A Prospective Randomized Controlled Trial of Irrigation "Bag Squeeze" to Manage Pain for Patients Undergoing Flexible Cystoscopy.

PURPOSE: We determined if the "bag squeeze" technique decreases pain during flexible cystoscopy in men. MATERIALS AND METHODS: This single center, prospective, double-blind, randomized controlled trial recruited 200 consenting participants who were ambulatory, outpatient males who had undergone prior cystoscopy and were not expected to require any secondary procedures. Men with prior urethral stricture or bladder neck contracture were excluded from study. Once eligibility was assessed and consent obtained, participants were randomized to undergo cystoscopy with the bag squeeze (group A) or the sham bag squeeze procedure (group B). Following cystoscopy, participants completed a pain questionnaire (visual analogue scale). Differences in mean pain score between groups were evaluated using Students' t-test with a 2-sided alpha of 0.05. RESULTS: A total of 200 patients were randomized and underwent flexible cystoscopy. Ten participants were ineligible because they required secondary procedures. Among the 190 eligible patients 97 were randomized to bag squeeze (group A) and 93 to sham bag squeeze (group B) with mean pain scores of 1.91 and 3.39, respectively (p <0.005). CONCLUSIONS: This study demonstrated a clinically meaningful decrease in pain for men undergoing flexible cystoscopy when the irrigation bag squeeze technique was used vs placebo bag squeeze. Accordingly, this useful, simple and free method to improve patient comfort during flexible cystoscopy should be adopted by clinicians.

A High Percent Free Prostate Specific Antigen in the Setting of Biochemical Recurrence after Radical Prostatectomy is Associated with Poorer Outcomes: A Validation Study Using Prospectively Collected Biobank Specimens.

PURPOSE: The role of percent free prostate specific antigen (%fPSA) in patients who have undergone radical prostatectomy and subsequently experienced disease relapse is unclear. We previously conducted 2 retrospective studies and found %fPSA 15 or greater in the setting of biochemical recurrence confers more aggressive disease. To validate that finding we used biobank specimens collected prospectively when patients were first diagnosed with biochemical recurrence. MATERIALS AND METHODS: Biobank specimens of patients with undetectable prostate specific antigen after radical prostatectomy and subsequent biochemical recurrence (prostate specific antigen 0.1 ng/ml or greater) were analyzed for %fPSA. Patients were stratified according to the %fPSA cutoff of 15. Univariable and multivariable logistic regression analysis was performed to predict covariates associated with a higher %fPSA. Cox proportional hazard models were performed to evaluate the prognostic effect of %fPSA on androgen deprivation therapy-free survival, metastasis-free survival, castration resistant-free survival and cancer specific survival. RESULTS: A total of 154 men were included in the study, of whom 126 (82%) had %fPSA less than 15 and 28 (18%) had %fPSA 15 or greater. Median followup for %fPSA less than 15 and %fPSA 15 or greater was 75 and 69 months, respectively. Patients with %fPSA 15 or greater had increased hazard of receiving androgen deprivation therapy (43% vs 25%, adjusted HR 2.40, 95% CI 1.12-5.11), metastatic disease (21% vs 7.9%, adjusted HR 4.10, 95% CI 1.11-15.2) and castration resistant prostate cancer (14% vs 4.0%, unadjusted HR 4.14, 95% CI 1.11-15.5) vs %fPSA less than 15, respectively. CONCLUSIONS: Patients with %fPSA 15 or greater were started on androgen deprivation therapy earlier, and they had progression to castration resistant prostate cancer and metastatic stage earlier. %fPSA 15 or greater in the setting of biochemical recurrence after radical prostatectomy is an indicator of a more aggressive disease. Unlike in the diagnostic setting, a higher %fPSA portends a worse clinical outcome.

Salvage radical prostatectomy following focal therapy: functional and oncological outcomes.

OBJECTIVES: To report the oncological and functional outcomes of salvage radical prostatectomy (sRP) after focal therapy (FT). PATIENTS AND METHODS: A retrospective review of all patients who underwent sRP after FT was performed. Clinical and pathological outcomes focussed on surgical complications, oncological, and functional outcomes. RESULTS: In all, 34 patients were identified. The median (interquartile range [IQR]) age was 61 (8.25) years. FT modalities included high-intensity focussed ultrasound (19 patients), laser ablation (13), focal brachytherapy (one) and cryotherapy (one). The median (IQR) time from FT to recurrence was 10.9 (17.6) months. There were no rectal or ureteric injuries. Two (5.9%) patients had iatrogenic cystotomies and four (11.8%) developed bladder neck contractures. The mean (sd) hospital stay was 2.5 (2.1) days. The T-stage was pT2 in 14 (41.2%) patients, pT3a in 16 (47.1%), and pT3b in four (11.8%). In all, 13 (38%) patients had positive surgical margins (PSMs). Six (17.6%) patients received adjuvant radiotherapy (RT). At a mean follow-up of 4.3 years, seven (20.6%) patients developed biochemical recurrence (BCR), and of these, six (17.6%) patients required salvage RT. PSMs were associated with worse BCR-free survival (hazard ratio 6.624, 95% confidence interval 2.243-19.563; P < 0.001). The median (IQR) preoperative International Prostate Symptom Score and International Index of Erectile Function score was 7 (4.5-9.5) and 23.5 (15.75-25) respectively, while in the final follow-up the median (IQR) values were 7 (3.5-11) and 6 (5-12.25), respectively (P = 0.088 and P < 0.001). At last follow-up, 31 (91.2%) patients were continent, two (5.9%) had moderate (>1 pad/day) incontinence, and one (2.9%) required an artificial urinary sphincter. CONCLUSIONS: sRP should be considered as an option for patients who have persistent clinically significant prostate cancer or recurrence after FT. PSMs should be recognised as a risk for recurrent disease after sRP.

Smarter screening for prostate cancer.

PURPOSE: Prostate cancer is the second commonest cancer among men. In the large European Randomized Study of Screening for Prostate Cancer (ERSPC) trial, prostate-specific antigen (PSA) screening has been shown to substantially reduce prostate cancer mortality. However, PSA screening is known to lead to more unnecessary prostate biopsies and over-diagnosis of clinically insignificant cancer. Therefore, it is imperative that smarter screening methods be developed to overcome the weaknesses of PSA screening. This review explores the novel screening tools that are available. METHODS: A comprehensive literature search was performed using PubMed regarding newer biomarkers, imaging techniques and risk-predicting models that are used to screen for prostate cancer in mainly biopsy-naïve men. RESULTS: Novel serum-based models like 4Kscore® and prostate health index (PHI) are generally better than PSA alone in detecting clinically significant cancer. Similarly, urine-based biomarkers like prostate cancer antigen 3 (PCA3) and HOXC6/DLX1 have been shown to be more accurate than PSA screening. More recently, multiparametric magnetic resonance imaging (mpMRI) is gaining popularity for its ability to detect clinically significant cancer. There is also evidence that combining individual tests to develop prediction models can reliably predict high-risk prostate cancers while reducing the number of unnecessary biopsies. Combinations such as the Stockholm-3 model (STHLM3) and other novel combinations are presented in this review. CONCLUSION: While we continue to find the smarter screening methods that are reliable, precise, and cost-effective, we continue to advocate shared decision-making in prostate cancer screening in order to work in our patients' best interests.

Oncological and functional outcomes of a large Canadian robotic-assisted radical prostatectomy database with 10 years of surgical experience.

INTRODUCTION: Robotic-assisted radical prostatectomy (RARP) has grown to be the predominant global surgical approach to treat localized prostate cancer. However, there is still limited access to robotic technology and little data from Canadian cohorts. Herein, we report on our oncological and functional outcomes after 10 years of surgical experience. MATERIALS AND METHODS: Prospective data from 1,034 RARP cases performed by two high-volume experienced surgeons at two academic centers were collected from October 2006 to June 2017. Preoperative characteristics, surgical, oncological and functional outcomes were assessed up to 72 months postoperative. RESULTS: D'Amico risk distribution was 26.1%, 59.8% and 14.1% for low, intermediate and high risk prostate cancer. Median (interquartile range) operative time, blood loss and hospital stay were 170 minutes (145-200), 200 mL (150-300) and 1day (1-1), respectively and 1.4% received blood transfusion. Intraoperative complications occurred in 3.8%. Postoperatively, 32 (3.1%) and 138 (13.3%) men harbored major (Clavien III-IV) and minor complications (Clavien I-II), respectively. Among the 630 men (64.2%) with pT2 and 349 men (35.6%) with pT3 disease, stage-specific positive surgical margin rates were 15.7% and 39.0%, respectively. Urinary continence rates at 6, 12 and 72 months were 72.7%, 83.5% and 84.9%, respectively. In men without preoperative erectile dysfunction, potency was observed in 45.6%, 59.4% and 69.5% at 6, 12 and 72 months, respectively. Biochemical recurrence occurred in 105 patients (10.2%). CONCLUSION: Mid-term oncological outcomes in two large Canadian centers demonstrate comparable results to non-Canadian centers of excellence. RARP appears to be safe with acceptable surgical, oncological and functional outcomes in a publicly funded single-payer healthcare system.

Multicentre international experience of 532-nm laser photoselective vaporization with GreenLight XPS in men with very large prostates.

OBJECTIVES: To describe peri-operative results, functional outcomes and complications of laser photoselective vaporization, using the GreenLight system, of prostate glands ≥200 mL in volume. METHODS: Retrospective analysis of a prospectively maintained multicentre database was performed to select a subgroup of patients with very large prostates (volume ≥200 mL) treated with the GreenLight XPS laser. A subgroup of patients with prostate volumes 100-200 mL was used for comparison. International Prostate Symptom Score, maximum urinary flow rate, postvoid residual urine volume and prostate-specific antigen levels were measured at 6, 12, 24, 36 and 48 months. Durability was evaluated using benign prostatic hyperplasia re-treatment rate at 12, 24 and 36 months. Additionally, complications were recorded using Clavien-Dindo classification. RESULTS: A total of 33 patients (38%) had prostates ≥200 mL. Baseline characteristics were similar between patients with prostates ≥200 mL and those with prostates 100-200 mL. Patients with very large prostates (≥200 mL) had longer operating times (129 vs 93 min), less energy delivered, a greater number of fibres used (3 vs 2) and a higher conversion rate to transurethral resection of the prostate (16% vs 4%). In terms of complications and functional outcomes, we did not find any differences between the groups. Retreatment rate was also comparable. CONCLUSIONS: Our results show that PVP GreenLight XPS-180W is an acceptable technique for very large prostates (≥200 mL); however, operating times, energy delivery, fibres used and conversion to TURP are a concern in this particular subgroup. This should be used for patient counselling and surgery planning.

Functional outcomes of robot-assisted radical prostatectomy in patients eligible for active surveillance.

OBJECTIVE: To assess the outcome of low risk prostate cancer (PCa) patients who were candidates for active surveillance (AS) but had undergone robot-assisted radical prostatectomy (RARP). METHOD: We reviewed our prospectively collected database of patients operated by RARP between 2006 and 2014. Low D'Amico risk patients were selected. Oncological outcomes were reported based on pathology results and biochemical failure. Functional outcomes on continence and potency were reported at 12 and 24 months. Continence was assessed by the number of pads per day. With respect to potency, it was assessed using the Sexual Health Inventory for Men (SHIM) and Erectile Hardness Scale (EHS). RESULTS: Out of 812 patients, 237 (29.2%) patients were D'Amico low risk and were eligible for analysis. 44 men fit Epstein's criteria. 134 (56.5%) men had pathological upgrading. Age and clinical stage were predictors of upgrading on multivariate analysis. 220 (92.8%) patients had available follow-up for biochemical recurrence, potency, and continence for 2 years. The mean and median follow-up was 34.8 and 31.4 months, respectively. Only 5 (2.3%) men developed BCR, all of whom had pathological upgrading. Extra capsular extension and positive surgical margins were observed in 14.8 and 19.1%, respectively. 0 pad was achieved in 86.7 and 88.9% at 1 and 2 years, respectively. Proportion of patients with SHIM > 21 at 1 and 2 years was 24.8 and 30.6%, respectively. Moreover, patients having erections adequate for intercourse (EHS ≥ 3) were seen in 69.6 and 83.1% at 1 and 2 years, respectively. Functional outcomes of patients fitting Epstein's criteria (n = 44) and patients with no upgrading on final pathology (n = 103) were not significantly different compared to the overall low risk study group. CONCLUSION: This retrospective study showed that RARP is not without harm even in patients with low risk disease. On the other hand, considerable rate of upgrading was noted.

Does surgical delay for radical prostatectomy affect biochemical recurrence? A retrospective analysis from a Canadian cohort.

AIM: We sought to explore the impact of surgical wait time (SWT) to robot-assisted radical prostatectomy (RARP) on biochemical recurrence (BCR). METHOD: Retrospective review of a prospectively collected database between 2006 and 2015 was conducted on all RARP cases. SWT was defined as period from prostate biopsy to surgery. Primary outcome was the impact on BCR, which was defined as two consecutive PSA ≥ 0.2 ng/dl, or salvage external beam radiation therapy and/or salvage androgen deprivation therapy. Patients were stratified according to D'Amico risk categories. Univariable analysis (UVA) and multivariable analyses (MVA) with a Cox proportional hazards regression model were used to evaluate the effect of SWT and other predictive factors on BCR, in each D'Amico risk group and on the overall collective sample. RESULTS: Patients eligible for analysis were 619. Mean SWT was 153, 169, 150, and 125 days, for overall, low-, intermediate-, and high-risk patients, respectively. Multivariate analysis on the overall cohort did not show a significant relation between SWT and BCR. On subgroup analysis of D'Amico risk group, SWT was positively correlated to BCR for high-risk group (p = 0.001). On threshold analysis, cut-off was found to be 90 days. SWT did not significantly affect BCR on UVA and MVA in the low- and intermediate-risk groups. CONCLUSION: Increased delay to surgery could affect the BCR, as there was a positive association in high-risk group. Further studies with longer follow-up are necessary to assess the impact of wait time on BCR, cancer specific survival and overall survival.

Use of the AccuVein AV400 during RARP: an infrared augmented reality device to help reduce abdominal wall hematoma.

INTRODUCTION: Abdominal wall hematoma (AWH) is a self-resolving, yet common complication from the insertion of trocars during laparoscopic surgery. Particularly, its appearance may increase patient anxiety and may reduce overall surgical satisfaction. MATERIALS AND METHODS: In a retrospective study analyzing data from 724 robot-assisted radical prostatectomy cases (RARP), trocar insertion sites were examined on postoperative day 7 with Foley removal for AWH. AWH was defined by a sizable collection of blood below the skin as a result of the surgery. The AccuVein AV400 system was utilized to generate real-time images of venous structures beneath the skin. Comparative outcomes were performed with a series of 114 men where the AccuVein AV400 device was applied over trocar insertion markings to help modify port placement. RESULTS: The pre-incision imaging of the AccuVein system modified port placement in 74 of 114 cases (65%), and reduced AWH from 8.8% to 2.6% (p = 0.03) as compared to transabdominal illumination. Port placement adjustments were most prevalent in the lateral regions of the abdomen, prompting attention for lateral trocar insertion to avoid vessels such as the thoracoepigastric veins. Notably, the body mass index (BMI) of patients experiencing AWH who received the pre-incision imaging of AccuVein was significantly higher than patients receiving standard transabdominal illumination (34.2 and 27.9 kg/m² respectively; p = 0.02). CONCLUSION: The AccuVein AV400 device appears to be an effective adjuvant for decreasing rates of AWH during lower abdominal wall trocar insertion, though its effectiveness is limited in patients with extreme BMI. Additionally, special attention should be directed towards trocar insertion in the lateral regions of the abdomen.

Validating the total cancer location density metric for stratifying patients with low-risk localized prostate cancer at higher risk of grade group reclassification while on active surveillance.

PURPOSE: To validate a previously proposed prognostic metric, Total Cancer Location (TCLo) density, in a contemporary cohort of men with grade group (GG) 1 prostate cancer (PCa) on active surveillance (AS). METHODS: We evaluated 123 patients who entered AS with maximum GG1 PCa at diagnostic and/or confirmatory biopsy. TCLo was defined as the total number of PCa locations identified on both biopsy sessions. TCLo density was calculated as TCLo / prostate volume [ml]. Primary endpoint was progression-free survival (PFS), defined as time from confirmatory biopsy to grade group reclassification (GGR) on repeat biopsy or prostatectomy. Optimal cut-point for TCLo density was predefined in a previously reported cohort and applied to this contemporary cohort. Kaplan-Meier and multivariable Cox regression analysis were used to estimate the association of predictors with PFS. RESULTS: During median follow-up of 7.8 years, (IQR 7.3-8.2) 34 men had GGR. Using previously defined cut-points, PFS at 5-years was 60% (95% CI: 44%-81%) vs. 89% (95% CI: 83%-96%) in men with high (≥0.06 ml-1) vs. low (<0.06 ml-1) TCLo density, and 63% (95% CI: 48%-82%) vs. 90% (95% CI: 83%-96%) in men with high (≥3) vs. low (≤2) TCLo (log-rank test: P < 0.0001, respectively). Adjusting for age, prostate volume, percent of positive cores and PSA, both higher TCLo density (HR [per 0.01 ml-1 increase]: 1.18, 95% CI: 1.05-1.33, P = 0.005) and TCLo (HR: 1.69, 95% CI: 1.20-2.38, P = 0.002) were associated with shorter PFS. CONCLUSION: The previously suggested prognostic value of TCLo density was confirmed in this validation cohort. TCLo alone performed similarly well. Patients with high TCLo density (≥0.06 ml-1) or TCLo (>2) were at greater risk of GGR while on AS. With external validation, these metric may help guide risk-adapted surveillance protocols.

Age related differences in primary testicular lymphoma: A population based cohort study.

INTRODUCTION: Primary testicular non-Hodgkin's lymphoma (PTL) is a very rare disease, comprising 1% of all non-Hodgkin's lymphoma and <5% of all cases of testicular tumors. With a median age at diagnosis of 67 years, PTL is the most common testicular malignancy in men aged >60 years. There is limited published data on PTL incidence and outcomes in younger patients. The aim of this study is to compare the clinical parameters and survival outcomes between the patients older and younger than 50. METHODS: The SEER database was queried for all patients diagnosed with PTL between 1983 and 2017. Data collected consisted of demographic, and clinical parameters, including staging, pathological assessments, and survival data. Patients were stratified according to their age and compared. RESULTS: There was a total of 1,581 patients diagnosed with PTL between the year 2000 and 2017, of whom 215 (13.6%) were younger than 50 years old. The median age at diagnosis was 41 (interquartile range [IQR] 1-50), and 72 (IQR 51-95) years old for patients ≤50 and patients > 50 years of age, respectively. Comparison of younger and older patients detected similarities in disease laterality (92% vs. 94%, P = 0.38) and Ann Arbor stage I to II at diagnosis (76% vs. 75%, P = 0.59). The most common diffuse large B-cell lymphoma (DLBCL) subtype was more common in older patients (61% vs. 87%, P < 0.001). Radical orchiectomy (71% vs. 79%, P = 0.004) and radiation treatment (40% vs. 37%, P = 0.49) rates were comparable between both groups. However, a higher proportion of younger patients underwent chemotherapy (83% vs. 72%, P < 0.001). Patients ≤50 and >50 years old had a hazard ratio (HR) of 0.63 (95% CI: 0.57-0.71) and 0.34 (95% CI: 0.31-0.37), respectively, for 10-year OS with a median survival time for patients >50 of 5.75 years (95% CI: 5.25-6.33), P < 0.001. Patients ≤50 years old had a HR of 0.33 (95% CI: 0.26-0.40) compared to HR of 0.40 (95% CI: 0.37-0.43) in patients >50 years old for cumulative disease-specific mortality (DSM, P = 0.0204). Age >50 years was associated with worse DSM with a HR of 1.39 (95% CI: 1.05- 1.86, P = 0.024). Ann Arbor stage II and higher was also associated with worse DSM, while undergoing surgery, radiotherapy, and chemotherapy were associated with improved DSM. CONCLUSIONS: PTL is the most common testicular malignancy in men older than 60 years of age, but more than a quarter of the patients are younger than 60 and more than 13% are ≤50 years. Younger patients are more likely to receive chemotherapy and radiation, and overall do better in terms of DSM. Being younger, having a lower Ann Arbor stage and being treated with chemotherapy and radiotherapy increase the chances of survival.

The prognostic value of urinary cytology after trimodal therapy (TMT) for muscle-invasive bladder cancer.

BACKGROUND: Urine cytology and cystoscopy are routinely employed during follow-up of patients after trimodal therapy (TMT) for muscle-invasive bladder cancer (MIBC). The significance of positive or equivocal cytology without visible disease recurrence on cystoscopy during follow-up is unknown, and studies informing outcomes in this scenario are lacking. This study aims to investigate the temporal trends of positive/equivocal cytology in the absence of visible disease recurrence and the association with bladder cancer recurrence and survival outcomes. METHODS: One hundred and twenty-nine patients with available post-TMT cytology data and negative cystoscopy from a single academic institution between 2002 and 2017 with a median follow-up of 3.4 (range 0.1-14.2) years were analyzed. Cytology results, first post-TMT cytology positive/equivocal (CP) and negative (CN), were evaluated for association with disease recurrence and survival. Kaplan. Meier and competing risks methods were used to assess time-to-negative cytology in CP patients with ≥2 interval post-TMT cytology results (n = 33), time-to-recurrence, and disease-specific mortality (DSM) stratified by first post-TMT cytology result. RESULTS: At first follow-up (6-8 weeks post-TMT completion), CP was observed in 41 (32%) and CN in 88 (68%) of patients. With further follow-up of CP patients with ≥2 interval post-TMT cytology results, the probability of developing negative cytology was 57% (95% CI 42, 77) at 6 months post-TMT, and the median time-to-negative cytology was 3.2 months (95% CI 2.99, 5.80). The median time-to-recurrence was reduced in CP patients compared to CN (24.3 vs. 78.1 months, p = 0.1), corresponding with an apparent increase in the cumulative incidence of recurrence rate at 3 years in the CP vs. CN group (62% vs. 42%, p = 0.1). No significant difference was observed in the 3-year DSM rates. On univariable analysis, the hazards of recurrence and DSM for patients with CP were 1.5 (95% CI 0.9, 2.5, p = 0.1) and 2.1 (95% CI 0.9, 4.7, p = 0.07) respectively. CONCLUSION: This is the first study to investigate the significance of a positive/equivocal cytology without visible disease following TMT for MIBC. Positive cytology is common and does not preclude subsequent negative cytology supporting a watchful waiting approach rather than proceeding immediately to biopsy. However, cytology that remains positive at subsequent follow-up may be associated with adverse recurrence and survival outcomes.

Single-night stay for open radical prostatectomy.

INTRODUCTION: The aim of this study was to assess the effect of an enhanced care pathway on length of stay (LOS) for open radical prostatectomy (RP) given that robotic-assisted laparoscopic prostatectomy (RALP) is not available to all patients in Canada. METHODS: A retrospective review was conducted of all RPs performed. An enhanced care pathway was established for RPs in 2011. Patients were compared in the period before (2005-2010) and after (2011-2019) the introduction of the pathway. RESULTS: During the study period, 581 RPs were performed by a single surgeon with a median followup of 66.9 months (range 3-176). A total of 211 (36.3%) RPs were performed from 2005-2010, while 370 (63.9%) were performed from 2011-2019. The median age at RP was 65 years (range 44-81). Following the introduction of an enhanced care pathway, there were significant decreases in intraoperative blood loss (350 ml vs. 200 ml; p=0.0001) and the use of surgical drains (90% vs. 9.5%; p=0.0001). The median LOS over the whole study period was one day (range 1-7), which significantly decreased with the enhanced care pathway (3 vs. 1 day; p=0.0001). Since introducing the enhanced care pathway in 2011, 344 (93%) patients were discharged day 1 following surgery. There were no differences in post-discharge presentations to the emergency department (5.7% vs. 9%; p=0.15) or 30-day readmission rates (3.8% vs. 3.8%; p=1.00). CONCLUSIONS: A single-night stay for open RP is safe and achievable for most patients. A dedicated, multifaceted pathway is required to attain targets for a safe and timely discharge.

Radical nephrectomy with resection of vena cava thrombus using extracorporeal circulation and deep hypothermic circulatory arrest.

INTRODUCTION: Patients with renal cell carcinoma (RCC) with level 3 or 4 caval thrombus have a poor prognosis, with reported five-year survival rates of 30-40%. The aim of this study was to assess the perioperative morbidity and long-term oncological outcomes for radical nephrectomy with resection of vena cava thrombus using a combined surgical approach, including extracorporeal circulation and deep hypothermic circulatory arrest. METHODS: A retrospective review was performed of the institutional case log to identify all radical nephrectomies with caval thrombus performed from January 2006 to May 2020. RESULTS: Twenty-five patients were identified with level 2 thrombus in one (4%), level 3 thrombus in eight (32%), and level 4 in 16 (64%). The median followup was 20.6 months (range 0.2-133.3). The median age at surgery was 68.4 years (range 44.2-85.5). Twenty-one (84%) patients were symptomatic at presentation. Six (24%) patients had distant metastases at diagnosis. The median circulatory arrest time was 15 minutes (range 6-35). The 30-day grade ≥3 complication rate was 8%. The 30-day mortality rate was 8%. The one-year, two-year, three-year, and five-year recurrence-free survival (RFS) rates were 53%, 18%, 10%, and 10%, respectively. The median time to systemic treatment was 7.7 months (range 1.2-25.7). The one-year, two-year, three-year, and five-year overall survival (OS) rates were 70%, 43%, 36%, and 31%, respectively. CONCLUSIONS: Radical nephrectomy with resection of vena cava thrombus using extracorporeal circulation and deep hypothermic circulatory arrest is associated with some morbidity and mortality but remains a safe and effective strategy for advanced RCC patients who would otherwise be managed palliatively.

Association between chronic bladder catheterisation and bladder cancer incidence and mortality: a population-based retrospective cohort study in Ontario, Canada.

OBJECTIVES: To compare the risk of bladder cancer and bladder cancer mortality among patients with chronic bladder catheterisation (indwelling or intermittent) to patients from the general population. DESIGN: Retrospective cohort study. SETTING: Population-based study in Ontario, Canada between 2003 and 2018. PARTICIPANTS: Adult patients 18-90 years of age with chronic bladder catheterisation were hard matched to patients from the general population without a history of bladder catheterisation. INTERVENTIONS: The presence of a chronic catheter was defined as a minimum of two physician encounters for bladder catheterisation, suprapubic tube insertion or home care for catheter care separated by at least 28 days. Urinary tract infection (UTI) rates were collected. MAIN OUTCOME MEASURES: Bladder cancer and bladder cancer-specific mortality after a 1-year lag period were compared between groups. RESULTS: We identified 36 903 patients with chronic catheterisation matched to 110 709 patients without a history of catheterisation. Patients were followed for a median of 8.8 years (IQR: 5.2-11.9 years). The median age was 62 years (IQR: 50-71) and 52% were female. More patients in the catheter group developed bladder cancer (393 (1.1%) vs 304 (0.3%),p<0.001). There were 106 (0.3%) bladder cancer deaths in the catheter group and 59 (0.1%) in the comparison group (p<0.001). Chronic catheterisation (adjusted subdistribution HR (sdHR)=4.80, 95% CI: 4.26 to 5.42,p<0.001) and the number of UTIs (adjusted sdHR=1.04 per UTI, 95% CI: 1.04 to 1.05,p<0.001) were independent predictors of bladder cancer. The relative rate of bladder cancer-specific death was more than eightfold higher among patients with chronic catheterisation (adjusted sdHR=8.68, 95% CI: 6.97 to 10.81,p<0.001). Subgroup analysis among patients with neurogenic bladder and bladder calculi similarly revealed an increased risk of bladder cancer diagnosis and mortality. Bladder cancer risk was highest among patients in the two longest catheter duration quintiles (2.9-5.9 and 5.9-15.5 years). CONCLUSIONS: This is the first study to quantify the increase in bladder cancer incidence and mortality in a large, diverse cohort of patients with chronic indwelling or intermittent bladder catheterisation. The risk was highest among patients with a chronic catheter beyond 2.9 years.

Characterization and management of NMIBC recurrences after TMT: a matched cohort analysis.

INTRODUCTION AND OBJECTIVE: Bladder preservation with trimodal therapy (TMT) has emerged as a feasible alternative strategy to treat localized muscle invasive bladder cancer (MIBC). There is lack of consensus regarding the treatment of local recurrence following TMT. The aim of this paper is to determine whether traditional NMIBC therapies can be applied to the management of NMIBC recurrences following TMT. METHODS: Using our institutional bladder cancer radiotherapy database, all patients with recurrent NMIBC following TMT were identified between 2008-2019. TMT patients were initially treated with maximal TURBT followed by combination chemotherapy/radiotherapy (weekly cisplatin 40 mg/m2 and 64-66 Gy to the bladder) with localizing Lipiodol injections. We compared NMIBC recurrent patients to a cohort of matched controls with primary NMIBC, hypothesizing that post-TMT patients treated with traditional NMIBC therapies would have outcomes similar to patients with primary NMIBC. Primary NMIBC patients were derived from our local NMIBC database and matching was based on clinical stage and grade in a 5:1 manner (controls:cases). Recurrences in the TMT group were managed according to the standard therapy for NMIBC. A descriptive analysis was performed between patients undergoing TMT with NMIBC recurrence and patients initially diagnosed with de novo NMIBC. Overall survival was calculated for each group and analyzed using the Kaplan-Meier method and Cox proportional hazards modeling. Recurrence-free and cystectomy-free survival were analyzed using competing risk methods. RESULTS: Twelve patients out of 124 patients in the TMT cohort had NMIBC recurrence and were compared to 60 patients in a control group who were diagnosed with de-novo NMIBC. Median age of the TMT group was 78 [54 - 84] years versus 66 [23 - 88] years for the non-TMT group. Median follow-up for was 3.6 years versus 5.4 years in the non-TMT group. The clinical stage of the TMT NMIBC recurrences was Ta (n = 4), T1 (n = 3), CIS (n = 5). During the follow-up period, 38 (63%) further recurrences occurred in the non-TMT group compared to 2 (17%) in TMT group (P = 0.004). One patient (8%) from the TMT group required a cystectomy compared to 11 (18%) in the non-TMT group (P = 0.68). There were 2 non-cancer deaths (17%) in TMT group compared to one (2%) in the non-TMT group. CONCLUSION: Our study demonstrates NMIBC recurrences post TMT can be successfully managed with endoscopic and adjuvant intravesical therapies.

Natural History of Renal Angiomyolipoma Favors Surveillance as an Initial Approach.

BACKGROUND: Traditionally, intervention was recommended for angiomyolipomas (AMLs) >4 cm due to the risk of catastrophic hemorrhage. OBJECTIVE: To delineate the natural history of AMLs, including growth rates and need for intervention. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review was performed of an AML series from 2002 to 2013, which have been followed prospectively until 2018. We defined lesion size by maximum axial diameter and categorized lesion size at baseline. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A total of 458 patients with 593 AMLs, with a median follow-up of 65.2 mo, were identified. At diagnosis, 534 (90.1%) lesions were ≤4 cm. Forty-three interventions were required for 34 (5.7%) AMLs: 30 were treated with embolization, seven surgery, two with radiofrequency ablation (RFA), three with mammalian target of rapamycin (mTOR) inhibitors, and one with nivolumab when epithelioid AML was confirmed. The median size at intervention was 4.9 cm (range 1.1-29 cm). RESULTS AND LIMITATIONS: Most (94%) of the lesions grew slowly (growth rate of <0.25 cm/yr) during the period of observation. The number of AMLs <4 cm needed to treat (NNT) prophylactically to prevent one emergent bleed would have been 136 or that to prevent one blood transfusion would have been 205. The NNT (<4 cm) prophylactically to prevent one elective intervention would have been 82. On multivariate analysis, there were significant differences in intervention rates based on tuberous sclerosis complex, size at presentation, and clinical presentation. CONCLUSIONS: This large single-institution updated series of renal AMLs demonstrates that early intervention is not required, regardless of the traditional 4 cm cut-off. The vast majority of AMLs are indolent lesions that are predominantly asymptomatic and slow growing. Follow-up should be no more frequent than annually. PATIENT SUMMARY: The majority of angiomyolipomas (AMLs) are indolent, slow-growing lesions that do not require intervention, regardless of size at presentation. We suggest that surveillance is a safe initial approach for patients presenting with AMLs.

Bladder-sparing treatment options in localized muscle-invasive bladder cancer.

Introduction: Bladder cancer is the 9th most common cancer in the world and the 4th and 8th most common cancer diagnosed in men in the United States and United Kingdom respectively. The standard of care for the treatment of MIBC is radical cystectomy. Bladder preserving treatment approaches are emerging for select patients and should be considered strongly in patients who decline a radical cystectomy.Areas covered: In this review we look at the European and American recommended guidelines, the current standard of care, bladder-preserving options in MIBC, trimodal therapy and discuss future developments in the identification of molecular biomarkers that can predict therapeutic outcomes.Expert opinion: We strongly advocate bladder preservation for the right patient with strict criteria for enrolling patients in bladder preservation. The development of a specialized bladder cancer clinic could facilitate the selection of patients to be offered trimodal therapy. We believe that the future of bladder cancer will involve individualized care plans based upon clinical, radiological, endoscopic and molecular assessments.

Utility of digital rectal examination in a population with prostate cancer treated with active surveillance.

INTRODUCTION: Digital rectal examination (DRE) is part of the clinical evaluation of men on active surveillance (AS). The purpose of the present study is to analyze the value of DRE as a predictor of upgrading in a population of men with prostate cancer (PCa) treated with AS. METHODS: We used the prostate biopsy (PBx) database from an academic center, including PBx from 2006-2018, and identified 2029 confirmatory biopsies (CxPBx) of men treated with AS, of which 726 men had both diagnostic (initial) and CxPBx information available. We did a descriptive analysis and evaluated sensitivity, specificity, and predictive values of DRE for the detection of clinically significant PCa (csPCa). Multivariable regression analysis was done to identify predictors of csPCa. The primary outcome was to evaluate DRE as a predictor of the presence of csPCa at CxPBx. RESULTS: Among the 2029 patients with a CxPBx, 75% had PCa, and of these, 30.3% had upgrading to International Society of Urologic Pathologists (ISUP) grade ≥2. Thirteen percent of men had a suspicious DRE (done by their treating physician). Sensitivity, specificity, negative and positive predictive values of DRE to detect csPCa were best with a prostate-specific antigen (PSA) <4 ng/ml (27%, 88%, 31%, and 87%, respectively). A suspicious DRE at CxPBx, particularly if the DRE at diagnosis was negative, was a predictor of csPCa (odds ratio [OR] 2.34, p=0.038). The main limitation of our study is the retrospective design and the lack of magnetic resonance imaging. CONCLUSIONS: We believe DRE should still be used as part of AS and can predict the presence of csPCa, even with low PSA values. A suspicious nodule on DRE represents a higher risk of upgrading and should prompt further assessment.

Canadian experience of neoadjuvant chemotherapy on bladder recurrences in patients managed with trimodal therapy for muscle-invasive bladder cancer.

INTRODUCTION: Bladder preservation with trimodal therapy (TMT) has emerged as a feasible alternative to radical cystectomy in patients with muscle-invasive bladder cancer. Neoadjuvant chemotherapy (NAC) was proven to cause pathological downstaging. For this reason, we evaluated whether receipt of NAC decreases local bladder recurrences in TMT patients. METHODS: We retrospectively analyzed our TMT database for all patients treated between 2003 and 2017. Patients were treated with maximal transurethral resection of bladder tumor (TURBT) followed by chemotherapy/radiotherapy with or without NAC. Baseline demographic and tumor characteristics were recorded. Rates of local and systemic recurrence were analyzed per receipt of NAC. Overall recurrence-free survival (RFS) and bladder (b)RFS were analyzed using the Kaplan-Meier method and Cox proportional hazards modelling. RESULTS: Median age and followup periods were 72 years and 3.6 years, respectively. Fifty-four patients had NAC and concurrent chemoradiation (NAC-TMT) vs. 70 patients who had concurrent chemoradiation only (TMT). Carcinoma in situ (CIS) was present in 31% of the patients in NAC-TMT group compared to 24% in TMT group (p=0.40). After treatment, 24 (44%) and 31 (44%) patients in NAC-TMT and TMT groups, respectively, had bladder tumor recurrence. Overall RFS at three years was 46% and 50% in NAC-TMT and TMT groups, respectively (p=0.70). BRFS at three years was 55% and 69% in NAC-TMT and TMT groups, respectively (p=0.27). Multivariable analyses found that the presence of concomitant CIS (hazard ratio [HR] 2.13; 95% confidence interval CI 1.06-4.27; p=0.0036) was the primary factor associated with local bladder recurrence. CONCLUSIONS: Receipt of NAC does not obviate the risk of bladder recurrence post-TMT. Patients with CIS should be monitored especially closely for local recurrence.