Diagnostic efficacy of free to total ratio of prostate-specific antigen and prostate-specific antigen velocity, singly and in combination, in detecting prostate cancer in patients with total serum prostate-specific antigen between 4 and 10 ng/ml

To assess the diagnostic efficacy of prostate-specific antigen (PSA)-related parameters, using a total of 226 patients with gray zone PSA who underwent prostate biopsy, various cutoff points of free to total ratio of PSA (f/t PSA) and PSA velocity (PSAV) were evaluated. Higher cutoff points of f/t PSA resulted in high sensitivity and negative predictive value (NPV): at f/t PSA <15%, sensitivity was 82.0% (41/50) and NPV 84.7% (50/59), and at f/t PSA <20%, 96.0% (48/50) and 92.3% (24/26). Lowering cutoff points also resulted in higher sensitivity and NPV: at PSAV ≥0.75 ng/ml per year, sensitivity was 71.4% (15/21) and NPV 82.4% (28/34), and at PSAV ≥0.40 ng/ml per year, 95.2% (20/21) and 95.2% (20/21). Further, among the patients with both of these parameters available, both sensitivity and NPV achieved 100% (10/10 and 7/7) when the indication for biopsy was determined as f/t PSA <15% or PSAV ≥0.40 ng/ml per year. Our results showed that unnecessary prostate biopsies could be more effectively avoided among patients with “gray zone PSA” by combination of f/t PSA and PSAV than single usage of these indexes.     

Association between percent-free prostate-specific antigen and glomerular filtration rate in transrectal ultrasound-guided biopsy-proven patients with prostate-specific antigen levels ranging from 4 to 10 ng/ml

Purpose

The aim of this study was to investigate the relationship between percent-free prostate-specific antigen (PSA) and estimated glomerular filtration rate (GFR) in men whose PSA level was 4–10 ng/ml with biopsy-proven prostate status.

Methods

Between 2004 and 2010, the medical records of 495 cases (404 cases without prostate cancer and 91 cases with prostate cancer) who underwent prostate biopsy were reviewed and their GFR was calculated using the Cockcroft–Gault equation, adjusted for body surface area. Correlation and multivariate regression analyses were conducted among percent-free PSA, body mass index, prostate size, and GFR in patients with and without prostate cancer, respectively.

Results

The mean patient age was 64.6 years, and the median PSA and free PSA were 5.64 and 0.87 ng/ml. The mean GFR was 61.02 mL/min/1.73 m², and mean percent-free PSA was 18.9 %. Correlation analysis showed that percent-free PSA was correlated with GFR, age, and prostate size in the non-cancer cohort and correlated with only prostate size in the cancer cohort. Multivariate regression analysis showed that percent-free PSA was influenced by GFR (p < 0.001) and prostate size (p < 0.001) independently in the non-cancer cohort, while only by prostate size (p = 0.008) in the cancer cohort.

Conclusions

Percent-free PSA has a negative relationship with GFR in the benign prostate group, while it does not in the prostate cancer group. Screening with current cutoff value of percent-free PSA can be applied to the patients with impaired renal function.     

Percent free prostate-specific antigen is effective to predict prostate biopsy outcome in Chinese men with prostate-specific antigen between 10.1 and 20.0 ng ml?1

Percent free prostatic-specific antigen (%fPSA) has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0–10.0 ng ml⁻¹, however, it remains controversial whether %fPSA is effective in PSA range of 10.1–20.0 ng ml⁻¹ in both Chinese and Western population. In this study, the diagnostic performance of %fPSA and serum PSA in predicting prostate cancer (PCa) and high-grade PCa (HGPCa) was analyzed in a multi-center biopsy cohort of 5915 consecutive Chinese patients who underwent prostate biopsy in 22 hospitals across China from January 1, 2010 to December 31, 2013. The indication for biopsy was PSA>4.0 ng ml⁻¹ or/and suspicious digital rectal examination. Total and free serum PSA determinations were performed by three types of electrochemiluminescence immunoassays with recalibration to the World Health Organization standards. The diagnostics accuracy of PSA, %fPSA and %fPSA in combination with PSA (%fPSA + PSA) was determined by the area under the receivers operating characteristic curve (AUC). %fPSA was more effective than PSA in men aged ≥60 years old. The AUC was 0.584 and 0.635 in men aged ≥60 years old with a PSA of 4.0–10.0 ng ml⁻¹ and 10.1–20.0 ng ml⁻¹, respectively. The AUC of %fPSA was superior to that of PSA in predicting HGPCa in patients ≥60 years old in these two PSA range. Our results indicated that %fPSA is both statistically effective and clinical applicable to predict prostate biopsy outcome in Chinese patients aged ≥60 years old with a PSA of 4.0–10.0 ng ml⁻¹ and 10.1–20.0 ng ml⁻¹.     

Should prostate-specific antigen velocity be abandoned？

Prostate-specific antigen (PSA) is the most widely used biomarker for prostate cancer, but may also be elevated in non-malignant conditions such as benign pro-...     

What does prostate-specific antigen recurrence mean?

The return of the prostate-specific antigen (PSA) to a detectable serum level (PSA recurrence) is usually the first sign of recurrent disease after radical prostatectomy. PSA recurrence generally occurs in men who are otherwise asymptomatic and may occur as late as 5 to 10 years after surgery. Men in this situation want to know what this means regarding the likelihood of clinical disease recurrence and, ultimately, survival. An evaluation for recurrent disease is warranted but generally does not reveal objective signs of clinical disease in the majority of men. Although select men may benefit from salvage local therapy, a PSA recurrence is most often an early sign of distant disease present since the time of surgery. The decision whether or not to initiate systemic therapy in these men is difficult and controversial. Fortunately, recent developments in determining the significance of a PSA recurrence may help the patient and his physician to make a more informed decision regarding treatment options.     

Racial differences in prostate-specific antigen–based prostate cancer screening: State-by-state and region-by-region analyses

Objective

Black men are more prone to harbor prostate cancer. They are more likely to succumb to this tumor than their White counterparts and may benefit from early detection and treatment. In this study, we assess the nationwide and regional disparity in prostate-specific antigen (PSA) screening for prostate cancer between Black men and non-Hispanic Whites (NHWs).

Do renal failure and hemodialysis have any effect on the elimination of free and total prostate-specific antigen?

OBJECTIVES: The aim of this study was first to determine the serum levels of free prostate-specific antigen (f-PSA), total prostate-specific antigen (t-PSA) and f-PSA/t-PSA ratios in patients with renal failure, and secondary, to investigate whether a significant difference between serum f-PSA and t-PSA levels consists in patients with end-stage renal disease before and after hemodialysis. METHODS: Serum concentrations of f-PSA and t-PSA were measured in 36 men with end-stage renal disease before and after hemodialysis and in 95 healthy controls. A chemiluminescent enzyme assay was used to determine the levels of f-PSA and t-PSA. RESULTS: The mean concentrations of serum t-PSA were 1.36+/-0.43 ng/ml in patients on hemodialysis and 1.08+/-0.60 ng/ml in controls. There was no significant difference in f-PSA and t-PSA levels between patients with renal failure and controls. F-PSA and t-PSA levels in patients with renal failure also showed no statistical differences before and after hemodialysis. CONCLUSIONS: The limited kidney reserve in patients with end-stage renal disease is sufficient to maintain the levels of t-PSA and f-PSA within normal ranges and hemodialysis does not alter the serum levels of different PSA forms.     

Do prostate-specific antigen parameters have a similar role in predicting prostate cancer regardless of serum testosterone levels in men with gray-zone prostate-specific antigen levels?

BackgroundTo evaluate whether various prostate-specific antigen (PSA) parameters have a similar diagnostic value in predicting prostate cancer (PCa) in men with gray-zone PSA levels (4.0–10.0 ng/mL) depending on different serum testosterone levels.MethodsWe retrospectively reviewed the data of 635 men with gray-zone PSA levels who underwent prostate biopsy between January 2015 and December 2019. The study cohort was divided into two groups according to serum testosterone levels: normal (≥300 ng/dL) and low (<300 ng/dL) testosterone. Using the area under the receiver-operating characteristic curve (AUC), we analyzed the diagnostic accuracy of PSA parameters (total PSA, free PSA, free-to-total PSA ratio, testosterone-to-PSA ratio, and PSA density) in predicting PCa and compared the results between the two groups.ResultsThe median age was 68 (range, 40–88) years, and 76.1% (483 of 635) of the men had low testosterone levels. The PCa incidence was higher in the low testosterone group than in the normal testosterone group (45.5% vs. 35.5%, P=0.030). The AUC of free-to-total PSA ratio for predicting PCa showed no difference between the normal and low testosterone groups (AUC 0.616 vs. 0.684, P=0.257). Moreover, total PSA, testosterone-to-PSA ratio, and PSA density showed similar performance in predicting PCa between the two groups.ConclusionsThe analyzed PSA parameters showed a similar diagnostic value in predicting PCa regardless of testosterone levels in men with gray-zone PSA levels.     

Prediction of prostate volume based on total and free serum prostate-specific antigen: is it reliable?

OBJECTIVE: To analyze the utility of total/free prostate-specific antigen (PSA) and age as predictors of the prostate volume in men with symptomatic benign prostatic hyperplasia (BPH) and no evidence of prostate cancer. PATIENTS AND METHODS: Total and free serum PSA were determined in 681 patients with normal digital rectal examination and symptomatic BPH using the Hybritech method. Prostate volume was measured by transrectal ultrasound (TRUS). TRUS-guided biopsy was performed in 459 (67.4%) of the patients with a serum PSA >4.0 ng/ml. RESULTS: The relationship with prostate volume was best described in a log linear fashion by free PSA (R(2) = 0.367), total PSA (R(2) = 0.264) and age (R(2) = 0.017). Multiple linear regression demonstrates no significant influence of age. Free PSA was able to predict the individual TRUS prostate volume +/-10% in 67% of the patients and +/-20% in 91.2% and total PSA in 63 and 90. 9%, respectively. CONCLUSION: Prostate volume is strongly related with free and total PSA. Both determinations would be able to predict the TRUS prostate volume +/-20% in more than 90% of the patients.     

Probability of prostate cancer as a function of the percentage of free prostate-specific antigen in patients with a non-suspicious rectal examination and total prostate-specific antigen of 4–10 ng/ml

Our aim was to assess the usefulness of measuring the percentage of free prostate specific antigen (PSA) in serum in relation to reducing the number of prostate biopsies in men with benign prostate examinations and serum PSA levels between 4 and 10 ng/ml. The percentage of free PSA (Immulite) in serum was analyzed prospectively in 500 men, all of whom underwent ultrasound-guided sextant prostate biopsies. Cancer was detected in 21.4% (107/500) of the patients. Using a free PSA cutoff of 23% as a criterion for performing prostate biopsy would have detected 94.4% of cancers, avoided 18.8% of benign biopsies and yielded a positive predictive value of 25.3%. The percentage of free PSA increased with prostate volume. Mean total PSA and mean free percent PSA values increased as patient age increased, influencing the calculation of cutoff values, sensitivity and specificity. PSA density had a sensitivity and specificity not significantly different than the percentage of free PSA. Measurement of the percentage of free serum PSA improves the specificity of prostate cancer detection in patients with elevated total serum PSA levels and benign prostate examinations.     

Would prostate cancer detected by screening with prostate-specific antigen develop into clinical cancer if left undiagnosed? A comparison of two population-based studies in Sweden

OBJECTIVE: To assess the risk of over-diagnosing and over-treating prostate cancer if population-based screening with serum prostate-specific antigen (PSA) is instituted. PATIENTS AND METHODS: From a serum bank stored in 1980, PSA was analysed in 658 men with no previously known prostate cancer from a well-defined cohort from G?teborg, Sweden (men born in 1913); the incidence of clinical prostate cancer was registered until 1995. From the same area, and with the same selection criteria, another cohort of 710 men born in 1930-31, who in 1995 accepted an invitation for PSA screening, was also analysed. RESULTS: Of men born in 1913, 18 (2.7%) had died from prostate cancer and the cumulative probability of being diagnosed with clinical prostate cancer was 11.1% (5.0% in those with a PSA level of < 3 ng/mL vs 32.9% in those with a PSA level of > 3 ng/mL, P < 0.01). The mean lead-time from increased PSA (> 3 ng/mL) to clinical diagnosis was 7 years. The prostate cancer detection rate in men born in 1930-31 was 4.4% (22% among those with increased PSA levels) and 30 of 31 detected cancers were clinically localized. CONCLUSIONS: Screening and sextant biopsies resulted in a lower detection rate (22%) than the cumulative risk of having clinical prostate cancer (33%) in men with increased PSA levels, indicating that under-diagnosis rather than over-diagnosis is the case at least with 'one-time' screening. Even if the stage distribution in screening-detected cancers seems promising (and thus may result in reduced mortality) it is notable that screening 67-year-old men will result in treatment a mean of 7 years before clinical symptoms occur and only one in four men anticipated to develop prostate cancer will die from the disease within 15 years. Large randomized screening trials seem mandatory to further explore the benefits and hazards of PSA screening.     

Association between laminin γ1 expression and meningioma grade, recurrence, and progression-free survival

Background

Laminins are central components of basement membranes and play important roles in cell adhesion, proliferation, and migration. However, the role of laminins in tumor progression has not been thoroughly investigated in meningiomas.

Objective

The aim of the present study is to evaluate the expression of laminin γ1 in various grades of meningiomas in Chinese patients.

Methods

In the current study, clinical and pathological data for 32 meningioma patients with various tumor grades were collected. The expression of laminin γ1 in each tumor was assessed by using quantitative real-time polymerase chain reaction (qPCR), Western blot and immunohistochemical analysis and was correlated with the meningioma grade, tumor recurrence and patient survival. Patient prognoses were attained and the progression-free survival was calculated based on the Kaplan-Meier method. A two-sided probability cutoff of 0.05 was chosen for statistical significance.

Results

A total of 32 meningioma patients with various pathological subtypes (WHO grade I: 13, grade II: 10 and grade III: 9) were enrolled in this study. The qPCR results showed that laminin γ1 mRNA expression was significantly higher in grade III meningiomas than in grade I meningiomas (p?<?0.05), although there was no significant difference in laminin γ1 expression between grade II and grade I meningiomas (p?>?0.05). Western blot and immunohistochemistry analysis confirmed that the expression of laminin γ1 protein was relatively higher in grade III meningiomas when compared with grade I meningiomas. Higher levels of laminin γ1 expression in meningiomas are associated with a significantly shorter tumor recurrence time (p?<?0.05) and a decreased patient survival time (p?<?0.05).

Conclusions

Our results suggest that laminin γ1 is associated with meningioma grades and could play a role in enhancing tumor invasion. Laminin γ1 could be used as a predictor for meningioma recurrence and patient survival. Furthermore, laminin γ1 may represent a druggable molecular target for future therapies for tumors that overexpress this marker.     

Performance of prostate cancer antigen 3 (PCA3) and prostate-specific antigen in Prescreened men: reproducibility and detection characteristics for prostate cancer patients with high PCA3 scores (≥ 100)

Background

Prostate cancer antigen 3 (PCA3) is considered to be prostate cancer (PCa) specific and highly overexpressed in cancer. Therefore a high PCA3 score should result in a high positive predictive value (PPV) and specificity for a positive biopsy.

Objective

Our aim was to reevaluate, retest PCA3, and rebiopsy men with an initial PCA3 ≥100 and no PCa detected and compare the results with a random cohort of men with an initial PCA3 < 100.

Design, setting, and participants

We invited men 63–75 yr of age with a PCA3 ≥100 for retesting and a control group with an initial PCA3 < 100 to participate in the European Randomized Study of Screening for Prostate Cancer, section Rotterdam.

Interventions

Blood and urine sampling were used to determine prostate-specific antigen (PSA) and PCA3. Prostate biopsies were performed if the PSA was ≥2.5 ng/ml and/or the PCA3 score was ≥35.

Measurements

We correlated the initial and reevaluated PCA3 scores. Our assessment of the PPV after rebiopsy was based on the newly determined PCA3 score.

Results and limitations

After a mean study period of 19 mo, more cases of PCa were detected in rebiopsied men with initial PCA3 scores ≥100 than in the controls with PCA3 scores <100 (30.0% vs 18.8%). Combining initial and rebiopsy data resulted in a PPV of 52.2% in men with PCA3 ≥100. Over time, changes in PSA and PCA3 levels were quite different.

Conclusions

In spite of our rescreened population, PPV and specificity were comparable with all reported studies of men with PCA3 scores ≥100. These findings do not explain why these PCA3 scores were excessively high in spite of the absence of biopsy-detectable PCa.     

Monoclonal antibodies: will they become an integral part of the evaluation and treatment of prostate cancer--focus on prostate-specific membrane antigen?

Over the past two decades, monoclonal antibody technology has had an increasing impact on clinical diagnostic and therapeutic options, and this is true in the realm of managing prostate cancer. Several targets such as prostate-specific antigen and prostatic acid phosphatase as well as, more recently, angiogenic antigens such as vascular endothelial growth factor have been examined for therapy. Prostate-specific membrane antigen, a type II integral membrane glycoprotein initially characterized by the monoclonal antibody 7E11, has shown promise. Recent evidence suggests that prostate-specific membrane antigen is also expressed in tumor-associated neovasculature of a wide variety of malignant neoplasms. With its expression in prostate secretory-acinar epithelium and the prostate and in the neovasculature associated with tumors, prostate-specific membrane antigen represents an excellent antigenic target for monoclonal antibody diagnostic and therapeutic options. As research continues, the role of monoclonal antibody imaging and therapy will become increasingly important in the management of prostate cancer.