Cancer Intervention Surveillance Modeling Network (CISNET): Modeling to Improve Prostate Cancer Outcomes Across Diverse Populations



The CISNET consortium is an international consortium of cancer modelers studying the roles of prevention, screening, and treatment in explaining population cancer trends. There are three groups working in prostate cancer (Fred Hutch, University of Michigan, and Erasmus University) and our group runs the coordinating center for this effort.

Our original goal was to determine the relative contributions of changing strategies for prostate cancer control by linking trends in disease incidence and mortality with trends in screening and treatment. We developed the first model of prostate cancer progression, detection, and prognosis that explicitly linked PSA growth with disease progression and metastasis. We used this model to project incidence and mortality trends that would result from discontinuation of PSA screening as recommended by the USPSTF and to develop recommendations for smarter screening strategies based on projection of harms and benefits over a wide range of candidate policies.

Current efforts include using modeling to reconcile the apparently conflicting findings from the ERSPC and the US-based Prostate, Lung, Colon and Ovarian (PLCO) trial, comparing immediate versus delayed treatment (e.g., in the setting of active surveillance), and interrogating race-specific trends in disease incidence and mortality for insights about differences in natural history by race and impacts of changes in screening and treatment on racial disparities in prostate cancer deaths.

Our recent renewal also includes aims to model prostate cancer in international settings, to develop recommendations for risk-stratified screening strategies bases on race, polygenic risk or baseline PSA levels, and to model post-diagnosis events and decisions.

This activity is supported by grants from the National Institute of Health/National Cancer Institute (U01 CA088160, U01 CA088160-S1, U01 CA157224, and U01 CA199338).


Ruth Etzioni
Alex Tsodikov
Harry de Koning
Roman Gulati
Eveline Heijnsdijk
Lurdes Inoue
Jeremy Taylor
John Gore
Matthew Cooperberg
Bruce Trock
Daniel Lin
Jenny Donovan
Nora Pashayan

CISNet map

PSA growth before and after onset of a latent prostate tumor

PSA growth before and after onset of a latent prostate tumor

Latent progression and diagnosis of a prostate tumor

Latent progression and diagnosis of a prostate tumor

Key CISNET Publications

Jiao B, Gulati R, Hendrix N, Gore JL, Rais-Bahrami S, Morgan TM, Etzioni R. Economic evaluation of urine-based or magnetic resonance imaging reflex tests in men with intermediate prostate-specific antigen levels in the United States. Value Health. 2021 Aug;24(8):1111-1117.

Hendrix N, Gulati R, Jiao B, Kader AK, Ryan ST, Etzioni R. Clarifying the trade-offs of risk-stratified screening for prostate cancer: A cost-effectiveness study. Am J Epidemiol. 2021 May 22:kwab155.

Gulati R, Carlsson SV, Etzioni R. When to discuss prostate cancer screening with average-risk men. Am J Prev Med. 2021 Aug;61(2):294-298.

Nyame YA, Gulati R, Heijnsdijk EAM, Tsodikov A, Mariotto AB, Gore JL, Etzioni R. The impact of intensifying prostate cancer screening in Black men: A model-based analysis. J Natl Cancer Inst. 2021 May 8:djab072.

Lange J, Remmers S, Gulati R, Bill-Axelson A, Johansson JE, Kwiatkowski M, Auvinen A, Hugosson J, Hu JC, Roobol MJ, Carlsson SV, Etzioni R. Impact of cancer screening on metastasis: A prostate cancer case study. J Med Screen. 2021 Feb 9:969141321989738.

Nyame YA, Gulati R, Tsodikov A, Gore JL, Etzioni R. Prostate-specific antigen screening and recent increases in advanced prostate cancer. JNCI Cancer Spectr. 2020 Oct 26;5(1):pkaa098.

Etzioni R, Nyame YA. Prostate cancer screening guidelines for black men: Spotlight on an empty stage. J Natl Cancer Inst. 2020 Nov 4:djaa172.

Shoag JE, Nyame YA, Gulati R, Etzioni R, Hu JC. Reconsidering the trade-offs of prostate cancer screening. N Engl J Med. 2020 Jun 18;382(25):2465-2468.

Heijnsdijk EAM, Gulati R, Tsodikov A, Lange JM, Mariotto AB, Vickers AJ, Carlsson SV, Etzioni R. Lifetime benefits and harms of prostate-specific antigen-based risk-stratified screening for prostate cancer. J Natl Cancer Inst. 2020 Oct 1;112(10):1013-1020.

Lange JM, Laviana AA, Penson DF, Lin DW, Bill-Axelson A, Carlsson SV, Newcomb LF, Trock BJ, Carter HB, Carroll PR, Cooperberg MR, Cowan JE, Klotz LH, Etzioni RB. Prostate cancer mortality and metastasis under different biopsy frequencies in North American active surveillance cohorts. Cancer. 2020 Feb 1;126(3):583-592.

Patel NA, Sedrakyan A, Bianco F, Etzioni R, Gorin MA, Hsu WC, Mao J, Nguyen PL, Schaeffer E, Shoag J, Vickers A, Hu JC. Definitive and sustained increase in prostate cancer metastases in the United States. Urol Oncol. 2019 Dec;37(12):988-990.

Gulati R, Morgan TM, A'mar T, Psutka SP, Tosoian JJ, Etzioni R. Overdiagnosis and lives saved due to reflex testing men with intermediate prostate-specific antigen levels. J Natl Cancer Inst. 2019 Jun 21.

Gulati R, Psutka SP, Etzioni R. Personalized risks of overdiagnosis for screen-detected prostate cancer incorporating patient comorbidities: Estimation and communication. J Urol. 2019 May 21.

Karlsson A, Jauhiainen A, Gulati R, Eklund M, Grönberg H, Etzioni R, Clements M. A natural history model for planning prostate cancer testing: Calibration and validation using Swedish registry data. PLoS One. 2019 Feb 14;14(2):e0211918.

Lange JM, Gulati R, Leonardson AS, Lin DW, Newcomb LF, Trock BJ, Carter HB, Cooperberg MR, Cowan JE, Klotz LH, Etzioni R. Estimating and comparing cancer progression risks under varying surveillance protocols. Ann Appl Stat. 2018 Sep;12(3):1773-1795.

Tsodikov A, Gulati R, Etzioni R. Reconciling the effects of screening on prostate cancer mortality in the ERSPC and PLCO trials. Ann Intern Med. 2018 Apr 17;168(8):608-609.

Etzioni R, Gulati R. When clinical trials disagree. J Urol. 2018 Mar 1.

Kaur D, Ulloa-Pérez E, Gulati R, Etzioni R. Racial disparities in prostate cancer survival in a screened population: Reality versus artifact. Cancer. 2018 Apr 15;124(8):1752-1759.

de Koning HJ, Gulati R, Moss SM, Hugosson J, Pinsky PF, Berg CD, Auvinen A, Andriole GL, Roobol MJ, Crawford ED, Nelen V, Kwiatkowski M, Zappa M, Luján M, Villers A, de Carvalho TM, Feuer EJ, Tsodikov A, Mariotto AB, Heijnsdijk EAM, Etzioni R. The efficacy of prostate-specific antigen screening: Impact of key components in the ERSPC and PLCO trials. Cancer. 2018 Mar 15;124(6):1197-1206.

Inoue LYT, Lin DW, Newcomb LF, Leonardson AS, Ankerst D, Gulati R, Carter HB, Trock BJ, Carroll PR, Cooperberg MR, Cowan JE, Klotz LH, Mamedov A, Penson DF, Etzioni R. Comparative analysis of biopsy upgrading in four prostate cancer active surveillance cohorts. Ann Intern Med. 2017 Nov 28.

Tsodikov A, Gulati R, de Carvalho TM, Heijnsdijk EAM, Hunter-Merrill RA, Mariotto AB, de Koning HJ, Etzioni R. Is prostate cancer different in black men? answers from 3 natural history models. Cancer. 2017 Apr 24.

Tsodikov A, Gulati R, Heijnsdijk EAM, Pinsky PF, Moss SM, Qiu S, de Carvalho TM, Hugosson J, Berg CD, Auvinen A, Andriole GL, Roobol MJ, Crawford ED, Nelen V, Kwiatkowski M, Zappa M, Luján M, Villers A, Feuer EJ, de Koning HJ, Mariotto AB, Etzioni R. Reconciling the effects of screening on prostate cancer mortality in the ERSPC and PLCO trials. Ann Intern Med. 2017 Oct 3;167(7):449-455.

Lange JM, Trock BJ, Gulati R, Etzioni R. A framework for treatment decision making at prostate cancer recurrence. Med Decis Making. 2017 Nov;37(8):905-913.

Gulati R, Albertsen PC. Insights from the PLCO trial about prostate cancer screening. Cancer. 2017 Feb 15;123(4):546-548.

Gulati R, Cheng HH, Lange PH, Nelson PS, Etzioni R. Screening men at increased risk for prostate cancer diagnosis: Model estimates of benefits and harms. Cancer Epidemiol Biomarkers Prev. 2017 Feb;26(2):222-227.

Gulati R, Feuer EJ, Etzioni R. Conditions for valid empirical estimates of cancer overdiagnosis in randomized trials and population studies. Am J Epidemiol. 2016 Jul 15;184(2):140-7.

Gulati R, Etzioni R. A matched cohort analysis of prostate cancer screening in younger men in Sweden. Eur Urol. 2017 Jan;71(1):53-54.

Roth JA, Gulati R, Gore JL, Cooperberg MR, Etzioni R. Economic analysis of prostate-specific antigen screening and selective treatment strategies. JAMA Oncol. 2016 Jul 1;2(7):890-8.

Etzioni R, Gulati R. Recent trends in PSA testing and prostate cancer incidence: A look at context. JAMA Oncol. 2016 Jul 1;2(7):955-6.

Etzioni R, Gulati R. Recognizing the limitations of cancer overdiagnosis studies: A first step towards overcoming them. J Natl Cancer Inst. 2015 Nov 18;108(3).

Birnbaum JK, Feng Z, Gulati R, Fan J, Lotan Y, Wei JT, Etzioni R. Projecting benefits and harms of novel cancer screening biomarkers: A study of PCA3 and prostate cancer. Cancer Epidemiol Biomarkers Prev. 2015 Apr;24(4):677-82.

Etzioni R, Xia J, Hubbard R, Weiss NS, Gulati R. A reality check for overdiagnosis estimates associated with breast cancer screening. J Natl Cancer Inst. 2014 Dec;106(12).

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.

Xia J, Trock BJ, Gulati R, Mallinger L, Cooperberg MR, Carroll PR, Carter HB, Etzioni R. Overdetection of recurrence after radical prostatectomy: Estimates based on patient and tumor characteristics. Clin Cancer Res. 2014 Oct 15;20(20):5302-10.

Etzioni R, Gulati R. Oversimplifying overdiagnosis. J Gen Intern Med. 2014 Sep;29(9):1218-20.

Etzioni RD, Thompson IM. What do the screening trials really tell us and where do we go from here? Urol Clin North Am. 2014 May;41(2):223-8.

Pataky R, Gulati R, Etzioni R, Black P, Chi KN, Coldman AJ, Pickles T, Tyldesley S, Peacock S. Is prostate cancer screening cost-effective? A microsimulation model of prostate-specific antigen-based screening for British Columbia, Canada. Int J Cancer. 2014 Aug 15;135(4):939-47.

Lansdorp-Vogelaar I, Gulati R, Mariotto AB, Schechter CB, de Carvalho TM, Knudsen AB, van Ravesteyn NT, Heijnsdijk EA, Pabiniak C, van Ballegooijen M, Rutter CM, Kuntz KM, Feuer EJ, Etzioni R, de Koning HJ, Zauber AG, Mandelblatt JS. Personalizing age of cancer screening cessation based on comorbid conditions: Model estimates of harms and benefits. Ann Intern Med. 2014 Jul 15;161(2):104-12.

Etzioni R, Gulati R. RE: A model too far. J Natl Cancer Inst. 2014 Apr;106(4):dju058.

Inoue LY, Trock BJ, Partin AW, Carter HB, Etzioni R. Modeling grade progression in an active surveillance study. Stat Med. 2014 Mar 15;33(6):930-9.

Gulati R, Inoue LY, Gore JL, Katcher J, Etzioni R. Individualized estimates of overdiagnosis in screen-detected prostate cancer. J Natl Cancer Inst. 2014 Feb;106(2):djt367.

Etzioni R, Durand-Zaleski I, Lansdorp-Vogelaar I. Evaluation of new technologies for cancer control based on population trends in disease incidence and mortality. J Natl Cancer Inst Monogr. 2013;2013(46):117-23.

Etzioni R, Gulati R, Mallinger L, Mandelblatt J. Influence of study features and methods on overdiagnosis estimates in breast and prostate cancer screening. Ann Intern Med. 2013 Jun 4;158(11):831-8.

Gulati R, Etzioni R. Alternative prostate cancer screening strategies--in response. Ann Intern Med. 2013 May 21;158(10):778-9.

Etzioni RD. Review of evidence concerning PSA screening for prostate cancer has limitations as basis for policy developmentEvid Based Med 2013 Apr;18(2):75-6.

Etzioni R, Gulati R. Response: reading between the lines of cancer screening trials: using modeling to understand the evidenceMed Care 2013 Apr;51(4):304-6.

Etzioni R, Gulati R, Cooperberg MR, Penson DM, Weiss NS, Thompson IM. Limitations of basing screening policies on screening trials: The US Preventive Services Task Force and prostate cancer screening. Med Care 2013 Apr;51(4):295-300.

Xia J, Gulati R, Au M, Gore JL, Lin DW, Etzioni R. Effects of screening on radical prostatectomy efficacy: The Prostate Cancer Intervention Versus Observation Trial. J Natl Cancer Inst 2013 Apr 17;105(8):546-50.

Gulati R, Gore JL, Etzioni R. Comparative effectiveness of alternative prostate-specific antigen--based prostate cancer screening strategies: Model estimates of potential benefits and harms. Ann Intern Med 2013 Feb 5;158(3):145-53.

Inoue LY, Gulati R, Yu C, Kattan MW, Etzioni R. Deriving benefit of early detection from biomarker-based prognostic models. Biostatistics 2013 Jan;14(1):15-27.

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.

Xia J, Trock BJ, Cooperberg MR, Gulati R, Zeliadt SB, Gore JL, Lin DW, Carroll PR, Carter HB, Etzioni R. Prostate cancer mortality following active surveillance versus immediate radical prostatectomy. Clin Cancer Res 2012 Oct 1;18(19):5471-8.

Etzioni R, Mucci LA, Chen S, Johansson JE, Fall K, Adami HO. Increasing use of radical prostatectomy for nonlethal prostate cancer in Sweden. Clin Cancer Res 2012 Dec 15;18(24):6742-7.

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.

Zeliadt SB, Buist DS, Reid RJ, Grossman DC, Ma J, Etzioni R. Biopsy follow-up of prostate-specific antigen tests. Am J Prev Med 2012 Jan;42(1):37-43.

Gulati R, Mariotto AB, Chen S, Gore JL, Etzioni R. Long-term projections of the harm-benefit trade-off in prostate cancer screening are more favorable than previous short-term estimates. J Clin Epidemiol 2011 Dec;64(12):1412-7.

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.

Gulati R, Inoue L, Katcher J, Hazelton W, Etzioni R. Calibrating disease progression models using population data: A critical precursor to policy development in cancer control. Biostatistics 2010 Oct;11(4):707-19.

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;101(6):374–83.

Fesinmeyer MD, Gulati R, Zeliadt S, Weiss N, Kristal AR, Etzioni R. Effect of population trends in body mass index on prostate cancer incidence and mortality in the United States. Cancer Epidemiol Biomarkers Prev. 2009 Mar;18(3):808-15.

Etzioni R, Gulati R, Mariotto AB. Overview of prostate cancer trends in the era of PSA screening. In: Ankerst DP, Tangen CM, Thompson IM, editors. Prostate Cancer Screening. 2nd ed. Humana Press, 2009, p. 3-14.

Etzioni R, Feuer E. Studies of prostate-cancer mortality: Caution advised. Lancet Oncol 2008 May;9(5):407-9.

Etzioni R, Gulati R, Falcon S, Penson DF. Impact of PSA screening on the incidence of advanced stage prostate cancer in the US: A surveillance modeling approach. Med Decis Making. 2008 Mar 4;28:323-331.

Inoue LYT, Etzioni R, Morrell C, Muller P. Modeling disease progression with longitudinal markers. J Am Stat Assoc. 2008 Mar;103(481):259-270.

Etzioni R, Tsodikov A, Mariotto A, Szabo A, Falcon S, Wegelin J, diTommaso D, Karnofski K, Gulati R, Penson DFG, Feuer EJ. Quantifying the role of PSA screening in the US prostate cancer mortality decline. Cancer Causes Control. 2008 Mar;19(2):175-81.

Telesca D, Gulati R, Etzioni R. Estimating lead time and overdiagnosis associated with PSA screening from prostate cancer incidence trends. Biometrics. 2008 Mar;64(1):10-9.

Mariotto AB, Etzioni R, Krapcho M, Feuer EJ. Reconstructing prostate-specific antigen (PSA) testing patterns among black and white men in the US from Medicare claims and the National Health Interview Survey. Cancer. 2007 Mar 19;109(9):1877-86.

Shaw PA, Etzioni R, Zeliadt SB, Mariotto M, Karnofski K, Penson DF, Weiss NS, Feuer EJ. An ecologic study of PSA screening and prostate cancer mortality in nine geographic areas of the US. Am J Epidemiol. 2004 Dec 1;160(11):1059-69.

Feuer EJ, Etzioni R, Cronin K, Mariotto A. The Use of Modeling to Understand the Impact of Screening on US Mortality: Examples from Mammography and PSA Testing. Stat Methods Med Res. 2004 Dec;13(6) 421-42.

Etzioni R, Penson DF, Legler JM, di Tommaso D, Boer R, Gann PH, Feuer EJ. Overdiagnosis due to prostate-specific antigen screening: Lessons from U.S. prostate cancer incidence trends. J Natl Cancer Inst 2002 Jul 3;94(13):981-90.

Etzioni R, Legler JM, Feuer EJ, Merrill RM, Cronin KA, Hankey BF. Cancer surveillance series: Interpreting trends in prostate cancer-part III: Quantifying the link between population prostate-specific antigen testing and recent declines in prostate cancer mortality. J Natl Cancer Inst 1999 Jun 16;91(12):1033-9.