quantifying the comparative harms of management options ......quantifying the comparative harms of...

ANNUALMEETING

OCT. 31-NOV. 2, 2017ARLINGTON, VA

#PCORI2017

Quantifying the Comparative Harms of Management Options for Localized Prostate Cancer

Daniel A. Barocas, MD, MPHAssociate Professor, Vanderbilt University Medical Center

@danbarocas

November 1, 2017

ANNUAL MEETING | #PCORI2017

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[Note to speaker: Please use only one of the next two slides depending on your disclosure information. ]

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Speaker Name

• Has nothing to disclose.

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Objectives

At the conclusion of this activity, the participant should be able to:• Identify the key components of shared decision-making around

management of localized prostate cancer (PCa)• Describe the data regarding comparative harms of

contemporary external beam radiation therapy (EBRT), radical prostatectomy (RP), and active surveillance (AS)

• Participate with the treatment team in shared decision-making around management of localized PCa, incorporating patient preferences with what is known about functional outcomes, general quality-of-life outcomes, and oncologic outcomes

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Components of shared decision-making for localized prostate cancer

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Shared Decision Making

• Bullet

November 5, 2017Source: Agency for Healthcare Research and Quality. The SHARE Approach. Content Last Reviewed February 2017. http://www.ahrq.gov/professionals/education/curriculum-tools/shareddecisionmaking/index.html.


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Surgery, Radiation, or Active Surveillance?Shared Decision-Making Process


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Comparative EffectivenessOncologic Outcomes for Surgery, Radiation, and Active Surveillance

• Highly controversial – limitations of the data• Depends on life expectancy • Depends on risk of progression

• PSA level at diagnosis• Clinical stage• Biopsy grade (Gleason score or ISUP/WHO grade group)• Maybe other biomarkers and imaging

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ISUP = International Society of Urological Pathology; PSA = prostate-specific antigen; WHO = World Health Organization


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Comparative EffectivenessSummary of Available Comparative Data (My Interpretation)

• Short-term outcomes equivalent: 5-year PCa survival ∼100%• Long-term outcomes

• Low risk• No survival benefit for treatment vs. AS

• Intermediate and high-risk• Untreated disease risk of disease progression, metastasis, death• Treatment likely lower risk of adverse oncologic outcomes• Equipoise between RP and EBRT (with caveats)

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Albertsen PC, Hanley JA, Fine J, et al. JAMA. 2005;293(17):2095-2101.Bill-Axelson A, Homberg L, Garmo H, et al. N Engl J Med. 2014;370(10):932-942.Hamdy FC, Donovan JL, Lane JA, et al; ProtecT Study Group. N Engl J Med. 2016;375(15)1415-1424.Sooriakumaran P, Nyberg T, Akre O, et al, BMJ. 2014;348:g1502. DOI: 10.1136/bmj.g1502.Wilt TJ, Brawer MK, Jones KM, et al; PIVOT Study Group. N Engl J Med. 2012;367(3):203-213.Wilt TJ, Jones KM, Barry MJ, et al. N Engl J Med. 2017;377(2):132-142.Zelefsky MJ, Eastham JA, Cronin AM, et al. J Clin Oncol. 2010;28(9):1508-1513.


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Comparative EffectivenessOncologic Outcomes for Surgery, Radiation, and Active Surveillance

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Comparative harms of management options for localized prostate cancer

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Background

• Historically, side effects of treatment are common.

• Sexual; urinary; bowel; hormonal (ADT)• Newer treatments are now available.

• Robotic RP; intensity-modulated EBRT; AS

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ADT = androgen deprivation therapy


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Objective

Compare functional outcomes associated with radical prostatectomy (RP), external beam radiation therapy (EBRT), and active surveillance (AS) in a contemporary, population-based cohort

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METHODS: Comparative Effectiveness Analysis of Surgery And Radiation for Prostate Cancer (CEASAR)1

• Prospective, population-based cohort study• Subjects accrued from 5 SEER registries and CaPSURE2 during

2011–2012• Patient questionnaire at baseline, 6 months, 12 months, and 3

years• Disease-specific QOL (EPIC-26)

• Domains scored from 0–100; a higher score indicates better function• Minimum clinically important difference is defined a priori3

• Chart review at 12 months (clinical and treatment data)

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CaPSURE = Cancer of the Prostate Strategic Urologic Research Endeavor; EPIC-26 = Expanded Prostate Cancer Index Composite – Short Form; QOL = quality of life; SEER = Surveillance, Epidemiology, and End Results

1 Barocas DA, Alverez J, Resnick MJ, et al. JAMA. 2017;317(11):1126-1140.2 CaPSURE https://urology.ucsf.edu/research/cancer/capsure3 Skolarus TA, Jacobs BL, Schroeck FR, et al. J Urol. 2015;193(5):1500-1506.


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Study Flow Chart for the CEASAR Study

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CEASAR Study: Demographics and Baseline Characteristics

November 5, 2017Source of Tabular Data: Barocas DA, Alverez J, Resnick MJ, et al. JAMA. 2017;317(11):1126-1140.


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Functional Outcomes

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Urinary Incontinence Domain Score on EPIC

• Bullet

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Moderate or big problem with urinary incontinence at 3 years14% RP 5% EBRT 6% AS

Minimum clinically important difference = 6 points

Source: Barocas DA, Alverez J, Resnick MJ, et al. JAMA. 2017;317(11):1126-1140.


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Urinary Irritative Domain Score on EPIC

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Sexual Function Domain Score on EPIC

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Minimum clinically important difference = 10 to 12 points



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Finer Points of Sexual Function Differences

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• > 40% had ED BEFORE treatment

• 45% of those undergoing EBRT had ADT

• Difference between RP and EBRT only significant among men with baseline function scores in the highest quartile

• Sexual function differences are not clinically relevant for all men



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Bowel Domain Score on EPIC

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Hormone Domain Score on EPIC

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Other Outcomes

• General quality of life – no difference between treatments

• Physical function• Emotional well-being• Energy/fatigue (vitality)

• Disease-specific survival – no difference between treatments

• Only 3 prostate cancer deaths in the first 3 years

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SUMMARY: Impact of Treatments on Function

• RP higher rate of urinary incontinence than with EBRT or AS.• “Moderate” or “big” problem reported by 14% for RP, 5% for EBRT, 6%

for AS.• RP better irritative urinary symptoms than with AS.• RP higher rate of sexual dysfunction than with EBRT or AS.

• Difference is significant only for men in the highest quartile of baseline function.

• EBRT worse bowel and hormonal outcomes, but only in first year.

• No differences in general quality of life or survival at 3 years.

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CONCLUSIONS: Despite Technological Advances, Treatments Have Significant Side Effects

• Baseline function and treatment are the strongest predictors.

• Consider baseline function and patient priorities when individualizing treatment recommendation.

• Population-based outcomes are worse than those reported from single-center or specialized multicenter series.

• Consider referral to a specialty center or experienced provider.

• Consider AS in appropriate candidates.

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CONCLUSIONS: Implications for Shared Decision-making• The CEASAR study,1 along with NC ProCESS,2 provides data

to inform comparative harms of contemporary treatments.• Health care providers also need to:

• Be well informed about comparative effectiveness data and facile in explaining the nuances and limitations of available data.

• Elicit patient’s preferences and priorities.• Communicate effectively.• Individualize treatment recommendations.

• Consider using available tools:• https://www.ahrq.gov/professionals/education/curriculum-

tools/shareddecisionmaking/index.html• http://www.auanet.org/guidelines/shared-decision-making

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1 Barocas DA, Alverez J, Resnick MJ, et al. JAMA. 2017;317(11):1126-1140.2 North Carolina Prostate Cancer Comparative Effectiveness and Survivorship Study. https://clinicaltrials.gov/ct2/show/NCT02564120.

https://www.ahrq.gov/professionals/education/curriculum-tools/shareddecisionmaking/index.html

http://www.auanet.org/guidelines/shared-decision-making


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Vanderbilt Coordinating Center CEASAR Investigators

• Tatsuki Koyama, PhD

• Karen E. Hoffman, MD, MHSc, MPH

• Matthew J. Resnick, MD, MPH

• Ralph Conwill (patient)

• Dan McCollum (patient)

• JoAnn Alvarez, MA

• Tara Sherfield, BS

• Eden Schaffer, MA

• Mark D. Tyson, MD

• Daniel Lee, MD

• David F. Penson, MD, MPH

• Michael Goodman, MD, MPH• Vivien Chen, PhD• Xiao-Cheng Wu, MD, MPH• Ann S. Hamilton, PhD, MA• Karen E. Hoffman, MD, MHSc, MPH• Antoinette Stroup, PhD• Mia Hashibe, PhD, MPH• Lisa E. Paddock, PhD, MPH• Antoinette M. Stroup, PhD• Matthew R. Cooperberg, MD, MPH• Shelly Greenfield, MD• Sherrie H. Kaplan, PhD, MS, MPH

The CEASAR study was funded by grants (1R01HS019356 and 1R01HS022640) from the Agency for Healthcare Research and Quality and an award (CE12-11-4667) from the Patient-Centered Outcomes Research Institute.


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Learn More

• www.pcori.org

• [email protected]

• #PCORI2017

• https://ww2.mc.vanderbilt.edu/prostatestudy/

November 5, 2017

https://ww2.mc.vanderbilt.edu/prostatestudy/


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Questions?

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Thank You!Daniel A. Barocas, MD, MPHAssociate Professor of Urologic Oncology

@danbarocas

November 1, 2017

quantifying the comparative harms of management options ......quantifying the comparative harms of...

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