Post-radical Prostatectomy Research Articles

Testosterone (T) challenge in men post-radical prostatectomy (RP) with profoundly low testosterone

ABSTRACT Introduction Prostate specific antigen is the primary marker of prostate cancer recurrence. PSA secretion is T dependent with T levels below saturation point associated with sub-optimal PSA production. Men with an undetectable PSA level after RP with very low T levels might have an artificially low PSA level. Objective We aimed to evaluate the effects of raising T level in such men. Methods Study population consisted of (i) men post-RP (ii) with undetectable PSA level (iii) total T levels <200 ng/dl (two levels, LCMS) who (iv) underwent in-office intramuscular injection of 100mg of T cypionate (v) had a PSA level checked 5 days later, and if undetectable every month after that, 3 months later then every 6 months and (vi) follow-up of at least 24 months on T therapy. Results 22 men have been challenged thus far. Mean age 62±18 years. Mean preoperative PSA 6.2. Mean post-RP TT value 140± 35 ng/dL 2.2. Median Gleason sum 7. 23% had GS ≥8. Mean post-RP, pre-challenge T value 140± 35 ng/dL. Mean time post-RP to challenge was 7± 9 months. Mean TT value 5 days after IMT challenge 640± 220 ng/dL, all with TT levels above 400. 5/22 has a PSA elevation, 2 immediately after IMT challenge (PSA values 0.07, 0.08). All other men started T therapy immediately and had PSA elevation at 9, 14 and 22 months after commencing T therapy (PSA values 0.08, 0.12, 0.11). All patients with PSA elevation had continued rise in PSA and had detectable disease on imaging. All men with PSA recurrence had either GS 7 with unfavorable pathology (2) or GS ≥8 (3). Conclusions This T challenge approach permits the early detection of prostate cancer recurrence permitting early intervention. About 10% of such men had a PSA rise immediately after T challenge. Disclosure Work supported by industry: no.

Identification of Potential Predictor of Biochemical Recurrence in Prostate Cancer.

BackgroundProstate cancer is a common malignancy in men. Radical prostatectomy is one of the primary treatment modalities for patients with prostate cancer. However, early identification of biochemical recurrence is a major challenge for post-radical prostatectomy surveillance. There is a lack of reliable predictors of biochemical recurrence. The purpose of this study was to explore potential biochemical recurrence indicators for prostate cancer.Materials and MethodsWe analyzed transcriptomic data of cases with biochemical recurrence in The Cancer Genome Atlas (TCGA). Then, we performed integrative bioinformatics analyses to establish a biochemical recurrence predictor model of prostate cancer.ResultsThere were 146 differentially expressed genes (DEGs) between prostate cancer and normal prostate, including 12 upregulated and 134 downregulated genes. Comprehensive pathway enrichment analyses revealed that these DEGs were associated with multiple cellular metabolic pathways. Subsequently, according to the random assignment principle, 208 patients were assigned to the training cohort and 205 patients to the validation cohort. Univariate Cox regression analysis showed that 7 genes were significantly associated with the biochemical recurrence of prostate cancer. A model consisting of 5 genes was constructed using LASSO regression and multivariate Cox regression to predict biochemical recurrence of prostate cancer. Expression of PAH and AOC1 decreased with an increasing incidence of prostate cancer, whereas expression of DDC, LINC01436 and ORM1 increased with increasing incidence of prostate cancer. Kaplan–Meier curves and receiver operator characteristic (ROC) curves indicated that the 5-gene model had reliable utility in identifying the risk of biochemical recurrence of prostate cancer.ConclusionThis study provides a model for predicting prostate cancer recurrence after surgery, which may be an optional indicator for postoperative follow-up.

68Ga-PSMA-11 PET/CT Initial Staging in Black and White South African Males with ISUP Grade Group 1 and 2 Prostate Adenocarcinoma.

Prostate adenocarcinoma (PCa) is a leading cause of mortality. Black males with high-risk PCa have a poorer prognosis compared to white males. Patients with International Society of Urological Pathology (ISUP) Grade Group (GG) 1 and 2 PCa have little potential for metastases post radical prostatectomy. 68Gallium prostate specific membrane antigen (68Ga-PSMA) PET/CT imaging for metastatic PCa is superior to conventional imaging in staging high-risk PCa. No strong evidence is available to support imaging low-risk patients. We aimed to evaluate the value of 68Ga-PSMA PET/CT in black and white South African (BSA and WSA) males with GG1 and 2 PCa at initial staging. We evaluated 25 WSA and 123 BSA males. The image findings were correlated with prostate specific antigen (PSA). PSA levels significantly correlated with both primary tumor and whole-body PSMA-tumor volume (PSMA-TV) and were higher in BSA males. No differences were noted in the occurrence of metastases; however, PSA, seminal vesicle invasion and black race predicted metastases. Our findings suggest higher PSMA expression and tumor burden in BSA with histologically low-risk PCa, and future research with immunohistochemistry evaluation will be essential to confirm these findings.

Acceptance and Commitment Therapy to Increase Compliance to Intracavernosal Injection Use (ICI) Following Radical Prostatectomy (RP): Preliminary Results from a Randomized Control Trial

ABSTRACT Introduction ICI is the cornerstone of many erectile rehabilitation programs (ERP). However, compliance with ICI is historically low. Objective This study tests a novel psychological intervention based on Acceptance and Commitment Therapy (ACT) concepts to help men reduce avoidance to ICI and commit to an ERP. Methods This ongoing study recruits men starting in our ERP. The recruitment goal is N=220. Subjects are randomized to ERP+ACT or ERP+Enhanced Monitoring and Education (EME). ERP+ACT receive ERP plus 3 ACT Sessions (30-45min) and 10 ACT Booster Sessions (10min). ERP+EME receive ERP plus 3 EME Sessions (30-45min) and 10 EME Booster Sessions (10min) delivered by a nurse practitioner who monitors ICI use, answers questions, and provides education. The interventions are delivered over a year. Eligibility includes: within 9m post RP; functional pre-RP erections (≥6/10). Subjects are assessed at entry and every 6m for two years. The primary outcomes are number of penile injections/week (verified by syringe count), and compliance (defined as ≥2 injections/week). Secondary outcomes are: ED treatment satisfaction, sexual self-esteem and relationship quality, sexual bother, prostate cancer treatment regret, the psychological impact of cancer, and depressive symptoms. Preliminary 6m data is presented. Groups are compared with ANCOVA. Since these are preliminary analyses, if differences were not statistically significant, effect sizes (d) are reported (d=0.2, small effect; d=0.5, medium effect; d=0.8, large effect). Results To date, 120 subjects have been randomized; 62 have completed the 6m assessment (ACT n=33, EME n=29). The mean age was 60±7 years and 81% were married. The mean erectile function grade pre-RP was 8.9±1 (0-10 scale). At 6m, the ACT group utilized more injections/week vs. the EM group (median: 2.06 vs. 1.17, p=0.01) and were more compliant with ICI vs. the EM group (70% vs. 45%, p=0.05, RR=1.55). The ACT group reported greater: satisfaction with ED treatment (d=0.6) and overall sexual relationship (d=0.2). The ACT group also reported lower: sexual bother (d=0.2), prostate cancer treatment regret (d=0.3), negative psychological impact of cancer (d=0.3), and depressive symptoms (d=0.2). Conclusions Preliminary analysis suggests ACT significantly increases ICI use. Data also indicate ACT helps increase men's satisfaction with injections and sexual relationship, while reducing sexual bother, prostate cancer treatment regret, the psychological impact of cancer, and depressive symptoms. Disclosure No

Testosterone (T) Challenge in Men Post-Radical Prostatectomy (RP) with Profoundly Low Testosterone

ABSTRACT Introduction Prostate specific antigen is the primary marker of prostate cancer recurrence. PSA secretion is T dependent with T levels below saturation point associated with sub-optimal PSA production. Men with an undetectable PSA level after RP with very low T levels might have an artificially low PSA level. Objective We aimed to evaluate the effects of raising T level in such men. Methods Study population consisted of (i) men post-RP (ii) with undetectable PSA level (iii) total T levels <200 ng/dl (two levels, LCMS) who (iv) underwent in-office intramuscular injection of 100mg of T cypionate (v) had a PSA level checked 5 days later, and if undetectable every month after that, 3 months later then every 6 months and (vi) follow-up of at least 24 months on T therapy. Results 22 men have been challenged thus far. Mean age 62±18 years. Mean preoperative PSA 6.2. Mean post-RP TT value 140± 35 ng/dL 2.2. Median Gleason sum 7. 23% had GS ≥8. Mean post-RP, pre-challenge T value 140± 35 ng/dL. Mean time post-RP to challenge was 7± 9 months. Mean TT value 5 days after IMT challenge 640± 220 ng/dL, all with TT levels above 400. 5/22 has a PSA elevation, 2 immediately after IMT challenge (PSA values 0.07, 0.08). All other men started T therapy immediately and had PSA elevation at 9, 14 and 22 months after commencing T therapy (PSA values 0.08, 0.12, 0.11). All patients with PSA elevation had continued rise in PSA and had detectable disease on imaging. All men with PSA recurrence had either GS 7 with unfavorable pathology (2) or GS ≥8 (3). Conclusions This T challenge approach permits the early detection of prostate cancer recurrence permitting early intervention. About 10% of such men had a PSA rise immediately after T challenge. Disclosure No

Tumor Necrosis Factor- α (TNF-α) and Rho-Associated Kinase 2 (ROCK2) Inhibitors Improve Erectile Function in a Bilateral Cavernous Nerve Injury Rat Model

ABSTRACT Introduction Prior studies suggest Rho-kinase (ROCK) upregulation and pro-inflammatory cytokines such as Tumor Necrosis Factor-α as causative factors of axonal degeneration, neuropathy, and penile fibrosis following peripheral cavernous nerve (CN) injury. We hypothesize, the combination therapy using inhibitors/antagonists of ROCK and TNF-α may prevent end-organ damage and neuroinflammation in the penis. The current study was designed to investigate selective inhibition of ROCK2 (SAR407899) and TNF-α (Infliximab) in a pre-clinical model of post-radical prostatectomy ED to prevent penile neuroinflammation, fibrosis, and preserve penile hemodynamics. Objective This study investigates the effect of FDA approved TNF- α inhibitor (Infliximab) in combination with ROCK2 selective inhibitor (SAR407899) on erectile function restoration in the bilateral crush nerve injury (BCNI) rat model. Methods Sprague Dawley rats were randomized to undergo either sham (6) or BCNI (28). The BCNI rats were further randomly stratified to receive saline (6), Infliximab (5 mg/kg once weekly) (6), low dose of SAR407899 (1.5 mg/kg QD) (5), high dose of SAR407899 (3 mg/kg QD) (5), or combination treatment SAR407899 (1.5 mg/kg QD) + Infliximab (5 mg/kg once weekly) (6). At 14 days after injury rats underwent cavernous nerve stimulation to determine erectile function. Penes were collected and immune infiltrate analyses were performed using multicolor flow-cytometry. Results Erectile response studies demonstrated that rodents treated with combination of Infliximab and SAR407899 had significantly improved (p<0.05) erectile function (ICP/MAP) at all voltages compared to BCNI alone (2V: 0.243 vs 0.051, 4V: 0.321 vs 0.0782, 6V: 0.456 vs 0.091, p <0.05). Peak ICP and total ICP were also significantly (p<0.05) improved compared to BCNI rats. Combination therapy, however, did not show a significant change compared to each treatment alone. Likewise, there was no significant difference between low and high dose SAR407899. Flow cytometry showed that Infliximab and SAR407899 significantly (p<0.05) decreased % of CD11b+ CD45+ monocytes in the penis. While combination therapy had no effect. The percent of CD11b+ MHCII+ CD45+ macrophages were increased (p<0.05) in the penes of rats treated with Infliximab and SAR407899 while combination therapy decreased penile macrophage population. We found no change in TNF- α+ monocytes and macrophages compared in penes from all groups investigated. Conclusions Our study suggests that treatment with commercially available TNF-α and ROCK2 inhibitors result in mitigation of erectile dysfunction in a BCNI rat model when administered at the time of nerve injury. The mechanism of the beneficial effects may involve reduction in macrophage population in the penis. Disclosure No

Adjuvant Versus Early Salvage Radiation Therapy After Radical Prostatectomy for pN1 Prostate Cancer and the Risk of Death.

PURPOSEAn association with a reduction in the risk of all-cause mortality (ACM) and the use of adjuvant as compared with early postradical prostatectomy salvage radiation therapy (sRT) in men with pN1 prostate cancer (PC) has been observed. Yet, whether this finding applies irrespective of the number of positive lymph nodes (LNs) after adjusting for the time-dependent use and duration of androgen deprivation therapy is unknown and is addressed in the current study.METHODSUnivariable and multivariable Cox regression was used to evaluate whether the ACM risk ratio for time-dependent use of adjuvant versus early sRT per unit increase in positive pelvic LNs was significantly reduced. Adjusted ACM estimates were calculated among men who received adjuvant, early salvage, or no RT stratified by one to three or four or more positive pelvic LNs.RESULTSAfter a median follow-up of 7.02 years, 986 (5.50%) men died, with 223 (22.62%) of PC. Adjuvant compared with early sRT was associated with a significantly lower ACM risk per unit increase in positive pelvic LNs (adjusted hazard ratio: 0.92; 95% CI, 0.85 to 0.99; P = .03). A significant difference in the 7-year adjusted ACM estimates favoring aRT versus early sRT was observed in men with four or more positive LNs (7.74% v 23.36%) in that the 95% CI for the 15.62% difference (5.90 to 25.35) excluded 0.00, but this was not true for men with 1-3 positive LNs (14.27% v 13.89%; 95% CI for the 0.38% difference [–7.02 to 7.79]).CONCLUSIONAdjuvant compared with early sRT in men with pN1 PC was associated with a decreased ACM risk, and this reduction increased with each additional positive pelvic LN.

PSMA PET/CT guided intensification of therapy in patients at risk of advanced prostate cancer (PATRON): a pragmatic phase III randomized controlled trial

BackgroundPositron emission tomography targeting the prostate specific membrane antigen (PSMA PET/CT) has demonstrated unparalleled performance as a staging examination for prostate cancer resulting in substantial changes in management. However, the impact of altered management on patient outcomes is largely unknown. This study aims to assess the impact of intensified radiotherapy or surgery guided by PSMA PET/CT in patients at risk of advanced prostate cancer.MethodsThis pan-Canadian phase III randomized controlled trial will enroll 776 men with either untreated high risk prostate cancer (CAPRA score 6–10 or stage cN1) or biochemically recurrent prostate cancer post radical prostatectomy (PSA > 0.1 ng/mL). Patients will be randomized 1:1 to either receive conventional imaging or conventional plus PSMA PET imaging, with intensification of radiotherapy or surgery to newly identified disease sites. The primary endpoint is failure free survival at 5 years. Secondary endpoints include rates of adverse events, time to next-line therapy, as well as impact on health-related quality of life and cost effectiveness as measured by incremental cost per Quality Adjusted Life Years gained.DiscussionThis study will help create level 1 evidence needed to demonstrate whether or not intensification of radiotherapy or surgery based on PSMA PET findings improves outcomes of patients at risk of advanced prostate cancer in a manner that is cost-effective.Trial registrationThis trial was prospectively registered in ClinicalTrials.gov as NCT04557501 on September 21, 2020.

Prediction of Postradical Prostatectomy Urinary Incontinence Through the Combination of the Urethral Pressure Profile With Electromyography of the Urethral Sphincter.

PurposeWe tested the hypothesis that the urethral pressure profile, in combination with electromyography of the urethral sphincter, may be useful as a predictor of urinary incontinence after radical prostatectomy (RP). The aim of this study was to assess whether the combination of these tests resulted in an improved tool for the prediction of post-RP urinary incontinence.MethodsPatients with indications for RP were included. The urethral pressure profile, including prostatic and sphincter components for maximum urethral closure pressure (MUCP) and functional urethral length, was recorded in combination with needle electromyography of the urethral sphincter. The mean and maximum amplitude of waves were measured twice: 1 month before RP and 6 months after the procedure. The 1-hour pad test was conducted in parallel with other tests. Patients completed the International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF). The relationship of the results of the tests with post-RP urinary incontinence was studied. Age, urodynamic parameters, pathologic stage, and surgical technique were recorded for analysis as potential confounding factors.ResultsNineteen patients were included within the 1-year study period. Their mean age was 63 years. According to the 1-hour pad test and ICIQ-SF, 42.1% of the sample had urinary incontinence after RP. Prostate MUCP with the mean and during-stress amplitude of waves predicted post-RP urinary incontinence with a sensitivity of 87.5% (P=0.002) in our model. Age, urodynamic parameters, pathological stage, and surgical technique were not related to incontinence after surgery.ConclusionsThe combination of the urethral pressure profile (prostatic MUCP) and electromyography of the urethral sphincter might be a useful prognostic predictor of post-RP urinary incontinence.

Salvage radiotherapy guided by functional imaging for macroscopic local recurrence following radical prostatectomy: A multicentric retrospective study.

251 Background: For prostate cancer (Pca), salvage radiotherapy (sRT) with or without androgen deprivation therapy (ADT) is currently the only curative treatment option in case of post-radical prostatectomy (RP) biochemical relapse (BR). Functional imaging techniques have shown that macroscopic recurrence (MR) in the prostate bed (PB) are frequent. In this study, we aimed to assess efficacy and safety of sRT in patients with MR inside the PB proven by functional imaging. Methods: A multicenter retrospective study was conducted in 16 European centers. Patients were included if they displayed BR after RP for Pca, with MR only in the PB proven by functional imaging. All patients had to be eligible for sRT. The overall population was divided along 4 groups according to the delivered treatment: dose escalation on MR (A), dose escalation on PB (B), double dose escalation MR+PB (C), no dose escalation (D). The primary endpoint was progression-free survival (PFS). Secondary outcomes included the metastasis-free survival (MFS), biochemical PFS (bPFS) and overall survival (OS). Grade ≥2 genito-urinary (GU) and gastro-intestinal (GI) acute and late toxicities were collected. Results: Between January 2000 and December 2019, 363 patients with isolated MR after RP for Pca were treated by sRT. The median pre-sRT PSA level was 0.63ng/mL (range, 0.2-23.6). At the time of BR, 266 (73%) patients presented MR in the PB proven by magnetic resonance imaging, and 110 (30%) by positron emission tomography. The median follow-up was 53.6 months (range, 47.52; 58.32). The 5-year PFS and MFS were 70% (95%CI [63.8-75.4]) and 83.7% (95%CI [78.4-87.8]), respectively. Grade ≥2 GU and GI late toxicities were found in 43 (12%) and 11 (3%) patients, respectively. A 5-year PFS benefit was highlighted for groups A, B and C (313 patients) when the MR dose was ≥72Gy: 72,8% (95%CI 64.6-79.4) versus 60.3% (95%CI 48,4-70,3), p = 0.03. Conclusions: In a modern series integrating functional imaging data, we confirmed that sRT is effective in the event of MR inside the PB, with an acceptable toxicity profile. Prospective data should further investigate the correlation between MR-targeted dose escalation and PFS.

Outcomes of Salvage Lymph Node Dissection in Oligorecurrent Prostate Cancer Post Radical Prostatectomy: Experience of an Oncologic Center in Spain

Introduction and ObjectivesWe report our experience with salvage lymph node dissection (sLND) in oligorecurrent prostate cancer (PCa) post radical prostatectomy (RP).Material and MethodsWe retrospectively analyzed data of 24 patients who underwent sLND for biochemical recurrence (BCR) post RP, from July 2012 to February 2018. sLND was performed following an extended bilateral template. Clinical and pathological characteristics of primary RP and sLND were reported. Biochemical response and initiation of additional therapy post sLND were analyzed. Survival analysis was performed using KaplanMeier curves.Results24 sLND were performed. RP specimens showed 58.3% of Gleason score 7 and 50% of locally advanced disease. Median time to BCR post RP was 24 months with a median PSA value of 1.4 ng/ml pre sLND. 75% of patients underwent imaging prior to sLND. sLND showed oligometastasis on the final pathology report in 54.2% of patients. Metastatic lymph nodes were mainly identified in the iliac artery territory (61.5%). Complete biochemical response (PSA < 0.2 ng/ml) was maintained throughout the first 12 months of follow-up in 20.83% of patients and 8.33% of patients at the end of the study (median follow-up 70 months). Survival rates free of additional therapy (ADT/RT) were 45.83% at one year and 25% at 5 years.ConclusionsWe observed a biochemical response post sLND in 20.83% of our patients, lasting throughout the first year of follow up, with survival rates free of ADT and/or RT of 45.83% at one year and 25% at 5 years.

A1158 - Urinary continence outcome of patients with epithelialized cavity formation after excessive vesicourethral anastomotic leak post radical prostatectomy

A1158 - Urinary continence outcome of patients with epithelialized cavity formation after excessive vesicourethral anastomotic leak post radical prostatectomy

Lower Urinary Tract Symptoms are Common After Artificial Urinary Sphincter Implantation

ObjectiveTo investigate lower urinary tract symptoms (LUTS) observed after artificial urinary sphincter (AUS) implantation for post-radical prostatectomy urinary incontinence (PRPUI). Materials and MethodsCases of AUS for PRPUI were evaluated. Stress urinary incontinence (SUI) was assessed using the Sandvik-incontinence severity index. Other LUTS were evaluated using the overactive bladder symptom score and international prostate symptom score. The prevalence and predictive risk factors for post-AUS LUTS were analyzed. ResultsOf 129 patients evaluated (mean follow-up = 42.3 months, mean age = 76.7 years), 8.5% had very severe SUI, 78.4% had moderately to severely symptomatic LUTS (IPSS = 8-35 points), and 45.2% were dissatisfied with their urinary condition. Nocturia was the most prevalent (48.0%). Maximum cystometric capacity (rho = –0.236, P = .007) and involuntary detrusor contraction (P = .002) were significantly related to the severity of post-AUS urgency urinary incontinence (UUI). Multivariable linear regression analysis indicated that involuntary detrusor contraction was more associated with post-AUS urgency (P <.001) and UUI (P = .006) than any other preoperative parameter. Age significantly correlated with the severity of post-AUS urgency (rho = 0.309, P <.001), UUI (rho = 0.196, P = .026), and the need for straining to void (rho = 0.240, P = .007). ConclusionEven after successful placement of an AUS, many patients were dissatisfied with various LUTS, ranging from the most frequent nocturia to the need for straining to void. Attention should be paid not only to SUI but also to non-SUI LUTS, which are observed in the general population in this age group and change over time. Counseling to educate patients about expected outcomes and continuous monitoring and treatment for LUTS should be provided for the PRPUI-AUS population.

Pre-diagnosis urine exosomal RNA (ExoDx EPI score) is associated with post-prostatectomy pathology outcome

PurposeExoDx Prostate IntelliScore (EPI) is a non-invasive urine exosome RNA-based test for risk assessment of high-grade prostate cancer. We evaluated the association of pre-biopsy test results with post-radical prostatectomy (RP) outcomes to understand the potential utility of EPI to inform invasive treatment vs active surveillance (AS) decisions.MethodsUrine samples were collected from 2066 men scheduled for initial biopsy with PSA between 2 and 10 ng/mL, no history of prostate cancer, and ≥ 50 years across multiple clinical studies. 310 men proceeded to RP, of which 111 patients had Gleason group grade 1 (GG1) at biopsy and would have been potential candidates for AS. We compared pre-biopsy urine scores with ERSPC and PCPT multivariate risk calculator scores for men with GG1 at biopsy to post-RP pathology.ResultsUrine EPI scores were significantly lower in men with GG1 at biopsy than in men with > GG1 (p = 0.04), while there were no differences in multivariate risk scores used in standard clinical practice (p > 0.05). Further, EPI scores were significantly lower in men with GG1 at biopsy who remained GG1 post-RP compared to men upgraded to ≥ GG3 post-RP (p < 0.001). In contrast, none of the multiparametric risk calculators showed significant differences (p > 0.05). Men with GG1 at biopsy and EPI score < 15.6 had zero rate of upgrading to ≥ GG3 post-RP compared to 16.0% for EPI scores ≥ 15.6.ConclusionsThe EPI urine biomarker outperformed the multivariate risk calculators in a homogenous risk group of pre-biopsy men. The EPI score was associated with low-risk pathology post-RP, with potential implications on informing AS decisions.Trial registration NCT02702856, NCT03031418, NCT03235687, NCT04720599.

68Ga-PSMA PET/CT Scan Leading to Diagnosis of PSMA-Positive Rectal Adenocarcinoma in a Patient With Prostate Cancer.

A 59-year-old prostate cancer patient, status post radical prostatectomy, was referred to our department for restaging with 68Ga-prostate-specific membrane antigen (PSMA) PET/CT scan. Aside multiple metastatic lesions involving pelvic lymph nodes as well as the right femoral trochanter, a PSMA-positive rectal wall thickening was detected. Colonoscopy correlation and tissue diagnosis, recommended to rule out accompanying primary malignancy, confirmed the presence of rectal adenocarcinoma. This case signifies the importance of requesting pathological correlation for unexplained PSMA-positive lesions, emphasizing the potential role PSMA ligands may play in detecting occult second primary malignancies, especially synchronous/metachronous colorectal cancers.

Male sling placement for post-prostatectomy incontinence can involve a lengthy learning curve: A multi-outcome assessment via cumulative sum failure analysis.

Little research exists on potential learning curve for male sling procedures. We aimed to perform a learning curve analysis of a single surgeon's experience of sling placement evaluating multiple outcomes and using the cumulative sum failure methodology. The study included 65 consecutive patients that underwent implantation of a fixed transobturator sling (TiLOOP Male) for post-radical prostatectomy stress incontinence at our institution from January 2013 to December 2018. Dichotomous outcomes evaluated with cumulative sum failure analysis included 12-months continence defined based on Patient Global Impression of Improvement (PGI-I) questionnaire (primary outcome), 24 h pad test and, 24 h pad use, operative time (⩽/>60 min), and complications (yes/no). Univariate and multivariate logistic regression analyses were performed to evaluate the association of the procedures' chronological sequence number with the outcomes. Cumulative sum failure curves revealed a clear and lengthy learning curve effect for most of subjective and quantitative continence outcomes and for operative time. For the primary outcome (at least much improved at PGI-I), 62 procedures were required to overcome the learning curve. Accordingly, multivariate analyses showed that the sequence number was statistically significant for predicting failures based on PGI-I (adjusted OR 0.95; 95% CI: 0.91-0.99; p = 0.02), objective outcomes, and operative time. An evident and lengthy learning curve was observed in our series of male sling placement to achieve the end level of proficiency, independently from case-mix. Individualized structured training on male sling surgery will benefit patients treated in the initial surgeon's experience. Surgical experience should be considered when reporting studies on male slings.

Artificial urinary sphincter outcomes for post-radical prostatectomy urinary incontinence. A narrative review

Urinary incontinence post-radical prostatectomy is a common complication that might negatively impact patients’ quality of life. Treatments include medical and surgical options, being the insertion of an artificial urethral sphincter (AUS) the gold standard. The aim of this narrative review is to evaluate the outcomes of artificial urinary sphincter implantation for urinary incontinence developed post-radical prostatectomy with and without radiation, in terms of urinary continence and complications. The MEDLINE and Scopus search returned 477 articles. A total of eleven articles were included for qualitative analysis. A total of 707 men that met the inclusion criteria were included. The 22.6% of the men (160 patients) received pelvic external beam radiotherapy prior to the implantation of the artificial urinary sphincter. The overall continence success rate was defined by the use of pads. Some authors reported a success rate of 0 pads per day (PPD) or ≤ 1 PPD in the last follow-up. The complications included urethral atrophy, mechanical failure, revision and/or removal of the device, infection and erosion. Further prospective studies should be done to clarify continence concepts after the placement of an AUS and long-term complications.

Taking Advantage of the Teachable Moment at Initial Diagnosis of Prostate Cancer—Results of a Pilot Randomized Controlled Trial of Supervised Exercise Training

Increased physical activity (PA) levels are associated with improved prostate cancer (PCa) outcomes. Sustainable PA has been linked to improved health-related quality of life (QoL) in cancer patients. The time of diagnosis of PCa may offer a critical time point when patients might be more likely to consider lifestyle changes. This, in turn, may contribute to sustainable PA and its likely benefits. The aims of this study were to determine if a structured PA intervention introduced at the time of diagnosis can (1) lead to sustainable PA and (2) help improve psychosocial and QoL outcomes as compared with usual PA. This was a pilot randomized controlled trial enrolling patients with intermediate-risk PCa into either arm A (supervised 8- to 12-week physical exercise program; n = 10) or control arm B (usual PA; n = 10). Primary outcome was PA at 6 months. Secondary outcomes were QoL, psychological well-being, physical fitness, and functional outcomes postintervention. Change over time was compared using a nonparametric Wilcoxon test. Demographic variables were the same between arms. Comparing parameters at the start and 6 months post-radical prostatectomy, PA significantly improved in arm A (self-reported Godin score 24.7 vs 42.8 units, P < .01, objective number of chair stands [14-19, P < .01]), but not in arm B. There were no significant differences between arms in QoL and psychosocial outcomes. A preoperative supervised exercise training program increases long-term PA. Future trials should evaluate PA sustainability beyond 6 months and if this leads to improved psychosocial and QoL outcomes.

Acupuncture for prostatectomy incontinence: study protocol for a multicenter single-blind randomized parallel controlled trial

BackgroundUrinary incontinence is a common complication post radical prostatectomy. Acupuncture is considered an effective treatment for post-prostatectomy incontinence (PPI), but the evidence is still limited. We propose to evaluate the effectiveness of acupuncture in a rigorously conducted trial.MethodsTwenty hospitals will recruit 340 participants with urinary incontinence after radical prostatectomy in China from April 2021 to April 2022. Participants will be randomly allocated to acupuncture or sham acupuncture with a 1:1 ratio using computerized simple random sampling. The study plan consists of 1-week baseline, 6-week treatment, and 18-week follow-up. Eighteen 30-min sessions of acupuncture or sham acupuncture treatment will be provided between weeks 1 and 6. The primary outcome is the change in the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF) score at the week 6 from the baseline. Secondary outcomes include the change in volume of urine leakage at weeks 4 and 6 from a baseline measured using the 1-h pad test; 72-h incontinence episode frequency based on a 72-h voiding diary; change in the Expanded prostate cancer Index Composite scale (EPIC-26); change in the Self-Rating Anxiety Scale; weekly consumption of pads; and the severity of urinary incontinence based on a 72-h bladder diary and self-assessment of the therapeutic effect. The safety of acupuncture will also be assessed.DiscussionThis trial will help to identify whether acupuncture is effective for PPI, and, if so, whether it exerts a therapeutic rather than a placebo effect.Trial Registrationwww.Chictr.org.cnChiCTR2100042500. Retrospectively registered on 22 January 2021.

Is there a role for stem cell therapy in erectile dysfunction secondary to cavernous nerve injury? Network meta-analysis from animal studies and human trials.

Introduction:We carried out systematic review and network meta-analysis to investigate the role of stem cell therapy (SCT) in the management of erectile dysfunction (ED) secondary to cavernous nerve injury in rats and post-radical prostatectomy (RP) in humans.Patients and Methods:The protocol was registered with PROSPERO database. We searched studies analyzing the efficacy of SCT for ED due to bilateral cavernous nerve injury (BCNI) in rats using Healthcare Databases Advanced Search (HDAS) Export software (MEDLINE, EMBASE, Scopus) from inception to September 2020. The outcome measurements, for 29 animal studies, were intracavernosal pressure (ICP), ICP/MAP (mean arterial pressure) ratio, and histological/molecular changes. All three available human trials evaluating SCT in post-RP ED were assessed for International Index for Erectile Function (IIEF) Score and Erection Hardness Score (EHS).Results:For ICP measurement, animal studies were divided into adipose-derived stem cells (ADSCs) subgroup and bone marrow–derived stem cells (BMSCs) subgroup. Pooled analysis of these studies showed a beneficial effect of SCT in improving erectile function in rats with BCNI using network meta-analysis (95% confidence interval, CI; p < 0.001). There was an increase in ICP/MAP ratio in stem cell groups (including co-intervention) compared with control BCNI group. Histological and molecular evaluation of penile tissue revealed an increase in neuronal nitric oxide synthase (nNOS), smooth muscle content, and anti-apoptotic activity. Human trials revealed improved IIEF (70–150% from baseline at 6 months) and EHS (80–200% from baseline).Conclusion:Our results confirm that SCT does improve the erectile function in rats having cavernous nerve injury. Similarly, early human results have shown promising results.PROSPERO registration ID:CRD42020201343.