Implementation of the enhanced recovery after surgery protocol for radical cystectomy patients: A single centre experience.

PURPOSE: The enhanced recovery after surgery (ERAS) protocol for radical cystectomy aims to facilitate postoperative recovery and hasten a return to normal daily activities. This study aims to report on the perioperative outcomes of implementation of an ERAS protocol at a single Australian institution. MATERIALS AND METHODS: We identified 73 patients with pT1-T4 bladder cancer who underwent open radical cystectomy at Western Health, Victoria between June 2016 and August 2021. A retrospective analysis of a prospectively maintained database was performed. Perioperative outcomes included length of hospital stay, nasogastric tube requirement and duration of postoperative ileus. RESULTS: The median age was 74 years (interquartile range [IQR] 66-78) for the ERAS group and 70 years (IQR 65-78) for the pre-ERAS group patients. All patients in each group underwent ileal conduit formation. The median length of hospital stay was 7.0 days (IQR 7.0-9.3) for the ERAS group and 12.0 days (IQR 8.0-16.0) for the pre-ERAS group (p=0.003). Within the ERAS group, 25.0% had a postoperative ileus, and 25.0% had a nasogastric tube inserted, compared with 64.9% (p=0.001) and 45.9% (p=0.063) respectively within pre-ERAS group. The median bowel function recovery time, defined as duration from surgery to first bowel action, was 5.0 days (IQR 4.0-7.0) in the ERAS group and 7.5 days (IQR 5.0-8.5) in the pre-ERAS group (p=0.016). CONCLUSIONS: Implementation of an ERAS protocol is associated with a reduction in hospital length of stay, postoperative ileus and bowel function recovery time.

The experience of a tertiary referral center with laparoscopic pyelolithotomy for large renal stones during 18 years.

This study aimed to evaluate the outcomes of laparoscopic pyelolithotomy, including its efficacy and feasibility in treatment of large renal stones. All patients who underwent laparoscopic pyelolithotomy operations in a referral center were enrolled from 2003 to 2020. The final analysis included 436 patients. The total stone free rate was 88.3% and the stone-free rate for staghorn/multiple stones versus other types of stones was 81% vs. 91% (P = 0.002). Likewise, the total operation duration was 158 ± 50 and the operation duration for staghorn/multiple stones versus other types of stones was 171 ± 51 min vs. 153 ± 49 min (P < 0.001). The operation duration (169 ± 51 vs. 155 ± 58 vs. 155 ± 42 min) and hospitalization (4.5 ± 2.3 vs. 4.0 ± 2.2 vs. 3.6 ± 1.8) decreased with increasing the surgeons' experience over time. The outcomes of laparoscopic pyelolithotomy for children versus adults versus geriatric patients and in patients with normal versus abnormal kidney anatomy did not reveal statistically significant differences. Laparoscopic pyelolithotomy could be employed as an alternative surgical approach for patients with large kidney stones of any age or with kidney abnormalities provided that appropriate expertise is available to carry out the procedure.

The effect of cisplatin-based neoadjuvant chemotherapy on the renal function of patients undergoing radical cystectomy.

INTRODUCTION: Cisplatin-based neoadjuvant chemotherapy (NAC) is the standard of care for patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC). Cisplatin, however, can induce renal toxicity. Furthermore, RC is an independent risk factor for renal injury, with decreases in estimated glomerular filtration rate (eGFR) of up to 6 mL/min/1.73 m2 reported at one year postoperatively. Our objective was to evaluate the effect of cisplatin-based NAC and RC on the renal function of patients undergoing both. METHODS: We analyzed a multicenter database of patients with MIBC, all of whom received cisplatin-based NAC prior to RC. eGFR values were collected at time points T1 (before NAC), T2 (after NAC but before RC), and T3 (one year post-RC). eGFR and proportion of patients with eGFR <60 ml/min/1.73m2 (chronic kidney disease [CKD] stage ≥3) were compared between these time points. As all patients in this dataset had received NAC, we identified a retrospective cohort of patients from one institution who had undergone RC during the same time period without NAC for context. RESULTS: We identified 234 patients with available renal function data. From T1 to T3, there was a mean decline in eGFR of 17% (13 mL/min/1.73 m2) in the NAC cohort and an increase in proportion of patients with stage ≥3 CKD from 27% to 50%. The parallel cohort of patients who did not receive NAC was comprised of 236 patients. The mean baseline eGFR in this cohort was lower than in the NAC cohort (66 vs. 75 mL/min/1.73 m2). The mean eGFR decline in this non-NAC cohort from T1 to T3 was 6% (4 mL/min/1.73 m2), and the proportion of those with stage ≥3 CKD increased from 37% to 51%. CONCLUSIONS: Administration of NAC prior to RC was associated with a 17% decline in eGFR and a nearly doubled incidence of stage ≥3 CKD at one year after RC. Patients who underwent RC without NAC had a higher rate of stage ≥3 CKD at baseline but appeared to have less renal function loss at one year.

Impact of Maximal Transurethral Resection on Pathological Outcomes at Cystectomy in a Large, Multi-institutional Cohort.

PURPOSE: While the presence of residual disease at the time of radical cystectomy for bladder cancer is an established prognostic indicator, controversy remains regarding the importance of maximal transurethral resection prior to neoadjuvant chemotherapy. We characterized the influence of maximal transurethral resection on pathological and survival outcomes using a large, multi-institutional cohort. MATERIALS AND METHODS: We identified 785 patients from a multi-institutional cohort undergoing radical cystectomy for muscle-invasive bladder cancer after neoadjuvant chemotherapy. We employed bivariate comparisons and stratified multivariable models to quantify the effect of maximal transurethral resection on pathological findings at cystectomy and survival. RESULTS: Of 785 patients, 579 (74%) underwent maximal transurethral resection. Incomplete transurethral resection was more frequent in patients with more advanced clinical tumor (cT) and nodal (cN) stage (P < .001 and P < .01, respectively), with more advanced ypT stage at cystectomy and higher rates of positive surgical margins (P < .01 and P < .05, respectively). In multivariable models, maximal transurethral resection was associated with downstaging at cystectomy (adjusted odds ratio 1.6, 95% CI 1.1-2.5). In Cox proportional hazards analysis, maximal transurethral resection was not associated with overall survival (adjusted HR 0.8, 95% CI 0.6-1.1). CONCLUSIONS: In patients undergoing transurethral resection for muscle-invasive bladder cancer prior to neoadjuvant chemotherapy, maximal resection may improve pathological response at cystectomy. However, the ultimate effects on long-term survival and oncologic outcomes warrant further investigation.

Medical Expulsive Therapy for Pediatric Ureteral Stones: A Meta-Analysis of Randomized Clinical Trials.

To evaluate the efficacy and safety of medical expulsive therapy (MET) for ureteral stones in pediatric patients, Cochrane, PubMed, Web of Science, Scopus, and the reference list of retrieved studies were searched up to September 2022 to identify RCTs on the efficacy of MET. The protocol was prospectively registered at PROSPERO (CRD42022339093). Articles were reviewed, data were extracted by two reviewers, and the differences were resolved by the third reviewer. The risk of bias was assessed using the RoB2. The outcomes, including the stone expulsion rate (SER), stone expulsion time (SET), episode of pain, analgesic consumption, and adverse effects, were evaluated. Six RCTs enrolling 415 patients were included in the meta-analysis. The duration of MET ranged from 19 to 28 days. The investigated medications included tamsulosin, silodosin, and doxazosin. The stone-free rate after 4 weeks in the MET group was 1.42 times that of the control group (RR: 1.42; 95% CI: 1.26-1.61, p < 0.001). The stone expulsion time also decreased by an average of 5.18 days (95% CI: -8.46/-1.89, p = 0.002). Adverse effects were more commonly observed in the MET group (RR: 2.18; 95% CI: 1.28-3.69, p = 0.004). The subgroup analysis evaluating the influence of the type of medication, the stone size, and the age of patients failed to reveal any impact of the aforementioned factors on the stone expulsion rate or stone expulsion time. Alpha-blockers as medical expulsive therapy among pediatric patients are efficient and safe. They increase the stone expulsion rate and decrease the stone expulsion time; however, this included a higher rate of adverse effects, which include headache, dizziness, or nasal congestion.

Multicenter evaluation of neoadjuvant and induction gemcitabine-carboplatin versus gemcitabine-cisplatin followed by radical cystectomy for muscle-invasive bladder cancer.

PURPOSE: Cisplatin-based chemotherapy followed by radical cystectomy (RC) is recommended in patients with muscle-invasive bladder cancer (MIBC). However, up to 50% of patients are cisplatin ineligible. The aim of this study was to compare clinical outcomes after ≥ 3 cycles of preoperative gemcitabine-carboplatin (gem-carbo) versus gemcitabine-cisplatin (gem-cis). METHODS: We identified 1865 patients treated at 19 centers between 2000 and 2013. Patients were included if they had received ≥ 3 cycles of neoadjuvant (cT2-4aN0M0) or induction (cTanyN + M0) gem-carbo or gem-cis followed by RC. RESULTS: We included 747 patients treated with gem-carbo (n = 147) or gem-cis (n = 600). Patients treated with gem-carbo had a higher Charlson Comorbidity Index (p = 0.016) and more clinically node-positive disease (32% versus 20%; p = 0.013). The complete pathological response (pCR; ypT0N0) rate did not significantly differ between gem-carbo and gem-cis (20.7% versus 22.1%; p = 0.73). Chemotherapeutic regimen was not significantly associated with pCR (OR 0.99 [95%CI 0.61-1.59]; p = 0.96), overall survival (OS) (HR 1.20 [95%CI 0.85-1.67]; p = 0.31), or cancer-specific survival (CSS) (HR 1.35 [95%CI 0.93-1.96]; p = 0.11). Median OS of patients treated with gem-carbo and gem-cis was 28.6 months (95%CI 18.1-39.1) and 45.1 months (95%CI 32.7-57.6) (p = 0.18), respectively. Median CSS of patients treated with gem-carbo and gem-cis was 28.8 months (95%CI 9.8-47.8) and 71.0 months (95%CI median not reached) (p = 0.02), respectively. Subanalyses of the neoadjuvant and induction setting did not show significant survival differences. CONCLUSION: Our results show that a subset of cisplatin-ineligible patients with MIBC achieve pCR on gem-carbo and that survival outcomes seem comparable to gem-cis provided patients are able to receive ≥ 3 cycles and undergo RC.

Neoadjuvant systemic therapy in patients undergoing nephroureterectomy for urothelial cancer: a multidisciplinary systematic review and critical analysis.

INTRODUCTION: The benefit of neoadjuvant systemic therapy (NAST) is not yet supported by randomized controlled trials in upper tract urothelial carcinoma (UTUC), but the evidence is increasing. This narrative systematic review was conducted to evaluate the available evidence on the role of NAST in patients undergoing radical nephroureterectomy (RNU) for UTUC. EVIDENCE ACQUISITION: We searched for all relevant articles or conference abstracts published and indexed in PubMed, Embase, and Scopus on July 19, 2021. The study was reported according to the PRISMA criteria and designed within the PICOS framework. We included studies comparing patients with non-metastatic UTUC who received neoadjuvant chemotherapy (NAC) or immunotherapy (NAI) with patients who underwent definitive surgery alone or surgery plus adjuvant systemic therapy. Prospective uncontrolled studies were also included. EVIDENCE SYNTHESIS: We identified 27 reports (NAC, N.=24 and NAI, N.=3) published between 2010 and 2021. Twenty of the 24 studies on NAC were retrospective comparative analyses, whereas the remaining four were prospective single-arm studies. One of the three NAI studies exclusively enrolled patients with UTUC. NAC was associated with improved survival and better pathological response relative to surgery alone, but there was no clear advantage when compared to surgery plus adjuvant chemotherapy. Overall, the drug-induced toxicity and risk of disease progression were acceptable but the inherent bias across study designs, inadequate reporting and heterogeneous definition of primary outcomes render it difficult to synthesize results, compare centers, and inform practice. CONCLUSIONS: The current level of evidence supporting NAST for UTUC is relatively low and the inability to predict responsiveness and thereby pinpoint the optimal candidates remains a major challenge. There is a need to compare NAST to adjuvant therapies using clearly defined primary endpoints as minimum reporting standards developed by a multidisciplinary team.

Evaluating the diagnostic role of in-bore magnetic resonance imaging guided prostate biopsy: a single-centre study.

BACKGROUND: To evaluate the role of in-bore MRI-guided biopsy (IB-MRGB) in the diagnosis of clinically significant prostate cancer (csPCa). METHODS: In this tertiary single centre study, a total of 125 consecutive patients receiving IB-MRGB over a three-year period were evaluated, including 73 patients who had prior biopsies and 52 biopsy-naïve patients. We assessed cancer detection rate of patients according to the degree of suspicion based on mpMRI findings. Histopathological data were reviewed by experienced uropathologists. RESULTS: The mpMRI was suspicious for PCa (PI-RADS 4/5) in 77% (96/125) and equivocal (PI-RADS 3) in 23% (29/125). The detection rate for csPCa was 54.2% (52/96) and 20.7% (6/29) for suspicious lesions (PI-RADS 4/5) and equivocal lesions (PI-RADS 3), respectively. In subgroup analysis, patients with previous negative biopsy, overall positive biopsy rate and csPCa detection rate were 48.3% (19/35) and 34.5% (13/35), respectively. In patients on AS, 36/44 (81.8%) and 21/44 (47.8%) had PCa and csPCa respectively. In biopsy-naïve patients 34/52 (65.4%) and 27/52 (51.92%) had PCa and csPCa respectively. Of the patients on AS, 18/44 (41.6%) upgraded from ISUP 1 to ISUP 2 PCa, and 4/44 (9.1%) upgraded from ISUP 1 to ISUP 3 PCa on IB-MRGB. A total of 14 Clavien-Dindo≤2 complications occurred in 14 patients (11.2%) that were directly related to the biopsy. No Clavien-Dindo≥3 complications occurred. CONCLUSION: MRI-targeted biopsy is suitable for assessment of csPCa. Given the favourable complications profile, its use may be considered in both the initial biopsy and re-biopsy settings.

Outpatient transperineal prostate biopsy under local anaesthesia is safe, well tolerated and feasible.

BACKGROUND: Transperineal biopsy (TPB) of the prostate has been increasingly utilized as it has reduced infection risks. Traditionally however, it is performed under general anaesthesia, thus it carries a differing set of risks. Recently, new studies have performed TPB under local anaesthesia with success. In the present study, we explored our experience of performing TPB under local anaesthesia in an Australian cohort. METHODS: In this prospective study based at a metropolitan outpatient clinic, patients were provided with TPB under local anaesthesia. We assessed prostate cancer detection rates, complication rates and patient tolerability. Pain tolerability was assess using patient reported pain score on the visual analogue scale. Follow up data was collected at days 7 and 30 post-biopsy via telephone interview. RESULTS: A total of 48 patients were enrolled in this study between June 2020 and March 2021. Median age was 65.5 years and median PSA was 6.95 ng/mL. Clinically significant prostate cancer was detected in 58% of patients. During the procedure, pain scores were rated the highest during infiltration of local anaesthetic agent with a median score of 5. By the conclusion of the procedure, median pain score was 1. Vast majority of patients (85.4%) would opt for a repeat TPB under local anaesthesia should the need for prostate biopsy arise again. Two of our patients experienced infectious complications, and one experienced urinary retention. CONCLUSION: Our data is in line with currently available data and confirms that TPB under local anaesthesia can be achieved in a safe and tolerable manner.

Identifying the Optimal Number of Neoadjuvant Chemotherapy Cycles in Patients with Muscle Invasive Bladder Cancer.

PURPOSE: We investigated the pathological response rates and survival associated with 3 vs 4 cycles of cisplatin-based neoadjuvant chemotherapy (NAC) in patients with cT2-4N0M0 muscle invasive bladder cancer. MATERIALS AND METHODS: In this cohort study we analyzed clinical data of 828 patients treated with NAC and radical cystectomy between 2000 and 2020. A total of 384 and 444 patients were treated with 3 and 4 cycles of NAC, respectively. Pathological objective response (pOR; ypT0-Ta-Tis-T1 N0), pathological complete response (pCR; ypT0 N0), cancer-specific survival and overall survival were investigated. RESULTS: pOR and pCR were achieved in 378 (45%; 95% CI 42, 49) and 207 (25%; 95% CI 22, 28) patients, respectively. Patients treated with 4 cycles of NAC had higher pOR (49% vs 42%, p=0.03) and pCR (28% vs 21%, p=0.02) rates compared to those treated with 3 cycles. This effect was confirmed on multivariable logistic regression analysis (pOR OR 1.46 p=0.008, pCR OR 1.57, p=0.007). On multivariable Cox regression analysis, 4 cycles of NAC were significantly associated with overall survival (HR 0.68; 95% CI 0.49, 0.94; p=0.02) but not with cancer-specific survival (HR 0.72; 95% CI 0.50, 1.04; p=0.08). CONCLUSIONS: Four cycles of NAC achieved better pathological response and survival compared to 3 cycles. These findings may aid clinicians in counseling patients and serve as a benchmark for prospective trials. Prospective validation of these findings and assessment of cumulative toxicity derived from an increased number of cycles are needed.

Early Experience of Transabdominal and Novel Transvaginal Robot-Assisted Laparoscopic Removal of Transvaginal Mesh.

Background: Mesh removal after transvaginal mesh placement has typically involved transvaginal, open pelvic, laparoscopic, or a combination of approaches. Robotic pelvic mesh removal has been described in a small number of cases only. This study aims at determining the feasibility and safety of using robot-assisted laparoscopic surgery in the removal of pelvic mesh via the transabdominal and novel transvaginal approach. Materials and Methods: This is a prospective case series study on women who underwent transabdominal or transvaginal robot-assisted removal of pelvic mesh. Women were offered participation in this study with pelvic mesh and a clinical indication for mesh removal if they were older than the age of 18. Alternative surgical options, including conventional open removal of mesh, were discussed and offered to patients. The primary outcome of this study is the rate of successful removal of mesh and the 30-day complication rates. Ethics approval was obtained for this study. Results: Thirty patients were included in this study. Median age was 62. Median operative and console time was 240 and 148 minutes, respectively. Concomitant reconstructive procedures were performed in 40% of patients. Complete or near-complete mesh removal was achieved in 83.3% of patients. For the remaining patients, partial removal of mesh was performed as planned preoperatively. Three Clavien-Dindo grade 3b complications resulted from mesh removal: concomitant ureteric and bladder injury, omental bleed, and groin wound infection. Conclusion: This study presents the early experience of robotic-assisted removal of transvaginal mesh with a transvaginal or transabdominal approach and demonstrates the feasibility of removal of both retropubic and transobturator mid-urethral synthetic sling as well as transvaginal prolapse meshes with transobturator and sacrospinous mesh arms. Further studies are required to expand understanding on the learning curve, operating times, complication rates, and functional outcome of this operation.

Molecular markers of systemic therapy response in urothelial carcinoma.

Identification of reliable molecular biomarkers that can complement clinical practice represents a fascinating challenge in any cancer field. Urothelial carcinoma is a very heterogeneous disease and responses to systemic therapies, and outcomes after radical cystectomy are difficult to predict. Advances in molecular biology such as next generation sequencing and whole genome or transcriptomic analysis provide promising platforms to achieve a full understanding of the biology behind the disease and can identify emerging predictive biomarkers. Moreover, the ability to categorize patients' risk of recurrence after curative treatment, or even predict benefit from a conventional or targeted therapies, represents a compelling challenge that may reshape both selection for tailored treatment and disease monitoring. Progress has been made but currently no molecular biomarkers are used in the clinical setting to predict response to systemic agents in either neoadjuvant or adjuvant settings highlighting a relevant unmet need. Here, we aim to present the emerging role of molecular biomarkers in predicting response to systemic agents in urothelial carcinoma.

Management of the Distal Ureter During Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Comprehensive Review of Literature.

PURPOSE: Radical open nephroureterectomy (ONU) with bladder cuff excision (BCE) is the traditional gold standard approach for management of high-risk non-metastatic upper tract urothelial cancer. ONU involves two separate procedures; the nephrectomy and distal ureterectomy, with each of these parts being able to be performed with an open or minimally-invasive approach. Multiple approaches have been described for the resection of the distal ureter and bladder cuff after mobilization of the kidney and upper ureter. MATERIALS AND METHODS: A Medline search of the literature including relevant articles up to March, 2020 was performed. Search terms included "nephroureterectomy", "upper tract urothelial carcinoma", "upper urinary tract carcinoma OR UTUC", "open OR conventional OR ONU OR conventional", "robotic-assisted nephroureterectomy OR RANU", "laparoscop* OR LNU OR LRNU" and "minimally-invasive nephroureterectomy". Original articles, case series and review articles were included. RESULTS: There are no randomised studies. Various techniques have been described to manage the distal ureter during nephroureterectomy. This review provides an overview of these techniques. The perioperative and oncological outcomes following open versus endoscopic techniques and minimally invasive techniques have been described. Although endoscopic approaches have more favourable perioperative outcomes, this comes at the expense of increased risk of tumour spillage and recurrence compared to the traditional open approaches. Minimally-invasive techniques (laparoscopic and robotic-assisted NU) largely have superior perioperative outcomes versus their open NU counterparts, with comparable oncological outcomes. CONCLUSION: Current non-randomised evidence is open to selection bias and is insufficient to support or refute endoscopic management of the distal ureter as an alternative to open bladder cuff excision. The optimal approach to nephroureterectomy and management of the distal ureter continues to remain a surgical dilemma.

Association of age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer.

PURPOSE: To assess the association of patient age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: We analyzed data from 1105 patients with MIBC. Patients age was evaluated as continuous variable and stratified in quartiles. Pathologic objective response (pOR; ypT0-Ta-Tis-T1N0) and pathologic complete response (pCR; ypT0N0), as well survival outcomes were assessed. We used data of 395 patients from The Cancer Genome Atlas (TCGA) to investigate the prevalence of TCGA molecular subtypes and DNA damage repair (DDR) gene alterations according to patient age. RESULTS: pOR was achieved in 40% of patients. There was no difference in distribution of pOR or pCR between age quartiles. On univariable logistic regression analysis, patient age was not associated with pOR or pCR when evaluated as continuous variables or stratified in quartiles (all p > 0.3). Median follow-up was 18 months (IQR 6-37). On Cox regression and competing risk regression analyses, age was not associated with survival outcomes (all p > 0.05). In the TCGA cohort, patient with age ≤ 60 years has 7% less DDR gene mutations (p = 0.59). We found higher age distribution in patients with luminal (p < 0.001) and luminal infiltrated (p = 0.002) compared to those with luminal papillary subtype. CONCLUSIONS: While younger patients may have less mutational tumor burden, our analysis failed to show an association of age with response to preoperative chemotherapy or survival outcomes. Therefore, the use of preoperative chemotherapy should be considered regardless of patient age.

Malignant ascites following radical nephrectomy for cystic renal cell carcinoma.

A 69-year-old man with a history of laparoscopic radical nephrectomy for papillary renal cell carcinoma presented with a 1-week history of generalised abdominal pain, distension and loss of appetite. Clinical examination and CT imaging demonstrated ascites associated with peritoneal nodules, raising the possibility of metastatic disease. Immunochemistry staining from ascites fluid cytology confirmed renal cell carcinoma. Following multidisciplinary discussions, the patient was commenced on a small-molecule tyrosine kinase inhibitor.

Ductal variant prostate carcinoma is associated with a significantly shorter metastasis-free survival.

BACKGROUND: Ductal adenocarcinoma is an uncommon prostate cancer variant. Previous studies suggest that ductal variant histology may be associated with worse clinical outcomes, but these are difficult to interpret. To address this, we performed an international, multi-institutional study to describe the characteristics of ductal adenocarcinoma, particularly focussing on the effect of presence of ductal variant cancer on metastasis-free survival. METHODS: Patients with ductal variant histology from two institutional databases who underwent radical prostatectomies were identified and compared with an independent acinar adenocarcinoma cohort. After propensity score matching, the effect of the presence of ductal adenocarcinoma on time to biochemical recurrence, initiation of salvage therapy and the development of metastatic disease was determined. Deep whole-exome sequencing was performed for selected cases (n = 8). RESULTS: A total of 202 ductal adenocarcinoma and 2037 acinar adenocarcinoma cases were analysed. Survival analysis after matching demonstrated that patients with ductal variant histology had shorter salvage-free survival (8.1 versus 22.0 months, p = 0.03) and metastasis-free survival (6.7 versus 78.6 months, p < 0.0001). Ductal variant histology was consistently associated with RB1 loss, as well as copy number gains in TAP1, SLC4A2 and EHHADH. CONCLUSIONS: The presence of any ductal variant adenocarcinoma at the time of prostatectomy portends a worse clinical outcome than pure acinar cancers, with significantly shorter times to initiation of salvage therapies and the onset of metastatic disease. These features appear to be driven by uncoupling of chromosomal duplication from cell division, resulting in widespread copy number aberration with specific gain of genes implicated in treatment resistance.

Local versus general anesthesia transperineal prostate biopsy: Tolerability, cancer detection, and complications.

Objectives: To compare data on transperineal template biopsy (TPTB) under general anesthesia (GA) compared with local anesthesia (LA) procedures using the PrecisionPoint™ Transperineal Access System (PPTAS) in relation to tolerability, cancer detection rate, complications, and cost. Methods: A prospective pilot cohort study of patients undergoing transperineal biopsy was performed. Patients were excluded if they had concurrent flexible cystoscopy or language barriers. Patients had a choice of GA or LA. A prospective questionnaire on Days 0, 1, 7, and 30 was applied. The primary outcome was patient tolerability. Secondary outcomes were cancer detection rate, complication rate, and theater utilization. Results: This study included 80 patients (40 GA TPTB and 40 LA PPTAS). Baseline characteristics including age, prostate-specific antigen (PSA), digital rectal examination (DRE), findings, and prostate volume were comparable between the groups (p = 0.3790, p = 0.9832, p = 0.444, p = 0.3939, respectively). Higher median prostate imaging-reporting and data system (PI-RADS) score of 4 (interquartile range [IQR] 2) versus 3 (IQR 1) was noted in the LA group (p = 0.0326). Pain was higher leaving recovery in the GA group however not significantly (p = 0.0555). Median pain score at LA infiltration was 5/10 (IQR 3), with no difference in pain at Days 1, 7, or 30 (p = 0.2722, 0.6465, and 0.8184, respectively). For GA versus LA, the overall cancer detection rate was 55% versus 55% (p = 1.000) with clinically significant cancer in 22.5% versus 35% (p = 0.217). Acute urinary retention (AUR) occurred in 5% of GA and 2.5% of LA patients (p = 1.000). The GA cohort spent longer in theater and in recovery with a median of 93.5 min versus 57 min for the LA group (p = <0.0001). Conclusion: This study demonstrates that transperineal biopsy is safely performed under LA with no difference between the cohorts in relation cancer detection or AUR. LA biopsy also consumed less theater and recovery resources. A further larger prospective randomized controlled trial is required to confirm the findings of this study.

Comparative effectiveness of neoadjuvant chemotherapy in bladder and upper urinary tract urothelial carcinoma.

OBJECTIVE: To assess the differential response to neoadjuvant chemotherapy (NAC) in patients with urothelial carcinoma of the bladder (UCB) compared to upper tract urothelial carcioma (UTUC) treated with radical surgery. PATIENTS AND METHODS: Data from 1299 patients with UCB and 276 with UTUC were obtained from multicentric collaborations. The association of disease location (UCB vs UTUC) with pathological complete response (pCR, defined as a post-treatment pathological stage ypT0N0) and pathological objective response (pOR, defined as ypT0-Ta-Tis-T1N0) after NAC was evaluated using logistic regression analyses. The association with overall (OS) and cancer-specific survival (CSS) was evaluated using Cox regression analyses. RESULTS: A pCR was found in 250 (19.2%) patients with UCB and in 23 (8.3%) with UTUC (P < 0.01). A pOR was found in 523 (40.3%) patients with UCB and in 133 (48.2%) with UTUC (P = 0.02). On multivariable logistic regression analysis, patients with UTUC were less likely to have a pCR (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.27-0.70; P < 0.01) and more likely to have a pOR (OR 1.57, 95% CI 1.89-2.08; P < 0.01). On univariable Cox regression analyses, UTUC was associated with better OS (hazard ratio [HR] 0.80, 95% CI 0.64-0.99, P = 0.04) and CSS (HR 0.63, 95% CI 0.49-0.83; P < 0.01). On multivariable Cox regression analyses, UTUC remained associated with CSS (HR 0.61, 95% CI 0.45-0.82; P < 0.01), but not with OS. CONCLUSIONS: Our present findings suggest that the benefit of NAC in UTUC is similar to that found in UCB. These data can be used as a benchmark to contextualise survival outcomes and plan future trial design with NAC in urothelial cancer.

Impact of sex on response to neoadjuvant chemotherapy in patients with bladder cancer.

OBJECTIVE: To assess the effect of patient's sex on response to neoadjuvant chemotherapy (NAC) in patients with clinically nonmetastatic muscle-invasive bladder cancer (MIBC). METHODS: Complete pathologic response, defined as ypT0N0 at radical cystectomy, and downstaging were evaluated using sex-adjusted univariable and multivariable logistic regression modeling. We used interaction terms to account for age of menopause and smoking status. The association of sex with overall survival and cancer-specific survival was evaluated using Cox regression analyses. RESULTS: A total of 1,031 patients were included in the analysis, 227 (22%) of whom were female. Female patients had a higher rate of extravesical disease extension (P = 0.01). After the administration of NAC, ypT stage was equally distributed between sexes (P = 0.39). On multivariable logistic regression analyses, there was no difference between the sexes or age of menopause with regards to ypT0N0 rates or downstaging (all P > 0.5). On Cox regression analyses, sex was associated with neither overall survival (hazard ratio 1.04, 95% confidence interval 0.75-1.45, P = 0.81) nor cancer-specific survival (hazard ratio 1.06, 95% confidence interval 0.71-1.58, P = 0.77). CONCLUSION: Our study generates the hypothesis that NAC equalizes the preoperative disparity in pathologic stage between males and females suggesting a possible differential response between sexes. This might be the explanation underlying the comparable survival outcomes between sexes despite females presenting with more advanced tumor stage.

Postoperative Renal Function in Patients Undergoing Unilateral Nephrectomy: Development of a Prediction Model Using Preoperative Risk Factors and 51Cr-EDTA Clearance.

Objectives: To analyze the preoperative variables associated to the postoperative glomerular filtration rate (GFR) outcomes after nephrectomy for benign and malignant conditions, measured by the reference isotopic technique 51Cr-ethylene diamine tetra-acetic (51Cr-EDTA) and to create a model to predict the short-term postoperative GFR. Secondary aim was to evaluate which of the common equations for GFR estimation (Cockcroft-Gault, Modification of Diet in Renal Disease [MDRD] or Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) has the best correlation with the 51Cr-EDTA. Methods: Patients undergoing unilateral nephrectomy from 2014 to 2018 were selected. Pre- and postoperative variables were prospectively collected. Univariate and multivariate analyses were done to identify independent risk factors associated with renal function outcomes and to create a model to predict the postoperative GFR. Correlation analyses were performed to evaluate the performance of various serum creatinine-based equations for GFR estimation compared with 51Cr-EDTA. Results: In total, 107 patients were evaluated. After univariate and multivariate analyses, older age (p = 0.008), higher split function of the operated kidney on dimercaptosuccinic acid (DMSA) scintigraphy (p < 0.001), and lower preoperative 51Cr-EDTA (p < 0.001) were independent risk factors for higher GFR decline. Correlation analyses showed that GFR estimated by CKD-EPI equation had the best concordance to GFR measured by 51Cr-EDTA. Conclusions: Based on our findings age, DMSA and lower preoperative 51Cr-EDTA are predictors of postoperative renal function after unilateral nephrectomy. For the assessment of estimated GFR, CKD-EPI equation appears to have the best concordance with 51Cr-EDTA.