Assessing the efficacy of pelvic floor muscle training and duloxetine on urinary continence recovery following radical prostatectomy: A randomized clinical trial.

BACKGROUND: Urinary incontinence (UI) can negatively impact quality of life (QoL) after robot-assisted radical prostatectomy (RARP). Pelvic floor muscle training (PFMT) and duloxetine are used to manage post-RARP UI, but their efficacy remains uncertain. We aimed to investigate the efficacy of PFMT and duloxetine in promoting urinary continence recovery (UCR) after RARP. METHODS: A randomized controlled trial involving patients with urine leakage after RARP from May 2015 to February 2018. Patients were randomized into 1 of 4 arms: (1) PFMT-biofeedback, (2) duloxetine, (3) combined PFMT-biofeedback and duloxetine, (4) control arm. PFMT consisted of pelvic muscle exercises conducted with electromyographic feedback weekly, for 3 months. Oral duloxetine was administered at bedtime for 3 months. The primary outcome was prevalence of continence at 6 months, defined as using ≤1 security pad. Urinary symptoms and QoL were assessed by using a visual analogue scale, and validated questionnaires. RESULTS: From the 240 patients included in the trial, 89% of patients completed 1 year of follow-up. Treatment compliance was observed in 88% (92/105) of patients receiving duloxetine, and in 97% (104/107) of patients scheduled to PFMT-biofeedback sessions. In the control group 96% of patients had achieved continence at 6 months, compared with 90% (p = 0.3) in the PMFT-biofeedback, 73% (p = 0.008) in the duloxetine, and 69% (p = 0.003) in the combined treatment arm. At 6 months, QoL was classified as uncomfortable or worse in 17% of patients in the control group, compared with 44% (p = 0.01), 45% (p = 0.008), and 34% (p = 0.07), respectively. Complete preservation of neurovascular bundles (NVB) (OR: 2.95; p = 0.048) was the only perioperative intervention found to improve early UCR. CONCLUSIONS: PFMT-biofeedback and duloxetine demonstrated limited impact in improving UCR after RP. Diligent NVB preservation, along with preoperative patient and disease characteristics, are the primary determinants for early UCR.

Unilateral Pelvic Lymph Node Dissection in Prostate Cancer Patients Diagnosed in the Era of Magnetic Resonance Imaging-targeted Biopsy: A Study That Challenges the Dogma.

PURPOSE: Bilateral extended pelvic lymph node dissection at the time of radical prostatectomy is the current standard of care if pelvic lymph node dissection is indicated; often, however, pelvic lymph node dissection is performed in pN0 disease. With the more accurate staging achieved with magnetic resonance imaging-targeted biopsies for prostate cancer diagnosis, the indication for bilateral extended pelvic lymph node dissection may be revised. We aimed to assess the feasibility of unilateral extended pelvic lymph node dissection in the era of modern prostate cancer imaging. MATERIALS AND METHODS: We analyzed a multi-institutional data set of men with cN0 disease diagnosed by magnetic resonance imaging-targeted biopsy who underwent prostatectomy and bilateral extended pelvic lymph node dissection. The outcome of the study was lymph node invasion contralateral to the prostatic lobe with worse disease features, ie, dominant lobe. Logistic regression to predict lymph node invasion contralateral to the dominant lobe was generated and internally validated. RESULTS: Overall, data from 2,253 patients were considered. Lymph node invasion was documented in 302 (13%) patients; 83 (4%) patients had lymph node invasion contralateral to the dominant prostatic lobe. A model including prostate-specific antigen, maximum diameter of the index lesion, seminal vesicle invasion on magnetic resonance imaging, International Society of Urological Pathology grade in the nondominant side, and percentage of positive cores in the nondominant side achieved an area under the curve of 84% after internal validation. With a cutoff of contralateral lymph node invasion of 1%, 602 (27%) contralateral pelvic lymph node dissections would be omitted with only 1 (1.2%) lymph node invasion missed. CONCLUSIONS: Pelvic lymph node dissection could be omitted contralateral to the prostate lobe with worse disease features in selected patients. We propose a model that can help avoid contralateral pelvic lymph node dissection in almost one-third of cases.

Neoadjuvant chemotherapy does not increase peri-operative morbidity following radical cystectomy.

OBJECTIVE: To determine whether use of neoadjuvant chemotherapy (NAC) is associated with a higher risk of post-operative complications following radical cystectomy (RC) for bladder cancer (BCa). MATERIALS AND METHODS: We retrospectively reviewed records of patients undergoing RC for non-metastatic urothelial BCa at 13 tertiary care centres from 2007-2019. Patients who received NAC ('NAC + RC' group) were compared with those who underwent upfront RC ('RC alone' group) for intra-operative variables, incidence of post-operative complications as per the Clavien-Dindo classification (CDC) and rates of re-admission and re-intervention. Multivariable logistic regression analysis was performed to determine predictors of CDC overall and CDC major (grade III-V) complications. We also analysed the trend of NAC utilization over the study period. RESULTS: Of the 3113 patients included, 968 (31.1%) received NAC while the remaining 2145 (68.9%) underwent upfront RC for BCa. There was no significant difference between the NAC + RC and RC alone groups with regards to 30-day CDC overall (53.2% vs 54.6%, p = 0.4) and CDC major (15.5% vs 16.5%, p = 0.6) complications. The two groups were comparable for the rate of surgical re-intervention (14.6% in each group) and re-hospitalization (19.6% in NAC + RC vs 17.9% in RC alone, p = 0.2%) at 90 days. On multivariable regression analysis, NAC use was not found to be a significant predictor of 90-day CDC overall (OR 1.02, CI 0.87-1.19, p = 0.7) and CDC major (OR 1.05, CI 0.87-1.26, p = 0.6) complications. We also observed that the rate of NAC utilization increased significantly (p < 0.001) from 11.1% in 2007 to 41.2% in 2019, reaching a maximum of 48.3% in 2018. CONCLUSION: This large multicentre analysis with a substantial rate of NAC utilization showed that NAC use does not lead to an increased risk of post-operative complications following RC for BCa. This calls for increasing NAC use to allow patients to avail of its proven oncologic benefit.

Pelvic lymph node dissection in high-risk prostate cancer.

INTRODUCTION: The therapeutic role of pelvic lymph node dissection (PLND) in prostate cancer (PCa) is unknown due to absence of randomized trials. OBJECTIVE: to present a critical review on the therapeutic benefits of PLND in high risk localized PCa patients. MATERIALS AND METHODS: A search of the literature on PLND was performed using PubMed, Cochrane, and Medline database. Articles obtained regarding diagnostic imaging and sentinel lymph node dissection, PLND extension, impact of PLND on survival, PLND in node positive "only" disease and PLND surgical risks were critically reviewed. RESULTS: High-risk PCa commonly develops metastases. In these patients, the possibility of presenting lymph node disease is high. Thus, extended PLND during radical prostatectomy may be recommended in selected patients with localized high-risk PCa for both accurate staging and therapeutic intent. Although recent advances in detecting patients with lymph node involvement (LNI) with novel imaging and sentinel node dissection, extended PLND continues to be the most accurate method to stage lymph node disease, which may be related to the number of nodes removed. However, extended PLND increases surgical time, with potential impact on perioperative complications, hospital length of stay, rehospitalization and healthcare costs. Controversy persists on its therapeutic benefit, particularly in patients with high node burden. CONCLUSION: The impact of PLND on biochemical recurrence and PCa survival is unclear yet. Selection of patients may benefit from extended PLND but the challenge remains to identify them accurately. Only prospective randomized study would answer the precise role of PLND in high-risk pelvis confined PCa patients.

Available evidence on HIFU for focal treatment of prostate cancer: a systematic review.

PURPOSE: Prostate cancer (PCa) is the second most common oncologic disease among men. Radical treatment with curative intent provides good oncological results for PCa survivors, although definitive therapy is associated with significant number of serious side-effects. In modern-era of medicine tissue-sparing techniques, such as focal HIFU, have been proposed for PCa patients in order to provide cancer control equivalent to the standard-of-care procedures while reducing morbidities and complications. The aim of this systematic review was to summarise the available evidence about focal HIFU therapy as a primary treatment for localized PCa. MATERIAL AND METHODS: We conducted a comprehensive literature review of focal HIFU therapy in the MEDLINE database (PROSPERO: CRD42021235581). Articles published in the English language between 2010 and 2020 with more than 50 patients were included. RESULTS: Clinically significant in-field recurrence and out-of-field progression were detected to 22% and 29% PCa patients, respectively. Higher ISUP grade group, more positive cores at biopsy and bilateral disease were identified as the main risk factors for disease recurrence. The most common strategy for recurrence management was definitive therapy. Six months after focal HIFU therapy 98% of patients were totally continent and 80% of patients retained sufficient erections for sexual intercourse. The majority of complications presented in the early postoperative period and were classified as low-grade. CONCLUSIONS: This review highlights that focal HIFU therapy appears to be a safe procedure, while short-term cancer control rate is encouraging. Though, second-line treatment or active surveillance seems to be necessary in a significant number of patients.

Impact of Focal Versus Whole Gland Ablation for Prostate Cancer on Sexual Function and Urinary Continence.

PURPOSE: Focal instead of whole gland ablation for prostate cancer has been proposed to decrease treatment morbidity. We sought to determine differences in erectile function and urinary continence after focal and whole gland ablation for prostate cancer. MATERIALS AND METHODS: From 2009 to 2018, 346 patients underwent high intensity focused ultrasound or cryotherapy for prostate cancer. Urinary continence was defined as use of no pads and sexual potency as enough erection for sexual penetration. Logistic regressions to treatment groups and covariates age, prostate specific antigen, International Society of Urological Pathology grading, prostate volume and energy modality were performed to access the effect of focal therapy in sexual potency and urinary continence after 3 and 12 months. IIEF-5 (International Index of Erectile Function) and I-PSS (International Prostate Symptom Score) questionnaires were evaluated. Propensity score matching was performed to adjust for potential baseline differences between groups. RESULTS: After exclusion, 195 post-focal therapy and 105 post-whole gland therapy patients were included in analysis. No significant difference was seen in baseline I-PSS and IIEF-5 scores. In multivariate models focal therapy was the most important factor related to sexual potency at 3 (OR 7.7) and 12 months (OR 3.9). Median IIEF-5 score at 3 months was 12 and 5 (p <0.001), and at 12 months was 13 and 9 (p=0.04) in focal therapy and whole gland therapy groups, respectively. Focal therapy was the only factor related to continence (OR 0.7, p <0.001). Results remained significant after propensity score matching. CONCLUSIONS: Focal ablation instead of whole gland therapy is the most important factor related to better sexual and urinary continence recovery after high intensity focused ultrasound and cryotherapy for prostate cancer.

Association between Lesion Location and Oncologic Outcomes after Focal Therapy for Localized Prostate Cancer Using Either High Intensity Focused Ultrasound or Cryotherapy.

PURPOSE: We assessed whether prostate cancer (PCa) location might affect oncologic outcomes after focal therapy (FT) for PCa. MATERIALS AND METHODS: We identified 274 men receiving FT for PCa using either high intensity focused ultrasound (HIFU) or cryotherapy at a high volume center between 2009 and 2018. Survival analyses using Kaplan-Meier method were used to assess any additional treatment and radical treatment rates according to PCa location. Propensity-score match analysis was used to compare oncologic outcomes of HIFU vs cryotherapy according to PCa location. Covariates were prostate specific antigen, clinical stage, prostate volume, Gleason score, maximum cancer core length, percentage of positive cores and treatment modality. RESULTS: A total of 166 and 108 men received FT with HIFU and cryotherapy, respectively. Overall, 39% (106) and 31% (85) received at least an additional treatment and a radical treatment after FT, respectively, with a median followup of 51 months. At 36 months' followup, the rates of any additional treatment-free survival were 71%, 75%, and 69% for patients with basal, mid-prostate and apical disease, respectively (p=0.7). At multivariable logistic regression analysis, PCa location was not significantly associated with higher risk of either any additional treatment or radical treatment (all p >0.4). After matching, there was no difference between HIFU vs cryotherapy in terms of any additional treatment rates according to PCa location. CONCLUSIONS: The PCa location does not significantly affect the rate of failure after FT. The presence of an apical lesion should not be considered an exclusion criteria for FT. Both HIFU and cryotherapy likely achieve similar medium-term oncologic results regardless of PCa location.

Optimal Surgical Outcome of Minimally Invasive Partial Nephrectomy (MIPN) Based on an Early Postoperative Estimated Glomerular Filtration Rate (eGFR).

PURPOSE OF REVIEW: To compare laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN) performed in two European tertiary centers using the classic optimal surgical definition - "MIC" - and a new optimal surgical definition: the "Novel TRIFECTA" (NT) concept. We sought to strengthen the PN evidence and to test the NT's performance. RECENT FINDINGS: The study population comprehended 505 cases of localized kidney cancer from two tertiary centers between 2012 and 2019. The NT achievement was higher in the RAPN group when compared to LPN (70.5 vs. 87.4%; p = 0.004), while no differences were found when considering the MIC criteria. Also, a similar high-grade complications rate (Clavien-Dindo > III) and operative time (105 min vs. 100 min; p = NS) were found. In the multivariable regression, the RAPN approach was a predictor of NT achievement (OR 2.45; p = 0.008). NT achievement was higher in the RAPN group, while similar results were found when evaluating the MIC criteria. The NT definition could be more sensitive to the individual-specific responses related to the PN.

Comparison of Initial Experience with Transrectal Magnetic Resonance Imaging Cognitive Guided Micro-Ultrasound Biopsies versus Established Transperineal Robotic Ultrasound Magnetic Resonance Imaging Fusion Biopsies for Prostate Cancer.

PURPOSE: We compared cancer detection rates in patients who underwent magnetic resonance imaging cognitive guided micro-ultrasound biopsy vs robotic ultrasound magnetic resonance imaging fusion biopsy for prostate cancer. MATERIALS AND METHODS: Among 269 targeted biopsy procedures 222 men underwent robotic ultrasound magnetic resonance imaging fusion biopsy and 47 micro-ultrasound biopsy. Robotic ultrasound magnetic resonance imaging fusion biopsy was performed using the transperineal Artemis™ device while micro-ultrasound biopsy was performed transrectally with the high resolution ExactVu™ system. Random biopsies were performed in addition to targeted biopsy in both modalities. Prostate cancer detection rates and concordance between random and target biopsies were also assessed. RESULTS: Groups were comparable in terms of age, prostate specific antigen, prostate volume and magnetic resonance PI-RADS (Prostate Imaging Reporting and Data System) version 2 score. The micro-ultrasound biopsy group presented fewer biopsied cores in random and target approaches. In targeted biopsies micro-ultrasound biopsy cases presented higher detection of clinically significant disease (Gleason score greater than 6) than the robotic ultrasound magnetic resonance imaging fusion biopsy group (38% vs 23%, p=0.02). When considering prostate cancer detection regardless of Gleason score or prostate cancer detection by random+target biopsies, no difference was found between the groups. However, on a per core basis overall prostate cancer detection rates favored micro-ultrasound biopsy in random and targeted scenarios. In addition, the PRI-MUS (Prostate Risk Identification Using Micro-Ultrasound) score yielded by micro-ultrasound visualization was independently associated with improved cancer detection rates of clinically significant prostate cancer. CONCLUSIONS: In our initial experience micro-ultrasound biopsy featured a higher clinically significant prostate cancer detection rate in target cores than robotic ultrasound magnetic resonance imaging fusion biopsy, which was associated with target features in micro-ultrasound (PRI-MUS score). These findings reinforce the role of micro-ultrasound technology in targeted biopsies.

Long-term functional and oncological outcomes of nerve-sparing and prostate capsule-sparing cystectomy: a single-centre experience.

OBJECTIVES: To evaluate the technical feasibility, oncological and functional outcomes of nerve sparing cystoprostatectomy (NSCP) and prostate capsule-sparing cystectomy (PCSC) for the treatment of organ-confined bladder cancer at a single referral centre. PATIENTS AND METHODS: From April 2001 to June 2012, 60 patients underwent PCSC and 47 were treated with NSCP. Inclusion criteria for PCSC were: fully informed consent for the well-motivated patient; negative transurethral resection of the bladder neck; normal prostatic specific antigen (PSA) level (defined as <4 ng/dL during the first year of the study, which was later lowered to 2.5 ng/dL); and normal transrectal ultrasonography, with biopsy for any suspicious nodule. Patients received a complete oncological and functional follow-up. The Kaplan-Meier method was used to depict survival outcomes after surgery. RESULTS: After a median follow-up of 73 and 62 months for PCSC and NSCP, respectively, the 5-year cancer-specific survival was 90% for the PCSC group and 78% for the NSCP group (P = 0.055). Considering complications within 30 days after surgery, 13% and 21% patients had Clavien ≥III complications in the PCSC and NSCP groups, respectively (P = 0.2). For functional outcomes, at 3 months after surgery, 54 (90%) and 24 (51%) patients reported full recovery of daytime urinary continence in the PCSC and NSCP groups, respectively (P < 0.001); and for erectile function recovery, 32 (53%) and four (9%) patients in the PCSC group and in the NSCP group were respectively potent without any treatment (P < 0.001). CONCLUSIONS: NSCP and PCSC are appropriate for a subset of patients with bladder cancer, with excellent oncological and functional results. These surgical procedures should be proposed to well-motivated patients.