Extremely conservative use of prostate specific antigen (PSA) screening and referral for biopsy only when PSA levels are significantly elevated are the only strategies that are cost-effective, especially when accompanied by active surveillance for low-risk prostate cancer, a comprehensive cost analysis indicates.
"Screening is costly, and the costs include not only the costs of the test but the costs of any false positives and also of overdiagnosed cases who end up being treated unnecessarily," senior author Ruth Etzioni, PhD, from the Fred Hutchinson Cancer Research Center, Seattle, Washington, told Medscape Medical News in an email.
"My hope is that physicians will recognize that they have to be either very conservative in their screening practice or very conservative in their treatment recommendations, because it is not cost-effective for us to be screening and treating aggressively," she commented.
The cost-analysis study was published online March 24 in JAMA Oncology.
Under lead author Joshua Roth, PhD, who is also affiliated with the Fred Hutchinson Cancer Research Center, the team used a microsimulation model of prostate cancer that links disease progression with individual PSA growth.
The model followed a simulated contemporary cohort of US men who began PSA testing at age 40 years. It explored 18 different strategies for how to use the test.
Two initial treatment scenarios were analyzed ― contemporary treatment practice, and selective treatment practice.
Contemporary treatment practices were those in which physicians treated all prostate cancers on the basis of patient age and cancer stage and grade, with an intent to cure.
Selective treatment practices consisted of only treating prostate cancers in which the Gleason score was 7 or higher and/or the tumors were more advanced than clinical stage T2a. All other prostate cancers were treated with conservative management, notably, active surveillance.
"Among the 18 screening strategies evaluated, all increased costs (range, $314 - $1371) and LYs [life-years] (range, 0.03 - 0.06) compared with no screening, but only strategies with the biopsy threshold at a PSA level higher than 10.0 ng/mL increased QALYs [quality-adjusted life-years] (range, 0.002 - 0.004)," Dr Roth reports.
Costs in this category of screening strategies (with biopsy at PSA>10 ng/mL), which increased QALY, ranged from $11,977 to $21,649 per life year, he adds.
However, only one screening strategy was possibly cost-effective with regard to cost per QALY, the researchers found.
This strategy involved screening men between the ages of 55 and 69 years every 4 years and referring them for a biopsy when their PSA levels were higher than 10.0 ng/mL.
"Selective treatment practices were implemented only for strategies with PSA thresholds lower than 10.0 ng/mL because cases of prostate cancer diagnosed with PSA levels higher than 10.0 ng/mL would not typically qualify as low risk or as candidates for delayed curative treatment," Dr Roth notes.
All selective treatment strategies increased cost, albeit modestly, from $263 to $703.
"However, in contrast to many strategies under contemporary treatments, all strategies under selective treatment practices increased QALYs (range, 0.002 - 0.004)," the study authors observe.
Clear Implications
Dr Roth and colleagues suggest that their findings have "clear implications" for PSA screening in the United States.
"Rather than stopping PSA screening, as recommended by the US Preventive Services Task Force, implementation of strategies that extend the screening interval and/or use higher PSA biopsy thresholds have the potential to preserve substantial benefit while controlling harm and costs," Dr Roth writes.
Referring men for a biopsy only when their PSA level is 10 ng/mL or higher is not likely to be "clinically appealing," he acknowledges.
Nevertheless, the results "reinforce the general conclusion that conservative patterns of screening and biopsy referral are important directions to consider if PSA screening is to be clinically effective and cost-effective."
Asked if she thought that physicians would be likely to adopt more conservative screening and treatment strategies, Dr Etzioni pointed to a growing trend ― the use of active surveillance for men with low-risk prostate cancer.
Unfortunately, she added, "all the incentives that are hardwired in our medical system encourage more rather than less intervention."
Ultimately, Dr Etzioni felt the issue of PSA screening should be decided by both physicians and their patients.
"I think for physicians and patients, the key question when deciding whether to screen for prostate cancer or not is, Can I decide not to treat if I am diagnosed with a low-risk cancer?" she said.
"I feel that if the answer to this question is no, then it may be prudent to think twice before screening," she said.
More Change Is Needed
In an accompanying editorial, Andrew Vickers, PhD, Memorial Sloan Kettering Cancer Center, New York City, comments that this cost-analysis study moves the debate over PSA screening away from whether or not to use the test toward the question, "How can we get physicians to follow best practice?"
Already, there have been significant changes in practice, he points out. Use of active surveillance for low-risk prostate cancer has increased fourfold in the past few years, although rates of unnecessary treatment remain too high (about 60%). The use of routine PSA testing in older men has fallen recently but still remains in practice (about 35% for those 75 years or older).
"More work needs to be done, and much more change needs to happen," Dr Vickers comments.
"[But] Roth et al clearly demonstrate that if we follow the literature on how to screen with PSA, and which screen-detected prostate cancers to treat, we will likely do more good than harm," he adds.
On the other hand, if physicians carry on as they have in the past — screening older men, aggressively treating low-risk disease ― "then we should call for PSA screening to end," Dr Vickers concludes.
The study was funded by the National Cancer Institute, the Sidney Kimmel Center for Prostate and Urologic Cancers, and David H. Kock, through the Prostate Cancer Foundation. The study authors have disclosed no relevant financial relationships. Dr Vickers is named on a patent application for a statistical method to detect prostate cancer, which has been commercialized by OPKO Health Inc. He also received royalties from any sales of the test and has stock options in OPKO Health Inc.
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