Risk of Fractures and Falls in Men with Advanced or Metastatic Prostate Cancer Receiving Androgen Deprivation Therapy and Treated with Novel Androgen Receptor Signalling Inhibitors: A Systematic Review and Meta-analysis of Randomised Controlled Trials.

CONTEXT: The addition of androgen receptor signalling inhibitors (ARSIs) to standard androgen deprivation therapy (ADT) has improved survival outcomes in patients with advanced prostate cancer (PCa). Advanced PCa patients have a higher incidence of osteoporosis, compounded by rapid bone density loss upon commencement of ADT resulting in an increased fracture risk. The effect of treatment intensification with ARSIs on fall and fracture risk is unclear. OBJECTIVE: To assess the risk of falls and fractures in men with PCa treated with ARSIs. EVIDENCE ACQUISITION: A systematic review of EMBASE, MEDLINE, The Cochrane Library, and The Health Technology Assessment Database for randomised control trials between 1990 and June 2023 was conducted in accordance with Preferred Reporting Items for Systematic Review and Meta-analyses guidance. Risk ratios were estimated for the incidence of fracture and fall events. Subgroup analyses by grade of event and disease state were conducted. EVIDENCE SYNTHESIS: Twenty-three studies were eligible for inclusion. Fracture outcomes were reported in 17 studies (N = 18 811) and fall outcomes in 16 studies (N = 16 537). A pooled analysis demonstrated that ARSIs increased the risk of fractures (relative risk [RR] 2.32, 95% confidence interval [CI] 2.00-2.71; p < 0.01) and falls (RR 2.22, 95% CI 1.81-2.72; p < 0.01) compared with control. A subgroup analysis demonstrated an increased risk of both fractures (RR 2.13, 95% CI 1.70-2.67; p < 0.01) and falls (RR 2.19, 95% CI 1.53-3.12; p < 0.0001) in metastatic hormone-sensitive PCa patients, and an increased risk of fractures in the nonmetastatic (RR 2.27, 95% CI 1.60-3.20; p < 0.00001) and metastatic castrate-resistant (RR 2.85, 95% CI 2.16-3.76; p < 0.00001) settings. The key limitations include an inability to distinguish fragility from pathological fractures and potential for a competing risk bias. CONCLUSIONS: Addition of an ARSI to standard ADT significantly increases the risk of fractures and falls in men with prostate cancer. PATIENT SUMMARY: We found a significantly increased risk of both fractures and falls with a combination of novel androgen signalling inhibitors and traditional forms of hormone therapy.

European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2023 Update.

CONTEXT: The European Association of Urology (EAU) guidelines panel on upper urinary tract urothelial carcinoma (UTUC) has updated the guidelines to aid clinicians in evidence-based management of UTUC. OBJECTIVE: To provide an overview of the EAU guidelines on UTUC as an aid to clinicians. EVIDENCE ACQUISITION: The recommendations provided in these guidelines are based on a review of the literature via a systematic search of the PubMed, Ovid, EMBASE, and Cochrane databases. Data were searched using the following keywords: urinary tract cancer, urothelial carcinomas, renal pelvis, ureter, bladder cancer, chemotherapy, ureteroscopy, nephroureterectomy, neoplasm, (neo)adjuvant treatment, instillation, recurrence, risk factors, metastatic, immunotherapy, and survival. The results were assessed by a panel of experts. EVIDENCE SYNTHESIS: Even though data are accruing, for many areas there is still insufficient high-level evidence to provide strong recommendations. Patient stratification on the basis of histology and clinical examination (including imaging) and assessment of patients at risk of Lynch syndrome will aid management. Kidney-sparing management should be offered as a primary treatment option to patients with low-risk UTUC and two functional kidneys. In particular, for patients with high-risk or metastatic UTUC, new treatment options have become available. In high-risk UTUC, platinum-based chemotherapy after radical nephroureterectomy, and adjuvant nivolumab for unfit or patients who decline chemotherapy, are options. For metastatic disease, gemcitabine/carboplatin chemotherapy is recommended as first-line treatment for cisplatin-ineligible patients. Patients with PD-1/PD-L1-positive tumours should be offered a checkpoint inhibitor (pembrolizumab or atezolizumab). CONCLUSIONS: These guidelines contain information on the management of individual patients according to the current best evidence. Urologists should take into account the specific clinical characteristics of each patient when determining the optimal treatment regimen according to the risk stratification of these tumours. PATIENT SUMMARY: Cancer of the upper urinary tract is rare, but because 60% of these tumours are invasive at diagnosis, timely and appropriate diagnosis is most important. A number of known risk factors exist.

Systematic Review of the Incidence of and Risk Factors for Urothelial Cancers and Renal Cell Carcinoma Among Patients with Haematuria.

CONTEXT: The current impact of haematuria investigations on health care organisations is significant. There is currently no consensus on how to investigate patients with haematuria. OBJECTIVE: To evaluate the incidence of bladder cancer, upper tract urothelial carcinoma (UTUC), and renal cell carcinoma (RCC) among patients undergoing investigation for haematuria and identify any risk factors for bladder cancer, UTUC, and RCC (BUR). EVIDENCE ACQUISITION: Medline, Embase, and Cochrane controlled trials databases and ClinicalTrials.gov were searched for all relevant publications from January 1, 2000 to June 2021 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Prospective, retrospective, and cross-sectional studies with a minimum population of 50 patients with haematuria were considered for the review. EVIDENCE SYNTHESIS: A total of 44 studies were included. The total number of participants was 229701. The pooled incidence rate for urothelial bladder cancer was 17% (95% confidence interval [CI] 14-20%) for visible haematuria (VH) and 3.3% (95% CI 2.45-4.3%) for nonvisible haematuria (NVH). The pooled incidence rate for RCC was 2% (95% CI 1-2%) for VH and 0.58% (95% CI 0.42-0.77%) for NVH. The pooled incidence rate for UTUC was 0.75% (95% CI 0.4-1.2%) for VH and 0.17% (95% CI 0.081-0.299%) for NVH. On sensitivity analysis, the proportions of males (risk ratio [RR] 1.14, 95% CI 1.10-1.17 for VH; 1.54, 95% CI 1.34-1.78 for NVH; p < 0.00001; moderate certainty evidence) and individuals with a smoking history (RR 1.41, 95% CI 1.24-1.61 for VH; 1.53, 95% CI 1.36-1.72 for NVH; p < 0.00001; moderate certainty evidence) appeared to be higher in BUR than in non-BUR groups. CONCLUSIONS: Male gender and smoking history are risk factors for BUR cancer in haematuria, with bladder cancer being the commonest cancer. The incidence of RCC and UTUC in NVH is low. The review serves as a reference standard for future policy-making on investigation of haematuria by global organisations. PATIENT SUMMARY: Our review shows that male gender and smoking history are risk factors for cancers of the bladder, kidney, and ureter. The review also provides information on the proportion of patients who have cancer when they have blood in their urine (haematuria) and will allow policy-makers to decide on the most appropriate method for investigating haematuria in patients.

Perioperative outcomes and safety of robotic vs open cystectomy: a systematic review and meta-analysis of 12,640 cases.

PURPOSE: Robotic radical cystectomy (RRC) has become a commonly utilised alternative to open radical cystectomy (ORC). We performed a systematic review and meta-analysis of RRC vs ORC focusing on perioperative outcomes and safety. METHODS: Medline, EMBASE and CENTRAL were searched from January 2000 to April 2020 following the Preferred Reporting Items for Systematic Review and Meta-analysis Statement for study selection. RESULTS: In total, 47 studies (5 randomised controlled trials, 42 non-randomised comparative studies) comprising 12,640 patients (6572 ORC, 6068 RRC) were included. There was no difference in baseline demographics between the groups apart from males were more likely to undergo ORC (OR 0.77, 95% CI 0.69-0.85). Those with muscle-invasive disease were more likely to undergo RRC (OR 1.21, 95% CI 1.09-1.34), and those with high-risk non-muscle-invasive bladder cancer were more likely to undergo ORC (OR 0.80, 95% CI 0.72-0.89). RRC had a significantly longer operating time, less blood loss and lower transfusion rate. There was no difference in lymph node yield, rate of positive surgical margins, or Clavien-Dindo Grade I-II complications between the two groups. However, the RRC group were less likely to experience Clavien-Dindo Grade III-IV (OR 1.56, 95% CI 1.30-1.89) and overall complications (OR 1.45, 95% CI 1.26-1.68) than the ORC group. The mortality rate was higher in ORC although this did not reach statistical significance (OR 1.52, 95% CI 0.99-2.35). CONCLUSION: RRC has significantly lower blood loss, transfusion rate and is associated with fewer high grade and overall complications compared to ORC.

Evidence-based protocol-led management of renal angiomyolipoma: A review of literature.

Renal angiomyolipomas (R-AMLs) are rare benign tumors, which occur sporadically and in association with genetic conditions such as tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis (LAM). The key clinical concern is life-threatening hemorrhage. There is uncertainty about the optimal management strategy for patients with R-AMLs. We aim to review the evidence and provide a protocolled approach for the management of R-AMLs. A literature search of R-AML was conducted using MEDLINE and EMBASE for articles published between January 1990 and March 2020. Patient with TSC and sporadic cases were included. Treatment strategies, including active surveillance, surgery, selective arterial embolization (SAE), ablation, and systemic therapies, were reviewed. Outcomes from contemporary case series of active surveillance, surgery, and SAE were collated. There were no randomized controlled trials on this topic. The retrospective case series reviewed showed that many R-AMLs can be managed safely with active surveillance. Tumor size is the most important predictor of bleeding, and other factors such as rate of growth, women of child-bearing age, aneurysm size, and symptoms should be considered when deciding on prophylactic treatment. There is limited evidence for the traditional 4-cm cutoff for treatment, which may lead to overtreatment. The primary intervention options are SAE and surgery; whereas SAE is a less invasive option, nephron sparing surgery offers a lower risk of recurrence. Both appear to have similar morbidity, and the current evidence does not recommend one over the other in most cases. Thermal ablation has promising results but has only been trialed in small case series. Patients with TSC can be offered mammalian target of rapamycin inhibitors of which everolimus appears to cause the greatest shrinkage of tumors with an acceptable side-effect profile. R-AMLs should be assessed for their risk of bleeding. Low-risk tumors should be treated with active surveillance. High-risk tumors should be treated with SAE or surgery. Systemic treatments are the first-line of treatment for patients with TSC to preserve renal parenchyma.

Trends in surgical and ablative treatment of localised renal cell carcinoma: A review of publication trends over 16 years (2000-2015).

Objective: To investigate the bibliometric (publication) trends in surgical and ablative treatment of localised renal cell carcinoma (RCC) over a period of 16-years, from 2000 to 2015, as publication trends reflect clinical practice and new innovations. Material and methods: We performed a systematic review using PubMed over a 16-year period from 2000 to 2015 for all published papers on surgical and ablative management of renal tumours. Data were further analysed in two time periods, period-1 (2000-2007) and period-2 (2008-2015). Results: During the last 16 years a total of 2415 papers were published on surgical (n = 1662, 69%) and ablative (n = 753, 31%) management of RCC. This included partial nephrectomy (PN; n = 1662, 69%), cryoablation (CA; n = 405, 17%), and radiofrequency ablation (RFA; n = 348, 14%). When comparing the two time periods for PN, during period-2, the change was +189% (P < 0.001), +69% (P = 0.004) and +4600% (P < 0.001) for open PN, laparoscopic PN and robotic PN, respectively. Regarding ablative techniques, a change of +109% (P = 0.002) and +78% (P = 0.036) was seen for CA and RFA, respectively. There was also a significant rise in percutaneous CA when compared to laparoscopic CA (P < 0.002). Conclusions: There has been a rise in all forms of PN and ablative techniques over the last 16 years. This rise has been particularly steep for robotic PN potentially reflecting a change in surgical practice. Abbreviations: CA: cryoablation; CC: correlation coefficient; MIS: minimally invasive surgery/surgical; NSS: nephron-sparing surgery; (L)(O)(R)PN: (laparoscopic) (open) (robotic) partial nephrectomy; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; RFA: radiofrequency ablation; RN: radical nephrectomy; SRM: small renal mass.

Rezum: a new transurethral water vapour therapy for benign prostatic hyperplasia.

Rezum is a minimally invasive transurethral water vapour therapy for benign prostatic enlargement which uses thermal energy for treatment. The short-term results show it to have good outcomes with a potential for outpatient-based treatment preserving sexual function. This review serves to provide an overview of the technique and evaluate its safety and efficacy.

Laparoscopic vs robotic nephroureterectomy: Is it time to re-establish the standard? Evidence from a systematic review.

OBJECTIVE: To conduct a systematic review of comparative studies of laparoscopic nephroureterectomy (LNU), the standard management for upper urothelial tumours, and robot-assisted NU (RANU) that has emerged as a viable alternative. METHODS: MEDLINE, EMBASE and the Cochrane Library were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify all studies reporting on both LNU and RANU for upper urothelial tract tumours. RESULTS: In all, 1630 patients were included, of which 838 underwent LNU and 792 RANU. Three studies reported on mean operative time and found it to be less in LNU, with two reporting this to be significant (RANU 298 vs LNU 251 min, P = 0.03; 306 vs 234 min, respectively, P < 0.001). Both studies reporting on median node count found this to be higher in the robotic groups: RANU 5.5 vs LNU 1.0 and RANU 21 vs LNU 11. Positive surgical margins (RANU 1.69% vs LNU 7.06%, P = 0.18), bladder recurrence (24.6% vs 36.89%, P = 0.09), and distant metastases (27.50% vs 17.50%, P = 0.29) were not significantly different between the two techniques. Disease-specific mortality did not differ between the two techniques (RANU 7.5% vs LNU 12.5%, P = 0.46), but postoperative mortality was reduced in RANU (0.14% vs 1.32%, P = 0.03). Overall complication rates were statistically lower in RANU, at 12.5% vs 18.8% (P < 0.001). CONCLUSIONS: This review suggests these techniques are equivalent in terms of perioperative and oncological performance. Furthermore, there may be a lower overall complication rate, as well as postoperative mortality in the robotic group. Further research in the form of a randomised controlled trial is warranted.

Bilateral Simultaneous Ureteroscopic (BS-URS) Approach in the Management of Bilateral Urolithiasis Is a Safe and Effective Strategy in the Contemporary Era-Evidence from a Systematic Review.

PURPOSE OF REVIEW: Ureteroscopic treatment of urolithiasis has become safer and more effective in the modern era. With a rise in the incidence of bilateral urolithiasis, management dilemma of staged single-side ureteroscopy versus bilateral simultaneous ureteroscopy (BS-URS) is often debatable. This review evaluates the current evidence base for bilateral simultaneous ureteroscopic approach in the modern era. RECENT FINDINGS: A systematic review was conducted from 1990 to June 2016 including all English language articles reporting on outcomes of BS-URS for urolithiasis. Data was split into two periods: period 1: 2003-2012 and period 2: 2013-2016, and analysed using SPSS version 21. A total of 11 studies (491 patients) were identified from a literature search of 148 studies with mean age of 45 years and a male: female ratio of 2:1 and a mean operative time of 69 min (SD = ±15). The initial and final stone-free rate (SFR) was 87 and 93%, respectively. Post-operative stents were placed in 89% of patients with a mean hospital stay of 1.6 days (SD = ±0.5). Overall, there was a significant negative association between case volume (procedures per month) and complication rate (p = 0.045). Mean hospital stay was significantly longer in period 1 (1.9 days, SD = ±0.5) than period 2 (1.3 days, SD = ±0.3) and complications were also significantly higher in period 1 (47%) compared to period 2 (12%) (p < 0.001). There were six studies examining holmium laser (HL) lithotripsy and three examining pneumatic lithotripsy (PL). There were significantly more complications after PL than HL; however, their SFR was similar. Our review shows that the complication rates and hospital stay are significantly reduced in the contemporary data suggesting an improving trend in outcomes following BS-URS. Simultaneous bilateral ureteroscopic treatment of urolithiasis is safe and effective in the modern era. Safety is increased in centers with increased number of procedures performed and with laser lithotripsy.

Intraoperative Frozen Section of the Prostate Reduces the Risk of Positive Margin Whilst Ensuring Nerve Sparing in Patients with Intermediate and High-Risk Prostate Cancer Undergoing Robotic Radical Prostatectomy: First Reported UK Series.

INTRODUCTION: Nerve sparing during robotic radical prostatectomy (RRP) considerably improves post-operative potency and urinary continence as long as it does not compromise oncological outcome. Excision of the neurovascular bundle (NVB) is often performed in patients with intermediate and high risk prostate cancer to reduce the risk of positive surgical margin raising the risk of urinary incontinence and impotence. We present the first UK series outcomes of such patients who underwent an intra-operative frozen section (IOFS) analysis of the prostate during RRP allowing nerve sparing. PATIENTS AND METHODS: We prospectively analysed the data of 40 patients who underwent an IOFS during RRP at our centre from November 2012 until November 2014. Our IOFS technique involved whole lateral circumferential analysis of the prostate during RRP with the corresponding neurovascular tissue. An intrafascial nerve spare was performed and the specimen was removed intra-operatively via an extension of the 12 mm Autosuture™ camera port without undocking robotic arms. It was then painted by the surgeon and sprayed with "Ink Aid" prior to frozen section analysis. The corresponding NVB was excised if the histopathologist found a positive surgical margin on frozen section. RESULTS: Median time to extract the specimen, wound closure and re-establishment of pneumoperitoneum increased the operative time by 8 min. Median blood loss for IOFS was 130 ± 97 ml vs. 90 ± 72 ml (p = NS). IOFS was not associated with major complications or with blood transfusion. PSM decreased significantly from non-IOFS RRP series of 28.7 to 7.8% (p < 0.05). Intra-operative PSM on the prostate specimen was seen in 8/40 margin analysis (20%) leading to an excision of the contra-lateral nerve bundle. On analysis of the nerve bundle on a paraffin embedded block, 6 nerve bundle matched tumor on the specimen whereas 2 NVB were retrospectively removed unnecessarily in our series. All 40 patients have undetectable PSA at a mean follow up of 21.2 months (SD 7.79). Functional data at 18 months confirms a reduction in the urinary incontinence from 37% in the IOFS group vs 57% in the non-IOFS group (p = NS). IOFS technique has resulted in a significant increase in intravesical nerve sparing in both T2/T3 patients with intermediate and high risk prostate cancer when appropriately counselled and selected (T2 from 100% in the IOFS group versus 67% and T3 from 100% in the IOFS group to 42%) (p < 0.05). CONCLUSION: Introduction of the IOFS analysis during intrafascial nerve spare RRP has reduced PSM and the rate of urinary incontinence.

Robot-assisted technique for Boari flap ureteric reimplantation: replicating the techniques of open surgery in robotics.

OBJECTIVE: To describe our robot-assisted Boari flap ureteric reimplantation (RA-BFUR) technique, Please see Video S1. METHODS: The RA-BFUR technique is based on the open surgical technique of Übelhör, and the experience includes 11 cases. RESULTS: Excellent results were achieved after a mean follow-up period of >12 months. CONCLUSION: The RA-BFUR technique could be considered a safe and effective method of ureteric reimplantation for long distal ureteric strictures.

Preliminary validation of Thiel embalmed cadavers for laparoscopic radical nephrectomy.

PURPOSE: This study evaluated face, content, construct validity, and reliability of Thiel embalmed cadavers (TEC) as a training tool for transperitoneal laparoscopic nephrectomy (TLN). MATERIALS AND METHODS: The study participants were prospectively recruited through an advanced laparoscopic renal resection teaching skill course. The participants were grouped into: nonexperts (performed fewer than 50 TLNs) and experts (performed more than 50 TLNs). All the participants performed TLN on TEC, which was video recorded. All participants rated their overall experience of performing TLN on TEC with emphasis on realism (face validity). The participants were asked to rate the appropriateness of TEC for training in TLN (content training). Two experienced laparoscopic surgeons, using validated modified Objective Structured Assessment of Technical Skills, assessed the individual videos. The parameters studied were: Respect for tissues, time and motion, and instrument handling for each step of laparoscopic nephrectomy (LN) (construct validity). Test-retest and interrater reliability was also evaluated. RESULTS: Twenty-four participants (4 experts and 20 nonexperts) took part in this study. The mean overall rating for the experience of TLN on TEC was 4.5 (Face Validity). The mean score for the appropriateness of TEC as a training tool for TLN was 4.6 (content validity) when evaluated by the four experts. The mean scores for the nonexperts and experts using video recordings for various variables were: Respect for tissue-1.74 (standard deviation [SD]-0.62) vs 3.63 (SD-1.06), (P<0.01), time and motion-1.74 (SD-0.58) vs 4 (SD-0.76), (P<0.01), and instrument handling-1.84 (SD-0.61) vs 4.25 (SD-0.71), (P<0.01) (construct validity). The study also suggested test-retest and interrater reliability. CONCLUSIONS: This study suggests face, content, and constructs validity and reliability of the TEC as a training tool for TLN.