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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.

Objective: The influence of age on the performance of percent free prostate-specific antigen (%fPSA) in diagnosing prostate cancer (PCa) in East Asians is controversial. We tested the diagnostic performance of %fPSA in a multi-center biopsy cohort in China and identified the proper age-specific cutoff values to avoid unnecessary biopsies., Methods: Consecutive patients with a prostate-specific antigen (PSA) level of 4.0-10.0 ng/ml or 10.1-20.0 ng/ml who underwent transrectal ultrasound-guided or transperineal prostate biopsy were enrolled from 22 Chinese medical centers from Jan 1, 2010 to Dec 31, 2013. The diagnostic accuracy of PSA and %fPSA was determined using the area under the receiver operating characteristic (ROC) curve (AUC). Age-specific cutoff values were calculated using ROC curve analysis., Results: The median %fPSA was much lower in younger patients compared with older patients with a PSA level of 4.0-10.0 ng/ml or 10.1-20.0 ng/ml. The AUC of %fPSA was higher than PSA only in older patients. In patients aged 50 to 59 years, %fPSA failed to improve the diagnosis compared with PSA in these two PSA ranges. Age-specific cutoff values were 24%, 27% and 32% for patients aged 60-69, 70-79 and ≥80 years, respectively, to reduce unnecessary biopsies in men with PSA levels of 4.0-10.0 ng/ml to detect 90% of all PCa., Conclusions: The effectiveness of %fPSA is correlated with age in the Chinese population. Age-specific cutoff values would help avoid unnecessary biopsies in the Chinese population.

Background: The use of serum [-2]proPSA (p2PSA) and its derivative, the prostate health index (PHI), in detecting prostate cancer (PCa) have been consistently shown to have better performance than total prostate-specific antigen (tPSA) in discriminating biopsy outcomes in western countries. However, little is known about their performance in Chinese men. Our objective is to test the performance of p2PSA and PHI and their added value to tPSA in discriminating biopsy outcomes in Chinese men., Methods: Consecutive patients who underwent prostate biopsy in three tertiary hospitals in Shanghai, China during 2012-2013 were recruited. Serum tPSA, free PSA (fPSA), and p2PSA were measured centrally using Beckman Coulter's DxI 800 Immunoassay System. The primary outcome is PCa and the secondary outcome is high-grade PCa (Gleason Score of 4 + 3 or worse). Discriminative performance was assessed using the area under the receiver operating characteristic curve (AUC), detection rate and Decision Curve Analysis (DCA)., Results: Among 636 patients who underwent prostate biopsy, PHI was a significant predictor of biopsy outcomes, independent of other clinical variables. The AUC in discriminating PCa from non-PCa was consistently higher for PHI than tPSA in the entire cohort (0.88 vs. 0.81) as well as in patients with tPSA at 2-10 ng/ml (0.73 vs. 0.53), at 10.1-20 ng/ml (0.81 vs. 0.58), and at tPSA >20 ng/ml (0.90 vs. 0.80). The differences were statistically significant in all comparisons, P < 0.01. To detect 90% of all PCa in the cohort, 362 and 457 patients would need to be biopsied based on PHI and tPSA cutoff, respectively, a 21% reduction for PHI. Similar results were found for discriminating high-grade PCa., Conclusions: PHI provides added value over tPSA in discriminating PCa and high-grade PCa in patients who underwent prostate biopsy in China., (© 2014 Wiley Periodicals, Inc.)

Objectives: To investigate the safety profile and short-term outcome of super-veil nerve-sparing extraperitoneal single-port robotic-assisted radical prostatectomy (espRARP) on da Vinci Si platform. Methods: From December 2018 to March 2021, 106 consecutive patients with treatment-naive prostate cancer were prospectively included. espRARP was performed on da Vinci Si surgical platform. Operative time, estimated blood loss, Clavien–Dindo complication classification, continence, potency recovery, quality-of-life scores, and postoperative prostate-specific antigen (PSA) were documented. Results: Patients aged 52–79 years (mean ± SD, 64.8 ± 6.15 yrs), with a median PSA of 9.2 ng/ml (IQR: 6.70, 16.83) and median prostate volume of 31.9 ml (IQR: 30.01, 38.54). 95.28% (101/106) were clinically localized. All patients underwent espRARP successfully with no open conversions. Operative time was 94.2 ± 30.26 min with an estimated blood loss of 68.5 ml (range, 50–120 ml). No Grade III complications or above were documented. Positive surgical margin was 17.9% (19/106). Median pain score at discharge was 0 (IQR: 0, 1.75) without use of opioid narcotics. Postoperative length of stay was 3 days (IQR: 1, 3), in which 28 patients were discharged within 24 h. Instant, 1-, 3-, and 6 month continence recovery was 18.9, 45.3, 79.2, 93.4, and 96.4%, respectively. Of the 43 patients who received nerve-sparing procedures, 13 (30.23%) resumed potency 6 months postoperatively. 12 month biochemical recurrence-free survival was 92.77% (77/83). Conclusions: Extraperitoneal single-port robotic-assisted radical prostatectomy is a safe and feasible technique. Combined with super-veil nerve-sparing procedures, it may provide satisfactory outcome in short-term functional recovery. [ABSTRACT FROM AUTHOR]

We conducted preclinical experiments and phase I clinical trial to investigate the safety, pharmacokinetics (PK) and antitumour effects of GT0918 in castration-resistant prostate cancer (CRPC). An androgen receptor (AR) competitive binding assay was performed, followed by evaluation of GT0918 on AR protein expression. The efficacy of GT0918 was investigated in a castration-resistant xenograft model. A phase I dose-escalation study of GT0918 in CRPC was also carried out to evaluate its safety, PK and antitumour efficacy. GT0918 was demonstrated to inhibit the binding of androgen to AR more potently than MDV3100, and to effectively reduce the AR protein level. GT0918 inhibited the transcriptional activity of wild-type AR and AR with clinically relevant ligand-binding domain mutations. Furthermore, GT0918 significantly inhibited the growth of prostate cancer. A total of 16 patients was treated with GT0918 at five dose levels. Among these 16 patients, 10 and 2 patients, respectively, completed a three-cycle and six-cycle treatment, in which MTD was not reached. All the treatment-related adverse events were grade I, including hypercholesterolemia, hypertriglyceridemia, fatigue and anaemia. PK parameters showed that drug exposure increased with dose proportionally from 50 to 300 mg and a saturation was observed between 300 and 400 mg. PSA declines of ≥30% and ≥50% were, respectively, observed in six and two cases. All the 12 patients with metastatic soft tissue lesions confirmed stable disease. GT0918, a full AR antagonist without agonist effect, has high binding affinity to AR with AR protein down-regulation activity. GT0918 is demonstrated to be well tolerated with a favourable PK profile and exhibits promising antitumour activity in CRPC. gov identifier CTR20150501. • GT0918 has high binding affinity to androgen receptor. • GT0918 reduces the androgen receptor protein level effectively. • GT0918 inhibits transcriptional activity of androgen receptor with mutations. • GT0918 is well tolerated with a favourable pharmacokinetics profile. • GT0918 has promising antitumour activity in castration-resistant prostate cancer. [ABSTRACT FROM AUTHOR]

Objective: Substantial differences exist in the relationship of prostate cancer (PCa) detection rate and prostate-specific antigen (PSA) level between Western and Asian populations. Classic Western risk calculators, European Randomized Study for Screening of Prostate Cancer Risk Calculator, and Prostate Cancer Prevention Trial Risk Calculator, were shown to be not applicable in Asian populations. We aimed to develop and validate a risk calculator for predicting the probability of PCa and high-grade PCa (defined as Gleason Score sum 7 or higher) at initial prostate biopsy in Chinese men.Materials and Methods: Urology outpatients who underwent initial prostate biopsy according to the inclusion criteria were included. The multivariate logistic regression-based Chinese Prostate Cancer Consortium Risk Calculator (CPCC-RC) was constructed with cases from 2 hospitals in Shanghai. Discriminative ability, calibration and decision curve analysis were externally validated in 3 CPCC member hospitals.Results: Of the 1,835 patients involved, PCa was identified in 338/924 (36.6%) and 294/911 (32.3%) men in the development and validation cohort, respectively. Multivariate logistic regression analyses showed that 5 predictors (age, logPSA, logPV, free PSA ratio, and digital rectal examination) were associated with PCa (Model 1) or high-grade PCa (Model 2), respectively. The area under the curve of Model 1 and Model 2 was 0.801 (95% CI: 0.771-0.831) and 0.826 (95% CI: 0.796-0.857), respectively. Both models illustrated good calibration and substantial improvement in decision curve analyses than any single predictors at all threshold probabilities. Higher predicting accuracy, better calibration, and greater clinical benefit were achieved by CPCC-RC, compared with European Randomized Study for Screening of Prostate Cancer Risk Calculator and Prostate Cancer Prevention Trial Risk Calculator in predicting PCa.Conclusions: CPCC-RC performed well in discrimination and calibration and decision curve analysis in external validation compared with Western risk calculators. CPCC-RC may aid in decision-making of prostate biopsy in Chinese or in other Asian populations with similar genetic and environmental backgrounds. [ABSTRACT FROM AUTHOR]