Diagnostic capability of 18F-PSMA PET-MRI and pelvic MRI plus bone scan in treatment-naive prostate cancer: a single-center paired validating confirmatory study.

BACKGROUND: Radical prostatectomy with pelvic lymph node dissection for the treatment of high-risk localized prostate cancer (PCa) results in long-term benefits in selected patients. But insufficient sensitivity of conventional examinations which are pelvic MRI and bone scan, limits the diagnosis of bone and lymph node metastasis of PCa. This affects the surgical management strategy of a large number of patients. The purpose of this study was to investigate whether 18F-prostate-specific membrane antigen (PSMA) PET-MRI could improve the clinical detection of PCa metastases compared with the conventional pelvic MRI plus bone scan. MATERIALS AND METHODS: From April 2020 to April 2023, we prospectively enroled 472 patients with histologically proven PCa in our centre, and 120 patients underwent 18F-PSMA PET-MRI, multiparametric MRI, and bone scan before laparoscopic radical prostatectomy plus lymph node dissection. The accuracy of imaging results in detecting lymph node and bone metastatic lesions was compared between PSMA PET-MRI and MRI plus bone scan. RESULTS: In diagnosing lymph node metastasis, PSMA PET-MRI had an area under the curve (AUC) of 0.844 (95% CI: 0.738-0.949, P < 0.001), sensitivity and specificity of 75% and 96%, which performed apparently better than MRI [AUC=0.615 (95% CI: 0.480-0.750, P =0.073)]. PSMA PET-MRI showed excellent expression in the diagnosis of bone metastases, with an AUC of 0.910 (95% CI: 0.840-0.981, P <0.001) compared to 0.700 (95% CI: 0.577-0.823, P =0.001) in bone scanning. PSMA PET-MRI also had higher sensitivity than bone scanning (90% vs. 43%), while lower specificity (92% vs. 97%). CONCLUSION: PSMA PET-MRI is superior to conventional imaging at diagnosing metastases in lymph nodes and bones in PCa and can provide a more accurate stagement.

Association of biopsy core number and location with pain in patients undergoing a transperineal prostate biopsy under local anaesthesia: a secondary analysis of the APROPOS trial.

BACKGROUND: APROPOS was a multicentre, randomized, blinded trial focus on investigating the perineal nerve block versus the periprostatic block in pain control for men undergoing a transperineal prostate biopsy. In the analysis reported here, the authors aimed to evaluate the association of biopsy core count and location with pain outcomes in patients undergoing a transperineal prostate biopsy under local anesthesia. METHODS: APROPOS was performed at six medical centers in China. Patients with suspected prostate cancer were randomized to receive either a perineal nerve block or a periprostatic block (1:1), followed by a transperineal prostate biopsy. The secondary analysis outcomes were the worst pain experienced during the prostate biopsy and postbiopsy pain at 1,6, and 24 h. RESULTS: Between 12 August 2020 and 20 July 2022, a total of 192 patients were randomized in the original trial, and 188 were involved in this analysis, with 94 patients per group. Participants had a median (IQR) age of 68 (63-72) and a median (IQR) prostate volume of 42.51 (30.04-62.84). The patient population had a median (IQR) number of biopsy cores of 15 (12-17.50), and 26.06% of patients had a biopsy cores count of more than 15. After adjusting the baseline characteristics, the number of biopsy cores was associated with the worst pain during the biopsy procedure in both the perineal nerve block group ( ß 0.19, 95% CI: 0.12-0.26, P <0.001) and the periprostatic block group ( ß 0.16, 95% CI: 0.07-0.24, P <0.001). A similar association was also evident for the postbiopsy pain at 1, 6, and 24 h. A lesser degree of pain in both groups at any time (r range -0.57 to -0.01 for both groups) was associated with biopsy cores from the peripheral zone of the middle gland, while other locations were associated with a higher degree of pain. In addition, the location of the biopsy core had less of an effect on pain during the biopsy (r range -0.01-0.25 for both groups) than it did on postbiopsy pain (r range -0.57-0.60 for both groups). CONCLUSIONS: In this secondary analysis of a randomized trial, biopsy core count and location were associated with pain in patients undergoing a transperineal prostate biopsy under local anesthesia. These results may be helpful for making clinical decisions about the anesthetic approach for scheduled transperineal prostate biopsies.

Perineal nerve block versus periprostatic block for patients undergoing transperineal prostate biopsy (APROPOS): a prospective, multicentre, randomised controlled study.

Background: We aimed to investigate perineal nerve block versus periprostatic block in pain control for men undergoing a transperineal prostate biopsy. Methods: In this prospective, randomised, blinded and parallel-group trial, men in six Chinese hospitals with suspected prostate cancer were randomly assigned (1:1) at the point of local anaesthesia to receive a perineal nerve block or periprostatic block and followed by a transperineal prostate biopsy. Centres used their usual biopsy procedure. Operators who performed anaesthesia were trained in both techniques before the trial and were masked to the randomised allocation until the time of anaesthesia and were not involved in the subsequent biopsy procedure and any assessment or analysis. Other investigators and the patients were masked until trial completion. The primary outcome was the level of the worst pain experienced during the prostate biopsy procedure. Secondary outcomes included pain (post-biopsy at 1, 6 and 24 h), changes in blood pressure, heart rate and breathing rate during the biopsy procedure, external manifestations of pain during biopsy, anaesthesia satisfaction, the detection rate of PCa and clinically significant PCa. This trial is registered on ClinicalTrials.gov, NCT04501055. Findings: Between August 13, 2020, and July 20, 2022, 192 men were randomly assigned to perineal nerve block or periprostatic block, 96 per study group. Perineal nerve block was superior for the relief of pain during the biopsy procedure (mean 2.80 for perineal nerve block and 3.98 for periprostatic block; adjusted difference in means -1.17, P < 0.001). Although the perineal nerve block had a lower mean pain score at 1 h post-biopsy compared with the periprostatic block (0.23 vs 0.43, P = 0.042), they were equivalent at 6 h (0.16 vs 0.25, P = 0.389) and 24 h (0.10 vs 0.26, P = 0.184) respectively. For the change in vital signs during biopsy procedure, perineal nerve block was significantly superior to periprostatic block in terms of maximum value of systolic blood pressure, maximum value of mean arterial pressure and maximum value of heart rate. There are no statistical differences in average value of systolic blood pressure, average value of mean, average value of heart rate, diastolic blood pressure and breathing rate. Perineal nerve block was also superior to periprostatic block in external manifestations of pain (1.88 vs 3.00, P < 0.001) and anaesthesia satisfaction (8.93 vs 11.90, P < 0.001). Equivalence was shown for the detection rate of PCa (31.25% for perineal nerve block and 29.17% for periprostatic block, P = 0.753) or csPCa (23.96% for perineal nerve block and 20.83% for periprostatic block, P = 0.604). 33 (34.8%) of 96 patients in the perineal nerve block group and 40 (41.67%) of 96 patients in the periprostatic block group had at least one complication. Interpretation: Perineal nerve block was superior to periprostatic block in pain control for men undergoing a transperineal prostate biopsy. Funding: Grant 2019YFC0119100 from the National Key Research and Development Program of China.

Extended Focal Ablation of Localized Prostate Cancer With High-Frequency Irreversible Electroporation: A Nonrandomized Controlled Trial.

Importance: Focal therapy of prostate cancer must balance the oncologic outcome and functional outcome. High-frequency irreversible electroporation (H-FIRE) can destroy cancer cells while selectively preserving surrounding nerves and blood vessels, but no clinical trials have been conducted, to our knowledge. Objective: To evaluate the efficacy and safety of H-FIRE in the treatment of localized prostate cancer (PCa). Design, Setting, and Participants: This was a single-group, objective performance criteria, nonrandomized controlled trial. Recruitment began on May 2, 2018, and ended March 27, 2019. The follow-up duration was 6 months. This was a multicenter trial conducted at 4 tertiary teaching hospitals in China. Patients with low or intermediate risk of biochemical recurrence of localized and locally advanced PCa were eligible. Key inclusion criteria were serum prostate-specific antigen (PSA) level less than 20 ng/mL, clinical stage of T2c or less, and Gleason score of 7 or less. Data were analyzed from January 20 to February 20, 2021. Intervention: H-FIRE ablation of all lesions identified with biopsy. Main Outcomes and Measures: The primary end point was 6-month clinically significant PCa (csPCa), which was defined as any biopsy core with Gleason score of greater than or equal to 7, or Gleason score of 6 plus maximum cancer core length of greater than 3 mm or an increase from the original cancer burden. Secondary outcomes were calculated in patients who actually received H-FIRE treatment. Results: A total of 117 patients (median [IQR] age, 67 [62-73] years) were recruited from 4 centers, and 109 patients (27 [24.8%] low risk and 82 [75.2%] intermediate risk) actually received H-FIRE. Median (IQR) PSA level was 9.0 (6.0-12.7) ng/mL. Among the 100 patients who underwent biopsy at 6 months, the 6-month csPCa rate was 6.0% (95% CI, 2.2%-12.6%; P < .001; 1 in the treatment zone and 5 outside the treatment zone). Superiority criteria vs the historical control of 20% was achieved. PCa was detected in 14 patients, with a Gleason score of 7 in 2 patients and 6 in the remaining 12 patients. At 6 months, median (IQR) PSA level was 1.08 (0.4-3.2) ng/mL, median (IQR) International Prostate Symptom Score was 4.5 (2.0-9.5), and median (IQR) International Index of Erectile Function 5 score was 2.0 (0.5-12.5). Superiority vs the 20% historical control was also met in the subgroup analysis that only included the 57 patients with Gleason score of 7 at baseline (3.5% 6-month csPCa; 95% CI, 0.4%-12.1%). Conclusions and Relevance: The rate of 6-month csPCa with H-FIRE ablation was lower than the historical control using other energy platforms. Trial Registration: ClinicalTrials.gov Identifier: NCT03838432.

A Prospective Study Comparing Cancer Detection Rates of Transperineal Prostate Biopsies Performed by Junior Urologists versus a Senior Consultant in a Real-World Setting.

INTRODUCTION: Prostate biopsy (PB) is a typical daily practice method for the diagnosis of prostate cancer (PCa). This study aimed to compare the PCa detection rates and peri- and postoperative complications of PB among 3 residents and a consultant. PATIENTS AND METHODS: A total of 343 patients who underwent PB between August 2018 and July 2019 were involved in this study. Residents were systematically trained for 2 weeks by a consultant for performing systematic biopsy (SB) and targeted biopsy (TB). And then, 3 residents and the consultant performed PB independently every quarter due to routine rotation in daily practice. The peri- and postoperative data were collected from a prospectively maintained database (www.pc-follow.cn). The primary outcome and secondary outcome were to compare the PCa detection rates and complications between the residents and consultant, respectively. RESULTS: There was no significant difference between the residents and consultant in terms of overall PCa detection rates of SB and TB or further stratified by prostate-specific antigen value and prostate imaging reporting and data system (PI-RADS) scores. We found the consultant had more TB cores (175 cores vs. 86-114 cores, p = 0.043) and shorter procedural time (mean 16 min vs. 19.7-20.1 min, p < 0.001) versus the residents. The complication rate for the consultant was 6.7% and 5%-8.2% for the residents, respectively (p = 0.875). CONCLUSIONS: The residents could get similar PCa detection and complication rates compared with that of the consultant after a 2-week training. However, the residents still need more cases to shorten the time of the biopsy procedure.

A Multicenter Single-Arm Objective Performance Criteria Trial to Determine the Efficacy and Safety of High-Frequency Irreversible Electroporation as Primary Treatment for Localized Prostate Cancer: A Study Protocol.

INTRODUCTION: The classical pathway for the therapy of low- to intermediate-risk localized prostate cancer is radical prostatectomy or radiation therapy, which has shown a high incidence of complications, including erectile dysfunction, urinary incontinence, and bowel injury. An alternative pathway is to perform an ablation by some energy to the localized lesion, known as focal therapy. High-frequency irreversible electroporation (H-FIRE) is nonthermal energy that can be used in cancer ablation to deliver pulsed high-voltage but low-energy electric current to the cell membrane and to invoke cell death. An H-FIRE pathway has been reported to be tissue-selective, which leads to fewer side effects. METHODS AND ANALYSIS: This is a multicenter and single-arm objective performance criteria (OPC) study, in which all men with localized prostate cancer are allocated to H-FIRE ablation. This trial will assess the efficacy and safety of the H-FIRE ablation for prostate cancer. Efficacy will be assessed by prostate biopsy 6 months after treatment while safety will be assessed by adverse event reports and questionnaires. The main inclusion criteria are moderate to low-risk prostate cancer in NCCN risk classification and had no previous therapy for prostate cancer. A sample size of 110 participants is required. The primary objective is to determine whether the detection rate of clinically significant cancer by prostate biopsy is less than 20% after the H-FIRE ablation. ETHICS AND DISSEMINATION: This study has obtained ethical approval by the ethics committee of all participating centers. The results of the study will be submitted for dissemination and publication in peer-reviewed journals. CONCLUSIONS: This multicenter single-arm objective performance criteria trial will evaluate the efficacy and safety of the use of high-frequency irreversible electroporation in treating prostate cancer. STRENGTHS AND LIMITATIONS OF THIS STUDY: A comprehensive evaluation of imaging and histopathology is used to determine the effect of treatment. Questionnaires were used to assess the treatment side effects. Multicenter and pragmatic designs capacitate higher generalizability. A limitation of this trial is that the prostate biopsy as an endpoint may not be as accurate as of the specimen from prostate prostatectomy. Another limitation is the 6-month follow-up time, making this trial challenging to come to firm conclusions regarding the efficacy and safety of IRE in the long term. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03838432.

Anaesthesia in PROstate Biopsy Pain Obstruction Study: A Study Protocol for a Multicentre Randomised Controlled Study Evaluating the Efficacy of Perineal Nerve Block in Controlling Pain in Patients Undergoing Transperineal Prostate Biopsy.

Introduction: Transperineal prostate biopsy is as effective as the transrectal biopsy in detecting prostate cancer and has a lower risk of infection. However, concerning the procedural pain of the transperineal route, a higher level of anaesthesia is needed, which prevents this approach from being widely used. Although several methods of local anaesthesia to relieve pain during transperineal biopsy have been described, few well-designed trials have been conducted to assess the efficacy of local anaesthesia. Methods: This is a prospective, multicentre, randomised controlled study in men suspected of having prostate cancer and planning to undergo transperineal prostate biopsy. The aim of this trial is to determine whether the perineal nerve block and periprostatic block relieve pain to different extents in men undergoing transperineal biopsy. The main inclusion criteria are men aged between 18 and 80 years old, a prostate-specific antigen (PSA) level of 4-20 ng/ml, or/and suspicious rectal examination findings. A sample size of 190 participants, accounting for a 10% loss, is required. All participants will be randomly allocated at a ratio of 1:1 to the perineal nerve block (n = 95) and periprostatic block groups (n = 95). The primary outcome will be the level of the worst pain experienced during the transperineal prostate biopsy procedure, which will be measured by a numerical rating scale (NRS). The key secondary outcomes will include the pain severity score at 1, 6, and 24 h after prostate biopsy. Results: The primary outcome is the level of the worst pain experienced during the prostate biopsy procedure. The main secondary outcomes are as follows: (1) Post-biopsy pain severity score at 1, 6, and 24 h after the prostate biopsy; (2) Changes in blood pressure, heart rate and breathing rate during the biopsy procedure; (3) External manifestations of pain during biopsy; (4) Anaesthesia satisfaction; (5) The detection rate for clinically significant prostate cancer and any prostate cancer. Conclusion: Anaesthesia in PROstate biopsy Pain Obstruction Study (APROPOS) is randomised controlled trial aiming to determine the efficacy of the perineal nerve block in controlling pain in patients undergoing prostate biopsy via the transperineal approach. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04501055.

Study protocol for a single-centre non-inferior randomised controlled trial on a novel three-dimensional matrix positioning-based cognitive fusion-targeted biopsy and software-based fusion-targeted biopsy for the detection rate of clinically significant prostate cancer in men without a prior biopsy.

INTRODUCTION: The classical pathway for diagnosing prostate cancer is systematic 12-core biopsy under the guidance of transrectal ultrasound, which tends to underdiagnose the clinically significant tumour and overdiagnose the insignificant disease. Another pathway named targeted biopsy is using multiparametric MRI to localise the tumour precisely and then obtain the samples from the suspicious lesions. Targeted biopsy, which is mainly divided into cognitive fusion method and software-based fusion method, is getting prevalent for its good performance in detecting significant cancer. However, the preferred targeted biopsy technique in detecting clinically significant prostate cancer between cognitive fusion and software-based fusion is still beyond consensus. METHODS AND ANALYSIS: This trial is a prospective, single-centre, randomised controlled and non-inferiority study in which all men suspicious to have clinically significant prostate cancer are included. This study aims to determine whether a novel three-dimensional matrix positioning cognitive fusion-targeted biopsy is non-inferior to software-based fusion-targeted biopsy in the detection rate of clinically significant cancer in men without a prior biopsy. The main inclusion criteria are men with elevated serum prostate-specific antigen above 4-20 ng/mL or with an abnormal digital rectal examination and have never had a biopsy before. A sample size of 602 participants allowing for a 10% loss will be recruited. All patients will undergo a multiparametric MRI examination, and those who fail to be found with a suspicious lesion, with the anticipation of half of the total number, will be dropped. The remaining participants will be randomly allocated to cognitive fusion-targeted biopsy (n=137) and software-based fusion-targeted biopsy (n=137). The primary outcome is the detection rate of clinically significant prostate cancer for cognitive fusion-targeted biopsy and software-based fusion-targeted biopsy in men without a prior biopsy. The clinically significant prostate cancer will be defined as the International Society of Urological Pathology grade group 2 or higher. ETHICS AND DISSEMINATION: Ethical approval was obtained from the ethics committee of Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. The results of the study will be disseminated and published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04271527).

Construction and Validation of a Clinical Predictive Nomogram for Improving the Cancer Detection of Prostate Naive Biopsy Based on Chinese Multicenter Clinical Data.

OBJECTIVES: Prostate biopsy is a common approach for the diagnosis of prostate cancer (PCa) in patients with suspicious PCa. In order to increase the detection rate of prostate naive biopsy, we constructed two effective nomograms for predicting the diagnosis of PCa and clinically significant PCa (csPCa) prior to biopsy. MATERIALS AND METHODS: The data of 1,428 patients who underwent prostate biopsy in three Chinese medical centers from January 2018 to June 2021 were used to conduct this retrospective study. The KD cohort, which consisted of 701 patients, was used for model construction and internal validation; the DF cohort, which consisted of 385 patients, and the ZD cohort, which consisted of 342 patients, were used for external validation. Independent predictors were selected by univariate and multivariate binary logistic regression analysis and adopted for establishing the predictive nomogram. The apparent performance of the model was evaluated via internal validation and geographically external validation. For assessing the clinical utility of our model, decision curve analysis was also performed. RESULTS: The results of univariate and multivariate logistic regression analysis showed prostate-specific antigen density (PSAD) (P<0.001, OR:2.102, 95%CI:1.687-2.620) and prostate imaging-reporting and data system (PI-RADS) grade (P<0.001, OR:4.528, 95%CI:2.752-7.453) were independent predictors of PCa before biopsy. Therefore, a nomogram composed of PSAD and PI-RADS grade was constructed. Internal validation in the developed cohort showed that the nomogram had good discrimination (AUC=0.804), and the calibration curve indicated that the predicted incidence was consistent with the observed incidence of PCa; the brier score was 0.172. External validation was performed in the DF and ZD cohorts. The AUC values were 0.884 and 0.882, in the DF and ZD cohorts, respectively. Calibration curves elucidated greatly predicted the accuracy of PCa in the two validation cohorts; the brier scores were 0.129 in the DF cohort and 0.131 in the ZD cohort. Decision curve analysis showed that our model can add net benefits for patients. A separated predicted model for csPCa was also established and validated. The apparent performance of our nomogram for PCa was also assessed in three different PSA groups, and the results were as good as we expected. CONCLUSIONS: In this study, we put forward two simple and convenient clinical predictive models comprised of PSAD and PI-RADS grade with excellent reproducibility and generalizability. They provide a novel calculator for the prediction of the diagnosis of an individual patient with suspicious PCa.

A Novel Perineal Nerve Block Approach for Transperineal Prostate Biopsy: An Anatomical Analysis-based Randomized Single-blind Controlled Trial.

OBJECTIVE: To develop and validate a novel perineal nerve block approach for transperineal prostate biopsy. PATIENTS AND METHODS: Five adult male cadavers were dissected to delineate the superficial and deep branches of the perineal nerve. Afterwards, 90 out of 115 patients were selected and randomly assigned to receive periprostatic, periapical triangle, or branches of perineal nerve (BPN) block. The primary outcome was the maximal pain intensity associated with transperineal prostate biopsy, which was assessed by the 10-point visual analog scale. The secondary outcomes included the number of biopsy with visual analog scale of ≥4 in each biopsy procedure, and the incidences of complications. RESULTS: On the horizontal line of the upper anal border, the locations of the superficial branch of perineal nerve on the left and right sides were 1.87 ± 0.05 cm and 1.86 ± 0.06 cm, respectively; and the deep branch were 2.15 ± 0.07 cm and 2.16 ± 0.06 cm, respectively, from the midline, and lied between the deep layer of superficial fascia and prostate capsule. The number of cases finally enrolled in data analysis in periprostatic block, periapical triangle block, and BPN block groups were 26, 27, and 30, respectively. The maximal pain intensities were 3.4 (3.1-3.7), 3.3 (3.0-3.6), and 1.8 (1.5-2.2) in the 3 groups, respectively, and the numbers of biopsy with the pain intensity of ≥4 were 4.0 (3.2-4.9), 4.2 (3.3-5.2), and 0.7 (0.1-1.2), respectively. There were 4, 3 and 4 cases developing hematuria, and 1, 1 and 2 burdened with urine retention after biopsy in the 3 groups, respectively. CONCLUSION: Collectively, BPN block is a safe, effective and repeatable local anesthesia approach for transperineal prostate biopsy.

Transrectal Ultrasound-Guided Transperineal Puncture: A Viable Alternative for Difficult Removal of an Indwelling Catheter in a Postrobot-Assisted Laparoscopic Radical Prostatectomy Patient.

Background: The inability to remove an indwelling urethral catheter in a postrobot-assisted laparoscopic radical prostatectomy (RALP) patient constitutes a serious problem to the urologist. If the proper deflation of the catheter balloon is not observed, forcible extraction can lead to devastating consequences such as urethral disruption and subsequent stricture formation. Case Presentation: A 60-year-old male patient developed lower urinary-tract symptoms 20 months after robotic prostatectomy for early prostate cancer. Cystourethroscopy revealed a migrated Hemo-lok clip that was extracted near the anastomotic site, followed by insertion of an indwelling Foley catheter. Two weeks later, the patient accidentally pulled the catheter into the urethra. Several attempts were done to deflate the catheter, which failed. Subsequently, a transrectal ultrasound (TRUS)-guided transperineal puncture was done to deflate the catheter balloon followed by effective catheter removal. Conclusion: TRUS-guided transperineal puncture (under local anesthesia) of an indwelling catheter balloon is a viable alternative for patients who have a history of RALP.

The previously uncharacterized lncRNA APP promotes prostate cancer progression by acting as a competing endogenous RNA.

Long noncoding RNAs (lncRNAs) promote cell proliferation, migration, invasion and castration resistance in prostate cancer (PCa). Understanding the inherited molecular mechanisms by which lncRNAs contribute to the progression of PCa to a lethal disease could have an important impact on cancer detection, diagnosis and prognosis. In our study, PCa-associated lncRNA transcripts from RNA-seq data were identified and screened via bioinformatics analysis, NCBI annotations and literature review. We identified a novel lncRNA, lncAPP (lncRNA activated in PCa progression), which activates in PCa progression and is expressed in primary tumor tissues and urine samples of patients with localized or advanced PCa. Urinary-based lncAPP is a promising biomarker for predicting PCa progression. In vitro and in vivo studies demonstrated that lncAPP enhanced cell proliferation and promoted migration and invasion. The underlying mechanism of lncRNA was investigated by RNA immunoprecipitation, dual-luciferase reporter system assay, etc. Upregulation of lncAPP promoted cell migration and invasion via competitively binding miR218 to facilitate ZEB2/CDH2 expression. In addition, in vivo subcutaneous tumor xenograft models and tail intravenously injection metastatic models were constructed to evaluate lncRNA function. Targeting lncAPP/miR218 axis in cell lines and tumor xenografts restrained tumor progression properties both in vitro and in vivo. These results establish that lncAPP/miR218 axis plays a critical role in PCa progression, and they also suggest new strategies to prevent tumor progression for therapeutic purposes.

Prostate cancer risk prediction models in Eastern Asian populations: current status, racial difference, and future directions.

Prostate cancer (PCa) risk calculators (RCs) with prostate-specific antigen (PSA) and other risk factors can greatly improve the accurate prediction of potential risk of PCa compared to PSA. The European Randomized Study of Screening for PCa Risk Calculator (ERSPC-RC) and the Prostate Cancer Prevention Trial Risk Calculator (PCPT-RC) are developed on the Western population. However, the Western RCs showed limited diagnostic efficacy in the Eastern Asian population, mainly due to racial differences between the two populations. We aimed to review the application of Western RCs and Eastern Asian RCs in Eastern Asian cohorts and to identify the characteristics and efficacy of these RCs.

Initial experience with a novel method for cognitive transperineal magnetic resonance imaging-targeted prostate biopsy.

A cognitive magnetic resonance imaging (MRI)-targeted prostate biopsy conducted by an experienced clinician enhances the detection rate of (high-grade) prostate cancer; however, this method is less successful in the hands of inexperienced surgeons. Therefore, an alternative method of conducting a cognitive MRI-targeted biopsy that can be successfully performed by the inexperienced clinicians should be developed. Ninety-six males suspected of prostate cancer were analyzed using systematic biopsy and cognitive MRI-targeted biopsy based on our novel three-dimensional matrix positioning method. Typically, the core principle of the latter procedure was to put the MRI and ultrasound images into the same virtual coordinate system. Afterward, the targeted biopsy was transformed to target a coordinate for the suspected lesion in the MRI. Subsequently, patients were assessed for the presence/absence of prostate cancer or high-grade prostate cancer. According to our results, the overall detection rate of prostate cancer was 70.8% (68/96), and the detection rate of high-grade prostate cancer was 56.3% (54/96). Specifically, the detection rate of prostate cancer by systematic biopsy was 54.2% (52/96) and that by targeted biopsy was 59.4% (57/96; P = 0.560). Clearly, the combined application of targeted biopsy could remarkably increase the detection rates of prostate cancer (P = 0.025) and high-grade prostate cancer (P = 0.009). Taken together, the findings of this study suggest that the combination of systematic biopsy with our three-dimensional matrix positioning-driven cognitive-targeted biopsy is superior to systematic biopsy in detecting prostate cancer and high-grade prostate cancer.

A Novel Prediction Tool Based on Multiparametric Magnetic Resonance Imaging to Determine the Biopsy Strategy for Clinically Significant Prostate Cancer in Patients with PSA Levels Less than 50 ng/ml.

PURPOSE: To develop and internally validate nomograms to help choose the optimal biopsy strategy among no biopsy, targeted biopsy (TB) only, or TB plus systematic biopsy (SB). PATIENTS AND METHODS: This retrospective study included a total of 385 patients who underwent magnetic resonance imaging (MRI)-guided TB and/or SB at our institute after undergoing multiparametric MRI (mpMRI) between 2015 and 2018. We developed models to predict clinically significant prostate cancer (csPCa) based on suspicious lesions from a TB result and based on the whole prostate gland from the results of TB plus SB or SB only. Nomograms were generated using logistic regression and evaluated using receiver-operating characteristic (ROC) curve analysis, calibration curves and decision analysis. The results were validated using ROC curve and calibration on 177 patients from 2018 to 2019 at the same institute. RESULTS: In the multivariate analyses, prostate-specific antigen level, prostate volume, and the Prostate Imaging Reporting and Data System score were predictors of csPCa in both nomograms. Age was also included in the model for suspicious lesions, while obesity was included in the model for the whole gland. The area under the curve (AUC) in the ROC analyses of the prediction models was 0.755 for suspicious lesions and 0.887 for the whole gland. Both models performed well in the calibration and decision analyses. In the validation cohort, the ROC curve described the AUCs of 0.723 and 0.917 for the nomogram of suspicious lesions and nomogram of the whole gland, respectively. Also, the calibration curve detected low error rates for both models. CONCLUSION: Nomograms with excellent discriminative ability were developed and validated. These nomograms can be used to select the optimal biopsy strategy for individual patients in the future.

Trans-Perineal Template-Guided Mapping Biopsy vs. Freehand Trans-Perineal Biopsy in Chinese Patients With PSA < 20 ng/ml: Similar Cancer Detection Rate but Different Lesion Detection Rate.

The present study aimed to investigate the diagnostic efficacy and the regional location of prostate cancer (PCa) as well as the accuracy of assessment between trans-perineal template-guided mapping biopsy (TTMB) and freehand trans-perineal biopsy (FTPB) for men with PSA < 20 ng/ml. Thus, we evaluated 623 consecutive patients with PSA < 20 ng/ml who had prostate biopsies in our institute between July 2017 and September 2018. Patients were divided into two groups based on different biopsy methods: 217 (34.83%) patients with TTMB and 406 (65.17%) with FTPB. Thirty six patients with TTMB and 80 with FTPB had continued undergone radical prostatectomy after a cancer diagnosis. Then the Gleason score of the biopsy and the post-radical prostatectomy specimens in each patient were compared. Overall, the PCa detection rate was 34.35%. There was no significant difference in PCa detection rate between TTMB and FTPB (35.48 vs. 33.74%, respectively; p = 0.663). Besides, the detection rate of significant PCa (Gleason score ≥ 7) in TTMB was 29.03% while FTPB was 23.89% (p = 0.162). The detection rate at the apex of the prostate was higher than the detection rate at the base of the prostate (9.80 vs. 5.79%; p < 0.01) when performing the TTMB. The FTPB would miss 10% of the positive diagnosis and almost half of the lesions. The upgraded of Gleason score from biopsy to post-radical prostatectomy was 16.67% with the TTMB and 36.25% with the FTPB (p = 0.034). The TTMB had a similar cancer detection rate, but a higher lesion detection rate and more accuracy in assess the actual Gleason score when comparing to FTPB for men with PSA < 20 ng/ml. By performing a 20-core TTMB, the cancer detection rate at the apex of the prostate was higher than the base.

Nomograms for predicting Gleason upgrading in a contemporary Chinese cohort receiving radical prostatectomy after extended prostate biopsy: development and internal validation.

The current strategy for the histological assessment of prostate cancer (PCa) is mainly based on the Gleason score (GS). However, 30-40% of patients who undergo radical prostatectomy (RP) are misclassified at biopsy pathologically. Thus, we developed and validated nomograms for the prediction of Gleason score upgrading (GSU) in patients who underwent radical prostatectomy after extended prostate biopsy in a Chinese population. This retrospective study included a total of 411 patients who underwent radical prostatectomy at our institute after having prostate biopsies between 2011 and 2015. The final pathologic GS was upgraded in 151 (36.74%) of the cases in all patients and 92 (60.13%) cases in men with GS=6. In multivariate analyses, the primary biopsy GS, secondary biopsy GS and obesity were predictive of GSU in the patient cohort assessed. In patients with GS=6, the significant predictors of GSU included the body mass index (BMI), prostate-specific antigen density(PSAD) and percentage of positive cores. The area under the curve (AUC) of the prediction models was 0.753 for the entire patient population and 0.727 for the patients with GS=6. Both nomograms were well calibrated, and decision curve analysis demonstrated a high net benefit across a wide range of threshold probabilities. This study may be relevant for improved risk assessment and clinical decision-making in PCa patients.

The mitotic regulator Hec1 is a critical modulator of prostate cancer through the long non-coding RNA BX647187 in vitro.

Hec1 (highly expressed in cancer) is a member of a conserved Ndc80 (nuclear division cycle 80) complex that regulates mitotic processes. Its overexpression is seen in various tumours and is associated with cancer progression. However, its expression pattern and role inhuman prostate cancer (PCa) still not clear. The aim of our study is to investigate the expression and functional role of Hec1 in human PCa. Hec1 expression was measured in 10 pairs of PCa cancerous and non-cancerous tissue samples by quantitative real-time (qRT)-PCR. The effects of Hec1 on PCa cells were studied by RNAi approach. Apoptosis and cell cycle were analysed by flow cytometry. Cells viability was evaluated using cell counting Kit-8. Cyclin B1-Cdc2 (cell division cycle 2) activity was measured by ELISA assay. Long non-coding (Lnc)RNAs regulated by Hec1 were gained from bioinformatics analysis. The role of LncRNA BX647187, regulated by Hec1, was finally characterized in PCa cells by siRNA. Our results showed that Hec1 mRNA and protein were significantly overexpressed in Human PCa tissues and several PCa cell lines. Silencing Hec1 markedly suppressed proliferation, promoted apoptosis and induced cell-cycle arrest in G2/M-phase in PCa cells. Through bioinformatics analysis and knockdown Hec1 in PCa cells, we found LncRNA BX647187 was positively regulated by Hec1. We further demonstrated that suppression of BX647187 in PCa cells significantly reduced cell proliferation and promoted apoptosis. Thus, we conclude that Hec1 is consistently overexpressed in human PCa and Hec1 is closely linked with human PCa progression through the meditator LncRNA BX647187. Our studies may contribute to understand the molecular mechanism of PCa pathogenesis and clinical therapy.

Percent free prostate-specific antigen for prostate cancer diagnosis in Chinese men with a PSA of 4.0-10.0 ng/mL: Results from the Chinese Prostate Cancer Consortium.

OBJECTIVE: To test the diagnostic performance of percent free prostate-specific antigen (%fPSA) in predicting any prostate cancer (PCa) and high-grade prostate cancer (HGPCa) in a retrospective multi-center biopsy cohort with a PSA level of 4.0-10.0 ng/mL in China. METHODS: Consecutive patients with a PSA of 4.0-10.0 ng/mL who underwent transrectal ultrasound-guided biopsy were enrolled at 16 Chinese medical centers from January 1st, 2010 to December 31st, 2013. Total and free serum PSA determinations were performed using three types of electro-chemiluminescence immunoassays recalibrated to the World Health Organization (WHO) standard. The diagnostic accuracy of PSA, %fPSA, and %fPSA in combination with PSA (%fPSA + PSA) was determined using the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: A total of 2310 consecutive men with PSA levels between 4.0 and 10.0 ng/mL were included, and the detection rate of PCa was 25.1%. The AUC of %fPSA and %fPSA + PSA in predicting any PCa was superior to PSA alone in men aged ≥60 years (0.623 vs. 0.534, p < 0.0001) but not in men aged 40-59 years (0.517 vs. 0.518, p = 0.939). Similar result was yield in predicting HGPCa. CONCLUSION: In a clinical setting of Chinese men with 4.0-10.0 ng/mL PSA undergoing initial prostate biopsy, adding %fPSA to PSA can moderately improve the diagnostic accuracy for any PCa and HGPCa compared with PSA alone in patients ≥60 but not in patients aged 40-59 years.