Gene‒Prostate-Specific-Antigen-Guided Personalized Screening for Prostate Cancer

(1) Background: A simulation approach for prostate cancer (PrCa) with a prostate-specific antigen (PSA) test incorporating genetic information provides a new avenue for the development of personalized screening for PrCa. Going by the evidence-based principle, we use the simulation method to evaluate the effectiveness of mortality reduction resulting from PSA screening and its utilization using a personalized screening regime as opposed to a universal screening program. (2) Methods: A six-state (normal, over-detected, low-grade, and high-grade PrCa in pre-clinical phase, and low-grade and high-grade PrCa in clinical phase) Markov model with genetic and PSA information was developed after a systematic review of genetic variant studies and dose-dependent PSA studies. This gene‒PSA-guided model was used for personalized risk assessment and risk stratification. A computer-based simulated randomized controlled trial was designed to estimate the reduction of mortality achieved by three different screening methods, personalized screening, universal screening, and a non-screening group. (3) Results: The effectiveness of PrCa mortality reduction for a personalized screening program compared to a non-screening group (22% (9%‒33%)) was similar to that noted in the universal screening group (20% (7%‒21%). However, a personalized screening program could dispense with 26% of unnecessary PSA testing, and avoid over-detection by 2%. (4) Conclusions: Gene‒PSA-guided personalized screening for PrCa leads to fewer unnecessary PSA tests without compromising the benefits of mortality reduction (as happens with the universal screening program).

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Overdiagnosis and Overtreatment of Prostate Cancer

American Society of Clinical Oncology Educational Book ◽

10.14694/edbook_am.2012.32.98 ◽

2012 ◽

pp. e35-e39 ◽

Cited By ~ 4

Author(s):

Ian M. Thompson

Keyword(s):

Prostate Cancer ◽

Active Surveillance ◽

Specific Antigen ◽

The United States ◽

Assessment Tools ◽

Low Grade ◽

High Grade ◽

Surveillance Strategy ◽

Psa Testing ◽

Prostate Cancer Prevention

Overview: Prostate cancer is a ubiquitous disease, affecting as many as two-thirds of men in their 60s. Through widespread prostate-specific antigen (PSA) testing, increasing rates of prostate biopsy, and increased sampling of the prostate, a larger fraction of low-grade, low-volume tumors have been detected, consistent with tumors often found at autopsy. These tumors have historically been treated in a manner similar to that used for higher-grade tumors but, more recently, it has become evident that with a plan of active surveillance that reserves treatment for only those patients whose tumors show evidence of progression, very high disease-specific survival can be achieved. Unfortunately, the frequency of recommendation of an active surveillance strategy in the United States is low. An alternative strategy to improve prostate cancer detection is through selected biopsy of those men who are at greater risk of harboring high-grade, potentially lethal cancer. This strategy is currently possible through the use of risk assessment tools such as the Prostate Cancer Prevention Trial Risk Calculator ( www.prostate.cancer.risk.calculator.com ) as well as others. These tools can predict with considerable accuracy a man's risk of low-grade and high-grade cancer, allowing informed decision making for the patient with a goal of detection of high-risk disease. Ultimately, other biomarkers including PCA3, TMPRSS2:ERG, and [-2]proPSA will likely aid in discriminating these two types of cancer before biopsy.

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PSA screening for prostate cancer

Revista da Associação Médica Brasileira ◽

10.1590/1806-9282.63.08.722 ◽

2017 ◽

Vol 63 (8) ◽

pp. 722-725 ◽

Cited By ~ 2

Author(s):

Marcus V. Sadi

Keyword(s):

Quality Of Life ◽

Prostate Cancer ◽

Early Diagnosis ◽

Prostate Specific Antigen ◽

Specific Antigen ◽

Low Grade ◽

Psa Screening ◽

Psa Testing ◽

Baseline Values

Summary Screening of prostate cancer with prostate-specific antigen (PSA) is a highly controversial issue. One part of the controversy is due to the confusion between population screening and early diagnosis, another derives from problems related to the quality of existing screening studies, the results of radical curative treatment for low grade tumors and the complications resulting from treatments that affect the patient’s quality of life. Our review aimed to critically analyze the current recommendations for PSA testing, based on new data provided by the re-evaluation of the ongoing studies and the updated USPSTF recommendation statement, and to propose a more rational and selective use of PSA compared with baseline values obtained at an approximate age of 40 to 50 years.

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Comparison of Sensitivity and Specificity of Biparametric versus Multiparametric Prostate MRI in the Detection of Prostate Cancer in 431 Men with Elevated Prostate-Specific Antigen Levels

Diagnostics ◽

10.3390/diagnostics11071223 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1223

Author(s):

Filippo Pesapane ◽

Marzia Acquasanta ◽

Rosario Di Meo ◽

Giorgio Maria Agazzi ◽

Priyan Tantrige ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Specific Antigen ◽

Sensitivity And Specificity ◽

Specific Antigen ◽

Low Grade ◽

High Grade ◽

Dynamic Contrast Enhancement ◽

Prostate Mri ◽

Endorectal Coil

(1) Background: the study of dynamic contrast enhancement (DCE) has a limited role in the detection of prostate cancer (PCa), and there is a growing interest in performing unenhanced biparametric prostate-MRI (bpMRI) instead of the conventional multiparametric-MRI (mpMRI). In this study, we aimed to retrospectively compare the performance of the mpMRI, which includes DCE study, and the unenhanced bpMRI, composed of only T2-weighted imaging and diffusion-weighted imaging (DWI), in PCa detection in men with elevated prostate-specific-antigen (PSA) levels. (2) Methods: a 1.5 T MRI, with an endorectal-coil, was performed on 431 men (aged 61.5 ± 8.3 years) with a PSA ≥4.0 ng/mL. The bpMRI and mpMRI tests were independently assessed in separate sessions by two readers with 5 (R1) and 3 (R2) years of experience. The histopathology or ≥2 years follow-up served as a reference standard. The sensitivity and specificity were calculated with their 95% CI, and McNemar’s and Cohen’s κ statistics were used. (3) Results: in 195/431 (45%) of histopathologically proven PCa cases, 62/195 (32%) were high-grade PCa (GS ≥ 7b) and 133/195 (68%) were low-grade PCa (GS ≤ 7a). The PCa could be excluded by histopathology in 58/431 (14%) and by follow-up in 178/431 (41%) of patients. For bpMRI, the sensitivity was 164/195 (84%, 95% CI: 79–89%) for R1 and 156/195 (80%, 95% CI: 74–86%) for R2; while specificity was 182/236 (77%, 95% CI: 72–82%) for R1 and 175/236 (74%, 95% CI: 68–80%) for R2. For mpMRI, sensitivity was 168/195 (86%, 95% CI: 81–91%) for R1 and 160/195 (82%, 95% CI: 77–87%) for R2; while specificity was 184/236 (78%, 95% CI: 73–83%) for R1 and 177/236 (75%, 95% CI: 69–81%) for R2. Interobserver agreement was substantial for both bpMRI (κ = 0.802) and mpMRI (κ = 0.787). (4) Conclusions: the diagnostic performance of bpMRI and mpMRI were similar, and no high-grade PCa was missed with bpMRI.

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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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