Clinically Significant Prostate Cancer Detection Following Transrectal and Transperineal Biopsy: Results of the Prostate Biopsy Efficacy and Complications Randomized Clinical Trial.

PURPOSE: The comparative effectiveness of transrectal and transperineal prostate biopsy in detecting clinically significant prostate cancer is not well understood. We conducted a randomized clinical trial to determine whether transperineal biopsy improves the detection of clinically significant prostate cancer. MATERIALS AND METHODS: Of the 840 men randomized, 93% were White, 44% had a previous biopsy, with a median age of 66 years and median PSA density of 0.14. Of these, 384 underwent transrectal and 398 underwent transperineal prostate biopsy. Prebiopsy prostate MRI was performed in 96% of men. Grade Group ≥ 2 prostate cancer was classified as clinically significant. Odds ratios were calculated using logistic regression to evaluate the effect of biopsy procedures on cancer detection rates. RESULTS: The detection rates of clinically significant prostate cancer were 47.1% and 43.2% (odds ratio 1.17; 95% CI, 0.88-1.55) for transrectal and transperineal biopsy, respectively. Age, PSA density, clinical stage and Prostate Imaging Reporting and Data System score were associated with the diagnosis of clinically significant cancer, whereas history of previous biopsy, anterior tumors, and biopsy procedure (transrectal or transperineal) were not. Clinically significant cancer detection rates in biopsy-naïve men undergoing MRI-targeted transrectal or transperineal biopsy were 59% and 62%, respectively. The overall cancer detection rates following transrectal and transperineal biopsy were 72.1% and 70.4%, respectively. CONCLUSIONS: There was no significant difference noted in the detection of clinically significant prostate cancer following transrectal or transperineal prostate biopsy. Urologists may utilize either biopsy procedure that best suits their patients' needs and practice setting.

Complications Following Transrectal and Transperineal Prostate Biopsy: Results of the ProBE-PC Randomized Clinical Trial.

PURPOSE: Transrectal prostate biopsy has come under scrutiny due to potential for postbiopsy infections and transperineal prostate biopsy is being offered as the safer alternative. However, there is a lack of randomized comparative studies. Our goal was to directly evaluate infectious and noninfectious complications following the 2 biopsy procedures. MATERIALS AND METHODS: We conducted a prospective, pragmatic, randomized clinical study in men undergoing prostate biopsy. The participants underwent either transrectal or transperineal prostate biopsy in the office under local anesthesia. The primary outcome was a 30-day composite infectious complication rate, comprising of 1 or more components including fever, genitourinary infection, antibiotic prescriptions, office or emergency visits, hospitalization, or sepsis. Secondary outcomes included 30-day composite noninfectious complications (urinary or hemorrhagic). RESULTS: Of the 763 randomized participants, 718 underwent either transrectal (351) or transperineal (367) prostate biopsy. A composite infectious complication event occurred in 9 participants (2.6%) in the transrectal and 10 participants (2.7%) in the transperineal group (odds ratio, 1.06; 95% CI, 0.43 to 2.65; P = .99). None of the participants developed sepsis in either group. There were no between-group differences in any of the individual component infectious events. A composite noninfectious complication occurred in 6 (1.7%) and 8 (2.2%) participants in the transrectal and transperineal groups, respectively (odds ratio, 1.28; 95% CI, 0.44 to 3.73; P = .79). No participants required hospitalization or other interventions. CONCLUSIONS: Among men undergoing transperineal or transrectal prostate biopsy, we could not demonstrate any difference in the infectious or noninfectious complications. Both biopsy approaches remain clinically viable and safe.

Interventions to Reduce Opioid Prescriptions following Urological Surgery: A Systematic Review and Meta-Analysis.

PURPOSE: Opioid prescriptions after surgery are major contributors to the opioid abuse epidemic. Several measures designed to limit opioid prescriptions at discharge have been evaluated. We conducted a comprehensive review and meta-analysis of the effectiveness of various types of interventions in reducing opioid prescriptions after urological surgery. MATERIALS AND METHODS: A systematic review including MEDLINE®, Web of Science™ and Cochrane databases was conducted to identify studies on opioid prescriptions and urological surgery. Twenty-two studies met the inclusion criteria, of which 19 were used for quantitative analysis for reduction in opioid prescriptions. Additional outcomes included opioid consumption and satisfaction with analgesia. RESULTS: Of the 8,318 patients, 53% were in the pre- and 47% in the post-intervention cohort. Overall mean reduction/patient in prescribed opioids was -67.59 (95% CI 54.23 to 80.94) morphine milligram equivalents (MME). Direct interventions, implemented by providers within their local department or hospital, were more effective in reducing prescribed opioids compared to indirect, or systemic, interventions, at -76.68 MME (95% CI 60.04 to -93.31) vs -46.72 MME (95% CI 24.20 to -69.23; p=0.04). Opioid consumption significantly decreased post-intervention with a mean reduction of -18.31 MME (95% CI 7.89 to 28.72). Patient satisfaction with analgesia remained unchanged between the pre- and post-intervention groups. CONCLUSIONS: Successful reduction in opioid prescriptions, without compromising pain control, can be achieved through a variety of interventions. Direct interventions appear to have a greater impact than indirect interventions in reducing opioid prescriptions. Despite the reduction, unused, excess prescription opioids were still noted, which provides an opportunity for further control on opioid prescriptions.

TGF-ß1-p53 cooperativity regulates a profibrotic genomic program in the kidney: molecular mechanisms and clinical implications.

Chronic kidney disease affects >15% of the U.S. population and >850 million individuals worldwide. Fibrosis is the common outcome of many chronic renal disorders and, although the etiology varies (i.e., diabetes, hypertension, ischemia, acute injury, and urologic obstructive disorders), persistently elevated renal TGF-ß1 levels result in the relentless progression of fibrotic disease. TGF-ß1 orchestrates the multifaceted program of renal fibrogenesis involving proximal tubular dysfunction, failed epithelial recovery and redifferentiation, and subsequent tubulointerstitial fibrosis, eventually leading to chronic renal disease. Recent findings implicate p53 as a cofactor in the TGF-ß1-induced signaling pathway and a transcriptional coregulator of several TGF-ß1 profibrotic response genes by complexing with receptor-activated SMADs, which are homologous to the small worms (SMA) and Drosophilia mothers against decapentaplegic (MAD) gene families. The cooperative p53-TGF-ß1 genomic cluster includes genes involved in cell growth control and extracellular matrix remodeling [e.g., plasminogen activator inhibitor-1 (PAI-1; serine protease inhibitor, clade E, member 1), connective tissue growth factor, and collagen I]. Although the molecular basis for this codependency is unclear, many TGF-ß1-responsive genes possess p53 binding motifs. p53 up-regulation and increased p53 phosphorylation; moreover, they are evident in nephrotoxin- and ischemia/reperfusion-induced injury, diabetic nephropathy, ureteral obstructive disease, and kidney allograft rejection. Pharmacologic and genetic approaches that target p53 attenuate expression of the involved genes and mitigate the fibrotic response, confirming a key role for p53 in renal disorders. This review focuses on mechanisms whereby p53 functions as a transcriptional regulator within the TGF-ß1 cluster with an emphasis on the potent fibrosis-promoting PAI-1 gene.-Higgins, C. E., Tang, J., Mian, B. M., Higgins, S. P., Gifford, C. C., Conti, D. J., Meldrum, K. K., Samarakoon, R., Higgins, P. J. TGF-ß1-p53 cooperativity regulates a profibrotic genomic program in the kidney: molecular mechanisms and clinical implications.

Anti-CD24 nano-targeted delivery of docetaxel for the treatment of prostate cancer.

Nanoparticle (NP)-mediated, noninvasively targeted and image-guided therapies have potential to improve efficacy and safety of cancer therapeutics. We report synthesis and use of poly(lactide-co-glycolide)-polyethylene glycol (PLGA-PEG) NPs for targeted delivery of docetaxel. We synthesized docetaxel encapsulated NPs conjugated to anti-CD24 (for targeting) and/or an optical probe (for tracking) and evaluated efficacy in a prostate cancer mouse model. We observed preferential accumulation of anti-CD24 conjugated NPs (encapsulating docetaxel) compared to the non-conjugated NPs 24 hours after a single injection into luciferase-expressing PC3M prostate cancer tumor. In the same mouse model, we found significant (P<0.01) accumulation of docetaxel (~10-fold higher) in tumor after treatment with PLGA-PEG NPs encapsulating docetaxel and conjugated to anti-CD24 compared to non-conjugated NPs. Enhanced accumulation was associated with reduced tumor mass and tumor viability. These data support the potential impact of nano-targeted delivery of chemotherapy in enhancing the differential tumor delivery and anticancer efficacy in prostate cancer.

Prostate Biopsy: Hyperbole and Misrepresentation Versus Scientific Evidence and Equipoise.

There are conflicting recommendations from the American Urological Association and the European Association of Urology guidelines regarding transrectal or transperineal prostate biopsy, driven by a lack of high-quality data. In the interest of evidence-based medicine, it is best to avoid passionate overstatement of facts or assign strong recommendations until comparative effectiveness data are available.

Inflammatory myofibroblastic tumor of the genitourinary tract: a narrative review.

Background and Objective: Inflammatory myofibroblastic tumor (IMT) is a rare entity that is described in several organ systems. This comprehensive review aims to identify IMTs occurring at various genitourinary (GU) organ sites and describe patterns of clinical management in adult and pediatric patients. Methods: A comprehensive search of PubMed and Web of Science was conducted according to the Preferred Reporting Items for Systematic Review and meta-analyses statement. Two reviewers performed independent initial screening of abstracts. Eligible articles underwent full review and data extraction. The clinical features, diagnostic tests, treatment, and outcomes at each GU organ site were analyzed individually and summarized into a comprehensive review. Key Content and Findings: Of the 270 articles identified, 112 met inclusion criteria. Articles primarily consisted of case reports or small series describing a total of 167 cases, of which 30 (18%) occurred in children. Most patients (96%) were symptomatic at presentation. The most frequently involved sites included bladder (106 cases) and kidney (n=33) followed by epididymis (n=6), urachus (n=6), ureter (n=5), prostate (n=4), testis (n=4), and spermatic cord (n=3). Complete surgical excision of the mass including partial or total removal of involved organs provided excellent outcomes. Incomplete excision was associated with early local recurrence and progression. Late recurrence or metastatic transformation was rarely noted (<2%). Conclusions: IMTs exhibit locally invasive, symptomatic and progressive phenotypes that affect all urologic organs in adults and children. Clinical features and imaging results are similar to those noted with urologic cancers. These tumors require complete surgical excision since incomplete resection increases the risk of symptomatic recurrence.

Correlation of urinary catheterization with histologic grading of eosinophilic cystitis: a single institutional review of 27 cases.

Eosinophilic cystitis (EC) is an uncommon diagnosis, mimicking urothelial carcinoma. Multiple etiologies including iatrogenic, infectious, and neoplastic have been suggested, effecting both adults and pediatric population. A retrospective clinicopathologic review of patients with EC in our institution between 2003 and 2021 was conducted. Age, gender, presenting symptoms, cystoscopic findings, and history of urinary bladder instrumentation were recorded. Histologically, urothelial and stromal changes were noted, and mucosal eosinophilic infiltration was graded as mild (scattered eosinophils in the lamina propria), moderate (visible small clusters of eosinophils without brisk reactive changes), or severe (dense eosinophilic infiltrate with ulcer formation and/or muscularis propria infiltration). Twenty-seven patients (male to female ratio = 18/9, median age 58 [12-85 years]), of whom two were in the pediatric age group were identified. Leading presenting symptoms were hematuria (9/27, 33%), neurogenic bladder (8/27, 30%), and lower urinary tract symptoms (5/27, 18%). Four of 27 (15%) patients had history of urothelial carcinoma of urinary bladder. Cystoscopy commonly revealed erythematous mucosa (21/27, 78%) and/or urinary bladder mass (6/27, 22%). Seventeen of 27 (63%) of patients had history of long-term/frequent catheterization. Mild, moderate, and severe eosinophilic infiltrates were seen in 4/27 (15%), 9/27 (33%), and 14/27 (52%) of cases. Proliferative cystitis (19/27, 70%) and granulation tissue (15/27, 56%) were additional common findings. All cases of long-term/frequent instrumentation cases had moderate or severe eosinophilic infiltrate. EC should be in the differential diagnosis; particularly in patients with long term/frequent catheterization.

Implementation and Assessment of No Opioid Prescription Strategy at Discharge After Major Urologic Cancer Surgery.

Importance: Postoperative opioid prescriptions are associated with delayed recovery, perioperative complications, opioid use disorder, and diversion of overprescribed opioids, which places the community at risk of opioid misuse or addiction. Objective: To assess a protocol for eliminating postdischarge opioid prescriptions after major urologic cancer surgery. Design, Setting, and Participants: This cohort study of the no opioid prescriptions at discharge after surgery (NOPIOIDS) protocol was conducted between May 2017 and June 2021 at a tertiary referral center. Patients undergoing open or minimally invasive radical cystectomy, radical or partial nephrectomy, and radical prostatectomy were sorted into the control group (usual opioids), the lead-in group (reduced opioids), and the NOPIOIDS group (no opioid prescriptions). Interventions: The NOPIOIDS group received a preadmission educational handout, postdischarge instructions for using nonopioid analgesics, and no routine opioid prescriptions. The lead-in group received a postdischarge instruction sheet and reduced opioid prescriptions at prescribers' discretion. The control group received opioid prescriptions at prescribers' discretion. Main Outcomes and Measures: Primary outcome measures included rate and dose of opioid prescriptions at discharge and for 30 days postdischarge. Additional outcome measures included patient-reported pain and satisfaction level, unplanned health care utilization, and postoperative complications. Results: Of 647 opioid-naive patients (mean [SD] age, 63.6 [10.0] years; 478 [73.9%] male; 586 [90.6%] White), the rate of opioid prescriptions at discharge for the control, the lead-in, and the NOPIOIDS groups was 80.9% (157 of 194), 57.9% (55 of 95), and 2.2% (8 of 358) (Kruskal-Wallis test of medians: P < .001), and the overall median (IQR) tablets prescribed was 14 (10-20), 4 (0-5.3), and 0 (0-0) per patient in the control, lead-in, and NOPIOIDS groups, respectively (Kruskal-Wallis test of medians: P < .001). In the NOPIOIDS group, median and mean opioid dose was 0 tablets for all procedure types, with the exception of kidney procedures (mean [SD], 0.5 [1.7] tablets). Patient-reported pain surveys were received from 358 patients (72.6%) in the NOPIOIDS group, demonstrating low pain scores (mean [SD], 2.5 [0.86]) and high satisfaction scores (mean [SD], 86.6 [3.8]). There was no increase in postoperative complications in the group with no opioid prescriptions. Conclusions and Relevance: This perioperative protocol, with emphasis on nonopioid alternatives and patient instructions, may be safe and effective in nearly eliminating the need for opioid prescriptions after major abdominopelvic cancer surgery without adversely affecting pain control, complications, or recovery.

Management of urologic cancers during the pandemic and potential impact of treatment deferrals on outcomes.

The COVID-19 pandemic-related constraints on healthcare access have raised concerns about adverse outcomes from delayed treatment, including the risk of cancer progression and other complications. Further, concerns were raised about a potentially significant backlog of patients in need of cancer care due to the pandemic-related delays in healthcare, further exacerbating any potential adverse outcomes. Delayed access to surgery is particularly relevant to urologic oncology since one-third of new cancers in men (20% overall) arise from the genitourinary (GU) tract and surgery is often the primary treatment. Herein, we summarize the prepandemic literature on deferred surgery for GU cancers and risk of disease progression. The aforementioned data on delayed surgery were gathered in the context of systemic delays present in certain healthcare systems, or occasionally, due to planned deferral in suboptimal surgical candidates. These data provide indirect, but sufficient insight to develop triage schemas for prioritization of uro-oncological cases. Herein, we outline the extent to which the pandemic-related triage guidelines had influenced urologic practice in various regions. To study the adverse outcomes in the pandemic-era, a survey of urologic oncologists was conducted regarding modifications in their initial management of urologic cancers and any delay-related adverse outcomes. While the adverse effects directly from COVID-19 related delays will become apparent in the coming years, the results showing short-term outcomes are quite instructive. Since cancer care was assigned a higher priority at most centers, this strategy may have avoided significant delays in care and limited the anticipated negative impact of pandemic-related constraints.

A rare case of urachal inflammatory myofibroblastic tumor.

Inflammatory myofibroblastic tumors (IMT) of the urachus is a rare neoplastic condition characterized by proliferation of spindle cell, likely derived from myofibroblasts or fibroblasts, with acute and chronic inflammatory infiltrate. Urachal IMT present with abdominal/pelvic pain and urinary symptoms. These often manifest as abdominal mass involving adjacent structures. We describe a case of young female with urachal IMT that was excised with a wide margin to ensure complete removal of all adjacent affected tissue using robotic-assisted laparoscopic approach. Immunohistochemical evidence of ALK and ALK gene rearrangement were confirmed in this tumor which are diagnostic of IMT.

Rationale and protocol for randomized study of transrectal and transperineal prostate biopsy efficacy and complications (ProBE-PC study).

BACKGROUND: Rrisk of infection and hospitalization after transrectal prostate biopsy (TRBx) has been increasing worldwide. Several modified antibiotic regimens have met with variable success in preventing such infections. Transperineal prostate biopsy (TPBx) is increasingly recommended as the preferred alternative due to a potentially lower risk of post-biopsy infections. Aim of this review is to define the magnitude of post-biopsy complications and the effectiveness of preventive strategies, including TPBx approach. METHODS: We performed a focused review of literature on infectious complications after TRBx and detailed the use of various preventive measures. We summarized the effectiveness of several preventive measures, including TPBx, and outlined the inconsistencies in reported outcomes. We identified potential barriers to the uptake of TPBx, including the gap in knowledge such as lack of high-quality evidence. RESULTS: Several antibiotic prophylaxis protocols, including targeted and augmented, have been utilized for TRBx without demonstrating a clearly superior regimen. Of the non-antibiotic preventive measure, povidone-iodine rectal prep appears to be most effective strategy. Several single-arm cohort studies have reported very low rates of infections after TPBx and demonstrated the feasibility of an office-based procedure. However, barriers to the adoption of TPBx exist including retrospective data, and conflicting results showing minimal reduction in complications with increased burden of resource utilization. Presently, there are no randomized studies comparing the infectious complications after TRBx and TPBx. We discuss the rationale and protocol for a randomized controlled trial to determine the comparative effectiveness of biopsy techniques. CONCLUSIONS: TPBx approach has the potential to lower the rate of post-biopsy infections and hospitalizations. However, there are several barriers to widespread adoption of this approach including inconsistencies in reported outcomes and lack of Level-1 evidence. Randomized controlled studies are required to directly compare the infectious complications associated with each biopsy procedure.