Minimally invasive interventions for lower urinary tract symptoms: What sits between medical therapy and transurethral resection of the prostate.

BACKGROUND: There are a variety of medical and surgical treatment options available today for the management of lower urinary tract symptoms (LUTS) secondary to bladder outlet obstruction due to benign prostatic hyperplasia (BPH). OBJECTIVE: The aim of this paper is to highlight the various treatment options available for the management of bladder outlet obstruction secondary to BPH and discuss the benefits and potential drawbacks of each. DISCUSSION: Lifestyle and dietary modification and medical therapies, such as an alpha-1 blocker as monotherapy, should be considered as first-line when initially counselling a patient for LUTS secondary to bladder outlet obstruction due to BPH. If bothersome LUTS persist despite medical management, or if medical management is not suitable or preferable, then surgical interventions can be considered. The mainstay of surgical intervention has traditionally been transurethral resection of the prostate (TURP); however, the treatment landscape is rapidly evolving with the development of minimally invasive procedures.

Do alpha blockers reduce the risk of urinary retention post-transperineal prostate biopsy? A systematic narrative review.

BACKGROUND: Transperineal Prostate Biopsy (TPB) is a commonly used technique for the diagnosis of prostate cancer due to growing concerns related to infectious complications associated with transrectal ultrasound-guided prostate biopsy (TRUSB). TPB is associated with an infective complication rate of near zero, however, acute urinary retention (AUR) remains the leading complication causing morbidity. Previously in TRUSB, there was weak evidence that alpha-blockers reduce AUR rates, and their usage has been extrapolated to clinical practice with TPB. This review aims to explore if there is an evidence base for using alpha-blockers to prevent AUR following TPB. METHODS: A systematic approach was used to search Ovid Medline and Embase using keywords related to "Transperineal" and "Retention". Articles were then screened by applying inclusion and exclusion criteria to find studies that compared alpha-blocker recipients to no alpha-blocker use in the perioperative period and the subsequent effect on AUR in TPB. RESULTS: 361 records were identified in the initial search to produce 5 studies included in the final review. No randomised controlled trials (RCTs) were identified. One observational study showed a reduction in AUR rate from 12.5% to 5.3% with a single dose of tamsulosin. A previous systematic review of complications associated with prostate biopsy concluded there may be a potential benefit to alpha-blockers given in the TPB perioperative period. Three observational studies demonstrated a harmful effect related to alpha-blocker use; however, this was well explained by their clear limitations. CONCLUSION: Based on this review and the extrapolation from TRUSB data, perioperative alpha-blockers may offer some weak benefits in preventing AUR following TPB. However, there is significant scope and need for an RCT to further develop the evidence base further given the significant gap in the literature and lack of a standard alpha blocker protocol in TPB.

Low-dose-rate brachytherapy and long-term treatment outcomes in patients younger than 60 years of age.

Purpose: Low-dose-rate (LDR) brachytherapy in young men remains controversial amongst urologists due to their concerns regarding long-term biochemical control and treatment-related toxicities. The purpose of this study was to evaluate the treatment outcomes of men under 60 years of age who underwent LDR brachytherapy with iodine-125 (125I) for clinically localized low- to intermediate-risk prostate cancer. Material and methods: All consecutive patients with clinically localized prostate cancer treated at our institution from 2003 to 2016 with 125I monotherapy were included in the study. Prescription dose was 145.0 Gy modified peripheral loading (MPD). All patients were assessed for biochemical progression-free survival using Phoenix definition (nadir +2 ng/ml), clinical progression-free survival, overall survival (OS), and any associated treatment toxicity. Results: A total of 161 patients were included, with a median follow-up of 6.8 years (range, 3-14.54 years). Median age at implant was 57 years (range, 53-59 years). Mean prostate specific antigen (PSA) level at diagnosis was 4.43 ng/ml (SD = 2.29). Majority of men had low-risk prostate cancer (70.2%). Biochemical progression-free survival at 8 years was 94% for the entire cohort. Median PSA at 4 years was 0.169 (IQR, 0.096-0.360), with 45% of patients having a PSA greater than 0.2. OS was 96.9%, with 5 deaths reported but only one was secondary to prostate cancer. Late grade > 2 genitourinary toxicities were reported in 18 patients (11.2%). Three patients (1.9%) developed secondary cancers, all considered unrelated to their LDR brachytherapy. Conclusions: With excellent long-term treatment outcomes and minimal associated toxicities, our results showed that LDR brachytherapy can be an effective treatment of choice in younger men.

Lessons from a population-based bladder cancer registry: exploring why survival is not improving.

OBJECTIVE: To explore the causes of the decrease in bladder cancer survival that has occurred over the past four decades. METHODS: We extracted data from the South Australian Cancer Registry. Data from the period 1 January 1977 to 31 December 2020 were extracted to explore changes in incidence and survival among a total of 8356 patients diagnosed with ≥pT1 disease. Invasive bladder cancer was defined as ≥pT1 in this study. RESULTS: Invasive bladder cancer age-standardized incidence decreased from 7.20 cases per 100 000 people in 1977 to 5.85 cases per 100 000 in 2020. The mean age at diagnosis increased from 68 years to 76 years. The crude incidence for patients aged 80 years and over increased by 3.3% per year (95% confidence interval [CI] 2.1 to 4.6). Overall survival decreased over the study period (hazard ratio [HR] 1.22 [95% CI 1.09 to 1.35]), however, survival increased after adjusting for age at diagnosis (HR 0.80 [95% CI 0.76 to 0.94]). Despite a decrease in non-bladder cancer-specific deaths in older people, there was no change in the bladder cancer-specific death rate in older people (HR 0.94 [95% CI 0.70 to 1.26]). Male sex was associated with higher survival (HR 0.87 [95% CI 0.83 to 0.92]), whereas socioeconomic advantage was not. CONCLUSIONS: Invasive bladder cancer survival has decreased over the past 40 years, with the age structure of the population being a significant contributing factor. PATIENT SUMMARY: We looked at why bladder cancer survival is decreasing using a large cancer registry with information from 1977 to 2020. We found that people are now more likely to be diagnosed at an older age. Older people often live for a shorter time with bladder cancer compared to younger people. Bladder cancer survival has decreased because there are more older people with the disease than previously.

Near-infrared spectroscopy as a novel method of ex vivo bladder cancer tissue characterisation.

OBJECTIVE: To evaluate near-infrared (NIR) spectroscopy in differentiating between benign and malignant bladder pathologies ex vivo immediately after resection, including the grade and stage of malignancy. PATIENTS AND METHODS: A total of 355 spectra were measured on 71 bladder specimens from patients undergoing transurethral resection of bladder tumour (TURBT) between April and August 2022. Scan time was 5 s, undertaken using a portable NIR spectrometer within 10 min from excision. Specimens were then sent for routine histopathological correlation. Machine learning models were applied to the spectral dataset to construct diagnostic algorithms; these were then tested for their ability to predict the histological diagnosis of each sample using its NIR spectrum. RESULTS: A two-group algorithm comparing low- vs high-grade urothelial cancer demonstrated 97% sensitivity, 99% specificity, and the area under the receiver operating characteristic curve (AUC) was 0.997. A three-group algorithm predicting stages Ta vs T1 vs T2 achieved 97% sensitivity, 92% specificity, and the AUC was 0.996. CONCLUSIONS: This first study evaluating the diagnostic potential of NIR spectroscopy in urothelial cancer shows that it can be accurately used to assess tissue in an ex vivo setting immediately after TURBT. This offers point-of-care assessment of bladder pathology, with potential to influence the extent of resection, reducing both the need for re-resection where invasive disease may be suspected, and also the potential for complications where extent of diagnostic resection can be limited. Further studies utilising fibre-optic probes offer the potential for in vivo assessment.

Fluoroquinolone resistance in urinary tract infections: Epidemiology, mechanisms of action and management strategies.

Background: Fluoroquinolone resistance is an issue of concern amongst physicians worldwide. In urology, fluoroquinolones are often used in the treatment of acute pyelonephritis and prostatitis, as well as infections caused by multidrug-resistant pathogens. Aims: We aim to highlight the importance of antimicrobial stewardship and the need for ongoing biomedical research to discover novel agents in our losing battle against resistant pathogens. Materials and methods: In this review, we survey the literature and summarise fluoroquinolone resistance as it pertains to pyelonephritis and prostatitis, as well as alternative treatment strategies and prevention of multidrug resistance. Results: The rise of fluoroquinolone resistance in bacteria has reduced the available treatment options, often necessitating hospital admission for intravenous antibiotics, which places an additional burden on both patients and the healthcare system. Many countries such as Australia have attempted to limit fluoroquinolone resistance by imposing strict prescribing criteria, though these efforts have not been entirely successful. Solutions to overcome resistance include prevention, combination therapy and the development of novel antimicrobial agents. Conclusions: Prevention of the proliferation of resistant organisms by antimicrobial stewardship is paramount, and urologists are obliged to be aware of responsible prescribing practices such as referring to local guidelines when prescribing. By reserving fluoroquinolones for infections in which they are truly indicated and by prescribing based on both patient and local environmental factors, we can preserve this effective resource for future use.

Intrarenal pressures during flexible ureteroscopy: an insight into safer endourology.

OBJECTIVES: To assess intrarenal pressures (IRPs) and complication rates after flexible ureteroscopy (fURS), and to assess factors that contribute to raised IRPs and postoperative complications. PATIENTS AND METHODS: After informed consent patients underwent fURS under general anaesthesia. The transducer of a 0.3556 mm (0.014″) pressure guidewire was placed in the renal pelvis for live recording of IRPs. The fURS procedures were performed in a routine manner under antibiotic cover with the aim of dusting the calculus to completion. The operating surgeon was blinded to the live-recorded IRPs. RESULTS: A total of 40 fURS procedures were performed in 37 patients (26 male and 11 female). The mean age was 50.5 years. As a cohort, the mean of average IRPs was 34.8 mmHg and the mean of maximal IRPs was 128.8 mmHg. Pearson's correlation showed a significant inverse correlation between the mean IRP and age (r[38]: -0.391, P = 0.013). Three cases experienced postoperative deviations from uncomplicated recovery, with two being hypotensive and one case being both hypotensive and hypoxic. Three cases returned to the emergency department within 30 days of surgery, with two cases of flank pain and one case of urosepsis with positive urine cultures. The patient presenting with urosepsis had exhibited IRPs exceeding the mean. CONCLUSION: The IRPs changed significantly from normal baseline levels during routine fURS. The mean IRP during fURS correlates with patient age, but not with other factors. The IRP may be related to increased complication rates at fURS. Understanding factors that influence IRP will allow urologists to better manage this intraoperatively.

Perspectives on technology: to use or to reuse, that is the endoscopic question-a systematic review of single-use endoscopes.

OBJECTIVE: To compare clinical outcomes of single-use endoscopes with those of reusable endoscopes to better define their role within urology. METHODS: A systematic search of electronic databases was performed. All studies comparing the clinical outcomes of participants undergoing urological procedures with single-use endoscopes to those of participants treated with reusable endoscopes were included. Results are reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. RESULTS: Twenty-one studies in 3943 participants were identified. Six different single-use flexible ureteroscopes and two different single-use flexible cystoscopes were assessed. There were no differences in mean postoperative infection rates (4.0% vs 4.4%; P = 0.87) or overall complication rates (11.5% vs 11.9%; P = 0.88) between single-use and reusable endoscopes. For patients undergoing flexible ureteroscopy there were no differences in operating time (mean difference -0.05 min; P = 0.96), length of hospital stay (LOS; mean difference 0.06 days; P = 0.18) or stone-free rate (SFR; 74% vs 74.3%; P = 0.54) between the single-use and reusable flexible ureteroscope groups. CONCLUSION: This study is the largest to compare the clinical outcomes of single-use endoscopes to those of reusable endoscopes within urology, and demonstrated no difference in LOS, complication rate or SFR, with a shorter operating time associated with single-use flexible cystoscope use. It also highlights that the cost efficiency and environmental impact of single-use endoscopes is largely dependent on the caseload and reprocessing facilities available within a given institution. Urologists can therefore feel confident that whether they choose to 'use' or to 'reuse' based on the financial and environmental implications, they can do so without negatively impacting patient outcomes.

Cost Effectiveness of Systemic Treatment Intensification for Metastatic Hormone-sensitive Prostate Cancer: Is Triplet Therapy Cost Effective?

BACKGROUND AND OBJECTIVE: There has been a shift toward systemic treatment intensification for men with metastatic hormone-sensitive prostate cancer (mHSPC). Recent trials have demonstrated the efficacy of triplet therapy with an androgen receptor signalling inhibitor (ARSI), docetaxel, and androgen deprivation therapy (ADT). However, ARSI treatment is expensive. The objective was to determine the cost effectiveness of current treatments strategies for men with mHSPC. METHODS: We developed a Markov state-transition model to simulate outcomes for men with newly diagnosed mHSPC. For the simulation, patients were entered in the model in the mHSPC disease state before progressing to castration-resistant disease and finally dying from prostate cancer. Costs were calculated from a USA health sector perspective in 2022 US dollars. Deterministic and probabilistic sensitivity analyses were conducted to account for uncertainty in the parameter estimates. We also performed scenario analyses for costs in the UK and Australian health sectors. KEY FINDINGS AND LIMITATIONS: Treatment intensification with doublet and triplet therapy resulted in an improvement in quality-adjusted survival for all strategies in comparison to ADT monotherapy. However, only docetaxel doublet therapy was cost effective at standard thresholds, with an incremental cost-effectiveness ratio of $13 647. The cost of ARSIs needed to be discounted by 47-70% before they were cost effective. Only medication costs impacted the model results. If the generic price for abiraterone acetate is used, then triplet therapy with abiraterone is the best-value option. Similar results were obtained for analyses for the UK and Australian health sectors. CONCLUSIONS AND CLINICAL IMPLICATIONS: Treatment intensification with ARSIs in men with mHSPC results in better quality-adjusted survival but is not cost effective according to standard thresholds. The costs of these medications would need to be heavily discounted before they are cost effective. The cost of generic ARSIs, once available, would render these strategies cost effective. PATIENT SUMMARY: This report examines whether increasing the number of systemic drugs used to treat a patient's metastatic hormone-sensitive prostate cancer is cost effective for the health care system. We found that the additional cost of triplet therapy does not justify the increase in patient benefit.

Seminal papers in urology: maintenance Bacillus Calmette-Guerin (BCG) immunotherapy for recurrent Ta, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized southwest oncology group study (SWOG-8507).

The South West Oncology Group's 2000 randomised-control trial investigated the addition of maintenance intravesical bacillus Calmette-Guerin (BCG) to non-muscle invasive urothelial carcinoma (NMIUC) treatment. The results were published when the efficacy of BCG immunotherapy maintenance was unclear.Randomisation produced two arms, each containing 192 patients assessed to be at high risk of recurrence following induction BCG therapy for NMIUC. The treatment arm went on to receive three successive weekly intravesical and percutaneous BCG administrations at three months, six months and then six monthly for three years from the start of induction therapy.Recurrence free-survival (RFS), was higher in the maintenance arm with 41% (95%CI 35-49) RFS at five years in the control arm and 60% RFS (53-67 95% CI) in the maintenance arm (p < 0.0001). Only 16% of patients in the treatment arm received all of the scheduled maintenance courses of BCG.The study's seminal results correlate with contemporary systematic review and have guided international guidelines.

Pre-gerotal fat patch-A novel alternative to haemostatic agents during partial nephrectomy.

Objective: This study aimed to determine if using a pre-gerotal fat patch at open partial nephrectomy (PN) as a haemostatic bolster is a viable alternative to using synthetic haemostatic agents. Materials and methods: Human Research Ethics Committee approval was obtained for audit of a prospectively kept database from July 2012 to July 2021, which followed outcomes of patients who received a low-tension pre-gerotal fat patch renorrhaphy at open PN. Patient demographics, intraoperative measures, histological outcomes and post-operative complications were analysed. Using a retroperitoneal approach, the peritoneum was mobilised and a vascularised pedicle of pre-gerotal fat was rotated in the direction of the kidney. Routine definition of the hilum, clamping of the hilar vessels and dissection of mass followed. After watertight closure and haemostasis, the harvested pre-gerotal fat patch was placed over the defect and secured using low-tension renorrhaphy. Two-layer closure of the abdominal wall with placement of a drain was routine. Results: A total of 55 patients underwent open PN. Mean age was 60.4 (35-77) years. There were 38 men and 17 women, and 32 right and 23 left PNs. Mean mass size was 31.9 mm (10-95 mm) and collecting system was breached in 36.5% of cases. One patient (1.9%) suffered a Clavien-Dindo IIIb complication requiring return to theatre and transfusion due to a bleed from an intercostal artery. There were no renal bed bleeds, urine leaks or urine fistulas detected. Mean intraoperative blood loss was 355 mL (50-1500 mL) and mean post-operative creatinine increased by 10.7 µmol/L (51-172 µmol/L). Mean follow up was 40.2 (4-109) months. Conclusion: Utilisation of an anatomical pre-gerotal fat patch to provide pressure at the renorrhaphy site during open PN is an effective technique to assist with surgical haemostasis. This simple technique avoids the costs of haemostatic agents, whilst adding minimal operating time to procedures.

PCNL in neurogenic bladder: A challenging population for both clinical management and analysis.

Objectives: To review the management of patients with neurogenic bladder undergoing percutaneous nephrolithotomy (PCNL) at our institution with the aim of assessing peri-operative morbidity. Subjects/patients and methods: We conducted a retrospective review of all neurogenic bladder patients who underwent PCNL at our hospital in the last decade with the aim of assessing peri-operative morbidity. Results: A total of 298 PCNL were performed during the study period of which 58 were in patients with a neurogenic bladder or urinary diversion, 33 of which were in SCI patients. Preoperative demographic and stone characteristics, intraoperative data and postoperative length of stay and complications are summarised in table form. Conclusion: PCNL remains an acceptably safe and efficacious treatment for upper tract stone disease in patients with neurogenic bladders and will continue to have a valuable role where SCI prevents alternative approaches such as ureteroscopy.

Progressing Towards Same-Day Discharges After Robotic-Assisted Radical Prostatectomy; Safe and Cost Effective to Discharge Without Routine Blood Tests.

Introduction: Changing population demographics and the recent SARS-CoV-2 pandemic have forever changed healthcare, with increasing demands on straining systems. The economic cost is yet to be fully realised, with growing concerns around the current system's ability to accommodate the ageing comorbid population. Consequently, a paradigm shift has taken place in healthcare systems, prioritizing cost accountability. In the absence of established guidelines or robust literature, the use of laboratory tests postoperatively is often guided solely by clinician preference. This study presents a retrospective analysis that investigates the utility and cost implications of routine postoperative investigation following robotic-assisted radical prostatectomies. The findings aim to emphasise the importance of evidence-based practices and cost-effective approaches in postoperative care. Materials/Methods: A retrospective analysis was performed on all robotic-assisted radical prostatectomies (RARP) identified from a single institution between 29th June 2017 to 28th June 2019. This interval was chosen in an attempt to avoid bias or confounding variables associated with the SRS-CoV-2 pandemic. A single clinician conducted a comprehensive medical record review using unit record numbers corresponding to identified procedural codes. Demographics and variables were recorded, including postoperative test results, hospital length of stay and 30-day readmission rates. Patients were assigned to either 'Routine Postoperative tests' (RPOT) or 'No Routine Postoperative tests' (No RPOT) and a comparative analysis was performed. Using the Australian National Pharmaceutical Benefits Scheme (PBS) pricing guide, total expenditure was calculated. Results: A total of 319 patients were included in the study with an average of 2.5 tests per patient within the first 24 hours. Routine postoperative tests had no bearing on outcomes, with comparable readmission rates between cohorts, and a significantly shorter length of stay in the "No routine postoperative tests" group when compared to the "Routine Postoperative Tests". A total of 1028 tests were performed within the first 48 hours following surgery with expenditure on routine testing totalling $20,516 based on the Australian PBS pricing schedule. Abnormal results were returned on 96% of patients. In the RPOT group, 18 out of the 20 common interventions occurred from 302 RARP. Among the patients in the RPOT group, eight individuals underwent blood transfusions. However, none of these patients met the hospital-specific criteria for transfusion, which require a hemoglobin level below 70 or symptomatic presentation with a hemoglobin level below 80. Conclusion: The data suggests routine postoperative laboratory has no bearing on re-admission rates, with patients experiencing significantly shorter hospital stays. Furthermore, our results indicate inefficient use of routine postoperative laboratory, with few clinical interventions, frequent abnormal results, and significant accumulative expenses.

Aquablation in men with benign prostate hyperplasia: A systematic review and meta-analysis.

Objective: The aim of the study is to investigate improvements in lower urinary tract symptoms in men with benign prostatic hyperplasia (BPH) treated with prostatic Aquablation. Materials and methods: We performed a literature search of clinical trials using the MEDLINE, Embase, and Cochrane Library databases and retrieved published works on Aquablation for the treatment of BPH up to August 2021. Unpublished works, case reports, conference proceedings, editorial comments, and letters were excluded. Risk of bias was assessed using the ROBINS-I tool. Raw means and mean differences were meta-analyzed to produce summary estimates for pre- versus post-International Prostate Symptom Scores, maximum flow rate, and male sexual health questionnaire value changes. An inverse-variance weighted random effects model was used. Results: Seven studies were included in this review (n = 551 patients) that evaluated various urological parameters. At 3 months, the International Prostate Symptom Scores raw mean difference from baseline was -16.475 (95% confidence interval [CI], -15.264 to -17.686; p < 0.001), with improvements sustained for 12 months. Similarly, maximum flow rate improved by +1.96 (95% CI, 10.015 to 11.878; p < 0.001) from pre to 3 months postoperatively. In addition, the male sexual health questionnaire change pooled effect size was -0.55 (95% CI, -1.621 to 0.531; p = 0.321) from preintervention to postintervention at 3 months. Meta-analyses of some outcomes showed large statistical heterogeneity or evidence of publication bias. Conclusions: Aquablation seems to improve lower urinary tract symptoms in men with BPH while providing relatively preserved sexual function. Further research is required to confirm these preliminary results.

Mechanism of urosepsis: relationship between intrarenal pressures and pyelovenous backflow.

To document the histological changes observed in renal units subjected to elevated intrarenal pressures (IRPs) and postulate the possible mechanisms of infectious complications after ureteroscopy. MATERIALS AND METHODS: Ex vivo studies were performed on porcine renal models. Each ureter was cannulated with a 10-F dual-lumen ureteric catheter. A pressure-sensing wire was inserted through one lumen and with the sensor positioned in the renal pelvis for IRP measurement. Undiluted India ink stain was irrigated through the second lumen. Each renal unit was subjected to ink irrigation at target IRPs of 5 (control), 30, 60, 90, 120, 150, and 200 mmHg. Three renal units were subjected to each target IRP. After irrigation, each renal unit was processed by a uropathologist. Macroscopically, the amount of renal cortex stained by ink was calculated as a percentage of the total perimeter. Microscopically, presence of ink reflux into collecting ducts or distal convoluted tubules, and pressure-related features, was noted at each IRP. RESULTS: Signs of pressure, as represented by collecting duct dilatation, was first observed at 60 mmHg. Ink staining was consistently observed in the distal convoluted tubules at IRPs ≥60 mmHg, and all renal units above this pressure showed renal cortex involvement. At ≥90 mmHg, ink staining was observed in venous structures. At 200 mmHg, ink staining was observed in supportive tissue, venous tributaries in the sinus fat, peritubular capillaries, and glomerular capillaries. CONCLUSION: Using an ex vivo porcine model, pyelovenous backflow occurred at IRPs of ≥90 mmHg. Pyelotubular backflow occurred when irrigation IRPs were ≥60 mmHg. These findings have implications for the development of complications after flexible intrarenal surgery.

5-alpha reductase inhibitors use in prostatic disease and beyond.

5-alpha reductase inhibitors (5-ARIs) are commonly used and widely available, with benefits observed from their effect on androgen signalling. Their effect relies on the inhibition of the 5-alpha reductase enzyme which aids in the conversion of testosterone to dihydrotestosterone. 5-ARIs have increasing clinical relevance outside of benign prostatic hyperplasia (BPH). Such development requires clinicians to have an updated review to guide clinical practices. This review details the pharmacology and mechanisms of action for 5-ARIs and how this relates to multiple clinical indications. Of note, is the debunked association between finasteride and increased risk of high-grade prostate cancer. Furthermore, adverse effects of 5-ARI use are detailed in this review, with specific mentions to post-finasteride syndrome. In addition to overviews pertaining to BPH and prostate cancer, much attention has also been focused on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The androgen axis may be associated with an increased virulence for SARS-CoV-2 in men, with some reporting a correlation between the severity of illness and androgenic alopecia. Since these observations, the role of antiandrogens, including 5-ARIs, has been explored further in SARS-CoV-2. Increasing understanding of pathological processes involving the androgen axis in which 5-ARIs work, has led to increasing clinical indications for 5-ARIs. Several novel off-label indications have been suggested including its potential role in the pathogenesis of SARS-CoV-2, but to date, these claims have not been substantiated. Previously held truths regarding the role of 5-ARIs and prostate carcinogenesis have been contested, inadvertently leading to the re-exploration of 5-ARIs utility in prostate cancer. With growing evidence into pathological processes involving the androgen axis, 5-ARIs are likely to become increasingly more used. This review serves as a timely update of 5 ARIs pharmacology, current indications and potential future directions.

Decade-long trends in prostate cancer biopsy grade groups and treatment within a population-based registry.

OBJECTIVE: To assess changes in diagnosis prostate cancer (PCa) grade, biopsy and treatment approach over a decade (2011-2020) at a population level within a clinical quality cancer registry. PATIENTS AND METHODS: Patients diagnosed by prostate biopsy between 2011 and 2020 were retrieved from the Victorian Prostate Cancer Outcomes Registry, a prospective, state-wide clinical quality registry in Australia. Distributions of each grade group (GG) proportion over time were modelled with restricted cubic splines, separately by biopsy technique, age group and subsequent treatment method. RESULTS: From 2011 to 2020, 24 308 men were diagnosed with PCa in the registry. The proportion of GG 1 disease declined from 36-23%, with commensurate rises in GG 2 (31-36%), GG 3 (14-17%) and GG 5 (9.3-14%) disease. This pattern was similar for men diagnosed by transrectal ultrasonography or transperineal biopsy. Patients aged <55 years had the largest absolute reduction in GG 1 PCa, from 56-35%, compared to patients aged 55-64 (41-31%), 65-74 (31-21%), and ≥75 years (12-10%). The proportion of prostatectomies performed for patients with GG 1 disease fell from 28% to 7.1% and, for primary radiation therapy, the proportion fell from 22% to 3.5%. CONCLUSION: From 2011 to 2020, there has been a substantial decrease in the proportion of GG 1 PCa diagnosed, particularly in younger men. The percentage of interventional management performed in GG 1 disease has fallen to very low levels. These results reflect the implementation of major changes to diagnostic and treatment guidelines and inform the future allocation of treatment methods.

New Approaches to Targeting Epigenetic Regulation in Bladder Cancer.

Epigenetics is a growing field and in bladder cancer, it is of particular interest in advanced or metastatic disease. As opposed to genetic mutations in which the nucleotide sequence itself is altered, epigenetic alterations refer to changes to the genome that do not involve nucleotides. This is of great interest in cancer research because epigenetic alterations are reversible, making them a promising target for pharmacological agents. While chemoimmunotherapy is the mainstay for metastatic disease, there are few alternatives for patients who have progressed on first- or second-line treatment. By targeting reversible epigenetic alterations, novel epigenetic therapies are important potential treatment options for these patients. A search of clinical registries was performed in order to identify and collate epigenetic therapies currently in human trials. A literature search was also performed to identify therapies that are currently in preclinical stages, whether this be in vivo or in vitro models. Twenty-five clinical trials were identified that investigated the use of epigenetic inhibitors in patients with bladder cancer, often in combination with another agent, such as platinum-based chemotherapy or pembrolizumab. The main classes of epigenetic inhibitors studied include DNA-methyltransferase (DNMT) inhibitors, histone deacetylase (HDAC) inhibitors, and histone methyltransferase (HMT) inhibitors. At present, no phase 3 clinical trials have been registered. Few trials have published results, though DNMT inhibitors have shown the most promise thus far. Many patients with advanced or metastatic bladder cancer have limited treatment options, particularly when first- or second-line chemoimmunotherapy fails. Epigenetic alterations, which are common in bladder cancer, are potential targets for drug therapies, and these epigenetic agents are already in use for many cancers. While they have shown promise in pre-clinical trials for bladder cancer, more research is needed to assess their benefit in clinical settings.