Overdiagnosis and Lives Saved by Reflex Testing Men With Intermediate Prostate-Specific Antigen Levels

Abstract Background Several prostate cancer (PCa) early-detection biomarkers are available for reflex testing in men with intermediate prostate-specific antigen (PSA) levels. Studies of these biomarkers typically provide information about diagnostic performance but not about overdiagnosis and lives saved, the primary drivers of associated harm and benefit. Methods We projected overdiagnoses and lives saved using an established microsimulation model of PCa incidence and mortality with screening and treatment efficacy based on randomized trials. We used this framework to evaluate four urinary reflex biomarkers (measured in 1112 men presenting for prostate biopsy at 10 US academic or community clinics) and two hypothetical ideal biomarkers (with 100% sensitivity or specificity for any or for high-grade PCa) at one-time screening tests at ages 55 and 65 years. Results Compared with biopsying all men with elevated PSA, reflex testing reduced overdiagnoses (range across ages and biomarkers = 8.8–60.6%) but also reduced lives saved (by 7.3–64.9%), producing similar overdiagnoses per life saved. The ideal biomarker for high-grade disease improved this ratio (by 35.2% at age 55 years and 42.0% at age 65 years). Results were similar under continued screening for men not diagnosed at age 55 years, but the ideal biomarker for high-grade disease produced smaller incremental improvement. Conclusions Modeling is a useful tool for projecting the implications of using reflex biomarkers for long-term PCa outcomes. Under simplified conditions, reflex testing with urinary biomarkers is expected to reduce overdiagnoses but also produce commensurate reductions in lives saved. Reflex testing that accurately identifies high-grade PCa could improve the net benefit of screening.

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7100 ORAL Prostate-specific Antigen and Long-term Prediction of Prostate Cancer Incidence and Mortality in the General Population

European Journal of Cancer ◽

10.1016/s0959-8049(11)72015-9 ◽

2011 ◽

Vol 47 ◽

pp. S504

Author(s):

D. Orsted ◽

B.G. Nordestgaard ◽

G.B. Jensen ◽

P. Schnohr ◽

S.E. Bojesen

Keyword(s):

Prostate Cancer ◽

General Population ◽

Prostate Specific Antigen ◽

Cancer Incidence ◽

Specific Antigen ◽

Prostate Cancer Incidence ◽

Term Prediction ◽

Incidence And Mortality ◽

Long Term Prediction

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Prostate-specific antigen and long-term prediction of prostate cancer incidence and mortality in the general population.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.5_suppl.5 ◽

2012 ◽

Vol 30 (5_suppl) ◽

pp. 5-5

Author(s):

David D Orsted ◽

Borge G. Nordestgaard ◽

Stig E. Bojesen

Keyword(s):

Prostate Cancer ◽

General Population ◽

Prostate Specific Antigen ◽

Cancer Incidence ◽

Specific Antigen ◽

Prostate Cancer Incidence ◽

Increased Risk ◽

Incidence And Mortality

5 Background: It is largely unknown whether prostate-specific antigen at first date of testing predicts long-term risk of prostate cancer incidence and mortality in the general population. We tested the hypothesis that baseline prostate-specific antigen levels predict long-term risk of prostate cancer incidence and mortality. Methods: Using a prospective study, we examined 4383 20-94 year old men from the Danish general population followed in the Copenhagen City Heart Study from 1981 through 2009. Prostate-specific antigen was measured in plasma samples obtained in 1981-83. Results: During 28 years of follow-up, 170 men developed prostate cancer and 94 died from prostate cancer. Median follow-up was 18 years (range 0.5-28 years). For prostate cancer incidence, the subhazard ratio was 3.0 (95% confidence interval (CI) 1.9-4.6) for a prostate-specific antigen level of 1.01-2.00 ng/ml, 6.8 (4.2-11) for 2.01-3.00 ng/ml, 6.6 (3.4-13) for 3.01-4.00 ng/ml, 16 (10.4-25) for 4.01-10.00 ng/ml, and 57 (32-104) for >10.00 ng/ml versus 0.01-1.00 ng/ml.. For prostate cancer mortality, corresponding subhazard ratios were 2.2 (1.3-3.9), 5.1 (2.8-9.0), 4.2 (1.8-10), 7.0 (3.8-14), and 14 (6.0-32). For men with prostate-specific antigen levels of 0.01-1.00 ng/ml, absolute 10-year risk of prostate cancer was 0.6% for age <45 years, 0.7% for 45-49 years, 1.1% for 50-54 years, 1.2% for 55-59 years, 1.3% for 60-64 years, 1.1% for 65-69 years, 1.3% for 70-74 years, and 1.5% for age≥75 years; corresponding values for prostate-specific antigen levels >10.00 ng/ml were 35%, 41%, 63%, 71%, 77%, 69%, 75%, and 88%, respectively. Conclusions: Stepwise increases in prostate-specific antigen at first date of testing predicted a 3-57 fold increased risk of prostate cancer, a 2-16 fold increased risk of prostate cancer mortality, and a 35-88% absolute 10-year risk of prostate cancer in those with prostate-specific antigen levels >10.00 ng/ml. Equally important, absolute 10-year risk of prostate cancer in those with levels 0.01-1.00 ng/ml was only 0.6-1.5%.

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Prostate-Specific Antigen and Long-Term Prediction of Prostate Cancer Incidence and Mortality in the General Population

European Urology ◽

10.1016/j.eururo.2011.11.007 ◽

2012 ◽

Vol 61 (5) ◽

pp. 865-874 ◽

Cited By ~ 30

Author(s):

David D. Ørsted ◽

Børge G. Nordestgaard ◽

Gorm B. Jensen ◽

Peter Schnohr ◽

Stig E. Bojesen

Keyword(s):

Prostate Cancer ◽

General Population ◽

Prostate Specific Antigen ◽

Cancer Incidence ◽

Specific Antigen ◽

Prostate Cancer Incidence ◽

Term Prediction ◽

Incidence And Mortality ◽

Long Term Prediction

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474: Prostate Specific Antigen (PSA) vs. Cancer Volume and High-Grade Cancer (PCA) Volume at Radical Prostatectomy (RP) in a Large European Cohort: Is the PSA Era Over in Europe as Well?

The Journal of Urology ◽

10.1016/s0022-5347(18)34727-x ◽

2005 ◽

Vol 173 (4S) ◽

pp. 130-130

Author(s):

Pierre I. Karakiewicz ◽

Paul Perrotte ◽

Thomas Steuber ◽

Alexander Haese ◽

Markus Graefen ◽

...

Keyword(s):

Radical Prostatectomy ◽

Prostate Specific Antigen ◽

Specific Antigen ◽

High Grade

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Clinical use of the SelectMDx urinary-biomarker test with or without mpMRI in prostate cancer diagnosis: a prospective, multicenter study in biopsy-naïve men

Prostate Cancer and Prostatic Diseases ◽

10.1038/s41391-021-00367-8 ◽

2021 ◽

Author(s):

Rianne J. Hendriks ◽

Marloes M. G. van der Leest ◽

Bas Israël ◽

Gerjon Hannink ◽

Anglita YantiSetiasti ◽

...

Keyword(s):

Prostate Cancer ◽

Risk Stratification ◽

Specific Antigen ◽

Low Grade ◽

Diagnostic Study ◽

High Grade ◽

Net Benefit ◽

Conditional Strategy ◽

Detection Rates ◽

Guided Biopsy

Abstract Background Risk stratification in men with suspicion of prostate cancer (PCa) requires reliable diagnostic tests, not only to identify high-grade PCa, also to minimize the overdetection of low-grade PCa, and reduction of “unnecessary” prostate MRIs and biopsies. This study aimed to evaluate the SelectMDx test to detect high-grade PCa in biopsy-naïve men. Subsequently, to assess combinations of SelectMDx test and multi-parametric (mp) MRI and its potential impact on patient selection for prostate biopsy. Methods This prospective multicenter diagnostic study included 599 biopsy-naïve patients with prostate-specific antigen level ≥3 ng/ml. All patients underwent a SelectMDx test and mpMRI before systematic transrectal ultrasound-guided biopsy (TRUSGB). Patients with a suspicious mpMRI also had an in-bore MR-guided biopsy (MRGB). Histopathologic outcome of TRUSGB and MRGB was used as reference standard. High-grade PCa was defined as ISUP Grade Group (GG) ≥ 2. The primary outcome was the detection rates of low- and high-grade PCa and number of biopsies avoided in four strategies, i.e., (1) SelectMDx test-only, (2) mpMRI-only, (3) SelectMDx test followed by mpMRI when SelectMDx test was positive (conditional strategy), and (4) SelectMDx test and mpMRI in all (joint strategy). A positive SelectMDx test outcome was a risk score of ≥−2.8. Decision curve analysis (DCA) was performed to assess clinical utility. Results Prevalence of high-grade PCa was 31% (183/599). Thirty-eight percent (227/599) of patients had negative SelectMDx test in whom biopsy could be avoided. Low-grade PCa was not detected in 35% (48/138) with missing 10% (18/183) high-grade PCa. Yet, mpMRI-only could avoid 49% of biopsies, not detecting 4.9% (9/183) of high-grade PCa. The conditional strategy reduces the number of mpMRIs by 38% (227/599), avoiding biopsy in 60% (357/599) and missing 13% (24/183) high-grade PCa. Low-grade PCa was not detected in 58% (80/138). DCA showed the highest net benefit for the mpMRI-only strategy, followed by the conditional strategy at-risk thresholds >10%. Conclusions SelectMDx test as a risk stratification tool for biopsy-naïve men avoids unnecessary biopsies in 38%, minimizes low-grade PCa detection, and misses only 10% high-grade PCa. Yet, using mpMRI in all patients had the highest net benefit, avoiding biopsy in 49% and missing 4.9% of high-risk PCa. However, if mpMRI availability is limited or expensive, using mpMRI-only in SelectMDx test positive patients is a good alternative strategy.

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