Rodney H. Breau

Pilot Study on Quality of Life and Sexual Function in Men-Who-Have-Sex-with-Men Treated for Prostate Cancer

INTRODUCTION There is limited data on post-treatment quality of life (QoL) for men-who-have-sex-with-men (MSM) with prostate cancer (PCa). QoL in MSM may not be reflected by assessment tools designed for the heterosexual population. AIMS Our goals were to evaluate post-treatment QoL in PCa patients who are MSM, and to investigate the utility of current QoL assessment tool. METHODS PCa patients treated with surgery and/or radiation were recruited from the local MSM community. Each participant completed the Expanded Prostate Cancer Index Composite (EPIC) questionnaire, Male Sexual Health Questionnaire (MSHQ), and a questionnaire focused on insertive and receptive roles of anal intercourse. MAIN OUTCOME MEASURES Response scores were calculated based on questionnaire design and compared by treatment modality. RESULTS Seven participants treated with surgery (mean age 58) and eight participants treated with radiation (mean age 67) were recruited. No participant in the surgical group received androgen deprivation therapy (ADT) while two in radiation group were treated with ADT. The sample size of this study did not permit formal statistical analysis, although potential differences in Urinary and Bowel Domains from EPIC and Ejaculation Scale from MSHQ were observed. More participants from the radiation group seemed to be able to maintain both insertive and receptive anal intercourse roles after treatment compared to participants who received surgery. CONCLUSIONS While the two validated assessment tools suggested similar QoL scores including sexual function for both surgical and radiation groups, post-treatment sexual function related to anal intercourse may be better in the radiation group, as compared to the surgical group. Larger studies in PCa patients from MSM community are warranted to verify these data.

The Risks and Benefits of Cavernous Neurovascular Bundle Sparing during Radical Prostatectomy: A Systematic Review and Meta-Analysis

Purpose: We summarize published data on associations between cavernous neurovascular bundle preservation (nerve sparing) during prostatectomy and positive surgical margins, erectile function, urinary function and other patient reported outcomes. Materials and Methods: A systematic literature search of MEDLINE®, Embase® and Cochrane Reviews databases was performed for interventional or observational studies published between 2000 and 2014. English language articles that compared clinical outcomes of patients undergoing nerve sparing and nonnerve sparing radical prostatectomy were included. Meta‐analyses were performed to calculate pooled relative risk estimates for positive surgical margins, erectile dysfunction and urinary incontinence in nerve sparing and nonnerve sparing groups. Sensitivity analyses compared outcomes among unilateral and bilateral nerve sparing vs nonnerve sparing groups. Results: Of the 1,883 articles identified, 124 studies (73,448 patients) were included in the analysis. Nerve sparing did not increase the risk of positive surgical margins in patients with pT2 (RR 0.92, 95% CI 0.75–1.13) or pT3 disease (RR 0.83, 95% CI 0.71–0.96), potentially due to appropriate patient selection. The risk of incontinence was lower in nerve sparing cases (RR 0.75, 95% CI 0.65–0.85 and RR 0.61, 95% CI 0.44–0.84) at 3 and 12 months, respectively. The relative risk of erectile dysfunction with nerve sparing was 0.77 (95% CI 0.70–0.85) at 3 months and 0.53 (95% CI 0.39–0.71) at 12 months. Subgroup analyses of unilateral and bilateral nerve sparing approaches demonstrated similar results. Conclusions: Among cohort studies nerve sparing was not associated with worse cancer outcomes. Nerve sparing is associated with better urinary and erectile function. These results should be interpreted with caution given the potential for selection bias and unadjusted confounding factors.

Multiparametric MRI of the anterior prostate gland: clinical-radiological-histopathological correlation.

Anterior prostate cancer (APC) is defined as a tumour in which more than half of malignant tissue is located anterior to the urethra. APCs are increasingly recognized as clinically important, particularly in patients undergoing active surveillance and for patients with negative non-targeted systematic transrectal ultrasound (TRUS)-guided biopsies but with persistent clinical suspicion of cancer. Multiparametric (mp) MRI has a crucial role for the diagnosis of anterior tumours, eventual histological sampling of suspicious lesions using image-guided targeted biopsy techniques, and potentially, to improve local staging of disease. mpMRI is accurate for the detection of APC and for differentiation of tumour from other anterior prostatic structures including benign prostatic hyperplasia (BPH) and the anterior fibromuscular stroma (AFMS). Characterization and reporting of APC should rely on the recently revised Prostate Imaging and Data Reporting System (PI-RADS) version 2.0 document. T2-weighted (T2W) imaging is emphasized as the determining sequence for assessment of the anterior prostate and specific features for APC on T2W imaging include: ill-defined/spiculated margin, lenticular shape, anterior/inferior location, and growth pattern (invasion of urethra or AFMS and crossing midline). Functional imaging, mainly with diffusion-weighted imaging, is also contributory and improves the sensitivity for detection of APC compared to T2W imaging alone. APCs commonly show positive surgical margins after radical prostatectomy and staging of disease extent using conventional clinical parameters is limited. mpMRI may have a future role to improve local staging of APC. This review illustrates the importance of mpMRI in APC using a clinical-radiological-histopathological approach.

Fish-Derived Omega-3 Fatty Acids and Prostate Cancer A Systematic Review

Background. The use of natural health products in prostate cancer (PrCa) is high despite a lack of evidence with respect to safety and efficacy. Fish-derived omega-3 fatty acids possess anti-inflammatory effects and preclinical data suggest a protective effect on PrCa incidence and progression; however, human studies have yielded conflicting results. Methods. A search of OVID MEDLINE, Pre-MEDLINE, Embase, and the Allied and Complementary Medicine Database (AMED) was completed for human interventional or observational data assessing the safety and efficacy of fish-derived omega-3 fatty acids in the incidence and progression of PrCa. Results. Of 1776 citations screened, 54 publications reporting on 44 studies were included for review and analysis: 4 reports of 3 randomized controlled trials, 1 nonrandomized clinical trial, 20 reports of 14 cohort studies, 26 reports of 23 case-control studies, and 3 case-cohort studies. The interventional studies using fish oil supplements in patients with PrCa showed no impact on prostate-specific antigen levels; however, 2 studies showed a decrease in inflammatory or other cancer markers. A small number of mild adverse events were reported and interactions with other interventions were not assessed. Cohort and case-control studies assessing the relationship between dietary fish intake and the risk of PrCa were equivocal. Cohort studies assessing the risk of PrCa mortality suggested an association between higher intake of fish and decreased risk of prostate cancer–related death. Conclusions. Current evidence is insufficient to suggest a relationship between fish-derived omega-3 fatty acid and risk of PrCa. An association between higher omega-3 intake and decreased PrCa mortality may be present but more research is needed. More intervention trials or observational studies with precisely measured exposure are needed to assess the impact of fish oil supplements and dietary fish-derived omega-3 fatty acid intake on safety, PrCa incidence, treatment, and progression.

Perineural invasion on biopsy is associated with upstaging at radical prostatectomy in Gleason score 3 + 4 = 7 prostate cancer

This study assesses if perineural invasion (PNI) detected on biopsy with Gleason score (GS) 3 + 4 = 7 prostate cancer (PCa) is associated with upstaging/upgrading of disease after radical prostatectomy (RP). 154 patients with GS 3 + 4 = 7 PCa diagnosed from biopsy who underwent RP were assessed for PNI. The percentage of biopsy sites with PNI (%PNI) was also calculated. Pattern 4 morphologies (ill‐defined glands [IDG], fused, cribriform, and glomerulations) were also assessed. Clinical information, GS and stage after RP were retrieved from the medical records. 45 % (69/154) of patients were upstaged (≥pT3) and 29 % (44/154) were upgraded to GS >3 + 4 = 7 after RP. 37 % (57/154) of patients had PNI which was associated with upstaging (RR 1.4; P = 0.04) but not upgrading (RR 0.9; P = 0.7). There was higher %PNI in upstaged patients (12.1 % ± 1.8 vs. 7.1 % ± 1.5, P = 0.03) with a significant correlation between %PNI and ≥pT3 (r = 0.178, P = 0.027). After multivariate analysis, only cribriform formations were significantly associated with upstaging (P = 0.009). The presence of PNI in biopsies with GS 3 + 4 = 7 PCa is associated with upstaging at RP but is a weaker predictor of ≥pT3 disease than cribriform morphology.

The Safety and Efficacy of Lysine Analogues in Cancer Patients: A Systematic Review and Meta-Analysis

Lysine analogues are effective agents used for the reduction of blood loss and transfusion. However, the safety of lysine analogues in cancer patients remains in question due to a potential risk of venous thromboembolism (VTE). The objective of our review is to investigate safety and efficacy of lysine analogue administration in the patients with cancer. Medline, Embase, and The Cochrane Library were searched from inception to June, 2016. Reference lists of retrieved studies were searched to identify additional publications. We included randomized clinical trials in adult cancer patients for which a lysine analogue was administered for the purpose of blood loss reduction. Abstract and full-text selection as well as data extraction and risk of bias assessment was done by 2 independent reviewers. The primary outcome was venous thromboembolic events. Secondary outcomes were other adverse events, blood transfusion, and blood loss. Overall, 11studies involving 1177 patients evaluated at least one of the primary or secondary outcomes. Nine studies evaluated the effects of tranexamic acid, one study evaluated the effects of aminocaproic acid and one study examined both agents. No increased risk of venous thromboembolism was observed for patients who received lysine analogues compared to control (Peto OR 0.58; 95% CI 0.26-1.28). The administration of a lysine analogue significantly decreased both transfusion risk (pooled RR 0.52, 95% CI 0.34-0.80) and blood loss (SMD -1.57, 95% CI -2.21 to -0.92). Among 3 eligible studies, no increased risk was observed for mortality (Peto OR 1.01; 95% CI 0.14-7.18) or infection (OR 0.58; 95% CI 0.27-1.27). The safety of lysine analogues in cancer patients has not been extensively studied. Based on the available literature, lysine analogue use has not been associated with increased risk of venous thromboembolism or other adverse events, while being effective in reducing blood loss and subsequent transfusion.

Risk Factors for Urinary Tract Infection following Mid Urethral Sling Surgery

Purpose: Mid urethral sling surgery is common. Postoperative urinary tract infection rates vary in the literature and independent risk factors for urinary tract infection are not well defined. We sought to determine the incidence of and risk factors for urinary tract infection following mid urethral sling surgery. Materials and Methods: A retrospective cohort of females who underwent sling surgery was captured from the 2006 to 2014 NSQIP® (National Surgical Quality Improvement Program®) database. Exclusion criteria included male gender, nonelective surgery, totally dependent functional status, preoperative infection, prior surgery within 30 days, ASA® (American Society of Anesthesiologists®) Physical Status Classification 4 or greater, concomitant procedure and operative time greater than 60 minutes. The primary outcome was the incidence of urinary tract infection within 30 days of mid urethral sling surgery. Risk factors for urinary tract infection were assessed by examining patient demographic, comorbidity and surgical variables. Logistic regression analyses were performed to estimate the ORs of individual risk factors. Multivariable logistic regression was then performed to adjust for confounding. Results: A total of 9,022 mid urethral sling surgeries were identified. The urinary tract infection incidence was 2.6%. Factors independently associated with an increased infection risk included age greater than 65 years (OR 1.54, 95% CI 1.07–2.22), body mass index greater than 40 kg/m2 (OR 1.89, 95% CI 1.23–2.92) and hospital admission (OR 2.06, 95% CI 1.37–3.11). Mid urethral sling surgery performed by urologists carried a reduced risk of infection compared to the surgery done by gynecologists (OR 0.52, 95% CI 0.40–0.69). Conclusions: The urinary tract infection risk following mid urethral sling surgery in NSQIP associated hospitals is low. Novel patient and surgical factors for postoperative urinary tract infection have been identified and merit further study.

Transforming the prostatic tumor microenvironment with oncolytic virotherapy

ABSTRACT Prostate cancer (PCa) was estimated to have the second highest global incidence rate for male non-skin tumors and is the fifth most deadly in men thus mandating the need for novel treatment options. MG1-Maraba is a potent and versatile oncolytic virus capable of lethally infecting a variety of prostatic tumor cell lines alongside primary PCa biopsies and exerts direct oncolytic effects against large TRAMP-C2 tumors in vivo. An oncolytic immunotherapeutic strategy utilizing a priming vaccine and intravenously administered MG1-Maraba both expressing the human six-transmembrane antigen of the prostate (STEAP) protein generated specific CD8+ T-cell responses against multiple STEAP epitopes and resulted in functional breach of tolerance. Treatment of mice with bulky TRAMP-C2 tumors using oncolytic STEAP immunotherapy induced an overt delay in tumor progression, marked intratumoral lymphocytic infiltration with an active transcriptional profile and up-regulation of MHC class I. The preclinical data generated here offers clear rationale for clinically evaluating this approach for men with advanced PCa.

The efficacy and safety of topical tranexamic acid: A systematic review and meta-analysis

Tranexamic acid (TXA) is an effective hemostatic agent used for the reduction of blood loss and transfusion. However, the safety profile of TXA remains in question due to a potential increased risk of venous thromboembolism. By applying TXA topically as opposed to intravenously, systemic absorption may be reduced and unwanted side-effects mitigated. The objective of our review is to investigate the efficacy and safety of topically applied tranexamic acid compared to both placebo, and the intravenous administration. Cochrane Central Register of Controlled Trials, MEDLINE, Embase, ISI Web of Science, PubMed, and Clinicaltrials.gov were searched from inception to November, 2016. We included randomized controlled trials that compared topical tranexamic acid to either placebo (or standard care) or intravenous administration, in adult patients. Surgical and non-surgical trials were included. Abstract, full-text selection, data extraction and risk of bias assessment were all performed in duplicate. In total, 67 studies involving 6,034 patients met inclusion criteria. The majority of trials evaluated orthopedic procedures. Compared to placebo, the administration of topical TXA significantly reduced the odds of receiving a blood transfusion (pooled OR 0.28, 95% CI 0.20 to 0.38; P < 0.001) and significantly reduced mean blood loss (WMD -276.6, 95% CI -327.8 to -225.4; P < 0.0001). When compared to the intravenous administration, there was no difference between the two groups in terms of transfusion requirements (pooled OR 1.03, 95% CI 0.72 to 1.46; P=0.88) or blood loss (WMD -21.95, 95% CI -66.61 to 27.71; P=0.34). There was no difference in the odds of developing a venous thromboembolic complication between the topical TXA and control groups (pooled OR=0.78, 95% CI 0.47 to 1.29; P=0.33) or the topical and intravenous groups (pooled OR=0.75, 95% CI 0.39 to 1.46; P=0.40). The topical application of TXA effectively reduces both transfusion risk and blood loss compared to placebo, without increasing thromboembolic risks. There were no major differences between topical and intravenous tranexamic acid with respect to safety and efficacy, and both were superior to placebo with regards to blood loss and transfusion requirements. Further study of the topical application is required outside of the field of orthopedics.

Complications after minimally invasive sacrocolpopexy with and without concomitant incontinence surgery: A National Surgical Quality Improvement Program (NSQIP) database study

To compare surgical complications for patients having minimally invasive sacrocolpopexy (MISCP) with concomitant incontinence procedure, to those having MISCP alone.