PSA Screening Cost Effective With ‘Smarter’ Approach
A combination of conservative screening and selective treatment strategies can make screening for prostate cancer cost effective, according to an economic analysis published March 24 in JAMA Oncology. According to testing of various models, less frequent screening and more restrictive biopsy criteria, when accompanied by active surveillance of low-risk cancer, hold the most economic promise. […]
A combination of conservative screening and selective treatment strategies can make screening for prostate cancer cost effective, according to an economic analysis published March 24 in JAMA Oncology. According to testing of various models, less frequent screening and more restrictive biopsy criteria, when accompanied by active surveillance of low-risk cancer, hold the most economic promise.
The incidence of early-stage prostate cancer and rates of prostate-specific antigen (PSA) screening have both declined following the 2012 U.S. Preventive Services Task Force (USPSTF) recommendation against PSA screening as routine primary care for men. While there have been calls for more personalized approaches for prostate cancer screening and management, there is no consensus strategy of how to implement screening that preserves the benefits of detection, while cutting the harm associated with overdiagnosis and overtreatment.
“This study provides, to our knowledge, the first quantitative framework to evaluate the comparative effectiveness of PSA-based screening strategies and selective treatment approaches, and it addresses an urgent need for direction concerning the future of PSA screening in the United States,” write the authors led by Joshua Roth, Ph.D., from University of Washington, Seattle. “Our work indicates that strategies with a conservative screening frequency (e.g., quadrennial) and/or a higher PSA biopsy threshold (e.g., 4.0 ng/mL) are potentially cost-effective when combined with the increased use of conservative management for low-risk cases.”
The Fred Hutchinson Cancer Center researchers recently undertook modeling of a variety of plausible screening strategies to assess their value. They used a microsimulation model of prostate cancer that links disease progression with individual PSA growth. For each strategy, the model simulated a cohort of men beginning at age 40 and projected prostate cancer outcomes over a lifetime. Each scenario was compared to no screening. The 18 screening strategies varied by start and stop age, screening interval (time or PSA-dependent), and PSA threshold for biopsy referral. The strategies also varied by treatment practice—either contemporary (receipt of curative treatment by all) or selective treatment practices (active surveillance or curative treatment).
|Little Genomic Diversity Seen in Metastasized Prostate Cancer Within Individual Men|
Among men with metastasized prostate cancer there is substantial heterogeneity of genomic alterations between men, but limited diversity among metastases within an individual, according to a study published Feb. 29 in Nature Medicine. The researchers say evaluating a single metastasis site provides a “reasonable” assessment of the major oncogenic driver alterations that are present in disseminated tumors within an individual.
The researchers analyzed multiple tumors from men with metastasized prostate cancer using whole-exome sequencing, array comparative genomic hybridization and RNA transcript profiling. The number of somatic mutations, the burden of genomic copy number alterations, and aberrations in known oncogenic drivers were all highly concordant in individuals. Metrics of androgen receptor activity and cell cycle activity were also similar within individuals.
“Although the analysis of a single metastatic tumor site clearly does underestimate the total burden of molecular aberrations found in the totality of all metastases, most drivers and actionable features are either represented as common roots across all tumors or result from convergent evolution conferred by therapeutic pressure, and most molecular differences between metastases do not seem to influence tumor phenotypes,” write the authors led by Akashi Kumar, M.D., Ph.D., candidate, from University of Washington, Seattle. “Although there are exceptions, these findings suggest that clinical decision-making on the basis of a biopsy from a single metastatic site is reasonable.”
Modeling results showed that all screening strategies were associated with increased life-years (LYs; range, 0.03 to 0.06) and costs ($263 to $1,371) versus no screening, yielding a cost per LY of $7,335 to $21,649. With contemporary treatment, the only possibly cost-effective 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. This yielded a cost per QALY of $92,446.
With selective treatment strategies, in which a Gleason score less than 7 and clinical T2a stage cancer or lower are treated only after clinical progression during active surveillance, all strategies were associated with increased QALYs (0.002 to 0.004) and several strategies were potentially cost-effective in terms of cost per QALY (incremental cost-effectiveness ratio, $70,831 to $136,332). Among the selective treatment practices (PSA less than 10 ng/mL) all strategies increased costs (range, $263-$703); however, in contrast to many strategies under contemporary treatments, all strategies under selective treatment practices increased QALYs (range, 0.002-0.004). All of these screening strategies have screening intervals of 2 to 4 years with PSA biopsy thresholds of 4.0, 3.0, and 3.0 ng/mL, yielding an incremental cost-effectiveness ratio of $89,333, $120,952, and $70,831 per QALY gained, respectively.
“Our findings have clear implications for the future of PSA screening in the United States,” write Roth and colleagues. “Rather than stopping PSA screening, as recommended by the USPSTF, 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.”
Takeaway: Concerns over the harms associated from PSA screening are not due to the screening test itself, but rather the action taken from test results. Modeling indicates that modifying screening strategies in terms of age of men screened, interval of screening, and PSA thresholds for biopsy referral may be able to improve identification of higher-risk cases of prostate cancer in a more cost-effective manner.
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