Limitations Of Prostate-specific Antigen Research Articles

Peripheral Coagulation Parameters and Prostate Cancer Association: A Retrospective Study and Mendelian Randomization.

The limitations of prostate-specific antigen (PSA) in diagnosing prostate cancer (PCa) necessitate the exploration of novel biomarkers. Recent studies suggest a potential link between coagulation markers, particularly fibrinogen and D-dimer, and PCa. A retrospective single-center analysis on 466 biopsy-undergone patients was conducted, categorized into PCa and benign prostatic hyperplasia (BPH) groups. Baseline and coagulation parameter levels were analyzed. Utilizing a Mendelian randomization (MR) approach, we investigated the causative relationship between D-dimer and PCa risk. Individuals with PCa, compared with those with BPH, exhibited significantly higher D-dimer levels (P < .001), total PSA (P < .001), and PSA density (P < .001). Fibrinogen levels did not exhibit significant differences (P = .505). The MR analysis suggested a probable causal link between elevated D-dimer levels and an increased risk of PCa (odds ratio: 1.81, 95% confidence interval: 1.48-2.21, P = 7.4 × 10-9). This research highlights D-dimer as a potential biomarker for diagnosing PCa, supported by clinical and MR analyses. The study paves the way for future large-scale, multi-center research to corroborate these findings and further explore the relationship between coagulation markers and PCa mechanisms.

Liquid biomarkers for early detection of prostate cancer and summary of available data for their use in African-American men.

Several liquid biomarker tests have been developed to account for the limitations of prostate specific antigen (PSA) screening prior to prostate biopsy. African ancestry is an established risk factor for prostate cancer (PCa) and must be particularly considered when evaluating patients with liquid biomarkers. While multiple tests have been developed over decades of exploration, recent advances can help patients and physicians incorporate data into a broader clinical context. We sought to review currently available liquid biomarker tests in a practical, clinically directed fashion with particular focus on performance in men with African ancestry. We reviewed discovery and validation studies and highlight important considerations for each test. We discuss the advantages and limitations of percent free PSA, Prostate Health Index, Progensa® PCA3, ExoDx® Prostate Test, SelectMDx®, 4Kscore® Test, and Mi-Prostate Score and summarize salient studies on their use. A literature review of evidence specifically for men with African ancestry was conducted and available studies were summarized. Liquid biomarkers can be useful tools for aiding in risk stratification prior to prostate biopsy. Use of such tests should be individualized based on a thorough knowledge of supporting evidence and the goals of the patient and physician. Further study should prioritize evaluation of such biomarkers in men with African ancestry.

Rapid Diagnosis of Prostate Cancer Disease Progression Using Paper Spray Ionization Mass Spectrometry.

The limitation of prostate specific antigen (PSA) for prostate cancer (PC) diagnosis is well-recognized. The Gleason score (GS) has been the most widely used grading system for prostate tumor differentiation and represents the best-established prognostic indicator for prostate cancer progression. However, a rapid and sensitive noninvasive diagnostic marker that differentiates GS-based prostate cancer disease progression is needed. As PC is becoming a leading cause of cancer related death for men in the U.S. and worldwide, an immediate need exists for an improved, sensitive, noninvasive, and rapid diagnostic test for PC screening. Here, we employed paper spray ionization-mass spectrometry (PSI MS)-based global metabolomics of urine liquid biopsies to distinguish between healthy (negative for any prostate specific health problems) and progressive PC states (low grade PC such as GS6 and high-grade PC such as GS7, GS8, and GS9). For PSI-MS-based direct untargeted metabolic investigation, a raw urine sample was directly pipetted onto a triangular paper substrate, without any additional sample preparation. Multivariate statistical analysis revealed distinct GS-specific metabolic signatures compared to a healthy control. Variable importance in projection from partial least-squares-discriminant analysis showed distinct metabolic patterns that were correlatively elevated with progressive disease and could serve as biomarkers for diagnosis of prostate cancer risk categorization.

Improving Detection of Clinically Significant Prostate Cancer: Magnetic Resonance Imaging/Transrectal Ultrasound Fusion Guided Prostate Biopsy

Given the limitations of prostate specific antigen and standard biopsies for detecting prostate cancer, we evaluated the cancer detection rate and external validity of a magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy system used at the National Institutes of Health. We performed a phase III trial of a magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy system with participants enrolled between 2012 and 2013. A total of 153 men consented to the study and underwent 3 Tesla multiparametric magnetic resonance imaging with an endorectal coil for clinical suspicion of prostate cancer. Lesions were classified as low or moderate/high risk for prostate cancer. Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy and standard 12-core prostate biopsy were performed and 105 men were eligible for analysis. Mean patient age was 65.8 years and mean prostate specific antigen was 9.5 ng/ml. The overall cancer detection rate was 62.9% (66 of 105 patients). The cancer detection rate in those with moderate/high risk on imaging was 72.3% (47 of 65) vs 47.5% (19 of 40) in those classified as low risk for prostate cancer (p<0.05). Mean tumor core length was 4.6 and 3.7 mm for fusion biopsy and standard 12-core biopsy, respectively (p<0.05). Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy detected prostate cancer that was missed by standard 12-core biopsy in 14.3% of cases (15 of 105), of which 86.7% (13 of 15) were clinically significant. This biopsy upgraded 23.5% of cancers (4 of 17) deemed clinically insignificant on 12-core biopsy to clinically significant prostate cancer necessitating treatment. Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy can improve prostate cancer detection. The results of this trial support the external validity of this platform and may be the next step in the evolution of prostate cancer management.

The confusion surrounding prostate cancer screening faced by family physicians

Primary care physicians, in the forefront of prostate cancer screening, are challenged with confusing and often conflicting guidelines. The lack of uniformity on the optimal prostate cancer screening recommendations stems from conflicting interpretations of the results of recent screening studies. Unfortunately, two large trials, initially planned to define the usefulness of screening, were both significantly flawed and provided conflicting results and further fueled the debate.1,2 Not surprisingly, these results have led to a lack of consensus on the best screening practices among various medical associations and guideline committees. The limitations of prostate-specific antigen (PSA) itself as a screening tool have precluded standardized and widely adopted guidelines from being developed to date.3 Several guidelines have been established; the American Urological Association and Canadian Urological Association favour the inclusion of PSA testing as a tool for prostate cancer screening,4,5 while the Canadian Task Force on Preventative Health Care and the U.S Preventative Services Task Force (USPSTF) recommend against screening.6,7 These are in addition to provincial and advocacy organizations’ recommendations – it is no wonder physicians and patients are confused. Controversy surrounding optimal prostate cancer screening for primary care physicians was renewed with the recent publication of the USPSTF statement, which attracted considerable media attention. Their recommendations were against PSA-based screening for prostate cancer in all men. PSA screening was labelled a “Grade D” recommendation, which states that there is moderate or high certainty that PSA screening has no benefit, or that the harms outweigh any benefits.7 It is important to stress the results of the European Randomized Study of Screening for Prostate Cancer, considered the best PSA screening study to date. It was demonstrated that screening reduced the rate of prostate cancer death by 20%, with additional two-year follow-up consolidating these findings.2,8 Being the largest trial to date and suffering fewer methodological limitations than its U.S. counterpart, this European study represents “level one” evidence that screening does reduce prostate cancer-specific mortality. It was proposed that the modest benefit conveyed should support a “grade C” recommendation; this leaves the decision regarding PSA screening to the patient and primary care physician.9 The results of the survey in this issue of CUAJ provide evidence to suggest that Ontario family physicians use their own management strategies in deciding whether to offer prostate cancer screening to their patients.10 As well, there is apparent heterogeneity in the use of screening, as well as in the attitudes concerning its value. Interestingly, although almost 80% screen for prostate cancer, a considerably lower percentage of family physicians believe that the benefits of screening outweigh its risks, which suggests that other patient factors prompt the decision to screen. Obviously, a primary weakness of the paper is the poor response rate. The results do, however, provide a glimpse into the practice patterns of physicians directly involved in screening. It is likely that the results can be extrapolated to the rest of the country, as these findings have been corroborated by other papers addressing the same question in Newfoundland and British Columbia.11,12 Most importantly, the survey shows the need not only to provide clear and evidence-based guidelines, but also for better education on prostate cancer screening for family physicians. A significant onus of responsibility for this lies with our own association and members. It highlights the importance of relaying our own CUA guidelines to family physicians, and educating them regarding the evidence and considerations surrounding prostate cancer screening.

Beyond Prostate-specific Antigen — Future Biomarkers for the Early Detection and Management of Prostate Cancer

Prostate-specific antigen is currently commonly used as a screening biomarker for prostate cancer, but it has limitations in both sensitivity and specificity. The development of novel biomarkers for early cancer detection has the potential to improve survival, reduce unnecessary investigations and benefit the health economy. Here we review the use and limitations of prostate-specific antigen and its subtypes, urinary biomarkers including PCA3, alpha-methylacyl-CoA racemase, the TMPRSS2-ERG fusion gene and microseminoprotein-beta, and other novel markers in both serum and urine. Many of these biomarkers are at early stages of development and require evaluation in prospective trials to determine their potential usefulness in clinical practice. Genetic profiling may allow for the targeting of high-risk populations for screening and may offer the opportunity to combine biomarker results with genotype to aid risk assessment.

Uses and Limitations of Prostate-Specific Antigen in the Laboratory Diagnosis of Prostate Cancer

We have studied the clinical utility of a recently developed assay for a prostate specific protein (prostate-specific antigen). Histochemical demonstration of prostate-specific antigen has a higher sensitivity and specificity for the diagnosis of prostate carcinoma than does prostatic acid phosphatase. Similarly, measurement of prostate-specific antigen by immunoassay in serum is a more sensitive indicator of tumor stage and recurrence after therapy than prostatic acid phosphatase. More information is needed, however, regarding the variation in this protein with different therapeutic methods.

Uses and Limitations of Prostate-Specific Antigen in the Laboratory Diagnosis of Prostate Cancer

We have studied the clinical utility of a recently developed assay for a prostate specific protein (prostate-specific antigen). Histochemical demonstration of prostate-specific antigen has a higher sensitivity and specificity for the diagnosis of prostate carcinoma than does prostatic acid phosphatase. Similarly, measurement of prostate-specific antigen by immunoassay in serum is a more sensitive indicator of tumor stage and recurrence after therapy than prostatic acid phosphatase. More information is needed, however, regarding the variation in this protein with different therapeutic methods.