Comparing Radiation Treatments for Prostate Cancer: What Does the Evidence Tell Us?

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1 Comparing Radiation Treatments for Prostate Cancer: What Does the Evidence Tell Us? Dan Ollendorf, MPH 2nd Annual W.B. Ingalls Memorial Prostate Seminar March 7, 2009

2 Institute for Clinical and Economic Review (ICER) Mission: To apply the evidence on effectiveness and value of treatment alternatives to assist in patient and physician decision-making Patients, physicians, insurers, manufacturers directly involved in reviews Independent and transparent research: ICER alone directs how research funding is used All reports available to general public at no cost Systematic review plus decision analytic modeling

3 Why Prostate Cancer? Common Lots of options for Rx that patients and families can consider Lots of variation in practice patterns Known wide variation in prices, incentives for doctors and hospitals Lots of evidence gaps making objective guidance hard to come by

4 Scope Localized, low-risk prostate cancer Treatments: comparing to IMRT Brachytherapy Proton beam therapy Key questions: Impact on survival, recurrence Side effects and radiation dose Financial impact of each treatment Appraisal of active surveillance and radical prostatectomy now underway

5 Evidence Quality Nearly all studies examined only one treatment option, and were conducted at one center Makes evaluation difficult: Hard to make statements about general impact of treatment based on experience at one center at a time Lack of comparison group receiving another therapy makes judgment of results difficult: How do you know if results indicate better or worse outcomes vs. another therapy given to the same population?

6 Survival, Recurrence Overall Survival (5-yr rates) Brachytherapy: 77-97% No data on IMRT or PBT Prostate Cancer Survival (at 5-12 years) Brachytherapy: % IMRT: 100% (1 study) No data on PBT Substantial overlap in estimates of prostate cancer recurrence : No evidence of difference between treatments

7 Side Effects Type of Side Effect Brachytherapy Proton beam IMRT Acute urinary retention (AUR) 9 studies 10% (2%-17%) N/A N/A Long-term urinary 12 studies 3 studies 5 studies 17% (8%-26%) 6% (5%-7%) 13% (8%-19%) Long-term GI 18 studies 3 studies 7 studies 4% (3%-5%) 17% (2%-32%) 7% (4%-9%) Erectile dysfunction 7 studies 32% (26%-39%) 0 studies 2 studies 48% (48%-49%)

8 Second Cancers Very little data on the risk of second cancers from radiation treatment Lifetime risk estimated to be 1% or less Generally thought to be higher for forms of external beam radiation (like IMRT and PBT) than for brachytherapy

9 Modeling Financial Impact of Radiation Treatment Initial treatment at diagnosis (IMRT, brachytherapy, or proton beam) Modeled in a group of hypothetical 65 year-old men with low-risk prostate cancer Financial impact included: Payment for treatment (based on Medicare rates) Time out of work for treatment and recovery Management of side effects Follow-up and monitoring

10 Prostate Cancer Treatment Proton Beam IMRT Brachytherapy Recurrence No Recurrence Metastatic CaP CaP Death Non-CaP Death

11 Model Results Brachytherapy provided slightly better quality of life based on side-effect/complication rates Patient time for treatment/testing also lowest for brachytherapy: 5 days vs days for IMRT and PBT Treatment costs main driver of long-term costs: Brachytherapy $10,000 IMRT $20,000 PBT $50,000 or more

12 Additional Analyses Group age changed from 65 to 58 years: No change in how treatments compared in terms of cost and quality of life Patient time costs removed from model: No change in treatment comparison

13 Summary of Key Judgments Lack of information comparing treatments of interest No evidence to support survival or recurrence advantage for any treatment Some trade-offs in side effects may be apparent, but quality and amount of evidence is poor Brachytherapy approximately half as costly as IMRT; one-fifth of PBT Over long-term, brachytherapy least costly and most effective for both older and younger men, with or without patient time costs included

14 ICER Integrated Evidence Rating Comparative Clinical Effectiveness Superior: A Incremental: B Comparable: C Unproven/Potential: U/P Insufficient: I Aa Ab Ac Ba Bb Bc Ca Cb Cc Ua Ub Uc I I I a High b Reasonable/Comp c Low Comparative Value

15 Integrated Evidence Rating : As Compared to IMRT Comparative Clinical Effectiveness Superior: A Incremental: B Comparable: C Unproven/Potential: U/P Insufficient: I Aa Ab Ac Ba Bb Bc BT=Ca Cb Cc Ua Ub Uc I I PBT=Ic a High b Reasonable/Comp c Low Comparative Value

16 Why Working with Patients Was and Is Important for ICER Get input on what the real questions are: the key outcomes and their perspectives on them (e.g., longterm side effects more important than acute ones) Frame how evidence needs to be presented so that it will be useful for patients Keep clinicians and other stakeholders honest You re never afraid to speak truth to power!

17 Questions? Full report and executive summary available at:

18 Backup Slides

19 Clinical Guidelines, Prior Technology Reviews Guidelines Available from multiple clinical organizations All treatments considered options for low-risk disease Prior Technology Reviews Agency for Healthcare Research & Quality (AHRQ, 2008): no evidence that any treatment is superior for low-risk prostate cancer Other groups have concluded that evidence supports use of brachytherapy for low-risk disease Evidence on IMRT and PBT much less extensive and conclusive

20 Review of Literature on Clinical Effectiveness: Objectives To compare clinical benefits of brachytherapy and PBT vs. IMRT and active surveillance Prostate cancer-related and overall survival Disease recurrence To compare side effects that require treatment Gastrointestinal Urinary Sexual Second cancer (from radiation)

21 Freedom from Recurrence 110% 100% 90% 80% 70% bfff (%) 60% 50% 40% Brachytherapy Proton Beam Therapy IMRT 30% 20% 10% NOTE: Bubble size indicates number of patients in study 0% Timepoint (yrs)

22 Model Overview Survival assumed to be the same regardless of treatment Included all major short- and long-term side effects for each treatment: Affected quality of remaining years of life Calculated as quality-adjusted life years (QALYs) Costs of each treatment included: Treatment and related follow-up Management of side effects Patient time for treatment, recovery, and testing

23 Results Strategy Cost Incremental Cost QALYs Incremental QALYs Brachytherapy $29,575 -$12, IMRT $41,591 reference reference PBT $72,789 $31,

24 Results: Alternative Strategies Active Surveillance Strategy Cost Incremental Cost QALYs Incremental QALYs ICER ($/QALY) Brachytherapy $29,575 reference reference reference AS --> BT $31,305 $1, $33,111 IMRT $41,591 $12, (Dominated) AS --> IMRT $42,118 $12, (Dominated) AS --> IMRT/ADT $48,110 $18, (Dominated) AS --> PBT $70,661 $41, (Dominated) PBT $72,789 $43, (Dominated)