Cost-effectiveness analysis of prostate cancer screening in the UK: A decision model analysis based on the CAP trial

Edna Keeney; Sabina Sanghera; Richard M Martin; Roman Gulati; Fredrik Wiklund; Eleanor I Walsh; Jenny L Donovan; Freddie C Hamdy; David Neal; J. Athene Lane; Emma L Turner; Howard H Z Thom; Mark Clements

doi:10.1007/s40273-022-01191-1

Cost-effectiveness analysis of prostate cancer screening in the UK: A decision model analysis based on the CAP trial

Edna Keeney^*, Sabina Sanghera, Richard M Martin, Roman Gulati, Fredrik Wiklund, Eleanor I Walsh, Jenny L Donovan , Freddie C Hamdy, David Neal, J. Athene Lane, Emma L Turner, Howard H Z Thom, Mark Clements

^*Corresponding author for this work

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Abstract

Background and Objective
Most guidelines in the UK, Europe and North America do not recommend organised population-wide screening for prostate cancer. Prostate-specific antigen-based screening can reduce prostate cancer-specific mortality, but there are concerns about overdiagnosis, overtreatment and economic value. The aim was therefore to assess the cost effectiveness of eight potential screening strategies in the UK.

Methods
We used a cost-utility analysis with an individual-based simulation model. The model was calibrated to data from the 10-year follow-up of the Cluster Randomised Trial of PSA Testing for Prostate Cancer (CAP). Treatment effects were modelled using data from the Prostate Testing for Cancer and Treatment (ProtecT) trial. The participants were a hypothetical population of 10 million men in the UK followed from age 30 years to death. The strategies were: no screening; five age-based screening strategies; adaptive screening, where men with an initial prostate-specific antigen level of < 1.5 ng/mL are screened every 6 years and those above this level are screened every 4 years; and two polygenic risk-stratified screening strategies. We assumed the use of pre-biopsy multi-parametric magnetic resonance imaging for men with prostate-specific antigen ≥ 3 ng/mL and combined transrectal ultrasound-guided and targeted biopsies. The main outcome measures were projected lifetime costs and quality-adjusted life-years from a National Health Service perspective.

Results
All screening strategies increased costs compared with no screening, with the majority also increasing quality-adjusted life-years. At willingness-to-pay thresholds of £20,000 or £30,000 per quality-adjusted life-year gained, a once-off screening at age 50 years was optimal, although this was sensitive to the utility estimates used. Although the polygenic risk-stratified screening strategies were not on the cost-effectiveness frontier, there was evidence to suggest that they were less cost ineffective than the alternative age-based strategies.

Conclusions
Of the prostate-specific antigen-based strategies compared, only a once-off screening at age 50 years was potentially cost effective at current UK willingness-to-pay thresholds. An additional follow-up of CAP to 15 years may reduce uncertainty about the cost effectiveness of the screening strategies.

Original language	English
Pages (from-to)	1207-1220
Number of pages	14
Journal	PharmacoEconomics
Volume	40
Issue number	12
Early online date	6 Oct 2022
DOIs	https://doi.org/10.1007/s40273-022-01191-1
Publication status	Published - 1 Dec 2022

Bibliographical note

Funding Information:
RMM is the lead principal investigator (and JLD, FCH and DEN co-PIs) of the CAP trial, funded by Cancer Research UK and the UK Department of Health (C11043/A4286, C18281/A8145, C18281/A11326, C18281/A15064 and C18281/A24432). RMM was supported by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme). RMM is a National Institute for Health Research Senior Investigator (NIHR202411). RMM and HT were supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. The ProtecT trial is funded by the UK National Institute for Health Research (NIHR) Health Technology Assessment Programme (NIHR HTA: projects 96/20/06, 96/20/99). RG was supported by the National Cancer Institute at the National Institutes of Health (U01 CA253915 and R50 CA221836). HT was supported by a MRC grant MR/S036709/1 for this research. MSC was supported by the Swedish Research Council (through the Swedish eScience Research Centre and project 2018-02526), Prostatacancerförbundet, Karolinska Institutet and Cancerfonden (project CAN 2018/539). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

Funding Information:
We acknowledge the contributions of all members of the CAP and ProtecT trial research groups, of all the CAP and ProtecT study participants and the CAP trial general practitioners and practice staff. We also acknowledge Ruth Etzioni, Shuang Hao and Andreas Karlsson for their contributions to the development of the simulation model.

Funding Information:
EK reports personal consulting fees unrelated to the present work from Pfizer, Roche, Novartis Pharma and BMS. SS reports a postdoctoral fellowship from the NIHR and support for travel from the University of Leeds. JD, RM, ET and EW report receiving grants to their institution from Cancer Research UK. RG reports receiving grants from the National Cancer Institute. HT reports receiving grants to his institution from the UK Medical Research Council, personal consulting fees unrelated to the present work from Pfizer, Roche, BMS, Eisai, Lundbeck, Merck, Novartis Pharma, and Janssen and owns stock in Clifton Insight (consulting company). MC reports receiving funding to his institution from the Swedish Research Council, the Swedish Cancer Society and the Swedish Prostate Cancer Federation.

Publisher Copyright:
© 2022, The Author(s).

Research Groups and Themes

ICEP
HEHP@Bristol

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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8074 (C18281/A29019) ICEP2 - Programme Award: Towards improved casual evidence and enhanced prediction of cancer risk and survival
Martin, R. M. (Principal Investigator)
1/10/20 → 30/09/25
Project: Research

Cite this

Keeney, E., Sanghera, S., Martin, R. M., Gulati, R., Wiklund, F., Walsh, E. I., Donovan , J. L., Hamdy, F. C., Neal, D., Lane, J. A., Turner, E. L., Thom, H. H. Z., & Clements, M. (2022). Cost-effectiveness analysis of prostate cancer screening in the UK: A decision model analysis based on the CAP trial. PharmacoEconomics, 40(12), 1207-1220. https://doi.org/10.1007/s40273-022-01191-1

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title = "Cost-effectiveness analysis of prostate cancer screening in the UK: A decision model analysis based on the CAP trial",

abstract = "Background and ObjectiveMost guidelines in the UK, Europe and North America do not recommend organised population-wide screening for prostate cancer. Prostate-specific antigen-based screening can reduce prostate cancer-specific mortality, but there are concerns about overdiagnosis, overtreatment and economic value. The aim was therefore to assess the cost effectiveness of eight potential screening strategies in the UK.MethodsWe used a cost-utility analysis with an individual-based simulation model. The model was calibrated to data from the 10-year follow-up of the Cluster Randomised Trial of PSA Testing for Prostate Cancer (CAP). Treatment effects were modelled using data from the Prostate Testing for Cancer and Treatment (ProtecT) trial. The participants were a hypothetical population of 10 million men in the UK followed from age 30 years to death. The strategies were: no screening; five age-based screening strategies; adaptive screening, where men with an initial prostate-specific antigen level of < 1.5 ng/mL are screened every 6 years and those above this level are screened every 4 years; and two polygenic risk-stratified screening strategies. We assumed the use of pre-biopsy multi-parametric magnetic resonance imaging for men with prostate-specific antigen ≥ 3 ng/mL and combined transrectal ultrasound-guided and targeted biopsies. The main outcome measures were projected lifetime costs and quality-adjusted life-years from a National Health Service perspective.ResultsAll screening strategies increased costs compared with no screening, with the majority also increasing quality-adjusted life-years. At willingness-to-pay thresholds of £20,000 or £30,000 per quality-adjusted life-year gained, a once-off screening at age 50 years was optimal, although this was sensitive to the utility estimates used. Although the polygenic risk-stratified screening strategies were not on the cost-effectiveness frontier, there was evidence to suggest that they were less cost ineffective than the alternative age-based strategies.ConclusionsOf the prostate-specific antigen-based strategies compared, only a once-off screening at age 50 years was potentially cost effective at current UK willingness-to-pay thresholds. An additional follow-up of CAP to 15 years may reduce uncertainty about the cost effectiveness of the screening strategies.",

author = "Edna Keeney and Sabina Sanghera and Martin, {Richard M} and Roman Gulati and Fredrik Wiklund and Walsh, {Eleanor I} and Donovan, {Jenny L} and Hamdy, {Freddie C} and David Neal and Lane, {J. Athene} and Turner, {Emma L} and Thom, {Howard H Z} and Mark Clements",

note = "Funding Information: RMM is the lead principal investigator (and JLD, FCH and DEN co-PIs) of the CAP trial, funded by Cancer Research UK and the UK Department of Health (C11043/A4286, C18281/A8145, C18281/A11326, C18281/A15064 and C18281/A24432). RMM was supported by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme). RMM is a National Institute for Health Research Senior Investigator (NIHR202411). RMM and HT were supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. The ProtecT trial is funded by the UK National Institute for Health Research (NIHR) Health Technology Assessment Programme (NIHR HTA: projects 96/20/06, 96/20/99). RG was supported by the National Cancer Institute at the National Institutes of Health (U01 CA253915 and R50 CA221836). HT was supported by a MRC grant MR/S036709/1 for this research. MSC was supported by the Swedish Research Council (through the Swedish eScience Research Centre and project 2018-02526), Prostatacancerf{\"o}rbundet, Karolinska Institutet and Cancerfonden (project CAN 2018/539). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Funding Information: We acknowledge the contributions of all members of the CAP and ProtecT trial research groups, of all the CAP and ProtecT study participants and the CAP trial general practitioners and practice staff. We also acknowledge Ruth Etzioni, Shuang Hao and Andreas Karlsson for their contributions to the development of the simulation model. Funding Information: EK reports personal consulting fees unrelated to the present work from Pfizer, Roche, Novartis Pharma and BMS. SS reports a postdoctoral fellowship from the NIHR and support for travel from the University of Leeds. JD, RM, ET and EW report receiving grants to their institution from Cancer Research UK. RG reports receiving grants from the National Cancer Institute. HT reports receiving grants to his institution from the UK Medical Research Council, personal consulting fees unrelated to the present work from Pfizer, Roche, BMS, Eisai, Lundbeck, Merck, Novartis Pharma, and Janssen and owns stock in Clifton Insight (consulting company). MC reports receiving funding to his institution from the Swedish Research Council, the Swedish Cancer Society and the Swedish Prostate Cancer Federation. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

day = "1",

doi = "10.1007/s40273-022-01191-1",

language = "English",

volume = "40",

pages = "1207--1220",

journal = "PharmacoEconomics",

issn = "1170-7690",

publisher = "Springer International Publishing AG",

number = "12",

}

TY - JOUR

T1 - Cost-effectiveness analysis of prostate cancer screening in the UK

T2 - A decision model analysis based on the CAP trial

AU - Keeney, Edna

AU - Sanghera, Sabina

AU - Martin, Richard M

AU - Gulati, Roman

AU - Wiklund, Fredrik

AU - Walsh, Eleanor I

AU - Donovan , Jenny L

AU - Hamdy, Freddie C

AU - Neal, David

AU - Lane, J. Athene

AU - Turner, Emma L

AU - Thom, Howard H Z

AU - Clements, Mark

N1 - Funding Information: RMM is the lead principal investigator (and JLD, FCH and DEN co-PIs) of the CAP trial, funded by Cancer Research UK and the UK Department of Health (C11043/A4286, C18281/A8145, C18281/A11326, C18281/A15064 and C18281/A24432). RMM was supported by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme). RMM is a National Institute for Health Research Senior Investigator (NIHR202411). RMM and HT were supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. The ProtecT trial is funded by the UK National Institute for Health Research (NIHR) Health Technology Assessment Programme (NIHR HTA: projects 96/20/06, 96/20/99). RG was supported by the National Cancer Institute at the National Institutes of Health (U01 CA253915 and R50 CA221836). HT was supported by a MRC grant MR/S036709/1 for this research. MSC was supported by the Swedish Research Council (through the Swedish eScience Research Centre and project 2018-02526), Prostatacancerförbundet, Karolinska Institutet and Cancerfonden (project CAN 2018/539). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Funding Information: We acknowledge the contributions of all members of the CAP and ProtecT trial research groups, of all the CAP and ProtecT study participants and the CAP trial general practitioners and practice staff. We also acknowledge Ruth Etzioni, Shuang Hao and Andreas Karlsson for their contributions to the development of the simulation model. Funding Information: EK reports personal consulting fees unrelated to the present work from Pfizer, Roche, Novartis Pharma and BMS. SS reports a postdoctoral fellowship from the NIHR and support for travel from the University of Leeds. JD, RM, ET and EW report receiving grants to their institution from Cancer Research UK. RG reports receiving grants from the National Cancer Institute. HT reports receiving grants to his institution from the UK Medical Research Council, personal consulting fees unrelated to the present work from Pfizer, Roche, BMS, Eisai, Lundbeck, Merck, Novartis Pharma, and Janssen and owns stock in Clifton Insight (consulting company). MC reports receiving funding to his institution from the Swedish Research Council, the Swedish Cancer Society and the Swedish Prostate Cancer Federation. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12/1

Y1 - 2022/12/1

N2 - Background and ObjectiveMost guidelines in the UK, Europe and North America do not recommend organised population-wide screening for prostate cancer. Prostate-specific antigen-based screening can reduce prostate cancer-specific mortality, but there are concerns about overdiagnosis, overtreatment and economic value. The aim was therefore to assess the cost effectiveness of eight potential screening strategies in the UK.MethodsWe used a cost-utility analysis with an individual-based simulation model. The model was calibrated to data from the 10-year follow-up of the Cluster Randomised Trial of PSA Testing for Prostate Cancer (CAP). Treatment effects were modelled using data from the Prostate Testing for Cancer and Treatment (ProtecT) trial. The participants were a hypothetical population of 10 million men in the UK followed from age 30 years to death. The strategies were: no screening; five age-based screening strategies; adaptive screening, where men with an initial prostate-specific antigen level of < 1.5 ng/mL are screened every 6 years and those above this level are screened every 4 years; and two polygenic risk-stratified screening strategies. We assumed the use of pre-biopsy multi-parametric magnetic resonance imaging for men with prostate-specific antigen ≥ 3 ng/mL and combined transrectal ultrasound-guided and targeted biopsies. The main outcome measures were projected lifetime costs and quality-adjusted life-years from a National Health Service perspective.ResultsAll screening strategies increased costs compared with no screening, with the majority also increasing quality-adjusted life-years. At willingness-to-pay thresholds of £20,000 or £30,000 per quality-adjusted life-year gained, a once-off screening at age 50 years was optimal, although this was sensitive to the utility estimates used. Although the polygenic risk-stratified screening strategies were not on the cost-effectiveness frontier, there was evidence to suggest that they were less cost ineffective than the alternative age-based strategies.ConclusionsOf the prostate-specific antigen-based strategies compared, only a once-off screening at age 50 years was potentially cost effective at current UK willingness-to-pay thresholds. An additional follow-up of CAP to 15 years may reduce uncertainty about the cost effectiveness of the screening strategies.

AB - Background and ObjectiveMost guidelines in the UK, Europe and North America do not recommend organised population-wide screening for prostate cancer. Prostate-specific antigen-based screening can reduce prostate cancer-specific mortality, but there are concerns about overdiagnosis, overtreatment and economic value. The aim was therefore to assess the cost effectiveness of eight potential screening strategies in the UK.MethodsWe used a cost-utility analysis with an individual-based simulation model. The model was calibrated to data from the 10-year follow-up of the Cluster Randomised Trial of PSA Testing for Prostate Cancer (CAP). Treatment effects were modelled using data from the Prostate Testing for Cancer and Treatment (ProtecT) trial. The participants were a hypothetical population of 10 million men in the UK followed from age 30 years to death. The strategies were: no screening; five age-based screening strategies; adaptive screening, where men with an initial prostate-specific antigen level of < 1.5 ng/mL are screened every 6 years and those above this level are screened every 4 years; and two polygenic risk-stratified screening strategies. We assumed the use of pre-biopsy multi-parametric magnetic resonance imaging for men with prostate-specific antigen ≥ 3 ng/mL and combined transrectal ultrasound-guided and targeted biopsies. The main outcome measures were projected lifetime costs and quality-adjusted life-years from a National Health Service perspective.ResultsAll screening strategies increased costs compared with no screening, with the majority also increasing quality-adjusted life-years. At willingness-to-pay thresholds of £20,000 or £30,000 per quality-adjusted life-year gained, a once-off screening at age 50 years was optimal, although this was sensitive to the utility estimates used. Although the polygenic risk-stratified screening strategies were not on the cost-effectiveness frontier, there was evidence to suggest that they were less cost ineffective than the alternative age-based strategies.ConclusionsOf the prostate-specific antigen-based strategies compared, only a once-off screening at age 50 years was potentially cost effective at current UK willingness-to-pay thresholds. An additional follow-up of CAP to 15 years may reduce uncertainty about the cost effectiveness of the screening strategies.

U2 - 10.1007/s40273-022-01191-1

DO - 10.1007/s40273-022-01191-1

M3 - Article (Academic Journal)

C2 - 36201131

SN - 1170-7690

VL - 40

SP - 1207

EP - 1220

JO - PharmacoEconomics

JF - PharmacoEconomics

IS - 12

ER -

Cost-effectiveness analysis of prostate cancer screening in the UK: A decision model analysis based on the CAP trial

Abstract

Bibliographical note

Research Groups and Themes

UN SDGs

Access to Document

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Projects

8074 (C18281/A29019) ICEP2 - Programme Award: Towards improved casual evidence and enhanced prediction of cancer risk and survival

Cite this