J. , Eastham J.A. , Sjoberg D.D. , Carlsson S.V. .
Source: Prostate Cancer And Prostatic Diseases, 2021-11-03 00:00:00.0; , .
EPub date: 2021-11-03 00:00:00.0.
PMID: 34732855
Related Citations

Step-adjusted tree-based reinforcement learning for evaluating nested dynamic treatment regimes using test-and-treat observational data.
Authors: Tang M. , Wang L. , Gorin M.A. , Taylor J.M.G. .
Source: Statistics In Medicine, 2021-09-07 00:00:00.0; , .
EPub date: 2021-09-07 00:00:00.0.
PMID: 34490942
Related Citations

Economic Evaluation of Urine-Based or Magnetic Resonance Imaging Reflex Tests in Men With Intermediate Prostate-Specific Antigen Levels in the United States.
Authors: Jiao B. , Gulati R. , Hendrix N. , Gore J.L. , Rais-Bahrami S. , Morgan T.M. , Etzioni R. .
Source: Value In Health : The Journal Of The International Society For Pharmacoeconomics And Outcomes Research, 2021 Aug; 24(8), p. 1111-1117.
EPub date: 2021-04-22 00:00:00.0.
PMID: 34372976
Related Citations

A copula-based approach for dynamic prediction of survival with a binary time-dependent covariate.
Authors: Suresh K. , Taylor J.M.G. , Tsodikov A. .
Source: Statistics In Medicine, 2021-06-14 00:00:00.0; , .
EPub date: 2021-06-14 00:00:00.0.
PMID: 34124771
Related Citations

Prostate Cancer Screening Guidelines for Black Men: Spotlight on an Empty Stage.
Authors: Etzioni R. , Nyame Y.A. .
Source: Journal Of The National Cancer Institute, 2021-06-01 00:00:00.0; 113(6), p. 650-651.
PMID: 33146382
Related Citations

Cost-effectiveness of multiparametric magnetic resonance imaging and MRI-guided biopsy in a population-based prostate cancer screening setting using a micro-simulation model.
Authors: Getaneh A.M. , Heijnsdijk E.A. , de Koning H.J. .
Source: Cancer Medicine, 2021 Jun; 10(12), p. 4046-4053.
EPub date: 2021-05-15 00:00:00.0.
PMID: 33991077
Related Citations

Active surveillance for prostate cancer.
Authors: Shill D.K. , Roobol M.J. , Ehdaie B. , Vickers A.J. , Carlsson S.V. .
Source: Translational Andrology And Urology, 2021 Jun; 10(6), p. 2809-2819.
PMID: 34295763
Related Citations

Clarifying the Trade-Offs of Risk-Stratified Screening for Prostate Cancer: A Cost-Effectiveness Study.
Authors: Hendrix N. , Gulati R. , Jiao B. , Kader A.K. , Ryan S.T. , Etzioni R. .
Source: American Journal Of Epidemiology, 2021-05-22 00:00:00.0; , .
EPub date: 2021-05-22 00:00:00.0.
PMID: 34023874
Related Citations

The Impact of Intensifying Prostate Cancer Screening in Black Men: A Model-Based Analysis.
Authors: Nyame Y.A. , Gulati R. , Heijnsdijk E.A.M. , Tsodikov A. , Mariotto A.B. , Gore J.L. , Etzioni R. .
Source: Journal Of The National Cancer Institute, 2021-05-08 00:00:00.0; , .
EPub date: 2021-05-08 00:00:00.0.
PMID: 33963850
Related Citations

When to Discuss Prostate Cancer Screening With Average-Risk Men.
Authors: Gulati R. , Carlsson S.V. , Etzioni R. .
Source: American Journal Of Preventive Medicine, 2021-05-06 00:00:00.0; , .
EPub date: 2021-05-06 00:00:00.0.
PMID: 33966938
Related Citations

Preoperative exercise interventions to optimize continence outcomes following radical prostatectomy.
Authors: Mungovan S.F. , Carlsson S.V. , Gass G.C. , Graham P.L. , Sandhu J.S. , Akin O. , Scardino P.T. , Eastham J.A. , Patel M.I. .
Source: Nature Reviews. Urology, 2021-04-08 00:00:00.0; , .
EPub date: 2021-04-08 00:00:00.0.
PMID: 33833445
Related Citations

Problems with Numbers in Decision Aids for Prostate-specific Antigen Screening: A Critical Review.
Authors: Carlsson S.V. , Vickers A.J. , Gonsky J.P. , Hay J.L. , Hu J.C. .
Source: European Urology, 2021 Mar; 79(3), p. 330-333.
EPub date: 2020-12-09 00:00:00.0.
PMID: 33309033
Related Citations

Impact of cancer screening on metastasis: A prostate cancer case study.
Authors: Lange J. , Remmers S. , Gulati R. , Bill-Axelson A. , Johansson J.E. , Kwiatkowski M. , Auvinen A. , Hugosson J. , Hu J.C. , Roobol M.J. , et al. .
Source: Journal Of Medical Screening, 2021-02-09 00:00:00.0; , p. 969141321989738.
EPub date: 2021-02-09 00:00:00.0.
PMID: 33563084
Related Citations

The comparative effectiveness of mpMRI and MRI-guided biopsy vs regular biopsy in a population-based PSA testing: a modeling study.
Authors: Getaneh A.M. , Heijnsdijk E.A.M. , de Koning H.J. .
Source: Scientific Reports, 2021-01-19 00:00:00.0; 11(1), p. 1801.
EPub date: 2021-01-19 00:00:00.0.
PMID: 33469144
Related Citations

Screening for Prostate Cancer.
Authors: Carlsson S.V. , Vickers A.J. .
Source: The Medical Clinics Of North America, 2020 Nov; 104(6), p. 1051-1062.
EPub date: 2020-09-16 00:00:00.0.
PMID: 33099450
Related Citations

Surgeon heterogeneity significantly affects functional and oncological outcomes after radical prostatectomy in the Swedish LAPPRO trial.
Authors: Nyberg M. , Sjoberg D.D. , Carlsson S.V. , Wilderäng U. , Carlsson S. , Stranne J. , Wiklund P. , Steineck G. , Haglind E. , Hugosson J. , et al. .
Source: Bju International, 2020-09-11 00:00:00.0; , .
EPub date: 2020-09-11 00:00:00.0.
PMID: 32916021
Related Citations

Assessment of harms, benefits, and cost-effectiveness of prostate cancer screening: A micro-simulation study of 230 scenarios.
Authors: Getaneh A.M. , Heijnsdijk E.A.M. , Roobol M.J. , de Koning H.J. .
Source: Cancer Medicine, 2020-08-19 00:00:00.0; , .
EPub date: 2020-08-19 00:00:00.0.
PMID: 32813910
Related Citations

"PSA Surveillance in the Septuagenarian": A Proposed New Terminology for Clinical Follow-up to Assess Risk of Prostate Cancer in Men Aged 70 Years and Older.
Authors: Carlsson S.V. , Eastham J.A. , Crawford E.D. , Harris R.G. .
Source: European Urology, 2020 08; 78(2), p. 136-137.
EPub date: 2020-04-06 00:00:00.0.
PMID: 32273182
Related Citations

Joint modeling and multiple comparisons with the best of data from a SMART with survival outcomes.
Authors: Chao Y.C. , Tran Q. , Tsodikov A. , Kidwell K.M. .
Source: Biostatistics (oxford, England), 2020-07-13 00:00:00.0; , .
EPub date: 2020-07-13 00:00:00.0.
PMID: 32659784
Related Citations

Risk of Recurrent Disease 6 Years After Open or Robotic-assisted Radical Prostatectomy in the Prospective Controlled Trial LAPPRO.
Authors: Nyberg M. , Akre O. , Bock D. , Carlsson S.V. , Carlsson S. , Hugosson J. , Lantz A. , Steineck G. , Stranne J. , Tyritzis S. , et al. .
Source: European Urology Open Science, 2020 Jul; 20, p. 54-61.
EPub date: 2020-08-19 00:00:00.0.
PMID: 34337458
Related Citations

Reconsidering the Trade-offs of Prostate Cancer Screening.
Authors: Shoag J.E. , Nyame Y.A. , Gulati R. , Etzioni R. , Hu J.C. .
Source: The New England Journal Of Medicine, 2020-06-18 00:00:00.0; 382(25), p. 2465-2468.
PMID: 32558473
Related Citations

Overdiagnosis and Lives Saved by Reflex Testing Men With Intermediate Prostate-Specific Antigen Levels.
Authors: Gulati R. , Morgan T.M. , A'mar T. , Psutka S.P. , Tosoian J.J. , Etzioni R. .
Source: Journal Of The National Cancer Institute, 2020-04-01 00:00:00.0; 112(4), p. 384-390.
PMID: 31225597
Related Citations

Lifetime benefits and harms of PSA-based risk screening for prostate cancer.
Authors: Heijnsdijk E.A.M. , Gulati R. , Tsodikov A. , Lange J.M. , Mariotto A.B. , Vickers A.J. , Carlsson S.V. , Etzioni R. .
Source: Journal Of The National Cancer Institute, 2020-01-09 00:00:00.0; , .
EPub date: 2020-01-09 00:00:00.0.
PMID: 32067047
Related Citations

Association of Baseline Prostate-Specific Antigen Level With Long-term Diagnosis of Clinically Significant Prostate Cancer Among Patients Aged 55 to 60 Years: A Secondary Analysis of a Cohort in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.
Authors: Kovac E. , Carlsson S.V. , Lilja H. , Hugosson J. , Kattan M.W. , Holmberg E. , Stephenson A.J. .
Source: Jama Network Open, 2020-01-03 00:00:00.0; 3(1), p. e1919284.
EPub date: 2020-01-03 00:00:00.0.
PMID: 31940039
Related Citations

A Gaussian copula approach for dynamic prediction of survival with a longitudinal biomarker.
Authors: Suresh K. , Taylor J.M.G. , Tsodikov A. .
Source: Biostatistics (oxford, England), 2019-12-10 00:00:00.0; , .
EPub date: 2019-12-10 00:00:00.0.
PMID: 31820798
Related Citations

Performance and inter-observer variability of prostate MRI (PI-RADS version 2) outside high-volume centres.
Authors: Kohestani K. , Wallström J. , Dehlfors N. , Sponga O.M. , Månsson M. , Josefsson A. , Carlsson S. , Hellström M. , Hugosson J. .
Source: Scandinavian Journal Of Urology, 2019-10-29 00:00:00.0; , p. 1-8.
EPub date: 2019-10-29 00:00:00.0.
PMID: 31661357
Related Citations

Prostate cancer mortality and metastasis under different biopsy frequencies in North American active surveillance cohorts.
Authors: Lange J.M. , Laviana A.A. , Penson D.F. , Lin D.W. , Bill-Axelson A. , Carlsson S.V. , Newcomb L.F. , Trock B.J. , Carter H.B. , Carroll P.R. , et al. .
Source: Cancer, 2019-10-22 00:00:00.0; , .
EPub date: 2019-10-22 00:00:00.0.
PMID: 31639200
Related Citations

Informed decision-making based on a leaflet in the context of prostate cancer screening.
Authors: Dierks T. , Heijnsdijk E.A.M. , Korfage I.J. , Roobol M.J. , de Koning H.J. .
Source: Patient Education And Counseling, 2019 Aug; 102(8), p. 1483-1489.
EPub date: 2019-04-13 00:00:00.0.
PMID: 31014933
Related Citations

Evaluating Parameter Uncertainty in a Simulation Model of Cancer Using Emulators.
Authors: de Carvalho T.M. , Heijnsdijk E.A.M. , Coffeng L. , de Koning H.J. .
Source: Medical Decision Making : An International Journal Of The Society For Medical Decision Making, 2019-06-10 00:00:00.0; , p. 272989X19837631.
EPub date: 2019-06-10 00:00:00.0.
PMID: 31179833
Related Citations

Personalized risks of overdiagnosis for screen-detected prostate cancer incorporating patient comorbidities: Estimation and communication.
Authors: Gulati R. , Psutka S.P. , Etzioni R. .
Source: The Journal Of Urology, 2019-05-21 00:00:00.0; , p. 101097JU0000000000000346.
EPub date: 2019-05-21 00:00:00.0.
PMID: 31112106
Related Citations

The Impact of Design and Performance in Prostate-Specific Antigen Screening: Differences Between ERSPC Centers.
Authors: Heijnsdijk E.A.M. , Adolfsson J. , Auvinen A. , Roobol M.J. , Hugosson J. , de Koning H.J. .
Source: European Urology, 2019-04-25 00:00:00.0; , .
EPub date: 2019-04-25 00:00:00.0.
PMID: 31031050
Related Citations

Baseline Prostate-specific Antigen Level in Midlife and Aggressive Prostate Cancer in Black Men.
Authors: Preston M.A. , Gerke T. , Carlsson S.V. , Signorello L. , Sjoberg D.D. , Markt S.C. , Kibel A.S. , Trinh Q.D. , Steinwandel M. , Blot W. , et al. .
Source: European Urology, 2019 03; 75(3), p. 399-407.
EPub date: 2018-09-17 00:00:00.0.
PMID: 30237027
Related Citations

Individual and Population Comparisons of Surgery and Radiotherapy Outcomes in Prostate Cancer Using Bayesian Multistate Models.
Authors: Beesley L.J. , Morgan T.M. , Spratt D.E. , Singhal U. , Feng F.Y. , Furgal A.C. , Jackson W.C. , Daignault S. , Taylor J.M.G. .
Source: Jama Network Open, 2019-02-01 00:00:00.0; 2(2), p. e187765.
EPub date: 2019-02-01 00:00:00.0.
PMID: 30707231
Related Citations

A natural history model for planning prostate cancer testing: Calibration and validation using Swedish registry data.
Authors: Karlsson A. , Jauhiainen A. , Gulati R. , Eklund M. , Grönberg H. , Etzioni R. , Clements M. .
Source: Plos One, 2019; 14(2), p. e0211918.
EPub date: 2019-02-14 00:00:00.0.
PMID: 30763406
Related Citations

Comparison of Physician-Documented Versus Patient-Reported Collection of Comorbidities Among Patients With Prostate Cancer Upon First Visit to the Urology Clinic.
Authors: Fleshner K. , Tin A. , Benfante N. , Carlsson S. , Vickers A.J. .
Source: Jco Clinical Cancer Informatics, 2018 12; 2, p. 1-10.
PMID: 30652570
Related Citations

The ERSPC Study: Quality Takes Time and Perseverance.
Authors: Roobol M.J. , Carlsson S.V. .
Source: Clinical Chemistry, 2018-11-20 00:00:00.0; , .
EPub date: 2018-11-20 00:00:00.0.
PMID: 30459163
Related Citations

Perspective on Prostate Cancer Screening.
Authors: Carlsson S.V. , Lilja H. .
Source: Clinical Chemistry, 2018-11-20 00:00:00.0; , .
EPub date: 2018-11-20 00:00:00.0.
PMID: 30459166
Related Citations

Functional and Oncologic Outcomes Between Open and Robotic Radical Prostatectomy at 24-month Follow-up in the Swedish LAPPRO Trial.
Authors: Nyberg M. , Hugosson J. , Wiklund P. , Sjoberg D. , Wilderäng U. , Carlsson S.V. , Carlsson S. , Stranne J. , Steineck G. , Haglind E. , et al. .
Source: European Urology Oncology, 2018 10; 1(5), p. 353-360.
EPub date: 2018-06-11 00:00:00.0.
PMID: 31158073
Related Citations

Reply to 'Clinical utility of the Prostate Health Index (phi) for biopsy decision management in a large group urology practice setting'.
Authors: Ehdaie B. , Carlsson S. .
Source: Prostate Cancer And Prostatic Diseases, 2018 09; 21(3), p. 446-447.
EPub date: 2018-06-01 00:00:00.0.
PMID: 29858593
Related Citations

ESTIMATING AND COMPARING CANCER PROGRESSION RISKS UNDER VARYING SURVEILLANCE PROTOCOLS.
Authors: Lange J.M. , Gulati R. , Leonardson A.S. , Lin D.W. , Newcomb L.F. , Trock B.J. , Carter H.B. , Cooperberg M.R. , Cowan J.E. , Klotz L.H. , et al. .
Source: The Annals Of Applied Statistics, 2018 Sep; 12(3), p. 1773-1795.
EPub date: 2018-09-11 00:00:00.0.
PMID: 30627300
Related Citations

Factors Influencing Men's Choice of and Adherence to Active Surveillance for Low-risk Prostate Cancer: A Mixed-method Systematic Review.
Authors: Kinsella N. , Stattin P. , Cahill D. , Brown C. , Bill-Axelson A. , Bratt O. , Carlsson S. , Van Hemelrijck M. .
Source: European Urology, 2018-03-26 00:00:00.0; , .
EPub date: 2018-03-26 00:00:00.0.
PMID: 29598981
Related Citations

Comparative effectiveness of prostate cancer screening between the ages of 55 and 69 years followed by active surveillance.
Authors: de Carvalho T.M. , Heijnsdijk E.A.M. , de Koning H.J. .
Source: Cancer, 2018-02-01 00:00:00.0; 124(3), p. 507-513.
EPub date: 2017-12-12 00:00:00.0.
PMID: 29231973
Related Citations