Budget Impact Model: Epigenetic Assay Can Help Avoid Unnecessary Repeated Prostate Biopsies, Reduce Spending

This is an abbreviated version of the original article that was recently published in American Health & Drug Benefits. 2013;6(1):15-24. Used with permission. The full version of this article is available at www.AHDBonline.com.

Prostate cancer is the most frequently detected cancer in men: 1 of 6 men will be diagnosed with prostate cancer during their lifetime based on Medicare enrollment data.1 In the United States, approximately 19 million men annually are screened by prostate-specific antigen (PSA) testing,2 resulting in approximately 4.7 million abnormal PSA test results (≥4.0 ng/mL)3 and approximately 1.3 million biopsy procedures.4

According to the National Cancer Institute, 241,740 men are diagnosed with prostate cancer annually, and 28,170 prostate cancer–related deaths were reported in 2012.5 Although some forms of prostate cancer are deadly, many forms are low grade and can be managed by active surveillance.

Aggressive variants of prostate cancer can be one of the deadliest cancers in men, and accurate diagnosis and follow-up remain a challenge and come at a considerable cost to the US healthcare system.

The Burden of PSA Screening

Despite the recent controversy that was raised by the US Preventive Services Task Force findings on PSA testing, leading to their recommendations to stop routine PSA-based screening,6 the American Urological Association (AUA) continues to recommend the PSA blood test, along with digital rectal examination (DRE), for screening men at risk for prostate cancer. (The AUA has just revised its screening recommendations. See article on page 15.)

Screening has led to detection of earlier-stage disease, resulting in an increased likelihood for curative treatment. If screening is eliminated, urologists fear an increased incidence of advanced cancers and an increase in healthcare costs to effectively treat these patients.7 Today, urologists typically perform a biopsy for high-risk patients with a rising PSA level and for patients with a PSA level ≥4.0 ng/mL, obtaining approximately 10 to 12 needle-core tissue samples according to the current standard of care.8,9

An abnormal PSA result can often be caused by factors other than cancer, including infection, inflammation, or other benign conditions, such as benign prostatic hyperplasia. This leads to the inclusion of many men with no cancer among those who are being subjected to prostate biopsies (ie, false-positive PSA screening). The rate of cancer detection in men undergoing prostate biopsies is approximately 30%, and approximately 75% of men undergoing biopsies have negative prostate biopsy results.2,3

An elevated PSA and/or abnormal DRE identify men at high risk for prostate cancer, and, as a result, many of these men will undergo a biopsy procedure. However, because of the nature of random and limited sampling of the prostate, many cancers are undetected by histopathologic review. Studies by urology and pathology opinion leaders report that initial prostate biopsy histopathology has a 20% to 30% false-negative rate.8,10,11 Given these false-negative rates for histology, many patients with persistently elevated PSA values are at risk for occult cancer. This uncertainty poses a diagnostic dilemma, resulting in many men receiving 2, 3, and sometimes 4 repeated biopsy procedures.12-14

Repeated biopsies expose patients to the discomfort and risk of complications associated with this invasive procedure1; they also generate high medical costs. Approximately $1.86 billion is spent annually on PSA tests alone.2,15 More than $4 billion is spent annually on therapies for prostate cancer, and this amount is expected to increase to $8.7 billion by 2019.16

Molecular Testing

With such high costs to the US healthcare system, as well as negative quality-of-life implications to patients, the AUA has called for new biomarkers for the improved diagnosis and treatment of prostate cancer.17 With the growing movement toward personalized medicine, the application of molecular testing to improve cancer detection and the management of patients represents an evolution in oncology.2,18

Epigenetic assays, in particular, have been reported to improve on the accuracy of prostate biopsies and histopathologic review.2,8 In a recent multicenter, blinded study, the epigenetic assay ConfirmMDx for Prostate Cancer was used to detect occult cancer in histopathologically negative prostate biopsies.8 The assay used multiplex methylation-specific polymerase chain reaction to assess the DNA methylation status of the GSTP1, APC, and RASSF1 genes associated with the presence of cancer in residual negative prostate biopsy tissue samples.3,8,10 Using this advanced molecular diagnostic test allows for a higher degree of accuracy that was previously unattainable through prostate biopsy procedures alone.

The results of this new epigenetic assay can guide urologists in decisions regarding the need to repeat a biopsy in patients with a previously negative biopsy who are still considered at risk for prostate cancer. The test is designed such that its high (90%) negative predictive value accurately distinguishes the patients with negative prostate biopsies from patients who may have occult cancer.8

A Budget Impact Analysis

A budget impact model was developed to assess whether the epigenetic assay can also produce financial benefits, beyond the reported clinical and health benefits. The model was designed to quantify the impact on the costs associated with repeated biopsies used for the screening and diagnosis of prostate cancer, and to test the hypothesis that the epigenetic assay produces a beneficial reduction in costs to commercial health plans, while providing guidance for patient management that leads to less invasive and less costly care.

The assumed membership of the hypothetical health plan is 1 million members, half of whom are males, aged 40 to 64 years (similar to those in a commercial health plan; younger and older men were excluded from the analysis). For men at risk of undergoing a repeated biopsy, the model allows for the simulation of the current (reference scenario) and a counterfactual reality (new scenario). In the reference scenario, the model uses current clinical patterns of care to simulate the treatment of men at risk of prostate cancer in the reference scenario; a molecular assay was not utilized for prostate cancer detection. In the new scenario, men at risk for repeated biopsy are evaluated with the epigenetic assay, and those with negative DNA methylation test results are spared a repeat of the biopsy, thereby reducing the number of unnecessary procedures.


Table 1


Table 2

In the budget impact model, under the reference scenario, 43% (903) of men at risk for repeat biopsy were referred for repeat biopsy. In the new scenario, testing the high-risk patients with the epigenetic assay significantly reduced the number of repeated biopsies by confirming the histopathologically negative biopsy results for 510 men. The epigenetic assay identified 365 men with positive DNA methylation results who would be referred for repeated biopsy (Table 1).

The average cost of a prostate biopsy procedure is $1946, which is a conservative estimate, based on decreased interim 2013 Medicare Physician Fee Schedule rates; this does not take into account prophylactic antibiotic, pain, or other concomitant medication costs. The total expected complication costs per patient for an initial or repeated biopsy were calculated using Surveillance, Epidemiology and End Results (SEER)-Medicare cancer registries’ reported incidence of infectious and noninfectious complications and the associated mean payment for the Medicare Severity-Diagnosis Related Groups (MS-DRGs) from the 2012 Centers for Medicare & Medicaid MS-DRG payment schedule. Table 2 shows the calculations for the average cost ($392) of complications per patient undergoing repeated prostate cancer biopsy. The total weighted cost of a fully burdened biopsy is $1946—the sum of the procedural cost and the cost of complications weighted by incidence. The retail price for the epigenetic assay is $206 per individual core, or $2060 for a 10-core biopsy. The model assesses the health plan’s costs compared with billed charges; therefore, the cost of this assay is discounted by 10%, to conservatively reflect payer costs, at $1855.02 per test.


Table 3

Results

The total cost of repeated biopsies avoided is $2,152,276 (1106 biopsies avoided × $1946 per biopsy). The total cost to the health plan in 1 year was calculated to be $2,864,142 in the reference scenario versus $2,333,341 with the epigenetic assay in the new scenario. To calculate the total diagnostic cost per patient in the reference scenario, the cost of a prostate biopsy ($1946) was applied and weighted to repeated biopsy distribution rates for the percentage of men who receive first, second, and third repeated biopsies of 43%, 44%, and 43%, respectively.13

For the new scenario, the total diagnostic cost per patient includes the cost of the assay plus the weighted biopsy cost, applied and weighted to 43% of men who have positive results based on the epigenetic assay (based on the sensitivity, specificity, and negative and positive predictive values).8 The total diagnostic cost per patient was $3172 in the reference scenario compared with $2584 in the new scenario, resulting in a savings of $588 per patient managed. This results in a total savings of $530,801 annually to the health plan, or –$0.0442 per member per month (Table 3).

This analysis demonstrates that the net cost to a commercial plan is lower if patients undergoing prostate cancer biopsies are managed using the assay. Although this involves an additional cost for the acquisition of the assay, using the assay results in a reduction of 1106 unnecessary biopsies in a health plan with 1 million members.

Implications

This analysis demonstrates that a commercial health plan would realize cost-savings with the coverage of the epigenetic assay. The upfront cost of the assay will be recovered based on the savings associated with avoided biopsies and the associated complications. The inclusion of the epigenetic assay in the management of men who are screened for prostate cancer would result in a net cost-savings of –$530,801 in the first year after the assay became available in the United States in a health plan with 1 million members.

The epigenetic assay provides clear and actionable results that aid the urologist in treatment decision-making, improving patient care, and yielding significant healthcare savings. A key assumption is that a health plan inclusion of the epigenetic assay in medical policy and coverage decisions will motivate a change in the behavior of urologists, resulting in a reduction of repeated biopsies. Policy tools that promote appropriate patient management according to evidence-based guidelines, such as value-based payment (eg, financial incentives for choosing evidence-based interventions) or coverage restrictions for repeated biopsies, may further enhance such outcomes.

References
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About the Authors
Dr Aubry is Associate Clinical Professor of Medicine, Philip R. Lee Institute for Health Policy Studies, University of California, San Francisco, and Senior Medical Director, Quorum Consulting, San Francisco, CA; Dr Lieberthal is Assistant Professor, Jefferson School of Population Health, Thomas Jefferson University, Philadelphia, PA; Dr A. Willis is Associate Dean of Clinical Sciences and Professor of Urology, Aureus University School of Medicine, Oranjestad, Aruba; Dr Bagley is Senior Advisor, HillCo HEALTH, Washington, DC; Mr S.M. Willis is a third-year medical student, Aureus University School of Medicine, Oranjestad, Aruba; and Mr Layton is Director, Information Technology, Quorum Consulting, San Francisco, CA.

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