Higher Prostate-specific Antigen Levels Research Articles

Biomarkers for determination prostate cancer: implication for diagnosis and prognosis.

Prostate cancer (PCa) belongs to most common cancers and it is the second leading cause of cancer death in men. Agenetic predisposition or acquired genetic and epigenetic changes with effect of other factors, such as advanced age, race and environmental factors contribute to PCa development. PCa is avery heterogeneous disease that is characterized by different clinical behavior, from indolent, slow-growing tumors to aggressive, fast-growing tumors with lethal progression. Early diagnostics and identification of PCa type are crucial prerequisites for efficient treatment of patients. Recently, the diagnostics of early stages of PCa is based mostly on evaluation of prostate-specific antigen (PSA) in serum of patients. Men with high levels of PSA undergo biopsy in order to determine histopatological grading of PCa - Gleason scoring which classifies tumors from most to least differentiated as well as staging - determination of the status of their primary tumors, with or without lymph node involvement. The results from this screening diagnosis lead into conventional treatment, including radical prostatectomy and brachytherapy. In case of advanced PCa, conventional treatment continues with androgen deprivation therapy. However, in many cases the cancer recurs. Therefore, the clinicians and researchers are forced to find more precise and sensitive biomarker suitable for PCa diagnostics as well as prognostics and therapy. This paper provides review of current most promising molecular and immunohistochemical biomarkers in PCa diagnosis, prognosis and clinical behavior.

Prostate-specific antigen-based population screening for prostate cancer: current status in Japan and future perspective in Asia.

In Western countries, clinical trials on prostate cancer screening demonstrated a limited benefit for patient survival. In the Asia-Pacific region, including Japan, the rate of prostate-specific antigen (PSA) testing remains very low compared with Western countries, and the benefits of population-based screening remain unclear. This review describes the current status of population screening and diagnosis for prostate cancer in Japan and discusses the efficacy of population screening for the Asian population. Since the 1990s, screening systems have been administered by each municipal government in Japan, and decreases in the prostate cancer mortality rate are expected in some regions where the exposure rate to PSA screening has increased markedly. A population-based screening cohort revealed that the proportion of metastatic disease in cancer detected by screening gradually decreased according to the increased exposure rate, and a decreasing trend in the proportion of cancer with high serum PSA levels after population screening was started. The prognosis of the prostate cancer detected by population screening was demonstrated to be more favorable than those diagnosed outside of the population screening. Recent results in screening cohorts demonstrated the efficacy of PSA. These recent evidences regarding population-based screening in Japan may contribute to establishing the optimal prostate cancer screening system in Asian individuals.

Preoperative parameters to predict incidental (T1a and T1b) prostate cancer.

Prostate cancer has been found incidentally in transurethral resection of the prostate (TURP) specimens without prior diagnosis in 5% to 13% of the patients. We evaluated whether incidental prostate cancer (stages T1a and T1b) could be predicted preoperatively. TURP was performed in 307 patients between 2006 and 2011. Patient age, prostate-specific antigen (PSA) level, total prostate volume, transitional zone volume, PSA density, history of needle biopsy, and pathological diagnosis on TURP specimen were assessed. We analyzed the association between these parameters and prostate cancer detection. Incidental prostate cancer was found in 31 patients (10.1%), and 13 cases (4.2%) had cancer with T1b and/or Gleason ≥7. Multivariate analysis demonstrated that age ≥75 years (odds ratio [OR] 2.58, p = 0.022), prostate volume ≤50 cc (OR 4.11, p < 0.001), and the absence of preoperative needle biopsy despite PSA ≥4 ng/mL (OR 2.65, p = 0.046) were independent risk factors. In patients who had 2 or 3 of these risk factors, incidental prostate cancer and cancer with T1b and/or Gleason ≥7 were observed in 25% to 50% and 16% to 25% cases, respectively. Older patient age, small prostate volume, and the absence of previous needle biopsy (despite a high PSA level) might be independent risk factors for detecting incidental prostate cancer, although external validation is warranted to confirm our results.

Impact of pelvic biometric measurements, visceral and subcutaneous adipose tissue areas on trifecta outcome and surgical margin status after open radical retropubic prostatectomy

Objective. There is no sufficient evidence to demonstrate whether more challenging pelvic anatomy affects the functional and oncological outcomes of radical retropubic prostatectomy (RP). The aim of this study was to investigate the impact of pelvic biometric measurements, visceral and subcutaneous adipose tissue areas on trifecta outcome (cancer control, continence and potency) and surgical margin status after open RP. Materials and methods. A retrospective study was performed on 270 patients who were diagnosed with clinically localized prostate cancer between 2005 and 2011 and underwent computed tomography imaging before RP. Pelvic bony and soft-tissue measurements, and visceral and subcutaneous adipose tissue area calculations were performed. Patients were evaluated for trifecta outcome and surgical margin status on univariate and multivariate analyses. Subgroup analysis was performed for prostate volume, body mass index (BMI) and D’Amico risk classification. Results. Univariate analysis revealed that patients with trifecta were younger, and had lower prostate-specific antigen (PSA) levels, wider symphysis angle, and narrower prostate width and soft-tissue width (p < 0.05). Patients with positive surgical margins were older, and had higher PSA levels, lower prostate volume and narrower prostate width (p < 0.05). Visceral adipose tissue area was lower in patients with trifecta when BMI was below 25 kg/cm² (p < 0.05). In multivariate analysis, PSA level and symphysis angle were statistically significant for trifecta while PSA level was the only statistically significant variable for positive surgical margins (p < 0.05). Interfemoral index was significant in the low-risk group of D’Amico classification for trifecta outcome. Conclusion. Pelvic biometric measurements and adipose tissue area calculations may help in preoperative planning and the management of RP.

A PSA-guided approach for a better diagnosis of prostatic adenocarcinoma based on MALDI profiling and peptide identification

BackgroundProstate cancer (PCa) is the second cause of mortality in men worldwide. The prostate-specific antigen (PSA) test is routinely adopted in diagnosis; nevertheless more reliable biomarkers are continuously under investigation by monitoring the release of molecules into the bloodstream. The serum protein profiles appear to provide cancer-specific fingerprints that help to discriminate patients (especially with low PSA level) from controls, improving the performance of existing clinical tests. MethodsSamples from healthy controls and PCa patients with low (≤4ng/mL) and high PSA (>4ng/mL) levels were analyzed by MALDI profiling, and by a multi fractionation approach coupled to ESI-MS for peaks identification. ResultsMALDI profiling achieved to detect 10 and 14 changed peaks (p-value <0.05), respectively, in PCa patients with low and high PSA versus controls. In particular, a peak identified as C3f fragment, resulted overexpressed in low PSA PCa patients. ConclusionsPSA test, coupled to MALDI profiling, is able to detect changes, specifically related to PCa, in low molecular weight protein range. Furthermore, for the first time in prostate cancer research, the identification and quantification of the small peptide C3f appears to be relevant for the detection of false negatives, providing an additive diagnostic power to PSA (p<0.01) and suggesting its use in clinical tests.

Abstract 676: Inhibition of FOXM1 targets both high and low PSA expressing prostate cancer cells resistant to Enzalutamide

Abstract Advances in castrate-resistant prostate cancer (CRPC) treatment using androgen receptor (AR) targeted therapies have produced striking survival advantages in clinical studies; recently approved AR inhibitor Enzalutamide (ENZ) prolongs survival of patients with incurable CRPC. Although enthusiasm for this approach remains high, prostate tumor heterogeneity and the inevitable development of resistance as seen currently in the clinic and in our pre-clinical model, dictates a critical need for a better understanding of the mechanisms of resistance. We have recently developed a unique model of LNCaP-CRPC-ENZ-resistance and found that cell lines derived from serially passaged ENZ resistant tumors express different levels of prostate specific antigen (PSA). Especially low PSA expressing cells are believed to be highly enriched with cancer stem cells with high self-renewal and these cells have been considered difficult to target with current therapies. To define molecular mechanisms contributing to treatment resistance in an unbiased manner, we performed gene profiling on LNCaP, CRPC and ENZ resistant cell lines expressing low and high levels of PSA. Using systems biological approaches, we found that several genes and pathways involved in stem cell maintenance were altered in Enzalutamide resistant cells. Interestingly, forkhead box M1 (FOXM1) was one of the key pathways potentially maintaining cancer stem cells and driving dedifferentiation during ENZ resistance. FOXM1 is a transcription factor that confers treatment resistance and is required for maintenance of pluripotency in stem cells and PCa CSC-like spheroid formation as well as induction of epithelial-to-mesenchymal transition and invasion. Interestingly, FOXM1 and its downstream targets were upregulated in both PSA high and low expressing ENZ resistant cells compared to CRPC cells and correlated with poor survival and Gleason score in CRPC. In addition, mining public data, we found that FOXM1 is highly expressed in prostate cancer cells with low PSA expression, indicating that also low PSA expressing prostate cancer stem cells could be targeted by inhibiting FOXM1. Using systems biological approaches, we further found out that the antibiotic ionophore and oxidative stress inducer Monensin, reduces FOXM1 pathway activity in ENZ resistant cells. The validation results indicated that Monensin reduced cell viability, FOXM1 transcriptional activity as well as FOXM1 protein, gene and its target gene expressions in both PSA high and low expressing ENZ resistant prostate cancer cells. Taken together, the results suggest that inhibition of FOXM1 by Monensin is a potent novel mean to target ENZ resistant cells including low PSA expressing prostate cancer stem cell-like cells. Citation Format: Kirsi Ketola, Jennifer Bishop, Ka Mun Nip, Soojin Kim, Fazli Ladan, Martin Gleave, Amina Zoubeidi. Inhibition of FOXM1 targets both high and low PSA expressing prostate cancer cells resistant to Enzalutamide. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 676. doi:10.1158/1538-7445.AM2014-676

Diagnostic value of biparametric magnetic resonance imaging (MRI) as an adjunct to prostate-specific antigen (PSA)-based detection of prostate cancer in men without prior biopsies.

To determine the diagnostic yield of analysing biparametric (T2- and diffusion-weighted) magnetic resonance imaging (B-MRI) for prostate cancer detection compared with standard digital rectal examination (DRE) and prostate-specific antigen (PSA)-based screening. Review of patients who were enrolled in a trial to undergo multiparametric-prostate (MP)-MRI and MR/ultrasound fusion-guided prostate biopsy at our institution identified 143 men who underwent MP-MRI in addition to standard DRE and PSA-based prostate cancer screening before any prostate biopsy. Patient demographics, DRE staging, PSA level, PSA density (PSAD), and B-MRI findings were assessed for association with prostate cancer detection on biopsy. Men with detected prostate cancer tended to be older, with a higher PSA level, higher PSAD, and more screen-positive lesions (SPL) on B-MRI. B-MRI performed well for the detection of prostate cancer with an area under the curve (AUC) of 0.80 (compared with 0.66 and 0.74 for PSA level and PSAD, respectively). We derived combined PSA and MRI-based formulas for detection of prostate cancer with optimised thresholds. (i) for PSA and B-MRI: PSA level + 6 x (the number of SPL) > 14 and (ii) for PSAD and B-MRI: 14 × (PSAD) + (the number of SPL) >4.25. AUC for equations 1 and 2 were 0.83 and 0.87 and overall accuracy of prostate cancer detection was 79% in both models. The number of lesions positive on B-MRI outperforms PSA alone in detection of prostate cancer. Furthermore, this imaging criteria coupled as an adjunct with PSA level and PSAD, provides even more accuracy in detecting clinically significant prostate cancer.

Expression of kallikrein-related peptidase 7 is decreased in prostate cancer

Recent evidence suggests that the human kallikrein 7 (KLK7) is differentially regulated in a variety of tumors. The aim of this study was to determine the expression of kallikrein-related peptidase 7 and KLK7 in our large collection of prostate samples. Between August 2000 and December 2012, 116 patients with histologically confirmed prostate cancer (PCa) and 92 with benign prostate hyperplasia (BPH) were recruited into the study. Using immunohistochemistry, quantitative reverse transcription polymerase chain reaction (RT-PCR) and western blot, kallikrein-related peptidase 7 expression in BPH and PCa tissues was determined at the mRNA and protein levels. The relationships between kallikrein-related peptidase 7 mRNA expression and clinicopathological features were analyzed. A total of 64 of 92 (69.57%) benign cases showed positive staining for KLK7 and 23 of 116 (19.83%) malignant cases showed positive, the difference of KLK7 expression between PCa and BPH was statistically significant (P < 0.001). The expression level of kallikrein-related peptidase 7 mRNA was significantly decreased in PCa tissues compared with that in BPH tissues and normal prostate tissue. Kallikrein-related peptidase 7 mRNA exhibited different expression patterns in terms of localization depending on pathological category of PCa. Similarly, our western immunoblot analyses demonstrated that the protein expression levels of KLK7 was lower in PCa than in BPH tissues and normal prostate tissue. Kallikrein-related peptidase 7 and KLK7 expression are down-regulated in PCa and lower expression of kallikrein-related peptidase 7 closely correlates with higher Gleason score and higher prostate-specific antigen level.

Toward Better Use of Bone Scans Among Men With Early-stage Prostate Cancer

To evaluate the performance of published guidelines compared with that of current practice for radiographic staging of men with newly diagnosed prostate cancer. Using data from the Michigan Urological Surgery Improvement Collaborative clinical registry, we identified 1509 men diagnosed with prostate cancer from March 2012 through June 2013. Clinical data included age, prostate-specific antigen (PSA) level, Gleason score (GS), clinical trial stage, number of biopsy cores, and bone scan (BS) results. We then fit a multivariate logistic regression model to examine the association between clinical variables and the occurrence of bone metastases. Because some patients did not undergo BS, we used established methods to correct for verification bias and estimate the diagnostic accuracy of published guidelines. Among 416 men who received a BS, 48 (11.5%) had evidence of bone metastases. Patients with bone metastases were older, with higher PSA levels and GS (all P <.05). In multivariate analyses, PSA (P <.001) and GS (P = .004) were the only independent predictors of positive BS. Guidelines from the American Urological Association and the National Comprehensive Cancer Network demonstrated similar performance in detecting bone metastases in our population, with fewer negative study results than those of the European Association of Urology guideline. Applying the American Urological Association recommendations (ie, image when PSA level >20 ng/mL or GS ≥ 8) to current clinical practice, we estimate that <1% of positive study results would be missed, whereas the number of negative study results would be reduced by 38%. Based on current practice patterns, more uniform application of existing guidelines would ensure that BS is performed for almost all men with bone metastases, while avoiding many negative imaging studies.

PSA, PSA derivatives, proPSA and prostate health index in the diagnosis of prostate cancer

Currently, prostate- specific antigen (PSA) is the most common oncological marker used for prostate cancer screening. However, high levels of PSA in benign prostatic hyperplasia and prostatitis decrease the specificity of PSA as a cancer marker. To increase the specificity of PSA, PSA derivatives and PSA kinetics have been used. However, these new techniques were not able to increase the diagnostic specificity for prostate cancer. Therefore, the search for new molecules and derivatives of PSA continues. With the aim of increasing the specificity of prostate cancer diagnosis, proPSA and the Prostate Health Index have been introduced. In this review, the roles of PSA, PSA derivatives, proPSA and the Prostate Health Index in Prostate Cancer diagnosis are examined.

The PXR rs7643645 polymorphism is associated with the risk of higher prostate-specific antigen levels in prostate cancer patients.

Levels of enzymes that determine testosterone catabolism such as CYP3A4 have been associated with prostate cancer (PCa) risk. Although some studies have related CYP3A4*1B allele, a gene polymorphism that modifies CYP3A4 expression level, with PCa risk, others have failed, suggesting that additional genetic variants may be involved. Expression of CYP3A4 is largely due to the activation of Pregnane X Receptor (PXR). Particularly, rs2472677 and rs7643645 PXR polymorphisms modify CYP3A4 expression levels. To evaluate whether PXR-HNF3β/T (rs2472677), PXR-HNF4/G (rs7643645), and CYP3A4*1B (rs2740574) polymorphisms are associated with PCa a case control-study was performed. The multiple testing analysis showed that the PXR-HNF4/G polymorphism was associated with higher levels of prostate-specific antigen (PSA) in patients with PCa (OR = 3.99, p = 0.03). This association was stronger in patients diagnosed at the age of 65 years or older (OR = 10.8, p = 0.006). Although the CYP3A4*1B/*1B genotype was overrepresented in PCa patients, no differences were observed in the frequency of this and PXR-HNF3β/T alleles between controls and cases. Moreover, no significant association was found between these polymorphisms and PSA, Gleason grade, or tumor lymph node metastasis.

Outcomes and predictive factors of prostate cancer patients with extremely high prostate-specific antigen level.

Prostate-specific antigen (PSA) is a useful biomarker of prostate cancer (PCa). High-risk localized PCa is defined using T stage, Gleason score (GS), and PSA. However, PSA level defining high-risk PCa is at most 20 ng/mL. In PCa patients with high PSA, it is unclear whether PSA itself can be a prognostic factor. Of 642 patients who were diagnosed as PCa, 90 patients with PSA > 100 ng/mL were retrospectively analyzed. Patients were divided into three groups according to PSA level: very high (>1,000 ng/mL), moderately high (200-1,000 ng/mL), and slightly high (100-200 ng/mL). There were no significant differences in overall survival or PCa-specific survival (PCaSS) among the three groups. Regardless of PSA level, high M stage and GS significantly reduced PCaSS. When the risk classification was made using M stage and GS (high risk = M1 and GS ≥ 9, low risk = M0 and GS < 9, and intermediate risk = others), PCaSS was significantly different among high-, intermediate-, and low-risk groups with 5-year survival rates of 58.2, 80.6, and 100 %, respectively. Although there were no differences in treatment performed during the castration-resistant stage, patients undergoing alternative anti-androgen and zoledronic acid treatment had better PCaSS after being castration-resistant. As PSA could not be a prognostic factor in PCa patients with high PSA > 100 ng/mL, the novel risk classification using M stage and GS may help clinicians to predict PCaSS and to plan follow-up schedules after diagnosis.

Association between obesity, prostate-specific antigen level and prostate-specific antigen density in men with a negative prostate biopsy.

To determine the association between body mass index (BMI), serum prostate-specific antigen (PSA) level and PSA density (PSAD) in patients with an elevated serum PSA level but a negative prostate biopsy. This retrospective study enrolled men with a negative prostate biopsy but a serum PSA level of 3.0-10 ng/ml. All men underwent anthropometric measurements, serum PSA determination and transrectal ultrasound examination. BMI was grouped according to the Asia-Pacific obesity criteria: nonobese (<25 kg/m(2)) versus obese (≥ 25 kg/m(2)). Partial correlation and linear regression models between PSA, PSAD and BMI were conducted after adjusting for age. A total of 907 men were enrolled in this study. On multivariate analyses, PSA showed no significant correlation with age or BMI, whereas PSAD had a negative correlation with age and BMI. Similar results were obtained when patients were categorized as having low (3.0 < PSA ≤ 6.5 ng/ml) or high PSA (6.5 < PSA ≤ 10.0 ng/ml) levels. PSAD, but not PSA, demonstrated a significant negative correlation with BMI. This indicates that a new strategy including PSAD rather than simple PSA levels should be adopted in the study of obesity-adjusted PSA cut-offs.

Clinical presentation of prostate cancer in black South Africans.

BackgroundCompared with White Americans, Black American men are at a significant increased risk of presenting with prostate cancer (PCa) and associated mortality, suggesting a link to African-ancestry. However, PCa status within Africa is largely unknown. We address the clinical presentation of PCa within Black South African men.MethodsOver 1,000 participants with or without PCa have enrolled in the Southern African Prostate Cancer Study (SAPCS). Using genome-wide profiling we establish a unique within Africa population substructure. Adjusting for age, clinical variables were assessed, compared against Black Americans and between rural and urban localities while addressing potential socio-demographic confounders.ResultsWe report a significant difference in the distribution of prostate specific antigen (PSA) levels skewed towards higher PSA levels in the PCa cases (83.0% present with a PSA ≥ 20 µg/L; median PSA = 98.8 µg/L) relative to men with no detectable PCa (18.5% present with a PSA ≥ 20 µg/L; median PSA = 9.1 µg/L). Compared with Black Americans, Black South Africans presented with significantly more aggressive disease defined by Gleason score >7 (17% and 36%, respectively) and PSA ≥ 20 µg/L (17.2% and 83.2%, respectively). We report exasperated disease aggression defined by Gleason score >7 (P = 0.0042) and poorly differentiated tumor grade (P < 0.0001) within rural versus urban localities.ConclusionBlack South African men present with higher PSA levels and histopathological tumor grade compared with Black Americans, which is further escalated in men from rural localities. Our data suggests that lack of PSA testing may be contributing to an aggressive PCa disease phenotype within South African men.

English

Prostate develops from a series of endodermal buds from the lining of primitive urethra and the adjacent portion of urogenital sinus during the first 3 months of intra-uterine life. A prostate needle biopsy is a surgical procedure in which a small sample of tissue is removed from the prostate gland and examined under the microscope by a pathologist. In all investigated individuals, the level of prostate-specific antigen (PSA) was determined in identical way. PSA was estimated in venous blood by electro-chemiluminescence method. Histopathological analysis of obtained material was done on standard hematoxylin-eosin (H&amp;E) preparations. Out of 60 patients studied, most of the patients 30 (50%) were diagnosed with benign prostatic hyperplasia (BHP). Higher levels of PSA (&gt;20) was found in 57.1% of patients of BHP with chronic prostatitis table 11. Out of the total number of adenocarcinoma patients, 77.8% of the patients were having preoperative PSA levels greater than 20. In our study, the positive predictive value for increasing PSA levels was 8.3% for PSA &lt;4 ng/ml, 16.6% for PSA &gt;4 ng/ml, 24.2% for PSA &gt;10 ng/ml and 83.3% for PSA &gt;100 ng/ml. Key words: Prostate, lesions, histopathology, needle biopsies, serum prostate-specific antigen (PSA).

MP67-08 IDENTIFICATION OF PATIENTS WHO CAN AVOID REPEAT BIOPSY USING MULTIPARAMETRIC MAGNETIC RESONANCE IMAGING

INTRODUCTION AND OBJECTIVES: The aim of our study is to determine if multiparametric magnetic resonance imaging (MRI) and/or clinical variables can discriminate between significant cancer and others (indolent or no cancers) before repeat biopsy and to identify men who can avoid repeat biopsy with low risk of missing significant cancer. METHODS: Between 2007 and 2010, 137 consecutive men who underwent repeat biopsy because of elevated or continuous high prostate-specific antigen (PSA) level after initial biopsy (n 1⁄4 88), atypical gland or prostatic intraductal neoplasia at previous biopsy (n 1⁄4 39), positive digital rectal findings (n 1⁄4 1), or patient desire (n 1⁄4 9) were prospectively evaluated. All men underwent 1.5T MRI, including T2-weighted, diffusion-weighted, and/or dynamic contrastenhanced imaging in the prebiopsy setting. Repeat biopsy protocol was 14to 28-core biopsy, including at least 4-core anterior samplings under transrectal ultrasound. Pathological specimens were evaluated according to the 2005 modified Gleason grading. Biopsy results were categorized into biopsy no cancer (BNC), biopsy indolent cancer (BIC), and biopsy significant cancer (BSC). We defined BIC as biopsy GS 3+4, clinical stage T1-T2a based on digital rectal findings (DRE), percent positive core 20%, and maximum cancer length < 5 mm. Cancer other than BIC was defined as BSC. Frequency of biopsy results according to MRI was evaluated. We also assessed clinical variables as predictors for BSC using logistic regression analysis in men with negative MRI. Clinical variables included age, PSA, free PSA, PSA at initial biopsy, rate of increase in PSA, DRE, prostate volume, number of days since initial biopsy, and pathology at previous biopsy. RESULTS: Median age and PSA were 66 years (range: 44e80) and 8.7 ng/ml (range: 1.1e58.6), respectively. The negative and positive MRI group included 84 and 53 men, respectively. The frequency of BNC/BIC/BSC was 76/19/5% in men with negative MRI and 36/19/45% in men with positive MRI. In men with negative MRI, multivariate analysis revealed that DRE was the only significant predictor of BSC. The frequency of BSC in men with negative MRI was 25% (2/8) in abnormal DRE and 3% (2/76) in normal DRE. CONCLUSIONS: Our results suggest that in repeat prostate biopsy setting, men with prebiopsy-negative MRI and normal DRE can avoid biopsy with a very low risk of missing significant cancer.

MP53-08 MAGNETIC RESONANCE IMAGING/ULTRASOUND FUSION-GUIDED BIOPSY FOR RE-TARGETING OF ATYPICAL SMALL ACINAR PROLIFERATION

INTRODUCTION AND OBJECTIVES: To overcome the wellknown prostate-specific antigen limits, several new biomarkers have been proposed. Since its introduction in clinical practice, the urinary prostate cancer gene 3 (PCA3) assay has shown promising results for prostate cancer (PC) detection. Furthermore, multiparametric magnetic resonance imaging (mMRI) has the ability to better describe several aspects of PC. METHODS: A prospective study of 171 patients with negative prostate biopsy findings and a persistent high prostate-specific antigen level was conducted to assess the role of mMRI and PCA3 in identifying PC. All patients underwent the PCA3 test and mMRI before a second transrectal ultrasoundguided prostate biopsy. The accuracy and reliability of PCA3 (3 different cutoff points) and mMRI were evaluated. Four multivariate logistic regression models were analyzed, in terms of discrimination and the cost benefit, to assess the clinical role of PCA3 and mMRI in predicting the biopsy outcome. A decision curve analysis was also plotted. RESULTS: Repeated transrectal ultrasound-guided biopsy identified 68 new cases (41.7%) of PC. The sensitivity and specificity of the PCA3 test and mMRI was 68% and 49% and 74% and 90%, respectively. Evaluating the regression models, the best discrimination (area under the curve 0.808) was obtained using the full model (base clinical model plus mMRI and PCA3). The decision curve analysis, to evaluate the cost/benefit ratio, showed good performance in predicting PC with the model that included mMRI and PCA3. CONCLUSIONS: mMRI increased the accuracy and sensitivity of the PCA3 test, and the use of the full model significantly improved the cost/benefit ratio, avoiding unnecessary biopsies. Source of Funding: none

MP53-07 PROSTATE CANCER ANTIGEN 3 (PCA3) AND MULTIPARAMETRIC MAGNETIC RESONANCE (MMRI) IN ASSOCIATION REDUCES UNNECESSARY BIOPSIES: DIGNOSTIC VALUE AND DECISION CURVE ANALYSIS

INTRODUCTION AND OBJECTIVES: To overcome the wellknown prostate-specific antigen limits, several new biomarkers have been proposed. Since its introduction in clinical practice, the urinary prostate cancer gene 3 (PCA3) assay has shown promising results for prostate cancer (PC) detection. Furthermore, multiparametric magnetic resonance imaging (mMRI) has the ability to better describe several aspects of PC. METHODS: A prospective study of 171 patients with negative prostate biopsy findings and a persistent high prostate-specific antigen level was conducted to assess the role of mMRI and PCA3 in identifying PC. All patients underwent the PCA3 test and mMRI before a second transrectal ultrasoundguided prostate biopsy. The accuracy and reliability of PCA3 (3 different cutoff points) and mMRI were evaluated. Four multivariate logistic regression models were analyzed, in terms of discrimination and the cost benefit, to assess the clinical role of PCA3 and mMRI in predicting the biopsy outcome. A decision curve analysis was also plotted. RESULTS: Repeated transrectal ultrasound-guided biopsy identified 68 new cases (41.7%) of PC. The sensitivity and specificity of the PCA3 test and mMRI was 68% and 49% and 74% and 90%, respectively. Evaluating the regression models, the best discrimination (area under the curve 0.808) was obtained using the full model (base clinical model plus mMRI and PCA3). The decision curve analysis, to evaluate the cost/benefit ratio, showed good performance in predicting PC with the model that included mMRI and PCA3. CONCLUSIONS: mMRI increased the accuracy and sensitivity of the PCA3 test, and the use of the full model significantly improved the cost/benefit ratio, avoiding unnecessary biopsies. Source of Funding: none

Looking to possible predictive factors of primary resistance to abiraterone acetate (AA) and enzalutamide (ENZ) in pretreated patients (pts) with castration-resistant prostate cancer (CRPC).

248 Background: Abiraterone acetate (AA) and enzalutamide (ENZ) are new generation hormonal agents (NHA) which demonstrated a survival gain in patients (pts) with castration-resistant prostate cancer (CRPC) pre-treated with docetaxel. Although all patients eventually became resistant to these NHAs, some of them show primary resistance, defined as an early progression within the first 3 months, which leads to an early treatment interruption. In the present analysis we have tried to identify which factor, if any, may predict primary resistance to AA and ENZ. Methods: We evaluated a consecutive series of 57 pts, treated in our hospital in two successive named patient programs conducted in our hospital to allow pre-treated CRPC patients to receive NHAs before their approval in Italy: 26 received AA (1,000 mg po + prednisone 10 mg po daily) and 31 ENZ (160 mg po daily). For each pt we have recorded the pre- and post-NHA clinical history, the treatment details and outcomes. We have also assessed the ability of a series of 24 selected clinical factors to predict NHAs resistance, through a logistic regression analysis. Continuous variables were categorized by quartiles and chosen for the initial model after a univariate chi-square analysis. Results: Among the 24 factors, the presence of pain at baseline, high baseline lactate dehydrogenase levels and prostate-specific antigen (PSA) levels after one month of treatment were predictive of primary NHA resistance at the univariate analysis. However, only PSA levels were confirmed at the multivariate analysis [exp(beta) 0.115; p = 0.007], as patients failing to achieve a 50% or more reduction in baseline PSA levels, were more likely to show primary NHA resistance (48% vs. 15%). Conclusions: Our results suggest that PSA trend may represent a simple and rapid method of identifying patients with primary resistance to NHAs, so patients failing to achieve a 50% or more reduction within the first month of treatment should undergo intensive investigations, to verify whether they have primary resistance to NHAs. These data should be confirmed in a larger patient population.

Prostate Cancer Contribution to Elevated PSA Levels : A Screening Study

Objective: To investigate the causes of elevated prostate specific antigen (PSA) levels in patients with lower urinary tract symptoms (LUTS) through transrectal ultrasound guided biopsy (TRUS biopsy), regardless of prostate volume. Methods: Retrospective study was conducted between January 2008 and December 2009 to find the cause of elevated PSA levels in sixty six (N=66) patients from the outpatient department in Guryyte General Hospital, Aljouf. Age of the patients was between 52 and 90 years and PSA level ranged between 5 ng/ml and 26 ng/ml. All patients were presented with some degree of lower urinary tract symptoms (LUTS) and high PSA levels for age. They underwent TRUS biopsies performed by a Radiologist and Urologist Results: Out of the total sixty six patients, twenty two (33%) of them with a PSA range between 5.1ng/ml and 26 ng/ml were found to have Benign Prostatic Hyperplasia (BPH) and Prostatitis. Eighteen patients (29.5%) with a PSA level between 9.3 ng/ml and 25.6 ng/ml were diagnosed as adenocarcinoma of the prostate. Sixteen patients with PSA between 12ng/ ml and 26 ng/ml were diagnosed as BPH. Ten patients with PSA between 9.3ng/ml and 16 ng/ml were found to have Prostatitis (15.15%). Conclusion: Benign prostate hyperplasia and chronic prostatitis are the two major causes of elevated serum PSA in our cohort followed by prostate cancer. With regards to the PSA level in chronic prostatitis and in prostate cancer, no significant difference was noted. The conclusion reached is that TRUS biopsy is mandatory to determine the exact cause of an elevated PSA level.