High-intensity focused ultrasound strategies for treating prostate cancer.

ABSTRACT: Prostate cancer (PCa) is a significant health concern globally, necessitating effective treatment options. Typical treatment methods for early stage, particularly localized PCa, encompass radical procedures, such as radical prostatectomy (RP) and radiotherapy (RT), and nonradical focal therapy (FT). FT is a focused approach mainly used for treating small lesions limited to a specific zone of the prostate. Its objective is to achieve cancer control when minimizing damage to benign tissue. High-intensity focused ultrasound (HIFU) is one of the most used modalities in FT for the management of PCa. The progress in HIFU technology showcases continuous advancements, offering clinicians a variety of strategies to cater to diverse patient requirements. The advancements include the development of transrectal and transurethral HIFU machines that offer enhanced treatment distances, magnetic resonance imaging (MRI) fusion capabilities, real-time monitoring, and precise ablation. These improvements contribute to increased treatment effectiveness and better outcomes for patients. This narrative review aims to summarize the use of HIFU technology and its evolution, offering diverse options to clinicians, and explores the safety, effectiveness, and quality of different HIFU strategies, such as whole-gland ablation, hemigland ablation, and focal ablation. We conclude that nonwhole-gland HIFU offers similar cancer control with better short-term functional outcomes and fewer complications compared to whole-gland ablation. Combining HIFU with transurethral resection of the prostate (TURP) improves urinary function and reduces catheterization time. Focal ablation and hemigland ablation show promise in achieving cancer control when preserving continence and potency.

"Seeing Is Believing": Additive Utility of 68Ga-PSMA-11 PET/CT in Prostate Cancer Diagnosis.

Widespread adoption of mpMRI has led to a decrease in the number of patients requiring prostate biopsies. 68Ga-PSMA-11 PET/CT has demonstrated added benefits in identifying csPCa. Integrating the use of these imaging techniques may hold promise for predicting the presence of csPCa without invasive biopsy. A retrospective analysis of 42 consecutive patients who underwent mpMRI, 68Ga-PSMA-11 PET/CT, prostatic biopsy, and radical prostatectomy (RP) was carried out. A lesion-based model (n = 122) using prostatectomy histopathology as reference standard was used to analyze the accuracy of 68Ga-PSMA-11 PET/CT, mpMRI alone, and both in combination to identify ISUP-grade group ≥ 2 lesions. 68Ga-PSMA-11 PET/CT demonstrated greater specificity and positive predictive value (PPV), with values of 73.3% (vs. 40.0%) and 90.1% (vs. 82.2%), while the mpMRI Prostate Imaging Reporting and Data System (PI-RADS) 4-5 had better sensitivity and negative predictive value (NPV): 90.2% (vs. 78.5%) and 57.1% (vs. 52.4%), respectively. When used in combination, the sensitivity, specificity, PPV, and NPV were 74.2%, 83.3%, 93.2%, and 51.0%, respectively. Subgroup analysis of PI-RADS 3, 4, and 5 lesions was carried out. For PI-RADS 3 lesions, 68Ga-PSMA-11 PET/CT demonstrated a NPV of 77.8%. For PI-RADS 4-5 lesions, 68Ga-PSMA-11 PET/CT achieved PPV values of 82.1% and 100%, respectively, with an NPV of 100% in PI-RADS 5 lesions. A combination of 68Ga-PSMA-11 PET/CT and mpMRI improved the radiological diagnosis of csPCa. This suggests that avoidance of prostate biopsy prior to RP may represent a valid option in a selected subgroup of high-risk patients with a high suspicion of csPCa on mpMRI and 68Ga-PSMA-11 PET/CT.

Safety and Efficacy of Immediate Hyperthermic Intravesical Chemotherapy Following Transurethral Resection of Bladder Tumour (I-HIVEC).

The recurrence rate following endoscopic treatment of non-muscle-invasive bladder cancer (NMIBC) remains high. Standard treatment includes intravesical instillation of chemotoxic agents such as mitomycin C (MMC) to reduce recurrence. It is postulated that upfront administration of hyperthermic intravesical MMC (HIVEC) immediately after transurethral resection of bladder tumour (TURBT) may enhance its efficacy, but evidence from human trials is scant. This pilot study explored the safety of immediate intravesical MMC instillation following TURBT using a conductive HIVEC system (Combat BRS). Patients diagnosed with papillary bladder tumours scheduled for TURBT were recruited. Among 29 patients treated with HIVEC, there was minimal additional postoperative morbidity. The majority (79.3%) were discharged after a hospital stay of 1 d, and no patient required bladder irrigation. There were six grade I-II adverse events (20.7%) and one grade III event (3.4%). No recurrences were observed within 3 mo, and the 12-mo recurrence rate was 4.5%. The study findings demonstrate that immediate HIVEC MMC instillation following TURBT is safe. Further research is needed to assess long-term efficacy in comparison to standard cold MMC. PATIENT SUMMARY: Non-muscle-invasive bladder cancer is treated with tumour removal via a telescope inserted into the bladder through the urethra (called TURBT). We tested the safety of treating the bladder with a warm solution of a chemotherapy drug (mitomycin C) immediately after TURBT, as this may prevent tumour recurrence. The treatment was safe and well tolerated. Further trials are needed with more patients and longer follow-up to confirm the results.

Patient Preference of Apalutamide Versus Enzalutamide for Recurrent or Metastatic Hormone-sensitive Prostate Cancer: An Open-label, Randomized, Crossover Trial.

BACKGROUND AND OBJECTIVE: Treatment preference regarding apalutamide versus enzalutamide in prostate cancer (PCa) and the factors influencing decisions are largely unknown. Our aim was to investigate the preference for apalutamide versus enzalutamide among prostate cancer patients and their physicians and caregivers, and factors influencing their decision. METHODS: This was a prospective, open-label, randomized, crossover trial. Patients with recurrence of localized PCa or with metastatic disease not considered as high-risk or high-volume and on continued androgen deprivation therapy were recruited. All subjects received a trial of two agents, apalutamide (A) and enzalutamide (E), for 12 wk each, with a 5-wk washout period in between. The sequencing of the drugs was randomized. The primary outcome was patient preference for one the drugs, assessed at the end of the study. Other outcomes included factors influencing patient preference, a comparison of side-effect profiles, and patients' quality of life (QoL). Physician and caregiver preferences for the drugs and factors affecting their choice were also assessed. KEY FINDINGS AND LIMITATIONS: A total of 74 patients met the eligibility criteria and were randomized to the A â†’ E or E â†’ A arm. Of these, 66 patients (89.1%; 32 A â†’ E, 34 E â†’ A) completed the study. Baseline characteristics were comparable between the two groups, and ∼90% of the patients had low-volume metastatic disease. After completion of both treatments for 12 wk each, the difference in preference for A over E was 17.8%, with similar trends for preference of A over E among physicians (18.2%) and caregivers (22.4%). Fewer side effect was the most critical factor influencing the preference of patients. Among the side effects, less fatigue was the benefit of A over E most frequently reported. No notable difference in QoL was observed between the two drugs. However, the study was terminated on interim analysis and the results might not be conclusive. CONCLUSIONS: There was a trend for preference of A over E among patients with predominantly low-volume recurrent or metastatic PCa and their physicians and caregivers. Fewer side effects was the most critical factor influencing their choice. PATIENT SUMMARY: Patients with low-volume recurrent or metastatic prostate cancer tended to prefer treatment with apalutamide over enzalutamide. Side effects were the most critical factor influencing treatment preference.

Patient preference on once-daily oral versus injectable androgen deprivation therapy for Asian patients with advanced prostate cancer.

PURPOSE: The study aimed at investigating prostate cancer patients' choice of androgen deprivation treatment (ADT) and possible factors that would affect their preferences of ADT. METHODS: This was a single-centre cross-sectional study investigating the usage and preferences of ADT. Consecutives prostate cancer patients who were receiving injectable luteinizing hormone-releasing hormone (LHRH) agonist or antagonist were recruited from the prostate cancer clinic in a tertiary academic hospital. Patients who received bilateral orchidectomy or those who could not consent to the study were excluded. Disease characteristics, treatment information and patient background were documented. The survey collected information related to their change in ADT regimen, preferences on drug usage (routes and frequency of administration) and their reasons. A hypothetical set of three drug formularies was designed. Questions regarding patient preference and the contributing reasons raised in the format of questionnaire. RESULTS: 100 patients completed the survey. Most patients started with more frequent injections (3-monthly, 54%; 1-monthly, 38%) and switched to 6-monthly injections (89%) at the time of the survey. Primary reasons for the change were healthcare opinion (72%) and less frequent treatment (51%). Three options of ADT (oral daily, 1-monthly and 6-monthly injection) with the same efficacies and side effect profile were offered: 61% preferred 6-monthly injection, 1% preferred 1-monthly injection and 38% preferred oral regimen. When patients were informed of lower cardiovascular side effects in 1-monthly injection or daily oral drug, patients' preference was 56% (6-monthly), 6% (1-monthly), and 39% (oral). Patients with polypharmacy (more than 5 regular medications) were more inclined to choose injections (p = 0.025). Patient age, educational background, employment status, marriage status and disease status were not found to be statistically significant contributing factors to patient preference. CONCLUSION: 6-monthly ADT injection was the preferred ADT despite greater cardiovascular risks. Among 1-monthly or daily oral LHRH antagonist, more patients prefer oral option. Convenience factor was highly valued.

Lower baseline testosterone level is related to earlier development of castration resistance in metastatic prostate cancer: a multi-center cohort study.

Purpose: In the era of concurrent combination therapy in metastatic hormone sensitive prostate cancer, the impact of the testosterone level before initiating androgen deprivation therapy on treatment outcome is still uncertain. We aimed to investigate its effect on time-to-castration-resistance in a metastatic hormone sensitive prostate cancer cohort. Methods: This is a multi-center retrospective study of 5 databases from China, Japan, Austria and Spain including 258 metastatic hormone sensitive prostate cancer patients with androgen deprivation therapy initiated between 2002 and 2021. Baseline testosterone was divided into high and low groups using 12 nmol/L as cutoff level. Primary outcome was time-to-castration-resistance. Secondary outcomes were survival functions. Kaplan-Meier method was employed to evaluate the correlation between baseline testosterone and time-to-castration-resistance. Subgroup analysis was performed to elucidate the effect of upfront combination-therapy and metastatic volume. Results: Median age was 72 years. Median follow-up time was 31 months. Median pre-treatment prostate-specific-antigen level was 161 ng/mL. Majority of case were graded as International-Society-of-Urological-Pathology grade 5 (63.6%). 57.8% patients had high volume disease and 69.0% received upfront combination treatment. 44.6% of the cohort developed castration-resistance. The low testosterone group demonstrated shorter mean-time-to-castration-resistance (19.0 vs 22.4 months, p=0.031). The variance was more significant in patients without combination therapy (13.2 vs 26.3 months, p=0.015). Cancer-specific and overall survival were inferior in the low baseline testosterone level group without receiving combination therapy (p=0.001). Conclusions: Lower pre-treatment testosterone level is correlated to shorter time-to-castration resistance and worse survival in metastatic prostate cancer patients without upfront combination therapy. Those with low baseline testosterone should be encouraged to adopt combination therapy to delay progression.

One-year clinical outcomes of MR-guided stereotactic body radiation therapy with rectal spacer for patients with localized prostate cancer.

BACKGROUND AND PURPOSE: This prospective study aimed to investigate adaptive magnetic resonance (MR)-guided stereotactic body radiation therapy (MRgSBRT) with rectal spacer for localized prostate cancer (PC) and report 1-year clinical outcomes. MATERIALS AND METHODS: Thirty-four consecutive patients with low- to high-risk localized PC that underwent 5-fraction adaptive MRgSBRT with rectal spacer were enrolled. The dosimetric comparison was performed on a risk- and age-matched cohort treated with MRgSBRT but without a spacer at a similar timepoint. Clinician-reported outcomes were based on Common Terminology Criteria for Adverse Events. Patient-reported outcomes were based on the Expanded Prostate Cancer Index Composite (EPIC) questionnaire at baseline, acute (1-3 months), subacute (4-12 months), and late (> 12 months) phases. RESULTS: The median follow-up was 390 days (range 28-823) and the median age was 70 years (range 58-82). One patient experienced rectal bleeding soon after spacer insertion that subsided before MRgSBRT. The median distance between the midline of the prostate midgland and the rectum after spacer insertion measured 7.8 mm (range 2.6-15.3), and the median length of the spacer was 45.9 mm (range 16.8-62.9) based on T2-weighted MR imaging. The use of spacer resulted in significant improvements in target coverage (V100% > 95% = 98.6% [range 93.4-99.8] for spacer vs. 97.8% [range 69.6-99.7] for non-spacer) and rectal sparing (V95% < 3 cc = 0.7 cc [range 0-4.6] for spacer vs. 4.9 cc [range 0-12.5] for non-spacer). Nine patients (26.5%) experienced grade 1 gastrointestinal toxicities, and no grade ≥ 2 toxicities were observed. During the 1-year follow-up period, EPIC scores for the bowel domain remained stable and were the highest among all other domains. CONCLUSIONS: MRgSBRT with rectal spacer for localized PC showed exceptional tolerability with minimal gastrointestinal toxicities and satisfactory patient-reported outcomes. Improvements in dosimetry, rectal sparing, and target coverage were achieved with a rectal spacer. Randomized trials are warranted for further validation.

A prospective cohort of men with localized prostate cancer on active surveillance protocol in Hong Kong, China: what did we learn?

This study aimed to report the outcomes of active surveillance (AS) in the management of low-risk prostate cancer (PCa). It recruited 87 men who were prospectively followed up according to the Prostate Cancer Research International Active Surveillance (PRIAS) protocol with local adaptation at SH Ho Urology Centre, Prince of Wales Hospital, Hong Kong, China. We investigated the predictors of disease progression and found that baseline prostate-specific antigen density (PSAD) and the presence of the highest Prostate Imaging-Reporting and Data System (PI-RADS) score 5 lesion on magnetic resonance imaging (MRI) are significantly correlated with disease progression. Moreover, men with PSAD >0.2 ng ml-2 or PI-RADS 4 or 5 lesions had significantly worse upgrading-free survival compared to those with PSAD ≤0.2 ng ml-2 and PI-RADS 2 or 3 lesions. The study concludes that AS is a safe and effective management strategy for selected patients to defer radical treatment and that most disease progression can be detected after the first repeated biopsy. The combination of PSAD >0.2 ng ml-2 and PI-RADS 4 or 5 lesions may serve as a useful predictor of early disease progression and provide a guide to optimize follow-up protocols for men in different risk groups.

Health-Related Quality of Life Assessment in Prostate Cancer Patient Undergoing Androgen Deprivation Therapy: Real-World Experience in the READT Study.

PURPOSE: To investigate the effect of androgen deprivation therapy (ADT) on health-related quality of life (HRQOL) in Asian men with all stages of prostate cancer. MATERIALS AND METHODS: READT (real-life evaluation of the effect of ADT in prostate cancer patients in Asia) was a multi-center, prospective observational study involving six sites across four Asian populations. We enrolled eligible prostate cancer patients, who opted for ADT alone or in combination without prior neoadjuvant or adjuvant ADT within 12 months. The EuroQoL-5 dimensions, 5 level scale (EQ-5D-5L) utility index scores and visual analog scale (VAS) were evaluated at baseline, month 6 and month 12. RESULTS: A total of 504 patients were recruited into READT between September 2016 and May 2020 with 52.9% diagnosed with metastatic prostate cancer. The EQ-5D-5L was evaluable in 442/504 (87.7%) of patients. Overall baseline EQ-5D-5L utility index score was 0.924 (interquartile range [IQR] 0.876-1.000). We observed a statistically significant difference in baseline EQ-5D-5L utility index score among different populations with a median EQ-5D-5L utility index score of 1 for Taiwan & Hong Kong, 0.897 for China and 0.838 for Malaysia. Similar trend was observed throughout multiple treatment time-points. Stage IV prostate cancer were significantly associated with a lower baseline EQ-5D-5L utility index score compared to stage I-III prostate cancer, producing a median disutility value of -0.080. Participants had a high median VAS (80, IQR 70-90), indicating good overall health on average during ADT initiation. CONCLUSIONS: The study highlights the differences in health state utility index scores among various Asian prostate cancer patients receiving ADT at real-world setting. Our findings will be informative and useful in cost-effectiveness evaluation and policy decision making.

SARS-CoV-2 infection correlates with male benign prostatic hyperplasia deterioration.

INTRODUCTION: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) affects extra-respiratory systems, with small-scale studies showing worsened male lower urinary tract symptoms (LUTS) after coronavirus disease 2019 (COVID-19). This study explores the correlation between SARS-CoV-2 infection and male benign prostatic hyperplasia (BPH) complications using large-scale real world data. MATERIALS AND METHODS: All male patients attending the public healthcare system in Hong Kong receiving alpha-blocker monotherapy for LUTS from 2021 to 2022 were included in this study. Patients with and without positive polymerase chain reaction (PCR) test for SARS-CoV-2 are selected as the exposure group and control group, respectively. Baseline characteristics are retrieved, with propensity score matching performed to ensure balance of covariates between the two groups. BPH complications were then compared and subgroup analyses were performed. RESULTS: After propensity score matching, 17,986 patients were included for analysis, among which half had PCR-confirmed SARS-CoV-2 infection (n = 8993). When compared to controls, the SARS-CoV-2 group demonstrated statistically significant higher incidence of retention of urine (4.55% vs. 0.86%, p < 0.001), haematuria (1.36% vs. 0.41%, p < 0.001), clinical urinary tract infection (UTI) (4.31% vs. 1.49%, p < 0.001), culture-proven bacteriuria (9.02% vs. 1.97%, p < 0.001) and addition of 5ARI (0.50% vs. 0.02%, p < 0.001). Subgroup analysis demonstrated similar differences across different age groups. There are no statistically significance differences in incidence of retention, haematuria, or addition of 5ARI across different COVID-19 severities. CONCLUSIONS: SARS-CoV-2 infection is associated with increased incidence of urinary retention, haematuria, UTI and the addition of combination therapy in the short term, regardless of COVID-19 severity. This is the largest study demonstrating the detrimental urological effects of SARS-CoV-2 infection.

A Territory-wide Study Investigating the Dose and Efficacy of Different Bacillus Calmette-Guérin Strains in Patients with Intermediate- and High-risk Non-muscle-invasive Bladder Cancer.

BACKGROUND: Current European Association of Urology (EAU) guidelines support adjuvant intravesical Bacillus Calmette-Guérin (BCG) treatment after Transurethral Resection of Bladder Tumor (TURB) for intermediate- or high-risk Non-Muscle-Invasive Bladder Cancer (NMIBC) patients, aiming to reduce the risk of tumor recurrence. The quality of data, however, does not allow definitive conclusions on whether different strains and dosages of BCG have different efficacies on long-term survival outcomes. OBJECTIVE: To evaluate the long-term survival outcomes of different strains and dosages of BCG in patients with NMIBC. DESIGN, SETTING, AND PARTICIPANTS: All NMIBC patients treated with intravesical BCG therapy from 2001 to 2020 were identified using a territory-wide database in Hong Kong. INTERVENTION: BCG strains and dosages (Connaught strain 81 mg, Connaught strain 27 mg, Tokyo strain 80 mg, and Danish strain 30 mg) were retrieved from medical records. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall Survival (OS), Cancer-Specific Survival (CSS), Recurrence-Free Survival (RFS), and Progression-Free Survival (PFS) were analyzed using the Kaplan-Meier method. A multivariable Cox regression analysis was used to adjust potential confounding factors, and to estimate Hazard Ratio (HR) and 95% confidence interval (CI) of different BCG strains. A further subgroup analysis on adequate versus inadequate BCG treatment was performed. RESULTS AND LIMITATIONS: A total of 2602 NMIBC patients treated with intravesical BCG were identified. Among them, 1291 (49.6%) received Connaught strain 81 mg, 199 (7.6%) received Connaught strain 27 mg, 1014 (39.0%) received Tokyo strain, and 98 (3.8%) received Danish strain. The median follow-up was 11.0 years. No statistically significant differences in OS, CSS, RFS, and PFS were detected among the different groups. At the multivariable analysis, the Connaught strain 27 mg group was inferior to the Connaught strain 81 mg group in terms of OS (HR: 1.26, 95% CI: 1.05-1.51), CSS (HR: 1.69, 95% CI: 1.08-2.66), and PFS (HR: 1.86, 95% CI: 1.20-2.88). Adequate BCG treatment was associated with improved OS (HR: 0.82, 95% CI: 0.73-0.92), CSS (HR: 0.64, 95% CI: 0.47-0.86), RFS (HR: 0.80, 95% CI: 0.70-0.92), and PFS (HR: 0.52, 95% CI: 0.39-0.68). Among patients treated with adequate BCG, at the multivariable analysis the Connaught strain 27 mg group showed worse results than the Connaught strain 81 mg group in terms of CSS (HR: 1.93, 95% CI: 1.07-3.51). Compared with the Connaught strain 81 mg group, both Tokyo and Danish strains had similar survival outcomes in the whole cohort and the adequate BCG treatment subgroup. CONCLUSIONS: Our findings suggest that adequate BCG remains the most important factor in optimizing survival outcomes in patients with intermediate- and high-risk NMIBC. No significant differences in survival outcomes were observed between full-dose Connaught, Tokyo, and Danish strains. Reduced-dose Connaught strain was associated with the worst survival outcomes. PATIENT SUMMARY: We evaluated the efficacy of different strains and dosages of bacillus Calmette-Guérin (BCG) in patients with intermediate- or high-risk non-muscle-invasive bladder cancer in the past two decades in Hong Kong. We conclude no significant differences in long-term survival outcomes in terms of full-dose Connaught, Tokyo, and Danish strains, while reduced-dose Connaught strain was inferior to the full-dose group. Adequate BCG treatment benefits long-term survival.

Dissecting the effects of METTL3 on alternative splicing in prostate cancer.

Although the role of METTL3 has been extensively studied in many cancers, its role in isoform switching in prostate cancer (PCa) has been poorly explored. To investigate its role, we applied standard RNA-sequencing and long-read direct RNA-sequencing from Oxford Nanopore to examine how METTL3 affects alternative splicing (AS) in two PCa cell lines. By dissecting genome-wide METTL3-regulated AS events, we noted that two PCa cell lines (representing two different PCa subtypes, androgen-sensitive or resistant) behave differently in exon skipping and intron retention events following METTL3 depletion, suggesting AS heterogeneity in PCa. Moreover, we revealed that METTL3-regulated AS is dependent on N6-methyladenosine (m6A) and distinct splicing factors. Analysis of the AS landscape also revealed cell type specific AS signatures for some genes (e.g., MKNK2) involved in key functions in PCa tumorigenesis. Finally, we also validated the clinical relevance of MKNK2 AS events in PCa patients and pointed to the possible regulatory mechanism related to m6A in the exon14a/b region and SRSF1. Overall, we characterize the role of METTL3 in regulating PCa-associated AS programs, expand the role of METTL3 in tumorigenesis, and suggest that MKNK2 AS events may serve as a new potential prognostic biomarker.

Urinary continence in high-risk prostate cancer after robot-assisted radical prostatectomy.

PURPOSE OF REVIEW: Urinary incontinence is common postoperative complication following robot-assisted radical prostatectomy (RARP) in patients with prostate cancer (PCa). Despite the increasing adoption of RARP in the treatment of high-risk PCa (HRPC), concerns persist regarding the adequacy of reported continence outcomes in this subgroup. This review aims to illuminate the state of continence recovery in HRPC patients post-RARP. RECENT FINDINGS: Urinary continence (UC) recovery rates in HRPC was reported to be lower than the intermediate/low-risk counterparts from 6 to 24 months post-RARP. Predictive models showed that age, obesity, race, disease status, and surgical approaches represent predictors of continence recovery. Special techniques like NeuroSAFE technique and Retzius-Sparing approach also play a role in reducing incontinence also in the high-risk scenario. SUMMARY: RARP for HRPC appears to be associated with worse continence compared with other risk groups. A multimodality approach for prediction and prevention of incontinence after RARP is vital. Further research into this area is necessary to enhance continence recovery outcomes in HRPC patients undergoing RARP.

Oncological results and cancer control definition in focal therapy for Prostate Cancer: a systematic review.

INTRODUCTION: Focal therapy (FT) is a promising alternative to whole-gland treatments for Localized Prostate Cancer. Ten different FT modalities have been described in literature. However, FT is not yet recommended by the International Guidelines, due to the lack of robust data on Oncological Outcomes. The objective of our Narrative Review is to evaluate the oncological profile of the available FT modalities and to offer a comprehensive overview of the definitions of Cancer Control for FT. MATERIAL AND METHODS: Literature search was performed on 21st February 2023 using PubMed, EMBASE, and Scopus, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA). Articles reporting whole gland-treatments were excluded. All articles reporting oncological outcomes were included. RESULTS: One-hundred-twenty-four studies, reporting data on more than 8000 patients treated with FT, were included. Overall, 40 papers were on High Intensity Focal Ultrasound (HIFU), 24 on Focal Cryotherapy, 13 on Irreversible Electroporation (IRE), 11 on Focal brachytherapy, 10 on Focal Laser Ablation (FLA), 8 on Photo-Dynamic Therapy (PDT), 3 on Microwave ablation, 3 on Robotic Partial Prostatectomy, 2 on bipolar Radio Frequency Ablation (bRFA), 1 on Prostatic Artery Embolization (PAE) and 9 comparative papers. Overall, the Biochemical Recurrence (BCR) rate ranged from 0% (Focal Brachytherapy) to 67.5% (HIFU); the Salvage treatment rate ranged from 1% (IRE) to 54% (HIFU) considering re-treatment with FT and from 0% (Focal Brachytherapy) to 66.7% considering standard Radical Treatments. There is no univocal definition of Cancer Control, however the "Phoenix criteria" for BCR were the most commonly used. CONCLUSIONS: FT is a promising alternative treatment for localized prostate cancer in terms of Oncological Outcomes, however there is a wide heterogeneity in the definition of cancer control, the reporting of oncological outcomes and a lack of high-quality clinical trials. Solid comparative studies with standard treatments and an unambiguous consensus on how to describe Cancer Control in the field of Focal Therapy are needed.

Functional outcomes and safety of focal therapy for prostate cancer: a systematic review on results and patient-reported outcome measures (PROMs).

INTRODUCTION: Focal therapy (FT) is a promising alternative with curative intent for Low- to Intermediate-risk localized Prostate Cancer (PCa), claiming better functional outcomes and safety profile than standard whole-gland treatments. Ten different FT modalities have been described in the literature. The objective of our narrative review is to evaluate the safety profile and functional outcomes of these different modalities and the current most used tools of assessment for those outcomes. MATERIAL AND METHODS: Literature search was performed on 21st February 2023 using PubMed, EMBASE, and Scopus, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA). Articles reporting whole-gland treatments were excluded. All articles reporting functional outcomes were included. RESULTS: One-hundred-seven studies, reporting data on 6933 patients, were included (26 on High Intensity Focal Ultrasound, 22 on Focal Cryotherapy, 14 on Irreversible Electroporation, 11 on Focal brachytherapy, 10 on Focal Laser Ablation, 8 on Photodynamic Therapy, 3 on Microwave ablation, 3 on Robotic Partial Prostatectomy, 2 on bipolar Radio Frequency Ablation, 1 on Prostatic Artery Embolization, and 7 studies comparing different FTs). Post-operative pad-free rate ranged between 92.3-100%. Greater heterogeneity exists considering the Change in Erectile Function, with Changing in Erectile function- rates ranging between 0-94.4% (Cryotherapy). The most used Patient-Reported Outcome Measures (PROMs) were the International Prostate Symptom Score and the International Index of Erectile Function for incontinence/urinary function and potency, respectively. The most common reported complications were hematuria, infections, and urethral strictures, with rates widely ranging among different treatments. The Clavien-Dindo Classification was the most used (40/88 papers) to describe adverse events. CONCLUSION: FT is a promising treatment for localized PCa, achieving excellent results in terms of safety and functional outcomes. There is a wide heterogeneity in the definition of PROMS and time of collection between studies. High quality comparative studies with standard treatments are needed to reinforce these findings.

Prostate Health Index Density Outperforms Prostate-specific Antigen Density in the Diagnosis of Clinically Significant Prostate Cancer in Equivocal Magnetic Resonance Imaging of the Prostate: A Multicenter Evaluation.

PURPOSE: We compare Prostate Health Index, Prostate Health Index density, and PSA density in predicting clinically significant prostate cancer in MRI-guided prostate biopsy. MATERIALS AND METHODS: This is a multicenter evaluation of prospectively maintained prostate biopsy databases at 10 urology centers. Men with Prostate Health Index and MRI-guided targeted and systematic prostate biopsy performed and without prior prostate cancer diagnosis were included. The additional value of PSA density, Prostate Health Index, and Prostate Health Index density to MRI PI-RADS (Prostate Imaging Reporting & Data System) score was evaluated with multivariable analyses, area under the curve, and decision curve analyses. The proportion of unnecessary biopsies that can be avoided are estimated for clinically significant prostate cancer (International Society of Urological Pathology group ≥2 prostate cancer). RESULTS: A total of 1,215 men were analyzed. Prostate cancer and clinically significant prostate cancer were diagnosed in 51% (617/1,215) and 35% (422/1,215) of men, respectively. Clinically significant prostate cancer was diagnosed in 4.4% (3/68), 15% (72/470), 39% (176/446), and 74% (171/231) of highest PI-RADS score of 2, 3, 4, and 5 lesions, respectively. In multivariable analyses, independent predictors for clinically significant prostate cancer detection included Prostate Health Index (OR 1.04), prostate volume (OR 0.97), and PI-RADS score 4 (OR 2.81) and 5 (OR 8.34). Area under the curve for clinically significant prostate cancer of PI-RADS + Prostate Health Index density (0.85) was superior to PI-RADS + PSA density (0.81), Prostate Health Index density (0.81), Prostate Health Index (0.78), PI-RADS (0.76), PSA density (0.72), and PSA (0.60) in the whole cohort, and the superiority of Prostate Health Index density was also observed in PI-RADS 3 lesions. Decision curve analysis showed Prostate Health Index density achieving the best net clinical benefit in PI-RADS 3 or 4 cases. Among PI-RADS 3 lesions, using cutoffs of PSA density 0.15, Prostate Health Index 38.0, and Prostate Health Index density 0.83 could reduce 58%, 67%, and 72% of unnecessary biopsies, respectively. CONCLUSIONS: Prostate Health Index density outperformed Prostate Health Index or PSA density in clinically significant prostate cancer detection in men with multiparametric MRI performed, and further reduced unnecessary biopsies in PI-RADS 3 lesions.

Moving the Needle: Antibiotic Prophylaxis Is No Longer Required in the Era of Transperineal Prostate Biopsy.

There is no significant difference in infective complications between patients who do and do not receive antibiotic prophylaxis before transperineal prostate biopsy. Antibiotic prophylaxis should not be given before transperineal prostate biopsy.

Global Trends of Prostate Cancer by Age, and Their Associations With Gross Domestic Product (GDP), Human Development Index (HDI), Smoking, and Alcohol Drinking.

BACKGROUND: We aimed to examine the global disease burden and trends of prostate cancer incidence and mortality by age, and their associations with gross domestic product (GDP), human development index (HDI), smoking, and alcohol drinking. MATERIALS AND METHODS: We retrieved the Global Cancer Observatory (GLOBOCAN) database for the incidence and mortality of prostate cancer in 2020; the World Bank for GDP per capita; the United Nations for HDI; the WHO Global Health Observatory for prevalence of smoking and alcohol drinking; the Cancer Incidence in 5 Continents (CI5), WHO mortality database, for trend analysis. We presented the prostate cancer incidence and mortality using age-standardized rates. We examined their associations with GDP, HDI, smoking, and alcohol drinking by Spearman's correlations and multivariable regression. We estimated the 10-year trend of incidence and mortality by joinpoint regression analysis with average annual percent change with 95% confidence intervals in different age groups. RESULTS: A wide variation in the burden of prostate cancer with the highest mortality found in low-income countries while the highest incidence was observed in high-income countries. We found moderate to high positive correlations for GDP, HDI, and alcohol drinking with prostate cancer incidence, whilst a low negative correlation was observed for smoking. Globally, there was an increasing incidence but decreasing mortality of prostate cancer, and such trends were particularly prominent in Europe. Notably, the incidence increase was also found in the younger population aged <50 years. CONCLUSIONS: There was a global variation in the burden of prostate cancer associated with GDP, HDI, smoking, and alcohol drinking.

A prospective evaluation of the effect of finasteride on prostate health index (phi).

PURPOSE: 5-alpha reductase inhibitor (5ARI) reduces prostate-specific antigen (PSA) by half but its effect on prostate health index (phi) is unknown. This study aims to investigate this effect and to enable accurate interpretation of phi in men with elevated PSA and on 5ARI. METHODS: This is a prospective study evaluating the effect of finasteride on PSA, free PSA (fPSA), [ - 2]proPSA (p2PSA) and phi at 6 and 12 moths in men with PSA 4-20 ng/mL, no prior 5ARI use, and one negative prostate biopsy within 6 months before recruitment. The 5ARI Finasteride (5 mg/day) for 1 year was offered if International Prostatic Symptom Score (IPSS) was ≥ 8 at baseline. 5ARI group included patients taking finasteride, while control group included patients not on finasteride. The blood results were compared with t-test between baseline and different time points in each group and between groups at 1 year. RESULTS: 164 men fit the inclusion criteria and 150 were analyzed. In 5ARI group (n = 100) at 1 year, mean PSA reduced by 51.4% from 8.9(± SD 3.7) to 4.4(± SD 2.8)ng/mL (paired t-test, p < 0.001), fPSA reduced by 52.4% from 1.6(± 0.6) to 0.8(± 0.4)ng/mL (p < 0.001), p2PSA reduced by 55.3% from 18.4(± 8.8) to 8.3(± 5.6)pg/mL (p < 0.001), and phi reduced by 34.2% from 33.7(± 11.9) to 22.4(± 12.5) (p < 0.001). PSA and phi values in the control group remained static over 1 year and significantly higher than those in 5ARI group. CONCLUSION: This study demonstrated p2PSA and phi are reduced by about 55% and 34% in men on 5ARI. A conversion factor of division by 0.66 is needed for phi in men on finasteride to allow the interpretation and use of phi in men on 5ARI.

Transperineal Targeted Microwave Ablation (TMA) of localized prostate cancer guided by MRI-Ultrasound fusion and organ-based tracking: a pilot study.

BACKGROUND: To investigate the efficacy of transperineal targeted microwave ablation (TMA) in treating localized prostate cancer (PCa). METHODS: This is a single-centre prospective phase 2 trial recruiting men with low to intermediate-risk localized PCa to undergo transperineal TMA. TMA was performed with MRI-Ultrasound fusion guidance and organ-based tracking. A per-protocol 6-month MRI and biopsy were performed for all patients. The primary outcome was any cancer detected on biopsy of each ablated area. Secondary outcomes included per-patient analysis of positive biopsy, complications, urinary symptom score, erectile function and quality of life (QOL) scores. RESULTS: In the first 15 men, 23 areas were being treated. The median age was 70 years, number of TMA ablations were 5 (range 2-8), and the total ablation time and operating time was 22 (IQR 14-28) and 75 (IQR 65-85) minutes, respectively. PSA level dropped from a median of 7.7 to 2.4 ng/mL. For the primary outcome, 91.3% (21/23) ablated area had no cancer in 6-month biopsy. In per-patient analysis, 33.3% (5/15) had in or out-of-field positive biopsy at 6 months. Among these five cases, four of them were amenable to active surveillance and 1 (6.7%) case with out-of-field ISUP grade group 2 cancer received radiotherapy. The urinary symptoms, uroflowmetry, erectile function, and QOL scores had no significant difference at 6 months. One patient (out of five patients with normal erection) in the cohort complained of significant worsening of erectile function after TMA. Grade 1 complications including hematuria (33.3%), dysuria (6.7%), and perineal discomfort (13.4%) were observed. CONCLUSIONS: In this first pilot study, transperineal TMA guided by MRI-Ultrasound fusion guidance and organ-based tracking was shown to be effective, safe, and easily applicable in men with localized PCa.