Serum PSA Levels Research Articles

MP19-02 DEEP LEARNING USING PREOPERATIVE MRI INFORMATION STRONGLY PREDICTS EARLY RECOVERY OF URINARY CONTINENCE AFTER ROBOT-ASSISTED RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy I (MP19)1 Apr 2020MP19-02 DEEP LEARNING USING PREOPERATIVE MRI INFORMATION STRONGLY PREDICTS EARLY RECOVERY OF URINARY CONTINENCE AFTER ROBOT-ASSISTED RADICAL PROSTATECTOMY Makoto Sumitomo*, Atsushi Teramoto, Naohiko Fukami, Kosuke Fukaya, Kenji Zennami, Manabu Ichino, Kiyoshi Takahara, Mamoru Kusaka, and Ryoichi Shiroki Makoto Sumitomo*Makoto Sumitomo* More articles by this author , Atsushi TeramotoAtsushi Teramoto More articles by this author , Naohiko FukamiNaohiko Fukami More articles by this author , Kosuke FukayaKosuke Fukaya More articles by this author , Kenji ZennamiKenji Zennami More articles by this author , Manabu IchinoManabu Ichino More articles by this author , Kiyoshi TakaharaKiyoshi Takahara More articles by this author , Mamoru KusakaMamoru Kusaka More articles by this author , and Ryoichi ShirokiRyoichi Shiroki More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000852.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urinary incontinence remains one of the most bothersome postoperative complications even after robot-assisted radical prostatectomy (RARP). We aimed to make a novel prediction system that can be used preoperatively to inform patients of the accuracy of early recovery of urinary continence after RARP using a deep learning (DL) model from magnetic resonance imaging (MRI) information and preoperative clinicopathological parameters. METHODS: A retrospective cohort study was conducted on prostate cancer (PC) patients who had undergone RARP at Fujita Health University Hospital between August 2015 and July 2019. Patients using no pads/no leakage of urine or the use of a safety pad within 3 months after RARP is categorized into “good” continence and others into “no good” continence. MRI DICOM data from axial, coronal and sagittal imaging as well as preoperative clinicopathological covariates (age, BMI, prostate volume, serum PSA level, Gleason score, clinical stage) and intraoperative covariates (main operator, operation time, console time, with or without nerve sparing, bleeding) were assessed. Supervised DL algorithms, which included AdaBoost, Naive Bayes, Neural Network, Random Forest, and SVM were trained and tested as binary classifiers (good or no good). To evaluate the DL models from the testing data set, their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), as well area under the receiver operating characteristic curve (AUC) were analyzed. RESULTS: Data were available for 497 patients in the study period. Continence rates at 1, 3, 6, and 12 months after RARP were 47%, 76%, 87%, and 94%, respectively. The AdaBoost DL algorithm using MRI information in addition to clinicopathological parameters had the highest performance with sensitivity at 92%, specificity at 77%, PPV at 79%, NPV at 91%, and AUC at 84% for predicting good continence, while that using clinicopathological parameters only had the performance with sensitivity at 50%, specificity at 69%, PPV at 60%, NPV at 60%, and AUC at 60%. Furthermore, little increase in AUC was observed in the DL algorithms using intraoperative parameters in addition to preoperative information. CONCLUSIONS: Our results suggest that the DL algorithms using MRI information are highlighted as an accurate method for strongly predicting early recovery of urinary continence after RARP. Thus, DL predictions may help allocation of treatment strategies for PC patients who dislike prolonged urinary incontinence after RARP. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e298-e298 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Makoto Sumitomo* More articles by this author Atsushi Teramoto More articles by this author Naohiko Fukami More articles by this author Kosuke Fukaya More articles by this author Kenji Zennami More articles by this author Manabu Ichino More articles by this author Kiyoshi Takahara More articles by this author Mamoru Kusaka More articles by this author Ryoichi Shiroki More articles by this author Expand All Advertisement PDF downloadLoading ...

MP79-05 NEOADJUVANT APALUTAMIDE (ARN-509) AND RADICAL PROSTATECTOMY IN TREATMENT OF INTERMEDIATE TO HIGH RISK PROSTATE CANCER (NEAR) PHASE II TRIAL

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) IV (MP79)1 Apr 2020MP79-05 NEOADJUVANT APALUTAMIDE (ARN-509) AND RADICAL PROSTATECTOMY IN TREATMENT OF INTERMEDIATE TO HIGH RISK PROSTATE CANCER (NEAR) PHASE II TRIAL XinYan Yang*, Edwin Jonathan Aslim, Nye Thane Ngo, Li Yan Khor, Tsung Wen Chong, John Shyi Peng Yuen, Kae Jack Tay, Henry Sun Sien Ho, and Lui Shiong Lee XinYan Yang*XinYan Yang* More articles by this author , Edwin Jonathan AslimEdwin Jonathan Aslim More articles by this author , Nye Thane NgoNye Thane Ngo More articles by this author , Li Yan KhorLi Yan Khor More articles by this author , Tsung Wen ChongTsung Wen Chong More articles by this author , John Shyi Peng YuenJohn Shyi Peng Yuen More articles by this author , Kae Jack TayKae Jack Tay More articles by this author , Henry Sun Sien HoHenry Sun Sien Ho More articles by this author , and Lui Shiong LeeLui Shiong Lee More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000971.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Apalutamide (ARN-509) exert near total antagonist activity at androgen receptors and is approved for treatment of M0 CRPC. ARN-509 as neoadjuvant treatment in organ confined disease has not been studied before. The NEAR trial is a phase II single arm study of neoadjuvant apalutamide (ARN-509) and radical prostatectomy (RP) in the treatment of D’Amico intermediate and high-risk prostate cancer (Clinicaltrials.gov identifier: NCT03124433). This study aims to report on the oncological and pathological outcomes of neoadjuvant ARN-509 before RP. METHODS: Eligibility criteria included patients between 21-75 years old diagnosed with conventional adenocarcinoma, excluding those with radio-recurrent disease, impaired liver function, and poor ECOG status (3 or below). Participants received ARN509 240mg daily for 12 weeks followed by RP within 6 weeks of the last dose of medication. Primary outcomes included tumour response defined by residual cancer burden (RCB), post-therapy morphologic characterization (groups A-C, with C being the worst response), and post-operative serum PSA levels (nadir defined as levels below 0.03ng/ml). Secondary outcomes included prevalence of significant adverse events (AE) with ARN509 and operative complications following RP. Statistical significance was defined as p<0.05. RESULTS: Of the 30 subjects enrolled, 25 participants completed the study. The median age was 68 years, and serum PSA at recruitment was 11.6ng/mL. They comprised D-Amico intermediate-risk n=12 (48%) and high-risk n=13 (52%), with ISUP grade group distributions of 1(n=1, 4%), 2(n=13, 52%), 3(n=8, 32%) and 4-5(n=3, 12%). 84% of subjects achieved post-prostatectomy nadir PSA levels, and the rest achieved nadir PSA levels of 0.03-0.05. The post-therapy morphology classifications were group A (50%), group B (10%) and group C (40%). The median reduction of serum PSA after neoadjuvant apalutamide alone was 97.3% (range 61.2 to 100.0, p<0.0001). There was one subject with an unrelated grade III AE, and no subjects with Clavien-Dindo grade III and above surgical complications. CONCLUSIONS: Results of the phase II NEAR trial show safe and reasonable oncological outcomes in patients with organ confined prostate cancer. Source of Funding: This study is supported by Johnson & Johnson IIET Grant. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1216-e1217 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information XinYan Yang* More articles by this author Edwin Jonathan Aslim More articles by this author Nye Thane Ngo More articles by this author Li Yan Khor More articles by this author Tsung Wen Chong More articles by this author John Shyi Peng Yuen More articles by this author Kae Jack Tay More articles by this author Henry Sun Sien Ho More articles by this author Lui Shiong Lee More articles by this author Expand All Advertisement PDF downloadLoading ...

Preliminary results of targeted prostate-specific membrane antigen imaging in evaluating the efficacy of a novel hormone agent in metastatic castration-resistant prostate cancer.

To investigate the feasibility and effectiveness of prostate‐specific membrane antigen (PSMA) imaging to make response assessment regarding novel hormone treatment and to predict the outcomes for metastatic castration‐resistant prostate cancer (mCRPC) patients. This retrospective study enrolled 68 mCRPC patients who had daily received a novel hormone agent named abiraterone. Tc‐99m PSMA single‐photon emission computed tomography (SPECT/CT) was performed at the baseline (SPECT/CT1) and after 3‐6 months of treatment (SPECT/CT2). The treatment response was determined by visual analysis based on molecular imaging PSMA (miPSMA) scores framework and was compared with conventional biochemical analysis. We chose either the hottest lesion (target A) or five of the hottest lesions (target B) to calculate the tumor/background ratio (TBR) and the maximum standardized uptake value (SUVmax) and compared their performances in predicting progression‐free survival (PFS). Changes in PSMA expression between SPECT/CT1 and SPECT/CT2 were well associated with the results of the visual analysis. The TBR and the SUVmax of both targets were significantly associated with the baseline serum PSA level (P < .0001). The biochemical and radiological responses were concordant in 56 of the 68 patients (P < .001). The median PFS of the nonresponse group patients was significantly shorter than that of the patients in the response group (6.8 vs 12.1 months, P = .012). For predicting PFS, most of the indexes tested were significant on SPECT/CT2, with %ΔTBR being the most significant prognostic factor. Our preliminary results suggest that molecular imaging‐targeted PSMA is of great value for treatment response assessment and clinical outcome prediction in mCRPC patients with long‐term abiraterone treatment.

Frequency of Carcinoma Prostate in Patients with Clinically Diagnosed Benign Prostatic Hyperplasia (BPH) and Prostate Specific Antigen d" 4ng/ml

Objectives: The present study was carried out in the Department of Urology, Sir Salimullah Medical College Mitford Hospital Dhaka between July 2009 to May 2010. To determine the frequency of prostate cancer in patients with BPH &amp; PSA level d” 4 ngm/ml. Methods: A total of 198 subjects aged above 50 years with serum PSA level of not more than 4.0 ng per milliliter , no suspicious nodule on digital rectal examination , homogenous echogenicity of prostate on ultrasonographic findings, peak urinary flow rate (Qmax) &lt; 10ml/sec in uroflowmetry and no clinically significant coexisting conditions were included in the study. All the patients presented with obstructive urinary symptoms attended at four tertiary hospitals in Dhaka city during the study period were evaluated with clinical history, physical examination and some investigations. All the patients were treated with transurethral resection of prostate (TURP). Chips were collected carefully and sent for histopathology. Results: The mean age was 65.1 ± 7.3 years. About 32% of patients had serum PSA level 2 ng/ml or less and 68.2% more than 2 ng/ml. The peak urinary flow rate was 7.2 ± 2.7 ml/sec. One hundred and ninety three (98%) patients were diagnosed as having benign prostatic hyperplasia (BPH) on histopathological examination and 5(2.5%) as having prostate carcinoma. Conclusion: Prostate cancer is not rare among men with PSA levels of 4.0 ng per milliliter or less Bangladesh Journal of Urology, Vol. 15, No. 2, July 2012 p.44-47

Oxidative Stress and Antioxidant Status in High-Risk Prostate Cancer Subjects.

The oxidant/antioxidant balance has been implicated in the pathophysiology of prostate cancer. We investigated oxidative damage and antioxidant status in high-risk prostate cancer subjects. Reduced glutathione (GSH) levels were measured in erythrocytes, 8-hydroxydeoxyguanosine (8-OHdG) in leukocytes and plasma levels of catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSH-R), glutathione S-transferase (GST), superoxide dismutase (SOD), and lipid peroxide products were measured in high-risk and age-matched healthy subjects. Serum PSA levels were significantly higher (p < 0.0001) in high-risk subjects, whereas GST (p < 0.0001) and GSH (p < 0.002) were higher in healthy controls. Levels of 8-OHdG, an oxidized nucleoside of DNA, were significantly increased (p < 0.0001) in high-risk subjects. No marked difference in the levels of CAT (p = 0.237), GSH-Px (p = 0.74), GSH-R (p = 0.344), SOD (p = 0.109), and lipid peroxide products (p = 0129) were observed between two groups. Pearson’s correlation between GST and PSA (r = −0.69 (p < 0.0001)), GST and 8-OHdG (r = −0.62 (p < 0.0004)), GSH and 8-OHdG (r= −0.39 (p = 0.038)), and CAT and GSH-Px (r= −0.33 (p = 0.04)) were found to be negatively correlated, whereas 8-OHdG and PSA were positively associated (r= 0.57 (p < 0.002). These results indicate a significant role of oxidative damage in prostate carcinogenesis, particularly during the early stages of development. In conclusion, our data support the importance of antioxidant defense as a valuable diagnostic and/or prognostic marker in prostate cancer.

Significance of Tumour Biological Markers for Overall Survival and Clinical Parameters for Disease-Free Survival in Patients with Prostate Cancer after Radical Prostatectomy

Objective: The aim of the study was to assess the prognostic significance of pretreatment serum PSA level, immunohistochemical expression (labelling index, LI) of Ki-67, prostate-specific membrane antigen (PSMA), glucose-1 transporter (GLUT-1), vascular endothelial growth factor (VEGF), human telomerase reverse transcriptase (hTERT), as well as micro vessel density (MVD) for overall survival (OS), local recurrence-free survival (LRFS), metastatic-free survival (MFS) and disease-free survival (DFS) in a group of 130 prostate cancer (PCa) patients treated with radical prostatectomy (RP) between 2007 and 2011. Methods: In order to investigate the prognostic value of the analyzed variables in univariate and multivariate Cox analysis, the patients were divided into two subgroups based on the marker cut-off points selected by the receiver operating characteristic curves. Results: There were 83 (63.8%) cases staged pT1-2 and 47 (36.1%) staged pT3-4. The majority of tumours (53.1%) were well-differentiated (grade group G1), 49 (37.7%) moderately differentiated (G2-3) and 12 (9.2%) poorly differentiated (G4-5). In 85 patients (65.4%) the surgery was radical, 59 (45.4%) had positive surgical margins (PSM), and in 23 (17.7%) seminal vesicle(s) involvement was diagnosed. Median followup was 79 (1-148) months, during which 55 (42.3%) men died, in 12 (9.2%) local relapse and in 13 (10%) distant metastases occurred. In multivariate Cox analysis, independent negative prognostic factors for OS were: Ki-67LI &gt;6.7% (p=0.010), PSMALI ≤51.7% (p=0.009), hTERTLI ≤20.5% (p=0.004) and lack of adjuvant treatment (AT) (p=0.013), while for MFS: seminal vesicle(s) involvement (p=0.007) and hTERTLI ≤43.8% (p=0.011). However, non-radical surgery (p=0.007), PSM (p=0.005) and AT (p=0.037) were negatively associated with DFS. Conclusion: Tumour biological markers are significant for OS and clinical parameters for DFS in PCa patients’ after RP.

Impact of 68Ga-PSMA-11 PET/CT on staging and management of prostate cancer patients in various clinical settings.

26 Background: The goal of this study was to determine the impact of 68Ga-PSMA-11 PET/CT on initial and subsequent management decisions in a cohort of PCa patients referred for various indications excluding the two main classical indications: BCR and pre-surgical staging. Methods: This is a prospective study of 197 patients that aimed to determine the impact of 68Ga-PSMA-11 PET/CT on PCa stage and management. Indications for PSMA PET/CT were initial staging of non-surgical candidates (30 patients) and re-staging after definitive treatment (n=168). The re-staging cohort comprised: patients re-staged with known advanced metastatic disease (n=103), after androgen deprivation therapy only (n=16), after surgery with serum PSA levels &lt;0.2 ng/ml (n=13), after radiation therapy (RT) not meeting the Phoenix criteria (n=22) and after other primary local treatments [i.e. HIFU, focal laser ablation, cryoablation, hyperthermia or irreversible electroporation] (n=13). Patients with BCR and candidates for curative surgery were excluded. Impact on management was assessed using pre- and post-PET questionnaires completed by referring physicians, electronic chart review and/or patient telephone encounters. Results: PSMA PET/CT changed disease stage in 135/197 (69%) patients (38% up-stage, 30% down-stage and no changes in stage in 32%). Management was affected in 104/182 (57%) patients. PSMA PET/CT had its greatest management impact in patients who were re-staged after RT. Conclusions: PSMA PET/CT has a profound impact on stage and management of PCa patients outside of the two main classical indications (BCR and presurgical staging) across all examined clinical scenarios. Clinical trial information: NCT04050215.

Deep learning using preoperative MRI information to predict early recovery of urinary continence after robot-assisted radical prostatectomy.

310 Background: Urinary incontinence remains one of the most bothersome postoperative complications even after robot-assisted radical prostatectomy (RARP). We aimed to make a novel prediction system that can be used preoperatively to inform patients of the accuracy of early recovery of urinary continence after RARP using a deep learning (DL) model from magnetic resonance imaging (MRI) information and preoperative clinicopathological parameters. Methods: A retrospective cohort study was conducted on prostate cancer (PC) patients who had undergone RARP at our hospital between August 2015 and July 2019. Patients using no pads/no leakage of urine or the use of a safety pad within 3 months after RARP is categorized into “good” continence and others into “no good” continence. MRI DICOM data from axial, coronal and sagittal imaging as well as preoperative clinicopathological covariates (age, BMI, prostate volume, serum PSA level, Gleason score, clinical stage) were assessed. Supervised DL algorithms, which included AdaBoost, Naive Bayes, Neural Network, Random Forest, and SVM were trained and tested as binary classifiers (good or no good). To evaluate the DL models from the testing data set, their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), as well as area under the receiver operating characteristic curve (AUC) were analyzed. Results: Data were available for 497 patients in the study period. The AdaBoost DL algorithm using MRI information in addition to clinicopathological parameters had the highest performance with sensitivity at 92%, specificity at 77%, PPV at 79%, NPV at 91%, and AUC at 84% for predicting good continence, while that using clinicopathological parameters only had the performance with sensitivity at 50%, specificity at 69%, PPV at 60%, NPV at 60%, and AUC at 60%. Conclusions: Our results suggest that the DL algorithms using MRI imaging information are highlighted as an accurate method for strongly predicting early recovery of urinary continence after RARP. Thus, DL predictions may help allocation of treatment strategies for PC patients who dislike prolonged urinary incontinence after RARP.

Phase I study of pasotuxizumab (AMG 212/BAY 2010112), a PSMA-targeting BiTE (Bispecific T-cell Engager) immune therapy for metastatic castration-resistant prostate cancer (mCRPC).

124 Background: mCRPC has a poor prognosis and immunotherapies are largely ineffective. PSMA is a promising therapeutic target in mCRPC. Pasotuxizumab is a PSMA x CD3 BiTE immune therapy that mediates killing of tumor cells by T cells. Methods: NCT01723475 was a first-in-human, multicenter, dose-escalation study in patients (pts) with mCRPC refractory to standard therapy. Pts received continuous IV infusion of pasotuxizumab in cohorts of 3–4 pts. Dose-escalation followed a continuous reassessment methodology. The primary objective was to determine safety and maximum tolerated dose (MTD); secondary objectives included pharmacokinetics, biomarkers, and tumor response. Results: 16 pts were enrolled into 5 dosing cohorts (5 µg/d, n=3; 10 µg/d, n=4; 20 µg/d, n=3; 40 µg/d, n=4; 80 µg/d, n=2). All pts had ≥1 AE of any grade; most common were fever (94%), chills (69%), and fatigue (50%). 13 pts (81%) had ≥1 AE of grade ≥3; most common were decreased lymphocytes and infections (both 44%). No grade 5 AE occurred. A serious drug-related AE was reported for 1 pt (fatigue, 20 µg/d). No antidrug antibodies were observed. Recruitment was stopped before MTD was reached to allow initiation of a new study sponsored by Amgen. Antitumor activity as indicated by PSA serum level decline was dose dependent, with a mean best PSA change per dosing cohort vs baseline of +0.74% (5 µg/d), −17.9% (10 µg/d), −37.4% (20 µg/d), −42.5% (40 µg/d) and −54.9% (80 µg/d). PSA decreases ≥50% occurred in 3 pts (n=1 each in 20 µg/d, 40 µg/d, 80 µg/d cohorts). One long-term PSA responder was treated for 14 months (40 µg/d) and one for 19.4 months (80 µg/d). The latter pt showed a complete regression of soft-tissue metastases and marked regression of bone metastases by PSMA-PET/CT, &gt;90% reduction in PSA and alkaline phosphatase, and a significant and durable improvement in disease related symptoms. Conclusions: Pasotuxizumab had an acceptable safety profile and dose-dependent clinical activity in mCRPC pts. There were two long term responders in the dose escalation. This is the first clinical study showing that a BiTE immune therapy can be efficacious in solid tumors. Clinical trial information: NCT01723475.

MRI combined with PSA density in detecting clinically significant prostate cancer in patients with PSA serum levels of 4∼10 ng/mL: Biparametric versus multiparametric MRI

PurposeTo compare the performance of biparametric magnetic resonance imaging (bpMRI) to that of multiparametric MRI (mpMRI) in combination with prostate-specific antigen density (PSAD) in detecting clinically significant prostate cancer (csPCa) in patients with PSA serum levels of 4∼10ng/mL. Materials and methodsA total of 123 men (mean age, 66.3±8.9 [SD]; range: 42–83 years) with PSA serum levels of 4∼10ng/mL with suspected csPCa were included. All patients underwent mpMRI at 3 Tesla and transrectal ultrasound-guided prostate biopsy in their clinical workup and were followed-up for >1 year when no csPCa was found at initial biopsy. The mpMRI images were reinterpreted according to the Prostate Imaging Reporting and Data System (PI-RADS, v2.1) twice in two different sessions using either mpMRI sequences or bpMRI sequences. The patients were divided into 2 groups according to whether csPCa was detected. The PI-RADS (mpMRI or bpMRI) categories and PSAD were used in combination to detect csPCa. Receiver operating characteristic (ROC) curve and decision curve analyses were performed to compare the efficacy of the different models (mpMRI, bpMRI, PSAD, mpMRI+PSAD and bpMRI+PSAD). ResultsThirty-seven patients (30.1%, 37/123) had csPCa. ROC analysis showed that bpMRI (AUC=0.884 [95% confidence interval (CI): 0.814–0.935]) outperformed mpMRI (AUC=0.867 [95% CI: 0.794–0.921]) (P=0.035) and that bpMRI and mpMRI performed better than PSAD (0.682 [95% CI: 0.592–0.763]) in detecting csPCa; bpMRI+PSAD (AUC=0.907 [95% CI: 0.841–0.952]) performed similarly to mpMRI+PSAD (AUC=0.896 [95% CI: 0.828–0.944]) (P=0.151) and bpMRI (P=0.224). The sensitivity and specificity were 81.1% (95% CI: 64.8–92.0%) and 88.4% (95% CI: 79.7–94.3%), respectively for bpMRI, and 83.8% (95% CI: 68.0–93.8%) and 80.2% (95% CI: 70.2–88.0%), respectively for mpMRI (P>0.999 for sensitivity and P=0.016 for specificity). Among the 5 decision models, the decision curve analysis showed that all models (except for PSAD) achieved a high net benefit. ConclusionIn patients with PSA serum levels of 4∼10ng/mL, bpMRI and bpMRI combined with PSAD achieve better performance than mpMRI in detecting csPCa; bpMRI has a higher specificity than mpMRI, which could decrease unnecessary biopsy, and may serve as a potential alternative to mpMRI to optimize clinical workup.

Detection of Prostate Cancer Antigen 3 and Prostate Cancer Susceptibility Candidate in Non-DRE Urine Improves Diagnosis of Prostate Cancer in Chinese Population.

Although prostate biopsy is the gold standard for the diagnosis of prostate cancer, it also leads to high incidence of negative biopsies and the diagnosis of clinically low-risk prostate cancer and the subsequent overtreatment. It remains an unmet need to discover new biomarkers in order to defer the unnecessary biopsies in clinical practice. In this study, we described a new method, LBXexo score, to measure the urine exosomal PCA3/PRAC expression from non-DRE urine as a noninvasive diagnosis to improve the detection rate in Chinese population with a low serum PSA level. First-voided urine samples were collected to isolate exosomes, and exosomal RNAs of PCA3 and PRAC were measured by quantitative reverse transcription PCR. A significant increase in exoPCA3/PRAC was observed in both any-grade and high-grade prostate cancer groups when compared with the biopsy-negative group. Receiver-operating characteristic curve analyses showed that the LBXexo score significantly improved diagnostic performance in predicting biopsy results, with AUCs of 0.723 (p=0.017) and 0.736 (p=0.038) for any-grade and high-grade (GS ≥ 7) prostate cancer, respectively. For high-grade cancer, LBXexo had the negative and positive predictive values of 100% and 27.59%, respectively, and could potentially avoid unnecessary biopsy. This is the first report in Chinese population that demonstrates the predictive value of the exosomal expression of PCA3 and PRAC derived from non-DRE urine in predicting prostate biopsy outcomes. It could be used in clinical practice to make a better informed biopsy decision and avoid unnecessary biopsies in Chinese population.

Incidence, predictive factors and survival outcomes of incidental prostate cancer in patients who underwent radical cystectomy for bladder cancer

BACKGROUND The aim of this study was to analyze the incidence, preoperative findings, pathological features and prognosis in patients with incidental prostate cancer (iPCa) detected at radical cystectomy (RC) for bladder cancer (BCa). METHODS We retrospectively reviewed data of patients who underwent RC for BCa at our Institution between January 2005 and March 2018. Data regarding patient's history, preoperative digital rectal examination (DRE), total serum PSA level were collected from the chart review. Univariable and multivariable Cox regression models addressed the association of iPCa with recurrence-free survival (RFS) and overall survival (OS). RESULTS We obtained a final study cohort of 177 patients. Median age was 69 years (IQR 42-89) and 80(45.2%) patients had iPCa. Patients with iPCa had higher age, preoperative PSA levels and a significant rate of suspicious DRE (all P<0.05). Four patients had BCR during a median follow-up of 28 months (IQR 6-159) and none died for prostate cancer. In multivariable analyses adjusted for age, bladder cancer BCa pT and pN stage and LVI the ten-years RFS and OS rates were not impacted by iPCa regardless of whether it is a clinically significant cancer or not (HR=1.25, 95% CI: 0.65-2.38, P=0.51 vs. HR=1.37, 95% CI: 0.71-2.64, P=0.35) (HR=1.04, 95% CI: 0.53-1.86, P=0.89 vs. HR=1.20, 95% CI: 0.22-6.72, P=0.83). CONCLUSIONS iPCa is quite common in our study group and most of cases are organ-confined and well differentiated. Regardless of clinical relevance, iPCa does not have an impact on survival outcomes as BCa is driving the prognosis of these patients.

Circulating Tumor Cells as a Marker of Disseminated Disease in Patients with Newly Diagnosed High-Risk Prostate Cancer.

The aim of this study was to investigate whether the enumeration of circulating tumor cells (CTCs) in blood can differentiate between true localized and metastatic prostate cancer. A cross-sectional study of 104 prostate cancer patients with newly diagnosed high-risk prostate cancer was conducted. In total, 19 patients presented metastatic disease and 85 were diagnosed with localized disease. Analyses included intergroup comparison of CTC counts, determined using the CellSearch® system, EPISPOT assay and GILUPI CellCollector®, and ROC analysis verifying the accuracy of CTC count as a maker of disseminated prostate cancer. The vast majority (94.7%) of patients with advanced-stage cancer tested positively for CTCs in at least one of the assays. However, significantly higher CTC counts were determined with the CellSearch® system compared to EPISPOT assay and GILUPI CellCollector®. Identification of ≥4 CTCs with the CellSearch® system was the most accurate predictor of metastatic disease (sensitivity 0.500; specificity 0.900; AUC (95% CI) 0.760 (0.613–0.908). Furthermore, we tried to create a model to enhance the specificity and sensitivity of metastatic prediction with CTC counts by incorporating patient’s clinical data, including PSA serum levels, Gleason score and clinical stage. The composite biomarker panel achieved the following performance: sensitivity, 0.611; specificity, 0.971; AUC (95% CI), 0.901 (0.810–0.993). Thus, although the sensitivity of CTC detection needs to be further increased, our findings suggest that high CTC counts might contribute to the identification of high-risk prostate cancer patients with occult metastases at the time of diagnosis.

PROSTATE-SPECIFIC ANTIGEN AND ITS MOLECULAR FORMS IN BLOOD SERUM OF HEALTHY WOMEN AND WOMEN WITH BREAST DISEASE

The purpose of the study was to provide data on the sources of prostate-specific antigen (Psa) in women, as well as on serum Psa levels in healthy women and in women with benign and malignant breast cancer. Material and methods. We analyzed 50 publications available from PubMed, Medline, Google scholar concerning non-prostatic sources of Psa and its use as a serum tumor-associated marker for benign and malignant breast tumors. Results. In our study, we focus on the recent findings on non-prostatic sources and regulation of Psa synthesis in women as well as on changes in serum concentrations of this marker in patients with benign and malignant breast tumors. Various Psa isoforms (total Psa and free Psa) and free/total ratio for the detection of breast cancer and the assessment of treatment response and early detection of breast cancer recurrence were analyzed. Conclusion . the results obtained highlight the value of the assessment of Psa isoforms for early detection, prediction of therapy response and detection of breast cancer relapse. However, further studies are needed to identify the role of Psa isoforms in the diagnosis and monitoring of breast cancer patients.

Clinical value of prostate-specific antigen combined with tumor abnormal protein (TAP) in the diagnosis of prostate puncture.

BackgroundIn this study, we aimed to test the clinical value of total prostate-specific antigen (T-PSA), free prostate-specific antigen (F-PSA), and T-PSA combined with tumor abnormal glycoprotein (TAP) for early diagnosis of prostate cancer.MethodsThe levels of serum T-PSA and F-PSA were measured in 105 malignant prostate tumors and 97 benign prostate tissues using chemiluminescence immunoassay. The concentration of TAP in the serum of patients was tested by the agglutination method. Differences in PSA levels and F-PSA/T-PSA ratio in two patient groups were analyzed by t-test. TAP concentrations were compared using Chi-square test. The sensitivity, specificity, and accuracy of PSA combined with TAP for the diagnosis of prostate cancer were analyzed.ResultsThe serum PSA level in patients with malignant tumors were higher than that in patients with benign tumors (P<0.0001). TAP positivity in patients with prostate cancer was higher than that in patients with benign tumors (P<0.0001). The number of cases with positive and weakly positive TAP values in three intervals of T-PSA concentrations was higher in patients with malignant tumors, while the number of negative cases was higher in patients with benign tumors (P<0.05). The sensitivity, specificity, and accuracy of T-PSA combined with TAP in the diagnosis of prostate cancer were 97.14%, 67.01%, and 81.68% respectively, which was higher compared to the other measured markers.ConclusionsThe results of our study indicate that PSA combined with TAP is a sensitive, specific, and accurate diagnostic marker of prostate cancer. Therefore, it has potential clinical relevance for the early screening of prostate cancer.

Loss of cytoplasmic survivin expression is an independent predictor of poor prognosis in radically operated prostate cancer patients.

Survivin is an inhibitor of apoptosis. Aberrant survivin expression occurs in malignant tumors and has often been linked to unfavorable patient outcome. Here we analyzed 12 432 prostate cancers by immunohistochemistry. Survivin immunostaining was regularly expressed at high levels in normal prostate epithelium but expression was often reduced in prostate cancers. Among 9492 evaluable prostate cancers, 9% expressed survivin strongly, 19% moderately, 28% weakly, and 44% lacked it. Loss of cytoplasmic survivin was seen in advanced tumor stage, higher Gleason score, preoperative PSA levels, and Ki‐67 labeling index, and associated with earlier PSA recurrence (P < .0001). Survivin loss was significantly more common in cancers carrying TMPRSS2:ERG fusions (61% survivin negative) than in ERG wild‐type cancers (32% survivin negative; P < .0001). Multivariate analysis revealed that reduced cytoplasmic survivin expression predicted poor prognosis independent from Gleason score, pT, pN, and serum PSA level. This was valid for ERG‐positive and ERG‐negative cancers. Survivin expression loss even retained its prognostic impact in 1020 PTEN deleted cancers, a group that is already characterized by dismal patient prognosis. In conclusion, reduced survivin expression is associated with more aggressive tumors and inferior prognosis in prostate cancer.

Prostate Specific Antigen Nadir After Radical Cystoprostatectomy in Patients With Benign Prostatic Tissue: A Benchmark To Define Biochemical Recurrence after Radical Prostatectomy.

Biochemical failure after radical prostatectomy has been defined based on retrospective studies in men who underwent RP for localized prostate cancer. Nevertheless, retrospective strategy and possibility of extra-prostatic extension overshadowed the accurateness of the aforementioned cut-off value. To define a more precise PSA nadir value, we estimated serum PSA after cystoprostatectomy in cases with bladder urothelial cancer and no evidence of prostate cancer. Study population consists of 52 subsequent patients who underwent radical cystoprostatectomy for muscle-invasive bladder cancer between December 2010 and December 2013. Patients with prostate adenocarcinoma and/or high grade prostate intraepithelial neoplasia were excluded from enrollment. Other exclusion criteria were prostate involvement with urothelial carcinoma, neoadjuvant or adjuvant chemotherapy and radiation therapy. Between all cases, 41 were enrolled for study. Serum PSA level was measured using immunochemiluminescence method among 6 months to 3 years after operation in study participants. Forty-one patients with mean age of 66.4 ± 8.9 were assessed in this study. Average serum PSA level after radical cysto-prostatectomy was .037 ± .031 ng/mL (from .002 to .1). Serum PSA level was not impressed with type of diversion or interval between operation and PSA measurement. Average serum PSA level in this study was meaningfully lesser than .2 ng/mL which is contemplated as PSA nadir value after RP. Serum PSA level of 0.2 ng/mL as the definition for biochemical recurrence after RP may delay salvage treatment. Our results showed that cut off value of ?0.1 ng/mL may be more precise in the era of early salvage treatment.

Role of Vitamin D in Prostate Cancer in Developing Country

Introduction: Vitamin D 3 deficiency continues to be an unrecognized epidemic in many populations around the world. Vitamin D is important for the absorption of calcium, and bone formation and maintenance Materials and Methods: 150 patients enrolled for the study along with control, serum analyzed by vitros – Eci- dry chemistry analyzer, (Johnson–Johnson). Study done in CRGH Hospital, in R.D. Gardi Medical College, Ujjain, Madhya Pradesh, during Dec. 2015- Sep. 2016. All data were analyzed by Graph pad. Prism 8. Results: We have found decrease level of Vitamin D in patients with higher serum PSA level, p value &lt; 0.0001. Conclusion: Supplementation of Vitamin D is required for developing countries especially for older having higher risk of prostate carcinoma.

Sexual and functional outcomes of prostate artery embolisation: A prospective long-term follow-up, large cohort study.

Among minimally invasive procedures for treating benign prostate hyperplasia (BPH) prostate artery embolisation (PAE) is described as safe and effective. Aim of this study is to report our results, focusing on sexual outcomes (erectile and ejaculatory functions sparing) of PAE in patients suffering from bladder outlet obstruction (BOO) secondary to BPH. We prospectively enrolled and submitted to PAE subjects suffering from BOO secondary to BPH. All patients were not suitable for surgery or declined invasive approaches. All subjects were preoperatively and postoperatively (3, 6, 12 and 18months after) evaluated by urinary flowmetry, post voiding residual volume, prostate volume, serum PSA levels, International Index of Erectile Function, International Prostate Symptom Score and QoL scores. PAE was performed in 147 patients (mean age 72.5 y.o.). PAE was technically successful in all patients. The procedure lasted a mean time of 94.3minutes, with a mean fluoroscopic time of 42.5minutes. Twelve months follow-up data were available for all patients, while 126 patients (85%) completed the 18months follow up. At 12months follow up, the mean IPSS and QoL scores significantly decreased, and all the objective parameters (mean Qmax, PVR and prostate volume) reported a significant improvement. A total of 130 patients (88.5%) at 12months reported the antegrade ejaculation preserved, and a slight not significant improvement of IIEF scores. The 18months after PAE outcomes confirmed the significant improvement of all the variables evaluated (even for PSA values and IIEF scores). No major complications occurred. Our results evidence prostate artery embolisation as highly feasible and safe procedure with interesting outcomes. In particular, in our study PAE reported promising results in preserving antegrade ejaculation and erectile function. Our data are in line with the literature, confirming how PAE reduces obstructive symptoms in BPH patients not suitable or refusing standard surgical approaches.

Efficacy and outcome of holmium laser enucleation of prostate in patients with urinary retention due to advanced prostate cancer

To evaluate the efficacy and safety of holmium laser enucleation of prostate (HoLEP) for treating urinary retention in patients with advanced prostate cancer. Thirty-eight cases of advanced prostate cancer with urinary retention were enrolled in this retrospective study. All the 38 patients were treated with CAB as a basis. Among them, 21 cases chose HoLEP additionally (HoLEP group). Seventeen cases stuck to CAB alone (CAB group). Serum PSA level, International Prostate Symptom Score (IPSS), quality of life score (QoLs), maximal flow rate (Qmax), and post-void residual volume (PVR) at 3, 6, 12, and 18 months after treatment were comparatively analyzed. The perioperative and postoperative parameters of HoLEP were assessed. Both groups demonstrated significant improvement in IPSS, QoLs, Qmax, and PVR during follow-up. But these parameters of HoLEP group improved more rapidly, significantly, and durably than CAB group. No serious complications were observed during and after HoLEP. PSA level of patients in both groups declined dramatically after surgery. But PSA in HoLEP group showed more dramatic and continuous drop. Besides, 1 of 21 patients in HoLEP group transferred into castration-resistant prostate cancer (CRPC) at 18th month of follow-up. While in CAB group, 5 of 17 patients developed into CRPC at 12th month of follow-up (P = 0.02 < 0.05). HoLEP was minimally invasive, safe, and effective, and could serve as a palliative approach to rapidly restore the patients' urine and play a cytoreductive role in advanced PCa to improve the oncological prognosis.