Prostate-specific Antigen Ratio Research Articles

Prebiopsy Multiparametric Magnetic Resonance Imaging for Prostate Cancer Diagnosis in Biopsy-naive Men with Suspected Prostate Cancer Based on Elevated Prostate-specific Antigen Values: Results from a Randomized Prospective Blinded Controlled Trial

BackgroundMultiparametric magnetic resonance imaging (MP-MRI) may improve the detection of clinically significant prostate cancer (PCa). ObjectiveTo compare MP-MRI transrectal ultrasound (TRUS)-fusion targeted biopsy with routine TRUS-guided random biopsy for overall and clinically significant PCa detection among patients with suspected PCa based on prostate-specific antigen (PSA) values. Design, setting, and participantsThis institutional review board-approved, single-center, prospective, randomized controlled trial (April 2011 to December 2014) included 130 biopsy-naive patients referred for prostate biopsy based on PSA values (PSA <20 ng/ml or free-to-total PSA ratio ≤0.15 and PSA <10 ng/ml). Patients were randomized 1:1 to the MP-MRI or control group. Patients in the MP-MRI group underwent prebiopsy MP-MRI followed by 10- to 12-core TRUS-guided random biopsy and cognitive MRI/TRUS fusion targeted biopsy. The control group underwent TRUS-guided random biopsy alone. InterventionMP-MRI 3-T phased-array surface coil. Outcome measurements and statistical analysisThe primary outcome was the number of patients with biopsy-proven PCa in the MP-MRI and control groups. Secondary outcome measures included the number of positive prostate biopsies and the proportion of clinically significant PCa in the MP-MRI and control groups. Between-group analyses were performed. Results and limitationsOverall, 53 and 60 patients were evaluable in the MP-MRI and control groups, respectively. The overall PCa detection rate and the clinically significant cancer detection rate were similar between the MP-MRI and control groups, respectively (64% [34 of 53] vs 57% [34 of 60]; 7.5% difference [95% confidence interval (CI), −10 to 25], p=0.5, and 55% [29 of 53] vs 45% [27 of 60]; 9.7% difference [95% CI, −8.5 to 27], p=0.8). The PCa detection rate was higher than assumed during the planning of this single-center trial. ConclusionsMP-MRI/TRUS-fusion targeted biopsy did not improve PCa detection rate compared with TRUS-guided biopsy alone in patients with suspected PCa based on PSA values. Patient summaryIn this randomized clinical trial, additional prostate magnetic resonance imaging (MRI) before prostate biopsy appeared to offer similar diagnostic accuracy compared with routine transrectal ultrasound–guided random biopsy in the diagnosis of prostate cancer. Similar numbers of cancers were detected with and without MRI. Trial registrationClinicalTrials.gov identifier: NCT01357512.

Prostate Specific Antigen Ratio is Negatively Associated with Blood Cadmium Concentration and Smoking Status

Smoking is a risk factor for several diseases, notably cardiovascular disease and lung cancer. There is evidence that smoking is associated with an increased risk of prostate cancer, though the mechanisms by and the extent to which smoking may affect prostate cancer risk are unknown. Tobacco smoke contains myriad carcinogens, including cadmium. Cadmium is a toxic transition metal and environmental pollutant found in tobacco, and environmental exposure to cadmium has been associated with greater risk of prostate cancer. We hypothesized that blood cadmium (BCd) would be associated with PSA ratio and that this association would depend on smoking status. We examined the level of prostate specific antigen (PSA), free PSA (fPSA), and fPSA ratio, which better predicts risk of advanced prostate cancer, BCd, and smoking status of 6,007 men in the National Health and Nutrition Examination Survey (NHANES) 2003‐2010. Multiple linear regression was used to predict PSA ratio from BCd, smoking status, age, and ethnicity. Current smokers (CS) were found to have significantly (P &lt; 0.05) lower fPSA and fPSA ratio, and greater BCd compared with non‐smokers (NS) and former smokers (FS) (CS vs. NS: fPSA, 0.31 vs. 0.38 ng/mL; fPSA ratio, 29.1% vs. 31.8%; BCd, 1.30 vs. 0.27 μg/L). Based on the final regression model, BCd was associated with a lower fPSA ratio among CS compared with NS and FS. Compared with NS and FS, for CS a 10% increase in BCd corresponded to a predicted decrease in fPSA ratio of 37% for White and Black men, 54% for Hispanic men, and 217% for other men. These results suggest that smoking is associated with a lower fPSA ratio – and thus potentially greater risk of prostate cancer – and that this effect may be partly attributable to cadmium exposure.Funding: NIH #1R03CA159421‐01A1

MP86-07 ASSOCIATION OF METFORMIN USE WITH PROSTATE CANCER INCIDENCE IN A PROSPECTIVE SCREENING TRIAL (ERSPC AARAU)

INTRODUCTION AND OBJECTIVES: There is conflicting data regarding the effect of the oral antidiabetic drug metformin on prostate cancer (PCa) incidence and mortality. We aimed to assess the effect of metformin on PCa incidence and mortality in men participating in a prospective, population-based screening trial. METHODS: Data of men who underwent PSA-screening in our population-based screening trial (ERSPC Aarau) were analysed. Information on metformin exposure before biopsy was obtained by a selfadministered questionnaire. Cox regression analysis was used to examine the relationship between covariates and PCa incidence. RESULTS: Overall, 4,314 men were observed during a mean follow-up time of 7.3 ( SD2.3) years. Mean age at baseline was 65.5 years (65.5 SD 4.4). Overall, n1⁄4150 (3.5%) men used metformin [metfþ] at baseline. Of those, 80% (88 of 110) who were actively screened during follow-up visit were still on metformin after 4 years whereas 105 men had new [metfþ] exposure. Mean baseline PSAlevels were comparable between both groups ([metfþ] 1.6ng/ml 2.4 vs. [metf-] 1.8ug/l 2.2, p1⁄40.4) while f/t-ratio was slightly higher in metformin users ([metfþ] 30.7% 10.9 vs. [metf-] 27.3% 10.9, p1⁄40.01). Overall, n1⁄4372 (8.6%) PCa cases were detected. Neither cumulative PCa incidence (n1⁄411; 7.3% [metfþ] vs. n1⁄4361 8.7% [metf-]; p1⁄40.5) nor d’Amico risk groups were significantly different between both groups. On multivariate analysis, only increasing baseline PSA (HR 1.11, 95%CI 1.09-1.13; p<0.0001) achieved an independent predictor status for PCa detection. An increasing freetotal PSA ratio was an independent predictor for a decreased risk for PCa detection during follow-up (HR 0.95, 95%CI 0.94-0.96; p<0.0001). Among 150 [metfþ] and 4164 [metf-] men, 1 (0.7%) and 1 (0.02) died from PCa (OR 27.94, 95%CI 1.73-448.84; p<0.0001) whereas 26 (17.3%) and 329 (7.9%) (unadjusted OR 2.50, 95%CI 1.59-3.82; p<0.0001) died from other causes during follow-up, respectively. In a competing risk analysis, [metfþ] exposure among men who died during follow-up had no influence on PCa incidence (SHR 0.91, 95%CI 0.50-1.66; p1⁄40.77). CONCLUSIONS: No significant differences in PSA levels or PCa incidence and grade were observed between metformin users and non users. The slightly higher f/t-ratio did not result in lower PCa detection rate. However, metformin users were at significantly higher risk to die from any cause. This underlines the idea of a risk-based strategy of early PCa detection with recognizing diabetes mellitus as an important competing comorbidity.

Genetic polymorphism in sex hormone metabolism and prostate cancer risk.

We compared single-nucleotide polymorphisms for point mutations in cytochrome P450 genes, including cytochrome P450c17α (CYP17), cytochrome P450 aromatase (CYP19), steroid-5-a-reductase (SRD5A2), and prostate-specific antigen (PSA) involved in androgen and estrogen production. Between January 2008 and January 2010, 90 patients were enrolled in the study. Of these patients, 28 were diagnosed with benign prostatic hyperplasia and 32 with prostate cancer, while 30 subjects were included as a control group. CYP19 1531 C>T, SRD5A2 gene V89L, CYP17 gene -34 T/C, PSA-158 (G/A) regions were evaluated for the association between polymorphisms and benign prostatic hyperplasia and prostate cancer in study population. Age, body mass index, peak urinary flow rate (Q max), voided urine volume, post-void residual urine volume, total PSA, free PSA, free/total PSA ratio, prostate weights measured by transrectal ultrasonography, erectile dysfunction score, and international prostate symptom score were compared between groups. No statistically significant difference in CYP19 1531 C>T, SRD5A2 V89L, and CYP17 -34T/C was observed in both groups when compared to the control group. The homozygote variant of PSA- 158 (G/A) was significantly lower for prostate cancer. Age, total PSA, free PSA, free/total PSA ratio, prostate weight, and Q max were evaluated using multi-variant analysis. Only Q max was significant for the homozygote variant. The probability of being homozygous was 5.8- fold higher in subjects with Q max >14 mL/s. In the Turkish population, the homozygote variant of PSA-158 (G/A) was significantly lower for prostate cancer.

Can Prostate-Specific Antigen Kinetics before Prostate Biopsy Predict the Malignant Potential of Prostate Cancer?

PurposeTo predict the malignant potential of prostate cancer (PCa) according to prostate-specific antigen velocity (PSAV), PSA density (PSAD), free/total PSA ratio (%fPSA), and digital rectal examination (DRE).Materials and MethodsFrom January 2009 to December 2012, 548 adult male patients were diagnosed with PCa by prostate biopsy at four hospitals in Korea. We retrospectively analyzed 155 adult male patients with an initial PSA level ≤10 ng/mL and whose PSA levels had been checked more than two times at least 6 months before they had been diagnosed with PCa, with test intervals of more than 3 months. Patients with a urinary tract infection, and patients who had previously undergone cystoscopy or surgery of the prostate were excluded. We separated patients into two groups according to Gleason sum [Gleason sum ≤7 (n=134) or Gleason sum ≥8 (n=21)] and the presence of extracapsular invasion [organ confined (n=129) or extracapsular invasion (n=26)]. Differences between the groups were compared.ResultsThe group with a Gleason sum ≥8 or extracapsular invasion of PCa showed high PSAV and significantly lower %fPSA. There were no significant differences in PSAD and the presence of an abnormality on DRE between two groups.ConclusionIn PCa patients treated with other therapies besides prostatectomy, a high PSA velocity and a low %fPSA may predict high grade PCa with a Gleason sum ≥8 or the presence of extracapsular invasion.

Two-dimensional neovascular complexity is significantly higher in nontumor prostate tissue than in low-risk prostate cancer.

PurposeProstate cancer is the most frequent cancer in men in Europe. A major focus in urology is the identification of new biomarkers with improved accuracy in patients with low-risk prostate cancer. Here, we evaluated two-dimensional neovascular complexity in prostate tumor and nontumor biopsy cores by use of a computer-aided image analysis system and assessed the correlations between the results and selected clinical and pathological parameters of prostate carcinoma.Materials and MethodsA total of 280 prostate biopsy sections from a homogeneous series of 70 patients with low-risk prostate cancer (Gleason score 3+3, prostate-specific antigen [PSA]<10 ng/mL, and clinical stage T1c) who underwent systematic biopsy sampling and subsequent radical prostatectomy were analyzed. For each biopsy, 2-µm sections were treated with CD34 antibodies and were digitized by using an image analysis system that automatically estimates the surface fractal dimension.ResultsOur results showed that biopsy sections without cancer were significantly more vascularized than were tumors. No correlations were found between the vascular surface fractal dimension and patient's age, PSA and free-to-total PSA ratios, pathological stage, Gleason score, tumor volume, vascular invasion, capsular penetration, surgical margins, and biochemical recurrence.ConclusionsThe value of angiogenesis in prostate cancer is still controversial. Our findings suggest that low-risk prostate cancer tissues are less vascularized than are nontumor tissues. Further studies are necessary to understand whether angiogenesis is a hallmark of intermediate- and high-risk prostate cancer.

The Cutoff Level of Free/Total Prostate Specific Antigen (f/t PSA) Ratios in the Diagnosis of Prostate Cancer: Current Status and Future Perspectives

The Cutoff Level of Free/Total Prostate Specific Antigen (f/t PSA) Ratios in the Diagnosis of Prostate Cancer: Current Status and Future Perspectives

The Use of Free-Total Prostate Specific Antigen Ratio in Screening Prostate Cancer in Men with Specific Elevations of Prostate Specific Antigen

Aim: To evaluate the diagnostic performance of free-total PSA ratio using the criteria of total PSA > 4.0 ng/ml as the cut-off for prostate cancer diagnosis in men. Method: A total of sixty patients (mean age 58.03 ± 9.82) were recruited as test subjects from the cancer unit of National Obstetric Fistula Center (NOFIC), Abakaliki, Ebonyi State, Nigeria. All the patients had total PSA value above 4.0ng/ml. Free and total PSA estimations were done using the principle of Enzyme Linked Immunosorbent Assay (ELISA). Result: Free-total PSA ratio indicated high sensitivity (98.2% and 98.2%), specificity (87.9% and 82.9%) and positive predictive values (93.3% and 90%) for detecting undiagnosed prostate cancer at cut-offs of 0.25 and 0.19 respectively. High sensitivity (97.6%) and moderate specificity (61.7%) and positive predictive value (70.0%) were observed at cut off of 0.10. Using the free-total PSA ratio cut-off of ≤ 0.10 for prostate cancer, 70% of the test subjects were diagnosed of prostate cancer, on the other hand when a cutoff of > 0.25 was used, 6.7% of the test subjects were diagnosed of a possible benign prostatic hyperplasia. Conclusion: Free-total PSA ratio is a highly sensitive, specific and useful diagnostic tool alternative to total PSA assay for the screening of undiagnosed prostate cancer. Furthermore, it is highly predictive of the risk for developing prostate cancer at specific cutoff levels.

The Finnish prostate cancer screening trial: analyses on the screening failures.

Prostate cancer (PC) screening with prostate-specific antigen (PSA) has been shown to decrease PC mortality in the European Randomized Study of Screening for Prostate Cancer (ERSPC). However, in the Finnish trial, which is the largest component of the ERSPC, no statistically significant mortality reduction was observed. We investigated which had the largest impact on PC deaths in the screening arm: non-participation, interval cancers or PSA threshold. The screening (SA) and control (CA) arms comprised altogether 80,144 men. Men in the SA were screened at four-year intervals and referred to biopsy if the PSA concentration was ≥ 4.0 ng/ml, or 3.0-3.99 ng/ml with a free/total PSA ratio ≤ 16%. The median follow-up was 15.0 years. A counterfactual exclusion method was applied to estimate the effect of three subgroups in the SA: the non-participants, the screen-negative men with PSA ≥ 3.0 ng/ml and a subsequent PC diagnosis, and the men with interval PCs. The absolute risk of PC death was 0.76% in the SA and 0.85% in the CA; the observed hazard ratio (HR) was 0.89 (95% confidence interval (CI) 0.76-1.04). After correcting for non-attendance, the HR was 0.78 (0.64-0.96); predicted effect for a hypothetical PSA threshold of 3.0 ng/ml the HR was 0.88 (0.74-1.04) and after eliminating the effect of interval cancers the HR was 0.88 (0.74-1.04). Non-participating men in the SA had a high risk of PC death and a large impact on PC mortality. A hypothetical lower PSA threshold and elimination of interval cancers would have had a less pronounced effect on the screening impact.

Influence of metformin use on PSA values, free-to-total PSA, prostate cancer incidence and grade and overall survival in a prospective screening trial (ERSPC Aarau).

To analyze the effect of the oral antidiabetic drug metformin on PSA level, free-to-total PSA ratio (f/t-ratio), PCa incidence and grade as well as mortality in men participating in a population-based screening trial. Data from 4,314 men aged 55-70 years from a population-based PSA-screening trial (ERSPC Aarau) were analyzed. Information on metformin exposure was obtained by a self-administered questionnaire. Serum PSA threshold at ≥3 ng/ml triggered prostate biopsy. Data on PCa incidence and mortality were obtained through registry linkages. Median follow-up time was 7.6 years. Mean age at baseline was 65.5 years (±SD 4.4). In all, n = 150 (3.5 %) men used metformin [metf+]. Mean baseline PSA levels were comparable between both groups ([metf+] 1.6 ng/ml ± 2.4 vs. [metf-] 1.8ug/l ± 2.2, p = 0.4) while f/t-ratio was slightly higher in metformin users ([metf+] 30.7 % ± 10.9 vs. [metf-] 27.3 % ± 10.9, p = 0.01). Overall, n = 372 (8.6 %) PCa cases were detected. Neither cumulative PCa incidence (n = 11; 7.3 % [metf+] vs. n = 361 8.7 % [metf-]; p = 0.5) nor d`Amico risk groups were significantly different between both groups. One man in each group (metf+ 0.7 % and metf- 0.02 %) died from PCa (p < 0.0001), respectively. All-cause mortality was significantly higher among met + compared to met- (adjusted OR 2.50, 95 %CI 1.59-3.82; p = 0.0001). No significant differences in PSA levels or PCa incidence and grade were observed. The slightly higher f/t-ratio did not result in lower PCa detection rate. Metformin users were at significantly higher risk of all-cause mortality. The relatively small number of men on metformin is a main limitation of the study.

Editorial Comment to Significance of early prostate-specific antigen values after salvage radiotherapy in recurrent prostate cancer patients treated with surgery.

Given that up to 35% of patients develop biochemical recurrence (BCR) after radical prostatectomy (RP), the use of salvage radiation therapy (SRT) to prevent progression and reduce mortality is appropriate for many patients. However, unlike RP or primary radiation where definitions of prostatespecific antigen (PSA) failure are widely accepted and allow early identification of patients for secondary treatments, there is no standard definition of PSA recurrence after SRT. Identifying PSA response criteria that predict tumor progression after SRT would allow the subset of men at greatest risk to receive early aggressive next-line treatment with the intent to improve long-term outcomes. To address this specific matter, Chang et al., in the current issue of International Journal of Urology, examined whether the absolute PSA value or changes in PSA after SRT predicted clinical recurrence-free survival among 167 men who received SRT after RP. During a 53-month median follow-up period, 12% of men had a clinical recurrence (local, nodal or distant metastases), with the majority being nodal or distant. Just two factors were significantly predictive of clinical recurrence: absolute PSA level at 4 months post-SRT (<0.2 ng/mL had better outcomes), and the ratio of PSA at 4-month post-SRT to pre-SRT PSA (ratios <0.45 had better outcomes). These results are indeed encouraging and if reproduced in larger studies, post-SRT PSA cut-offs could translate into clinical practice to help practitioners caring for SRT patients. However, before these results can be utilized in clinical practice, other clinical and pathological factors that lead to a poor PSA response after SRT, such as pre-SRT PSA levels, PSA doubling time and adverse pathological features after RP, should also be investigated in larger studies with longer follow up. Specifically, PSA doubling time was not evaluated in the present study, though others have shown it predicts response to SRT. In putting these results in context, it is likely that men with an inadequate PSA response to SRT have residual disease outside the area of radiation, and are no longer candidates for further local treatment. As such, these men might be considered to harbor micrometastatic disease, and thus could benefit from early initiation of systemic therapy (i.e. androgen deprivation therapy). Although this issue can only be solved by prospective clinical trials, these men at the least are at high risk of clinical progression and require close follow up.

Predictive values for extracapsular extension in prostate cancer patients with PSA values below 10 ng/mL.

We aimed to determine predictive values of extracapsular extension (ECE) in patients who had undergone radical retropubic prostatectomy (RRP) with prostate-specific antigen (PSA) values below 10 ng/mL. We retrospectively scanned data of 167 patients with PSA values below 10 ng/mL who had undergone radical retropubic prostatectomy (RRP) between April 2004 and August 2011 in our clinic. Age, PSA, PSA ratio, PSA density, digital rectal examination (DRE) findings, biopsy total Gleason score, perineural invasion (PNI), and lymphovascular invasion (LVI) were analyzed. Parameters of the groups with or without extracapsular extension in RRP pathology specimens were compared. The mean age of patients was 66.4±12.3 years. According to histopathological analysis of the specimens of RRP of 167 patients, 45 (26.9%) had extracapsular extension (pT3-4) (Group 1); 122 (73.1%) were confined to the prostate (pT2) (Group 2). The mean PSA level was high in Group 1 (p= 0.114), PSA ratio was higher in Group 2 (p=0.09). PSA density was 0.17 in Group 1 and 0.24 in Group 2 (p=0.03). DRE positivity was 53.3% and 57.1%, respectively (p=0.71). Biopsy total Gleason score was higher in Group 1 than Group 2 with a statistically significant difference (p=0.04). A statistically significant difference was found between the rates of PNI and LVI (28.9% and 1.63%, respectively) (p=0.002). There was no statistically significant difference between both groups as for surgical margin positivity (p=0.18). In PCa patients with PSA values below 10 ng/mL, PSA density, lymphovascular invasion and biopsy Gleason total score were statistically significant in predicting extracapsular invasion. Therefore, these results must be considered in preoperative evaluation.

Early PSA level decline is an independent predictor of biochemical and clinical control for salvage postprostatectomy radiotherapy

BackgroundTo improve the early detection of responders to salvage external beam radiotherapy (RT) after radical prostatectomy (RP). MethodsBetween 2002 and 2007, in a single institution, 136 consecutive patients received salvage RT to a dose of 66Gy without androgen-deprivation therapy after RP for a rising prostate-specific antigen (PSA) level. PSA measurements were systematically performed before RT (PSART), at the fifth week of RT (PSA5), and in the follow-up at least twice a year (every 6mo). The PSA level decline during RT was expressed as PSA ratio (PSA5/PSART). Two different definitions of biochemical failure after salvage RT were considered: PSA level>0.4ng/ml and PSA>PSA nadir post-RT +0.4ng/ml. Statistical analyses included univariate and multivariate Cox regression models. ResultsThe median follow-up was 60 months. The 5-year freedom from biochemical and clinical failure rates were 57% (95% CI: 48%–66%) and 92% (95% CI: 87%–97%), respectively. The mean PSA5 was 0.61ng/ml (range: 0–7) and the mean PSA ratio was 0.67 (0–1.7). A PSA ratio<1 was a significant prognostic factor in multivariate analysis for both definitions of biochemical failure (P = 0.01 for both) and for clinical failure (P = 0.005). ConclusionsFor patients undergoing salvage RT after RP for a rising PSA level, the absence of PSA level decline during RT is predictive of biochemical and clinical failure and may be used to rapidly identify poor responders.

Next-generation prostate-specific antigen test: precursor form of prostate-specific antigen.

An urgent need exists to develop a more sophisticated screening system in order to improve diagnostic accuracy of clinically significant cancer and also to reduce the drawbacks of prostate-specific antigen (PSA) screening including overdetection and overtreatment. The most promising next-generation PSA test, which can improve the management of prostate cancer, may be proenzyme PSA (proPSA) or precursor PSA (pPSA). proPSA has pro-leader peptide sequences of seven or less amino acids and previous studies demonstrated that [-2]proPSA, which contains only a 2-amino-acid propeptide leader, could be more useful not only to distinguish between men with and without cancer, but also between tumors with aggressive features with performance exceeding other classical PSA-related indices including ratio of free PSA to total PSA (%f-PSA) and PSA density. Recently, it was demonstrated that baseline [-2]proPSA-related indices were independent factors to predict pathological reclassification at one year or several years after entering active surveillance. Furthermore, a retrospective study suggested that [-2]proPSA might be a useful predictive marker for future developing clinically manifested prostate cancer as well as aggressive tumors. ProPSA-related indices may have the potential for developing a more ideal risk classification for men at risk for prostate cancer, with a screening system maintaining the sensitivity of detecting clinically significant prostate cancer while saving cost, individualized treatment strategies, and follow-up procedures of active surveillance or active treatments. At a minimum, proPSA will be one of the most important new markers on the prostate cancer management in the near future.

Gleason underestimation is predicted by prostate biopsy core length.

To evaluate whether core length impacts biopsy accuracy and Gleason score underestimation compared to radical prostatectomy (RP) specimens. From 2010 to 2011, 8,928 cores were trans-rectal obtained from 744 consecutive patients (178 RP, 24%), 557 by an experienced performer (>250/year) and 187 (25%) by in-training urology residents. Prospectively analyzed variables were core length, age, prostate volume, free and total prostate-specific antigen (PSA), PSA density and free/total PSA ratio. Mean core length for Gleason upgrading on RP (42.7%, n = 76) was 11.61 (±2.5, median 11.40) compared to 13.52 (±3.2, median 13.70), p < 0.001 for perfect biopsy-RP Gleason agreement (57.3%, n = 102). In multivariate analysis, for each unit of core length increment in millimeter, the Gleason upgrading risk decreased 89.9%, p = 0.049 [odds ratio (OR) 0.10, 95% confidence interval (CI) 0.01-0.99]. Biopsy positivity between experienced (35.5%) and in-training performer (30.1%) was not significantly different (p = 0.20), with comparable mean patient age (65.1 vs. 64.1), prostate volume (52.3 vs. 50.7) and median PSA (5.2 vs. 5.1), respectively. Denoting wider variability in terms of core length, in-training performers obtained significantly larger cores for positive biopsies (11.33 ± 3.42 vs. 10.83 ± 3.68), p = 0.043, compared to experienced performer (11.39 ± 3.36 vs. 11.37 ± 3.64), p = 0.30. In multivariate analysis, PSA density (OR 1.14, 95% CI 1.02-1.28) and age (OR 1.04, 95% CI 1.01-1.07) were significantly associated with biopsy positivity, p = 0.021 and p = 0.011, respectively. While core length on trans-rectal biopsy independently affects Gleason upgrading on RP specimens, performer experience has minor impact on Gleason discordance or biopsy positivity due to a sharp learning curve.

Use of Free to Total Prostate-Specific Antigen Ratio to Improve Differentiation of Prostate Cancer from Benign Prostate Hyperplasia

Article History Objectives: The aim of this study is to evaluate the use of F/TPSA ratio to improve differentiation of Prostate Cancer from Benign Prostatic Hyperplasia in Sudanese patients in Khartoum state. Methods: A prospective, analytical, hospital based, Case control study. This study was carried out in Fedail Medical Hospital during the period of 2010 to 2012. This study was performed on 200 patients as study group and 100 healthy volunteer as control group. Serum levels of TPSA and FPSA were measured by Roche immunoassay e411. Results: Detection rate of PCa for serum TPSA level 4- 10 ng/ml and serum TPSA level of 10 to 20 ng/ml was (32%) and (54%), respectively. Mean F/TPSA ratio value was significantly lower in PCa patients (16 ± 9ng/ml) than in BPH group (30±7g/ml). Among patients with serum PSA level of 4 to 10 ng/ml (n = 93), mean F/TPSA ratio in BPH group (n =63) was (32 ± 5) and in PCa group (n = 30) was (14 ±5) (P <0.001). For serum PSA level of 10-20 ng/ml (n = 43), mean F/TPSA ratio in BPH group (n = 18) was (25 ±7) and in PCa group (n = 25) was (16 ± 9) (P <0 .001). Conclusion: Determination of F/TPSA ratio improves differentiation of PCa from BPH. This study recommends a cut-off value of 18% to be applied to Sudanese patients.

The combination of ovarian volume and outline has better diagnostic accuracy than prostate-specific antigen (PSA) concentrations in women with polycystic ovarian syndrome (PCOs)

ObjectivesThe aim of this study was to determine the performance of prostate specific antigen (PSA) and ultrasound parameters, such as ovarian volume and outline, in the diagnosis of polycystic ovary syndrome (PCOS). Study designThis prospective, observational, case-controlled study included 43 women with PCOS, and 40 controls. Between day 3 and 5 of the menstrual cycle, fasting serum samples were collected and transvaginal ultrasound was performed. The diagnostic performance of each parameter [total PSA (tPSA), total-to-free PSA ratio (tPSA:fPSA), ovarian volume, ovarian outline] was estimated by means of receiver operating characteristic (ROC) analysis, along with area under the curve (AUC), threshold, sensitivity, specificity as well as positive (+) and negative (-) likelihood ratios (LRs). Multivariate logistical regression models, using ovarian volume and ovarian outline, were constructed. ResultsThe tPSA and tPSA:fPSA ratio resulted in AUC of 0.74 and 0.70, respectively, with moderate specificity/sensitivity and insufficient LR+/− values. In the multivariate logistic regression model, the combination of ovarian volume and outline had a sensitivity of 97.7% and a specificity of 97.5% in the diagnosis of PCOS, with +LR and −LR values of 39.1 and 0.02, respectively. ConclusionsIn women with PCOS, tPSA and tPSA:fPSA ratio have similar diagnostic performance. The use of a multivariate logistic regression model, incorporating ovarian volume and outline, offers very good diagnostic accuracy in distinguishing women with PCOS patients from controls.

The cutoff level of free/total prostate specific antigen (f/t PSA) ratios in the diagnosis of prostate cancer: A validation study on a Turkish patient population in different age categories

We investigated an optimal cutoff level of free/total PSA ratios (f/t PSA) in predicting prostate cancer in different age groups, focusing on the avoidance of unnecessary prostate biopsies. A total of 4955 men were enrolled into the study. Serum tPSA, fPSA, and f/t PSA ratios were determined for the study population. All males who had suspicious digital rectal examination and tPSA > 4 ng/mL underwent transrectal ultrasonography-guided prostate biopsy. Receiver operating characteristic (ROC) curves for each group were generated by plotting the sensitivity versus 1-specificity for the f/t PSA ratio. The sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were obtained using various f/t PSA ratio cutoffs for different age groups. There were 657 patients with a PSA level of 4–10 ng/mL. According to sensitivity and specificity f/t% PSA cutoff points were determined to be 10%, 15%, 15%, and 10% in 50–59 years, 60–69 years, >70 years, and all ages categories, respectively, in patients with initial PSA level of 4–10 ng/mL. f/t PSA ratio had an area under the curve (AUC) value of 0.81 (95% confidence level: 0.80–0.82) for all age groups in detecting prostate cancer. f/t PSA ratio has an AUC value of 0.669 (0.632–0.705) in detecting prostate cancer among patients with a PSA level of 4–10 ng/mL. Ten percent of f/t PSA ratio had the highest specificity with PLR and 30% f/t PSA ratio had the highest sensitivity with lower NLR in the all-age categories. The current study shows that the use of f/t PSA ratio in patients with PSA levels of 4–10 ng/mL should enhance the specificity of PSA screening and decrease the number of unnecessary biopsies. The age-related changes warrant further investigation in a large, multicentric, and multinational population to improve the clinical use of f/t PSA cutoffs.

Prostatic and testicular parameters in lepromatous patients

To evaluate PSA (Prostate-specific antigen) parameters in patients with lepromatous leprosy (LL). In a retrospective study, 23 male patients with LL were evaluated. PSA parameters (serum total PSA (tPSA), free PSA (fPSA), free-to-total PSA ratio (f/tPSA), PSA Density (PSAD)) were assessed. PSA parameters were compared with a control group. The mean tPSA, fPSA, f/tPSA, prostate volume, and PSAD values of the patient group with LL were 1.87 +/- 0.81 ng/ml, 0.67 +/- 0.29 ng/ml, 0.36 +/- 0.11, 41.08 +/- 23.65 ml and 0.055 +/- 0.037, respectively. The mean tPSA, fPSA, f/tPSA, prostate volume, and PSAD values of the control group were 2.71 +/- 0.91 ng/ml, 0.80 +/- 0.34 ng/ml, 0.30 +/- 0.08, 65.0 +/- 28.73 ml and 0.049 +/- 0.028, respectively. The mean tPSA and prostate volume values were found to be significantly lower in the patient group with LL (p = 0.002 and 0.004, respectively). No significant difference was found between two groups in terms of mean fPSA and PSAD values (p = 0.18 and 0.5, respectively). The mean f/tPSA value was found to be significantly higher in the patient group with LL (p = 0.02). Testes in 16 (69%) patients with LL were bilaterally atrophic. Serum tPSA values and prostate volumes in the patients with LL were significantly reduced and f/tPSA values were significantly increased. Testicular atrophy in the lepromatous cases might be due to leprosy-related orchitis and associated with a reduction in prostatic volume.

Role of PSA-Related Variables in Improving Positive Ratio of Biopsy of Prostate Cancer within Serum PSA Gray Zone

The aim of this study was to assess the validity of predictors of prostate biopsy outcome in order to improve their positive predictive value (PPV). The related variables of PSA such as free/total PSA ratio (F/T), complexed/total PSA ratio (C/T), density of PSA (PSAD) were studied to improve early diagnosis for early PCa within serum PSA gray zone. Samples of venous blood were collected early in the morning from 459 patients, aged 50 to 88 years (average 70.5 years old), whose serum T-PSA was between 4 to 10 ng/mL (153 cases of Pca, 306 cases of BPH). Serum T-PSA, F-PSA and C-PSA were determined by ELISA method; prostate volume was measured by transrectal ultrasound, then prostate biopsy was taken for all patients. Out of f 459 patients, 153 cases of Pca and 306 of BPH were diagnosed by prostate biopsy, whose mean values of T-PSA were 7.2 ± 1.25 ng/mL and 6.8 ± 0.96 ng/mL, respectively (P<0.05), of F/T were 0.117 ± 0.018 and 0.196 ± 0.021 (P<0.01), and of C/T they were 0.890 ± 0.023 and 0.754 ± 0.015 (P<0.01), of PSAD were 0.197 ± 0.023 and 0.106 ± 0.019 (P<0.01). The threshold of F/T>0.16 diagnosed 91 cases of cancer (59.5%), of C/T>0.84 88 cases (57.5%), of PSAD>0.15 94 cases (61.4%), and especially, of F/T>0.16 combined PSAD>0.15 80 cases whose sensitivity, specificity, accuracy, positive predictive values were 52.3%, 76.1%, 68.2%, 52.3%, respectively (P<0.05). There are some defects only in taking T-PSA as a biomarker for the diagnosis of PCa within serum PSA gray zone, and the threshold of F/T>0.16 combined PSAD>0.15 may be a new and significant indicator to provide a better basis for the diagnosis of early PCa.