Sensitivity For Prostate Cancer Detection Research Articles

Contemporary Update on Clinical and Experimental Prostate Cancer Biomarkers: A Multi-Omics-Focused Approach to Detection and Risk Stratification.

Prostate cancer remains a significant health challenge, being the most prevalent non-cutaneous cancer in men worldwide. This review discusses the critical advancements in biomarker discovery using single-omics and multi-omics approaches. Multi-omics, integrating genomic, transcriptomic, proteomic, metabolomic, and epigenomic data, offers a comprehensive understanding of the molecular heterogeneity of prostate cancer, leading to the identification of novel biomarkers and therapeutic targets. This holistic approach not only enhances the specificity and sensitivity of prostate cancer detection but also supports the development of personalized treatment strategies. Key studies highlighted include the identification of novel genes, genetic mutations, peptides, metabolites, and potential biomarkers through multi-omics analyses, which have shown promise in improving prostate cancer management. The integration of multi-omics in clinical practice can potentially revolutionize prostate cancer prognosis and treatment, paving the way for precision medicine. This review underscores the importance of continued research and the application of multi-omics to overcome current challenges in prostate cancer diagnosis and therapy.

Validation and three years of clinical experience in using an artificial intelligence algorithm as a second read system for prostate cancer diagnosis—real-world experience

BackgroundProstate cancer ranks as the most frequently diagnosed cancer in men in the USA, with significant mortality rates. Early detection is pivotal for optimal patient outcomes, providing increased treatment options and potentially less invasive interventions. There remain significant challenges in prostate cancer histopathology, including the potential for missed diagnoses due to pathologist variability and subjective interpretations. MethodsTo address these challenges, this study investigates the ability of artificial intelligence (AI) to enhance diagnostic accuracy. The Galen™ Prostate AI algorithm was validated on a cohort of Puerto Rican men to demonstrate its efficacy in cancer detection and Gleason grading. Subsequently, the AI algorithm was integrated into routine clinical practice during a 3-year period at a CLIA certified precision pathology laboratory. ResultsThe Galen™ Prostate AI algorithm showed a 96.7% (95% CI 95.6–97.8) specificity and a 96.6% (95% CI 93.3–98.8) sensitivity for prostate cancer detection and 82.1% specificity (95% CI 73.9–88.5) and 81.1% sensitivity (95% CI 73.7–87.2) for distinction of Gleason Grade Group 1 from Grade Group 2+. The subsequent AI integration into routine clinical use examined prostate cancer diagnoses on >122,000 slides and 9200 cases over 3 years and had an overall AI Impact ™ factor of 1.8%. ConclusionsThe potential of AI to be a powerful, reliable, and effective diagnostic tool for pathologists is highlighted, while the AI Impact™ in a real-world setting demonstrates the ability of AI to standardize prostate cancer diagnosis at a high level of performance across pathologists.

Detection of clinically significant prostate cancer in MRI-negative prostate zones: saturation biopsy is necessary

Introduction: Multiparametric MRI (mpMRI) improves the sensitivity of prostate cancer detection. There is debate on the usefulness of saturation biopsies in combination targeted biopsy. Histology findings from trans-perineal template biopsies (TPTBs) were compared with suspected findings on mpMRI.

Differentiating cancer types using a urine test for volatile organic compounds

Background. In the human body, volatile organic compounds (VOCs) are produced by different tissues then secreted in different body fluids and subsequently excreted. Here we explore a non-invasive method for the detection of liver, prostate and bladder cancers. Methods. We recruited 140 cases. There were 31 hepatocellular carcinomas (HCC), 62 prostate carcinomas, 29 bladder carcinomas and 18 non-cancer cases. Male to female ratio was 5:1 and mean age was 72 years. Urinary VOCs were detected by applying solid-phase microextraction (SPME) technique. Results. The sensitivity for detection of HCC with normal alpha fetoprotein (AFP) was 68% (SE 0.06, 95% CI 0.54 to 0.81 and P < 0.005). The VOCs sensitivity in the detection of HCC cases with raised AFP was 83%. (SE 0.05, 95% CI 0.73 to 0.93 and P < 0.0001). The VOCs sensitivity for prostate cancer detection was 70% (SE 0.049, 95% CI 0.60 to 0.79 and P < 0.0002) and sensitivity for bladder cancer detection was 81% (SE 0.052, 95% CI 0.70 to 0.91 and P < 0.0001). Conclusions. SPME urinary VOCs analysis was able to differentiate between controls and each of hepatocellular, prostate and bladder cancers. This suggests that urinary VOCs are cancer specific and could potentially be used as a diagnostic method.

Prostate cancer and the role of biomarkers.

To review available prostate cancer biomarkers and their performance in a clinical order, from prostate cancer detection, to treatment of localized and advanced disease. We used an electronic literature search of the PubMed database using the key words "prostate biomarkers," "genomic markers," and "prostate cancer screening," as well as specific biomarkers, until March 2019. Prostate-specific antigen (PSA) lacks sensitivity for prostate cancer detection, and PSA derivatives have slightly improved its specificity, but have not resolved the limitations of PSA screening. Prostate cancer biomarkers have emerged as an ancillary tool to guide the clinical decision-making in different clinical scenarios. Urine-based tests can identify patients who may benefit from a prostate biopsy, and issue-based markers are helpful in guiding the decision regarding a second biopsy, stratifying patient with newly diagnosed prostate cancer to active surveillance or treatment, and identifying patients who may benefit from adjuvant treatment after surgery. New biomarkers have improved risk stratification in diagnosing and treating prostate cancer. Many of these markers are still considered experimental, and their efficacy and cost utility have not been determined.

IMPROD biparametric MRI in men with a clinical suspicion of prostate cancer (IMPROD Trial): Sensitivity for prostate cancer detection in correlation with whole-mount prostatectomy sections and implications for focal therapy.

Prostate MRI is increasingly being used in men with a clinical suspicion of prostate cancer (PCa). However, development and validation of methods for focal therapy planning are still lagging. To evaluate the diagnostic accuracy on lesion, region-of-interest (ROI), and voxel level of IMPROD biparametric prostate MRI (bpMRI) for PCa detection in men with a clinical suspicion of PCa who subsequently underwent radical prostatectomy. Prospective single-institution clinical trial (NCT01864135). Sixty-four men who underwent radical prostatectomy after IMPROD bpMRI performed in prebiopsy settings. IMPROD bpMRI consisted of T2 -weighted imaging (T2 w) and three separate diffusion-weighted imaging acquisitions with an average acquisition time of 15 minutes. The diagnostic accuracy of prospectively reported manual cancer delineations and regions increased with 3D dilation were evaluated on the voxel level (volume of 1.17 mm3 , 1 mm3 , 125 mm3 ) as well as the 36 ROI level. Only PCa lesions with a diameter ≥ 5 mm or any Gleason Grade 4 were analyzed. All data and protocols are freely available at: http://petiv.utu.fi/improd STATISTICAL TESTS: Sensitivity, specificity, accuracy. In total, 99 PCa lesions were identified. Forty (40%, 40/99) had a Gleason score (GS) of >3 + 4. Twenty-eight PCa lesions (28%, 28/99) were missed by IMPROD bpMRI, three (7.5%, 3/40) with GS >3 + 4. 3D dilation of manual cancer delineations in all directions by ~10-12 mm (corresponding to the Hausdorff distance) was needed to achieve sensitivity approaching 100% on a voxel level. IMPROD bpMRI had a high sensitivity on lesion level for PCa with GS >3 + 4. Increasing 3D lesion delineations by ~10-12 mm (corresponding to the Hausdorff distance) was needed to achieve high sensitivity on the voxel level. Such information may help in planning ablation therapies. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1641-1650.

Unexpected significant findings non-related to prostate cancer identified using combined prostate-specific membrane antigen positron emission tomography/CT and diagnostic CT scan in primary staging for prostate cancer.

There is increasing scientific evidence that whole-body Gallium-68 prostate-specific membrane antigen (68 Ga-PSMA) positron emission tomography/computed tomography (PET/CT) improves the sensitivity of prostate cancer detection above standard staging radiology. Diagnostic IV-contrasted CT scanning offers high-quality recognition and delineation of organs and structures with a high sensitivity and specificity for diagnoses of many non-prostate pathologies. At our institution, imaging for prostate cancer staging and restaging involves a 68 Ga-PSMA PET/CT scan combined with a diagnostic IV-contrasted CT scan of the head, neck, chest, abdomen and pelvis. In this study, we aimed to determine the incidence of significant findings unrelated to prostate cancer identified when this combined imaging approach is utilized for prostate cancer imaging. In this single-centre retrospective review, 68 Ga-PSMA PET/CT and diagnostic IV-contrasted CT scans undertaken for prostate cancer staging over a 12-month period (n=1200) were reviewed for significant findings not related to prostate cancer. In cases with a significant other finding, follow-up imaging and/or pathology results were reviewed, where available. The overall incidence of significant other non-prostate cancer findings was determined, as was the incidence of unsuspected neoplasms. Significant findings, unrelated to prostate cancer, were identified in a total of 5.7% of scans (n=68) with 3.2% (n=38) of findings being unsuspected neoplasms. Diagnostic quality IV-contrasted CT combined with 68 Ga-PSMA PET/CT for staging of prostate cancer identified significant other non-prostate cancer findings, including renal, lung, gastrointestinal and haematological malignancies. Many of these conditions impact on patient management and required further investigation or treatment prior to management of the prostate cancer.

The Influence of Background Signal Intensity Changes on Cancer Detection in Prostate MRI.

The objective of this study was to develop a scoring system for background signal intensity changes or prostate homogeneity on prostate MRI and to assess these changes' influence on cancer detection. This institutional review board-approved, HIPAA-compliant, retrospective study included 418 prostate MRI examinations in 385 men who subsequently underwent MRI-guided biopsy. The Likert score for suspicion of cancer assigned by the primary radiologist was extracted from the original report, and histopathologic work-up of the biopsy cores served as the reference standard. Two readers assessed the amount of changes on T2-weighted sequences and assigned a predefined prostate signal-intensity homogeneity score of 1-5 (1 = poor, extensive changes; 5 = excellent, no changes). The sensitivity and specificity of Likert scores for detection of prostate cancer and clinically significant cancer (Gleason score ≥ 3+4) were estimated in and compared between subgroups of patients with different signal-intensity homogeneity scores (≤ 2, 3, and ≥ 4). Interreader agreement on signal-intensity homogeneity scores was substantial (κ = 0.783). Sensitivity for prostate cancer detection increased when scores were better (i.e., higher) (reader 1, from 0.41 to 0.71; reader 2, from 0.53 to 0.73; p ≤ 0.007, both readers). In the detection of significant cancer (Gleason score ≥ 3+4), sensitivity also increased with higher signal-intensity scores (reader 1, from 0.50 to 0.82; reader 2, from 0.63 to 0.86; p ≤ 0.028), though specificity decreased significantly for one reader (from 0.67 to 0.38; p = 0.009). Background signal-intensity changes on T2-weighted images significantly limit prostate cancer detection. The proposed scoring system could improve the standardization of prostate MRI reporting and provide guidance for applying prostate MRI results appropriately in clinical decision-making.

Abstract 2755: Comparison of blood based liquid biopsy methodologies for improved risk assessment of prostate cancer (PCa)

Abstract Approximately 28,000 men die from prostate cancer in the US each year. Predictive biomarkers can provide patient risk assessment to enable therapeutic decision making. Compared to tumor, blood based liquid biopsies offer greater flexibility for noninvasive sample collection and allows for continuous monitoring of treatment response. While various liquid biopsy sample types and methodologies are currently available, it is critical to identify which method offers the highest sensitivity and specificity for clinical decision making. In this study we systematically compared specificity and sensitivity of prostate cancer detection using a pre-selected panel of PCa specific mRNA transcripts using four different methodologies. In this prospective laboratory study, we collected five blood tubes from a cohort of 40 metastatic castrate resistant prostate cancer (mCRPC) patients and 20 age matched healthy volunteers (HV). Circulating tumor cells (CTCs) were enumerated and blood samples enriched for CTCs were isolated for mRNA evaluation. Two tubes of plasma samples were utilized to isolate exosomes using ExoRNAeasy columns and CellSearch EpCAM capture respectively, while RNA was extracted directly from whole blood collected in PAXgene tubes. RNA isolated from blood samples enriched for CTCs, two exosome preps and whole blood samples were tested using qPCR (Fluidigm) for a panel of 48 prostate specific mRNA transcripts and three endogenous controls previously shown to be detected in whole blood. Receiver operator analysis (ROC) was performed to compare expression of mRNA transcripts across all four methods. Results showed PCa specific genes were detected in whole blood, Exo-52 exosome prep and samples enriched for CTCs, while exosomes isolated using CellSearch EpCAM capture failed to detect any PCa transcripts. ROC showed ExoRNAeasy exosome prep detected PCa specific mRNA transcripts with significantly higher sensitivity and specificity compared to three other methodologies. Area under curve (AUC) for ExoRNA prep 0.65 to 0.75 (average of z score at 3.27 p= 0.0023), compared to AUC for PAXgene is 0.55 to 0.83, (average of z score at 2.64 and p=0.05) and CTC samples is 0.52 to 0.67, (average of z score at 1.63 and p= 0.19). For CellSearch exosome method, the AUC is 0.47 to 0.52, average of z score at 0.66 and p= 0.32). These early results support the utility of exosome derived mRNA assay as a viable alternative to whole blood and CTC based assays. Further testing for expression of markers associated with prognosis and treatment response is necessary to warrant its prognostic or predictive clinical utility. Citation Format: Yashoda Rajpurohit, Shibu Thomas, Jaymala Patel, Dong Shen, Michael Gormley, Denis Smirnov, Deborah Ricci. Comparison of blood based liquid biopsy methodologies for improved risk assessment of prostate cancer (PCa) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2755. doi:10.1158/1538-7445.AM2017-2755

The CHAPPP study: Changing care with PSMA-PET for prostate cancer—A retrospective study of the role of PSMA imaging in altering treatment pathways.

13 Background: The low sensitivity of standard imaging (SI) techniques in detecting metastases (Ms) may lead to unnecessary local treatment for patients (Pts) with newly diagnosed or recurrent prostate cancer (PC). Ga-68-PSMA (Prostate Specific Membrane Antigen)-PET-CT is a novel imaging technique with increased sensitivity in detection of PC especially at low PSA values and may change the decision to pursue primary local or salvage treatment. This study quantified changes in definitive local treatment secondary to occult Ms detected on Ga-68-PSMA not visualized on SI. Methods: A retrospective study was performed of 509 consecutive PSMA scans (and 481 Pts) at our tertiary cancer centre, the Royal Brisbane and Women’s Hospital between Sept 2014 and Dec 2015. PSMA imaging was compared with a CT scan and bone scan to determine whether PSMA results altered the decision to pursue local treatment. Results: 81 (16%) Pts had PSMA-PET-CT scan and no Ms on SI, 40 prior to definitive local treatment and 41 as work up for recurrence. 9/40 Pts (23%) undergoing primary work-up had PSMA-identified Ms not visible on SI and altered these patients treatment pathway (mean PSA 20.5 ng/mL). Because of PSMA-diagnosed Ms, 3 did not receive local treatment. 4 had pelvic nodal involvement and received definitive radiotherapy (RT) including nodal fields. 2 Pts proceeded to radical prostatectomy with the addition of lymph node dissection. 41 Pts investigated for recurrence following local treatment had SI for comparison, (mean PSA 4.7, range 0.11 – 35 ng/mL). 11/41 (27%) were found to have distant or nodal Ms not visualized on SI. 7/11 with prior surgery did not proceed to salvage RT and the remaining Pts who had Ms were referred for an earlier medical oncology opinion. In total 20/81 (25%) of Pts had a direct change in treatment due to the additional information conferred by PSMA imaging. Conclusions: PSMA is more sensitive in the detection of prostate cancer Ms for patients being evaluated for primary treatment or looking for recurrence following local treatment. These results show clinically meaningful changes in management with avoidance of local treatment because of enhanced detection of metastases.

Multiparametric Magnetic Resonance Imaging of Prostate Cancer: Association of Quantitative Magnetic Resonance Parameters with Histopathologic Findings

Background: Prostate cancer continues to be diagnosed with increasing frequency. Multiparametric magnetic resonance imaging (MP-MRI) has a favorable correlation with prostatectomy histopathology findings. These advanced functional imaging techniques may help increase the sensitivity of prostate cancer detection and the accuracy of predicting the Gleason score (GS), which is a measure of cancer aggressiveness. Objectives: The purpose of this study was to determine associations between MP-MRI parameter and whole-mount pathological finding as reference standard. Patients and Methods: Twenty-four consecutive prostate cancer patients who underwent an MRI exam followed by radical prostatectomy were incorporated in this study. The average time between MRI and prostatectomy was 40 days (7 - 100 days). All patients had biopsy proven adenocarcinoma of the prostate and the mean GS was 6.7 (median, 7; range 6 - 9). Results: The mean age was 59 ± 7 years. The mean serum prostate specific antigen (PSA) was 7.81 ± 5.73 ng/mL. The GS ranged from 6 to 9 and most patients (79%) had a GS of 7. MRI data were correlated to biopsy results. Pearson correlation analysis revealed a significant negative correlation between GS and apparent diffusion coefficient (ADC) measurements (r = -0.926, P = 0. 01), and a strong positive correlation between Gleason scores and MRS measurements (r = 0.965, P = 0.01). No significant correlation was observed between any of the dynamic contrast enhanced MRI (DCE-MRI) parameters and GS. Conclusion: Combining anatomical and functional MRI significantly improves prostate cancer localization. It is a useful tool in the diagnosis and management of prostate cancer as well as a valid tool for assessing men on active surveillance. However, it should not be seen as a replacement for tissue biopsy.

Abstract 1564: Evaluation and characterization of anti-RalA autoantibody as a potential biomarker in human prostate cancer

Abstract Autoantibodies against intracellular tumor associated antigens (TAAs) are commonly found in various types of human cancers. Their utility in providing insights into tumor biology and as potential cancer biomarkers is well documented. In this study, serum autoantibodies to the Ras family small GTP binding protein (RalA) were detected by immunofluorescence assay, enzyme-linked immunosorbent assay (ELISA), and immunoblotting in 353 sera from patients with prostate cancer (PCa), benign prostatic hyperplasia (BPH), and normal controls. Expression of RalA in prostate tumor tissues was evaluated by immunohistochemistry. The cumulative positive rate of autoantibodies against RalA in PCa reached 18.4%, higher than that in sera with BPH (14.7%) and normal human sera (NHS) (2.25%, P&amp;lt;0.01). Twenty seven of 32 (84.4%) sera with positive OD values were consistently positive in immunoblots. The sensitivity and specificity of anti-RalA antibody in PCa detection was 18.4% and 97.8%, respectively. Representative PCa sera showed a cytoplasmic immunofluorescence staining pattern, with more intense staining in the perinuclear regions or partial staining in intracellular membrane. This pattern was similar to that produced by monoclonal RalA antibody. Strong expression of RalA was observed in 76.5% of prostate tumor tissues. Anti-RalA and PSA simultaneously used as diagnostic markers improved the sensitivity of PCa detection to 57.4%. In addition, the appearance of autoantibodies to RalA was assessed over time in the serially collected samples after surgery in cases. In all cancer patients with anti-RalA positive, autoantibodies were detected in 6 of 54 serial samples taken after surgery with a median lead time of 121 days (Interquartile Range, IQR 0-360). In conclusion, autoantibody to RalA might be a potential serological biomarker for the immunodiagnosis of early stage PCa. We are currently identifying additional novel TAAs targeted by serum autoantibodies in PCa by using two-dimensional gel electrophoresis (2DE) and liquid chromatography-tandem-mass spectrometry (LC-MS/MS). The combination of RalA with PSA, and with other antigens in PCa-specific TAA arrays has the potential for significantly improving the sensitivity of early PCa detection and management in diverse populations. Key words: anti-RalA autoantibody; tumor-associated antigens (TAAs); cancer immunodiagnosis; prostate cancer Citation Format: jitian li, Liping Dai, Carlos A. Casiano, Jianying Zhang. Evaluation and characterization of anti-RalA autoantibody as a potential biomarker in human prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1564. doi:10.1158/1538-7445.AM2015-1564

The role of transrectal ultrasound-guided biopsy in diagnosis of prostate cancer

Objectives The aim of this study was to evaluate the role of transrectal ultrasonography (TRUS)-guided biopsy in the detection of prostate cancer in patients on the basis of elevated prostate-specific antigen levels and abnormal digital rectal examination (DRE) results. Background The TRUS-guided biopsy technique was regarded as the golden standard method for diagnosis of prostate cancer. This study aimed to identify an appropriate prostate biopsy protocol for the detection of prostate cancer. Materials and methods This study included 30 patients having symptoms suggestive of prostatic diseases. All these patients were subjected to DRE, serum prostate-specific antigen testing, transabdominal ultrasound examination and TRUS, as well as biopsy taking. Results Among the 30 patients studied, final diagnosis by TRUS-guided biopsy revealed benign prostatic hyperplasia in 16 patients (53.3%), which was the most common pathology, precancerous lesions in seven patients, prostatitis in four patients (13.3%), and prostatic adenocarcinoma in three patients (10%). Among the patients with precancerous lesions, five (16.7%) had prostatic intraepithelial neoplasia and two (6.7%) had atypical adenomatous hyperplasia. Conclusion Correlation of prostate-specific antigen levels and findings from DRE and TRUS images with biopsy results is considered the most useful method to improve sensitivity of prostate cancer detection.

Abstract 4542: Early detection of clinically significant prostate cancer at diagnosis: A prospective study using a novel panel of TMPRSS2:ETS fusion gene markers

Abstract Background and objectives: The fusion of TMPRSS2 gene to an oncogenic ETS transcription factor gene (e.g. ERG) is both prevalent and unique to prostate cancer (PCa). We previously reported a panel of TMPRSS2:ERG fusion subtype markers for urine-based PCa detection with high specificity and sensitivity. Our current objectives are to investigate prospectively the sensitivity of a new panel of both common and low-prevalent TMPRSS2:ETS fusion gene markers for urine-based PCa detection, and to develop individualized molecular scores to predict the risk of cancer occurrence or the risk of aggressive cancer in PSA-screened patients at diagnostic biopsy. Participants and methods: A total of 92 subjects who were PSA screened and scheduled for diagnostic biopsy were enrolled from a prostate biopsy clinic at MUHC to form a pre-biopsy cohort. This cohort was designed for prospective molecular diagnosis of PCa using a panel of molecular markers in urine. Urine was collected after attentive digital rectal exam prior to biopsy and was coded for blind laboratory tests. RNA from urine sediments was analyzed using a panel of cancer-specific markers consisting of 6 TMPRSS2:ETS (i.e. ERG, ETV1, ETV4, ETV5) fusion genes/subtypes and 5 additional markers using established qPCR methods. Results: The pathology reported 39 biopsy-positive cases from 92 patients, a 42% biopsy-positive rate. In urine test, 10 unique combinations of fusion genes/subtypes or “fusion-types” were detected in 32 of 92 (34.8%) pre-biopsy samples. We identified a novel combination of fusion-types, termed Fx (III, V, ETS), that had a sensitivity of 51.3%, a specificity of 90.6% and an odds ratio of 10.1 in detecting PCa on biopsy. By incorporating the fusion-types Fx (III, V, ETS) with urine PCA3 and serum PSA, a regression model was developed to calculate individualized molecular scores for significantly improved prediction of biopsy outcomes and for stratification of pre-biopsy patients into distinct risk groups. As such, the sensitivity of PCa detection was 81% in a high risk group but only 16% in a low risk group. On the other hand, the overexpression profiles of the same set of informative fusion markers were shown to be significantly associated with high-grade cancers (Gleason &amp;gt; 6) and used to develop a novel regression model to predict the risk of aggressive cancer when coupled with PSA density. We demonstrated that the molecular scores for aggressiveness were highly correlated with Gleason scores (r = 0.64, p &amp;lt; 0.0001), the number of positive cores (r = 0.48, p &amp;lt; 0.01) and the % of cancer involvement (r = 0.59, p &amp;lt; 0.0001) in 39 PCa patients. Conclusions: We have identified multiple alternative fusion-types very specific to clinically significant prostate cancer in urine and developed highly effective regression models to predict the risk of cancer occurrence or the risk of aggressive cancer at diagnosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4542. doi:1538-7445.AM2012-4542

Dynamische kontrastmittelunterstützte MRT der Prostata: Vergleich von zwei Auswerteverfahren

To evaluate the usefulness of a commercially available post-processing software tool for detecting prostate cancer on dynamic contrast-enhanced magnetic resonance imaging (MRI) and to compare the results to those obtained with a custom-made post-processing algorithm already tested under clinical conditions. Forty-eight patients with proven prostate cancer were examined by standard MRI supplemented by dynamic contrast-enhanced dual susceptibility contrast (DCE-DSC) MRI prior to prostatectomy. A custom-made post-processing algorithm was used to analyze the MRI data sets and the results were compared to those obtained using a post-processing algorithm from In vivo Corporation (Dyna CAD for Prostate) applied to dynamic T 1-weighted images. Histology was used as the gold standard. The sensitivity for prostate cancer detection was 78 % for the custom-made algorithm and 60 % for the commercial algorithm and the specificity was 79 % and 82 %, respectively. The accuracy was 79 % for our algorithm and 77.5 % for the commercial software tool. The chi-square test (McNemar-Bowker test) yielded no significant differences between the two tools (p = 0.06). The two investigated post-processing algorithms did not differ in terms of prostate cancer detection. The commercially available software tool allows reliable and fast analysis of dynamic contrast-enhanced MRI for the detection of prostate cancer.

Evaluation of the potential of diffusion-weighted imaging in prostate cancer detection

Conventional T2-weighted (T2W) imaging alone has a poor sensitivity for prostate cancer detection. To evaluate combined T2W and diffusion-weighted magnetic resonance imaging (DW-MRI) versus T2W MRI alone for identifying tumor in patients with prostate cancer. Fifty-four consecutive patients with prostate cancer (46 stage 1 and 2, 8 stage 3) and sextant biopsies within the previous 3 months were studied. Endorectal MR images were analyzed by two radiologists (1 experienced, 1 trainee) blinded to patient information and histopathology. T2W images were scored first, followed by combined T2W and isotropic apparent diffusion coefficient (ADC) maps calculated from DW-MRI (b = 0, 300, 500, and 800 s/mm(2)). Gland apex, middle, and base for each side were scored negative, indeterminate, or positive for tumor. Imaging data for each sextant were compared with histology. Sensitivity, specificity, and interobserver agreement were calculated. Sensitivity and specificity for tumor identification significantly improved from 50% and 79.6% (T2W alone, experienced observer) to 73.2% and 80.8% (P<0.001), respectively. For the trainee observer, there was no improvement (44.3% and 72% T2W alone vs. 45.1% and 69.2% T2W plus ADC maps). Interobserver agreement was moderate for T2W imaging alone (kappa 0.51) and fair for T2W plus ADC maps (kappa 0.33). In an experienced observer, DW-MRI together with T2W imaging can significantly improve tumor identification in prostate cancer.

Citrate Concentrations in Human Seminal Fluid and Expressed Prostatic Fluid Determined via 1H Nuclear Magnetic Resonance Spectroscopy Outperform Prostate Specific Antigen in Prostate Cancer Detection

We compared the performance of citrate concentration measurements in unprocessed human semen and expressed prostatic secretions from controls and from patients with biopsy confirmed prostate cancer to that of prostate specific antigen testing with respect to specificity and sensitivity for prostate cancer detection. Semen and expressed prostatic secretions were collected in biopsy proven, prostate cancer bearing and noncancer bearing cases. Citrate concentrations were determined by quantitative in vitro, high field, water suppressed proton nuclear magnetic resonance spectroscopy. Assessments of the diagnostic performance of citrate and prostate specific antigen results in our study populations were made by ROC curve analysis. Citrate was measured in samples from 61 participants, of whom 16 without and 21 with cancer donated semen, and 17 without and 7 with cancer donated expressed prostatic secretions. Mean citrate +/- SE compared to that in controls was 2.7-fold lower in patients with cancer samples in semen (132.2 +/- 30.1 vs 48.0 +/- 7.9 mM, p < 0.05) and expressed prostatic secretions (221.4 +/- 55.4 vs 81.5 +/- 36.0 mM, p < 0.05). ROC curve analysis showed that measurements of citrate in semen performed as well as measurements of citrate in expressed prostatic secretion for detecting prostate cancer (AUC 0.81, 95% CI 0.60 to 0.92 and AUC 0.73, 95% CI 0.38 to 0.90, respectively, p > 0.05). ROC curve analysis also showed that the measurement of citrate in either fluid outperformed prostate specific antigen measurement for detecting prostate cancer in these subjects (AUC 0.61, 95% CI 0.44 to 0.74). In vitro nuclear magnetic resonance spectroscopic measurement of the citrate concentration in semen or expressed prostatic secretions outperforms prostate specific antigen testing for detecting prostate cancer.

UP-02.21: The evolution of radioimmunoscintigraphy: sharper images and outcomes data

The practical ability to label tissue-specific antibodies has long been sought to both improve detection and to provide novel therapeutic applications. One of the most intriguing targets for prostate cancer is the prostate-specific membrane antigen (PSMA), a 100 kD transmembrane glycoprotein that is up regulated in prostate cancer and its metastases. Early investigations with the radiolabelled 7E11 antibody, capromab pendetide (ProstaScint), significantly improved sensitivity for prostate cancer detection compared to standard crossectional imaging based on tissue confirmation. However, image acquisition and interpretation was erratic and the imaging technology was not widely embraced.

Prostate-specific antigen and related isoforms in the diagnosis and management of prostate cancer.

Despite its unparalleled merits for prostate cancer detection and staging, prostate-specific antigen (PSA) is not a marker for prostate cancer only, but also is expressed in benign conditions. For early detection, limitations of PSA are obvious. Its widespread use has led to an extensive amount of expensive and often unnecessary diagnostic procedures associated with significant morbidity. Total PSA derivatives may enhance the accuracy of prostate cancer diagnosis. The ratio of free-to-total PSA improves specificity while maintaining a high sensitivity for prostate cancer detection for men with a total PSA of 2.5 to 10 ng/mL. Human glandular kallikrein also has the potential to be a valuable tool in combination with total and free PSA for early diagnosis of prostate cancer. Complex PSA seems to be a reliable tool to improve specificity at high sensitivity levels in men with suspected prostate cancer (mainly in PSA levels below 4 ng/mL). Newly discovered isoforms of free PSA also may impact early detection of prostate cancer with encouraging preliminary results that warrant further clinical investigation.

Complexed PSA performance for prostate cancer detection in an African-American population

Objectives Complexed prostate-specific antigen (cPSA) has been shown to improve the differentiation of benign and malignant disease compared with total PSA (tPSA) in studies evaluating predominantly white populations of men. We sought to evaluate the diagnostic performance of cPSA relative to tPSA in a population of African-American men. Methods Consecutive African-American men scheduled for prostate biopsy were enrolled prospectively at the Louisiana State University Medical Center, New Orleans. Serum was collected before the biopsy procedure and tested with the Immuno 1 tPSA and cPSA methods. Receiver operating characteristic curve analysis was performed and the area under the curve was calculated for tPSA and cPSA. Results A total of 156 patients were evaluated, 51 (32.7%) of whom were diagnosed with prostate cancer. The median PSA value for men with prostate cancer was 4.96 ng/mL and for those with benign disease was 3.93 ng/mL. The receiver operating characteristic analysis indicated that the area under the curve for cPSA (0.679) was statistically greater than that achieved for tPSA (0.642, P = 0.004). Using cutoff values for cPSA of 2.3 ng/mL and for tPSA of 2.85 ng/mL provided a specificity of 31.4% and 26.7%, respectively, at a sensitivity for prostate cancer detection of 95%. This was not statistically significant ( P = 0.18). Conclusions cPSA offers modest improvement in prostate cancer detection compared with tPSA in African-American men, but not at the clinically relevant 95% sensitivity level. Additional work is needed to improve prostate cancer detection in this high-risk cohort of patients.