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.

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.

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.

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.

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.

Robotic versus other nephroureterectomy techniques: a systematic review and meta-analysis of over 87,000 cases.

PURPOSE: To perform a systematic review and meta-analysis of the literature inherent robotic nephroureterectomy (RNU) and to compare its outcomes with those of other nephroureterectomy (NU) techniques. METHODS: A systematic literature search was performed up to April 2019 using PubMed, Embase®, and Web of Science. The Preferred Reporting Items for Systematic Review and Meta-analysis Statement was followed for study selection. The following data were extracted for each study: baseline features, surgical outcomes, oncological outcomes, and survival outcomes. Stata® 15.0 was used for statistical analysis. RESULTS: Literature search identified 80 studies eligible for the meta-analysis and overall 87,291 patients were included in the analysis: open NU (ONU; n = 45,601), hand-assisted laparoscopic NU (HALNU; n = 442), laparoscopic NU (LNU n = 31,093), and RNU (n = 10,155). RNU was more likely to be performed in those patients with multifocal tumor location (proportion: 0.19; 95% CI 0.14, 0.24) and high-grade disease (proportion: 0.70; 95% CI 0.53, 0.68). The lowest EBL was recorded in the RNU group (weighted mean (WM) 163.31 mL; 95% CI 88.94, 237.68), whereas the highest was in the ONU group (414.99 mL; 95% CI 378.52, 451.46). Operative time was shorter for ONU (224.98 mL; 95% CI 212.26, 237.69). RNU had lower rate of intraoperative complications (0.02; 95% CI 0.01, 0.05). ONU showed higher odds of transfusions (0.20; 95% CI 0.15, 0.25). LOS was statistically significantly shorter for the RNU group (5.35 days; 95% CI 4.97, 5.82). HALNU seemed to present lower risk of PSM (0.02; 95% CI - 0.01, 0.05), and lower risk of recurrence (0.22; 95% CI 0.15, 0.30), metastasis (0.07; 95% CI 0.05, 0.10), and cancer-related death (0.03; 95% CI 0.01, 0.06). ONU showed the lowest 5 years cancer specific survival (proportion: 0.77; 95% CI 0.74, 0.80). No correlation was found between the surgical technique and recurrence-free and cancer-specific survival. CONCLUSIONS: Evidence regarding RNU for the treatment of UTUC is increasing but it remains quite sparse and of low quality. Despite this, RNU seems to be safe, and to offer the advantages of a minimally invasive approach without impairing the oncological outcomes. Nevertheless, ONU, HALNU, and LNU still represent a valid, and commonly used surgical treatment option. As RNU becomes more popular, and concerns related to its use remain, the best surgical technique for NU remains to be determined.

Minimally Invasive Radical Prostatectomy after Previous Bladder Outlet Surgery: A Systematic Review and Pooled Analysis of Comparative Studies.

PURPOSE: Prostate cancer surgery after previous bladder outlet surgery of benign prostatic hyperplasia is an uncommon yet challenging scenario. We performed a systematic review and pooled analysis of comparative studies on laparoscopic and robotic minimally invasive radical prostatectomy after bladder outlet surgery. MATERIALS AND METHODS: We searched the literature on PubMed®, Embase® and Web of Science™ up to February 2019 according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement to identify eligible studies. Surgical, oncologic and functional outcomes in patients who underwent minimally invasive radical prostatectomy after bladder outlet surgery were compared to those without a history of bladder outlet surgery. Sensitivity analysis was done according to surgical technique (laparoscopic or robotic). RevMan 5.3 was used for statistical analysis. RESULTS: A total of 12 comparative studies were included in analysis. Patients who underwent minimally invasive radical prostatectomy after bladder outlet surgery were older (p ≤0.00001) and had a smaller prostate (p = 0.04) and lower prostate specific antigen (p = 0.003). The previous bladder outlet surgery group had lower odds of nerve sparing procedures, longer operative time, a higher rate of bladder neck reconstruction (each p <0.0001) and longer catheter time (p = 0.03). They were at higher risk for intraoperative (p = 0.001), overall (p <0.00001) and major complications (p = 0.0008), a higher positive surgical margin rate (p = 0.0005) and biochemical recurrence (p = 0.05). Moreover, potency (p = 0.03) and continence recovery (p = 0.007) at 12 months were lower in men with previous bladder outlet surgery. Robotic surgery seemed to offer better outcomes than laparoscopy. CONCLUSIONS: Minimally invasive radical prostatectomy after previous bladder outlet surgery represents a challenging surgical task with a higher risk of complications, and higher odds of worse functional and oncologic outcomes. Patients should be aware of these drawbacks and these factors should be considered during patient counseling. When surgery is pursued, robot-assisted radical prostatectomy should be preferred over laparoscopic radical prostatectomy since it can offer superior outcomes. The overall literature on this topic is of low quality and further efforts should be made to obtain higher levels of evidence.

Neoadjuvant Dose Dense MVAC versus Gemcitabine and Cisplatin in Patients with cT3-4aN0M0 Bladder Cancer Treated with Radical Cystectomy.

PURPOSE: Level I evidence supports the usefulness of neoadjuvant cisplatin based chemotherapy for muscle invasive bladder cancer. Since dose dense MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) has mostly replaced traditional MVAC, we compared pathological response and survival rates in patients with locally advanced bladder cancer who received neoadjuvant chemotherapy with dose dense MVAC vs gemcitabine and cisplatin. MATERIALS AND METHODS: We retrospectively reviewed the records of patients with urothelial cancer who received neoadjuvant chemotherapy and underwent cystectomy at a total of 20 contributing institutions from 2000 to 2015. Patients with cT3-4aN0M0 disease were selected for this analysis. The rates of ypT0N0 and ypT1N0 or less were compared between the gemcitabine and cisplatin, and dose dense MVAC regimens. Two multivariable Cox proportional hazards regression models of overall mortality were generated using preoperative and postoperative data. RESULTS: Of the patients who underwent neoadjuvant chemotherapy and radical cystectomy during the study period 319 met our inclusion criteria. A significantly lower rate of ypT0N0 was observed in the gemcitabine and cisplatin arm than in the dose dense MVAC arm (14.6% vs 28.0%, p = 0.005). The rate of ypT1N0 or less was 30.1% for gemcitabine and cisplatin compared to 41.0% for dose dense MVAC (p = 0.07). The mean Kaplan-Meier estimates of overall survival in the gemcitabine and cisplatin, and dose dense MVAC groups were 4.2 and 7.0 years, respectively (p = 0.001). On multivariable cox regression analysis based on preoperative data patients who received gemcitabine and cisplatin were at higher risk for death than patients who received dose dense MVAC (HR 2.07, 95% CI 1.25-3.42, p = 0.003). Lymph node invasion (HR 1.97, 95% CI 1.15-3.36, p = 0.01) and hydronephrosis (HR 2.18, 95% CI 1.43-3.30, p <0.001) were also associated with higher risk of death. CONCLUSIONS: In our retrospective cohort of patients with locally advanced bladder cancer dose dense MVAC was associated with higher complete pathological response and improved survival rates compared to gemcitabine and cisplatin. A clinical trial is warranted to validate these hypothesis generating results to test the superiority of neoadjuvant dose dense MVAC in patients with locally advanced bladder cancer.

The impact of the United States Preventive Services Task Force (USPTSTF) recommendations against prostate-specific antigen (PSA) testing on PSA testing in Australia.

OBJECTIVE: To assess the impact of the United States Preventive Services Task Force (USPTSTF) recommendations on prostate-specific antigen (PSA) testing, prostate biopsy, and prostatectomy in Australian men based on the available Medicare data. PATIENTS AND METHODS: Events were identified using Medicare item numbers for PSA testing (66655, 66659), prostate biopsy (37219), prostatectomy (37210), and prostatectomy with lymph node dissection (37211). The occurrences of each procedure was queried per 100 000 capita for consecutive financial years over the period 2000-2015. For each item number, reports were also generated for all Australian States. For PSA testing the data was stratified into three age groups of 45-54, 55-64, and 65-74 years. For assessing the rate of prostatectomy the capita rate values for two item numbers of prostatectomy (37210) and prostatectomy with lymph node dissection (37211) were combined. RESULTS: Steady declines in per capita incidences of all five item numbers assessed were seen for the three consecutive financial years (2013-2015) since the publication of the USPTSTF recommendation statement. These declines were seen across all Australian States. When examining the rate of PSA testing for the three age brackets 45-54, 55-64, and 65-74 years, similar trends were identified. CONCLUSIONS: Since the introduction of the USPTSTF recommendation statement there has been a steady nationwide decline in per capita incidences of PSA testing, prostate biopsy, and prostatectomy based on the Australian Medicare data. Whether these declines are in the right direction toward reduction in over-diagnosis and overtreatment of clinically insignificant prostate cancer or stage migration toward more locally advanced disease due to lost opportunity in diagnosing and treating early clinically significant prostate cancer will remain to be seen.

Assessing the effects of modality of surgery on postoperative weight loss in patients undergoing partial nephrectomy.

PURPOSE: To compare the early BMI changes postoperatively between patients undergoing open partial nephrectomy (OPN) and robotic partial nephrectomy (RPN). METHODS: Patients undergoing open NSS for a single renal tumor between 2010 and 2013 were retrospectively selected for the study. These patients were matched with RPN patients based on preoperative BMI and tumor R.E.N.A.L nephrometry score (1:1 matching). RESULTS: A total of 568 patients (284 pairs) met our inclusion criteria. The median time to lowest BMI was comparable between the OPN and RPN groups (24 vs. 29 days; p = 0.7). The mean BMI preservation was lower for the OPN group (96.8 ± 4.4 vs. 98.1 ± 4.7 %). On multivariable analysis after controlling for age, CCI, gender, tumor size, nephrometry score, estimated blood loss, occurrence of major complications and preoperative renal function, the modality of surgery favoring the RPN approach and the occurrence of major complications remained significant predictors for BMI preservation after surgery. CONCLUSIONS: Occurrence of major complications is associated with weight loss after NSS. Minimally invasive NSS delivered by RPN had lower impact on BMI loss in patients undergoing the procedure compared to OPN. This finding further suggests that RPN delivers minimally invasive surgery beyond the boundaries of just smaller incision sites.

Dose dense MVAC prior to radical cystectomy: a real-world experience.

PURPOSE: Our primary endpoint was to assess pathological response rate (pT0N0 and ≤pT1N0) for patients with BCa treated with the accelerated or dose dense MVAC (ddMVAC) chemotherapy followed by radical cystectomy (RC) in this real-word multi-institutional cohort. MATERIALS AND METHODS: We retrospectively reviewed records of patients with urothelial cancer who underwent ddMVAC and RC at seven contributing institutions from 2000 to 2015. Patients with cT2-4a, M0 BCa were included. Presence of cT3-4 disease, hydronephrosis, lymphovascular invasion and/or existence of sarcomatoid, or micropapillary features on the initial transurethral resection of bladder tumor specimen was defined as high-risk disease. Logistic regression models for prediction of pT0N0 and ≤pT1N0 were generated for the entire cohort as well as for the cN0 subgroup. The multivariable Cox proportional hazards regression model for survival using post RC data was used to assess hazard ratios (HRs) for the variables of interest. RESULTS: A total of 345 patients received ddMVAC chemotherapy during the study period; 85% had high-risk features. The median number of chemotherapy cycles was 4 (IQR 4-4); >90% of patients completed all scheduled cycles. The observed rates of pT0N0 and ≤pT1N0 were 30.4 and 49.3%, respectively, among cN0 patients. On the multivariable regression model, the presence of more than one clinical high-risk element was associated with 70% [OR 0.30 95% CI (0.10-0.86); p = 0.02] reduction in the odds of achieving partial pathological response. CONCLUSIONS: A complete response (pT0N0) was observed in one-third of patients after neoadjuvant ddMVAC therapy, and a partial response (≤pT1N0) was observed in nearly half of the cases in this real-world experience with this regimen. To our knowledge, this represents the largest experience outside clinical trial settings.

Robot-assisted ureteral reconstruction using a tubularized peritoneal flap: a novel technique in a chronic porcine model.

OBJECTIVE: To evaluate the feasibility and functional outcomes in porcine models of a novel robotic surgical technique for the treatment of complex ureteral injuries and strictures. MATERIALS AND METHODS: Six pigs underwent robotic ureteral reconstruction using a long tabularized peritoneal flap and followed for 6-9 weeks after the surgery. Ureteral flap vascularity, intra-renal pressure, patency of the conduct, endoscopic aspect of the flap, renal function and histopathology were evaluated. RESULTS: All animals successfully underwent ureteral reconstruction using a tubularized peritoneal flap. Median operative time was 223 min (162-360). Flap tubularization suture took 31 min (19-47), and proximal anastomosis took 20 min (15-38). Bladder mobilization with psoas hitch and distal anastomosis took 9 min (7-12) and 23 min (13-46), respectively. On follow-up, significant shrinkage of the ureteral flap in both length and width was observed. Antegrade pyelograms confirmed dilation and tortuosity of the proximal ureter, dilation of the renal pelvis, and major and minor calyxes without any definitive strictures. Microscopically, focal urothelial lining was seen in the neoureter. Creatinine level was significantly higher at the end of the follow-up period (p = 0.003). CONCLUSIONS: Robot-assisted ureteral reconstruction using a tubularized peritoneum flap is technically feasible and reproducible. The flap sustained abundant vascular supply after different intervals of follow-up and the peritoneal mesenchymal cells differentiated into urothelium and myofibroblasts. Further studies are needed to address the issue of functional obstruction to improve long-term renal function outcomes.

Perioperative epidural analgesia is not associated with increased survival from renal cell cancer, but overall survival may be improved: a retrospective chart review.

PURPOSE: We investigated the possible association between perioperative epidural and both cancer-specific survival (CSS) and overall survival (OS) in patients undergoing partial or radical nephrectomy for localized renal cell carcinoma (RCC). METHODS: A retrospective chart review was performed on patients who underwent complete surgical resection of localized RCC from 1994-2008 at our institution. Baseline demographics and pathological and survival data were collected. Patients with clinically or pathologically positive lymph nodes or metastatic disease at the time of surgery were excluded. Patients with pathologically positive surgical margins were also excluded. Patients were divided into two groups, systemic analgesia and epidural analgesia. Multivariable Cox regression analysis was used to determine CSS and OS, and survival curves were generated using the Kaplan-Meier method. RESULTS: Four hundred thirty-eight patients were included in the analysis. Baseline characteristics of both groups were similar. Median follow-up was 77 months. On multivariable analysis, patient age (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.02 to 1.07), epidural status (HR, 0.5; 95% CI, 0.4 to 0.8), year of surgery (HR, 0.9; 95% CI, 0.89 to 0.95), and pathologic T-stage (pT-stage) ≥ 2 (pT-stage2: HR, 2.2; 95% CI, 1.2 to 4.1 and pT-stage3: HR, 3.1; 95% CI, 2.0 to 4.7) were independent predictors of OS. Nevertheless, epidural status did not significantly predict CSS (P = 0.73), while T-stage and year of surgery maintained their respective predictive significance. Tumour grade did not significantly affect OS or CSS. CONCLUSIONS: Our retrospective analysis suggests that epidural at the time of surgical excision of localized RCC does not significantly impact CSS. Nevertheless, use of epidural was associated with significantly improved OS. Future prospective clinical and laboratory studies are warranted in order to characterize these associations further and determine the underlying mechanisms.

Final Pathological Stage after Neoadjuvant Chemotherapy and Radical Cystectomy for Bladder Cancer-Does pT0 Predict Better Survival than pTa/Tis/T1?

PURPOSE: We assessed survival dependent on pathological response after neoadjuvant chemotherapy in a large multicenter patient cohort, with a particular focus on the difference between the absence of residual cancer (pT0) and the presence of only nonmuscle invasive residual cancer (pTa, pTis, pT1). MATERIALS AND METHODS: We retrospectively reviewed records of patients with urothelial cancer who received neoadjuvant chemotherapy and underwent radical cystectomy at 19 contributing institutions from 2000 to 2013. Patients with cT2-4aN0M0 and eventual pN0 disease were selected for this analysis. Estimated overall survival was compared between patients with pT0 and pTa/Tis/T1 disease. A multivariable Cox proportional hazards regression model for overall survival was generated to evaluate hazard ratios for variables of interest. RESULTS: Of 1,543 patients treated with neoadjuvant chemotherapy and radical cystectomy during the study period 257 had pT0N0 and 207 had pTa/Tis/T1N0 disease. The Kaplan-Meier mean estimates of overall survival for pT0 and pTa/Tis/T1 cases were 186.7 months (95% CI 145.9-227.6, median 241.1) and 138 months (95% CI 118.2-157.8, median 187.4), respectively (p=0.58). In the Cox proportional hazards regression model for overall survival pTa/Tis/T1N0 status (HR 0.36, 95% CI 0.23-0.67) and pT0N0 status (HR 0.28, 95% CI 0.17-0.47) compared to pT2N0 pathology, positive surgical margin (HR 1.75, 95% CI 1.07-2.86), and receiving a methotrexate, vinblastine, doxorubicin and cisplatin regimen compared to an "other" regimen (HR 0.45, 95% CI 0.27-0.76) were predictors of overall survival. CONCLUSIONS: pTa/Tis/T1N0 and pT0N0 stage on the final cystectomy specimen are strong predictors of survival in patients treated with neoadjuvant chemotherapy and radical cystectomy. We did not discern a statistically significant difference in overall survival when comparing these 2 end points.

Risks and Benefits of Pharmacological Prophylaxis for Venous Thromboembolism Prevention in Patients Undergoing Robotic Partial Nephrectomy.

PURPOSE: We investigate the safety and efficacy of pharmacological venous thromboembolism prophylaxis in patients treated with robotic partial nephrectomy at our center. MATERIALS AND METHODS: We retrospectively examined our robotic partial nephrectomy database for cases performed between 2006 and 2014. Clinical venous thromboembolism episodes within 6 months from surgery were documented. Patients were stratified according to the administration of pharmacological venous thromboembolism prophylaxis into pharmacological prophylaxis (222) and no pharmacological prophylaxis (762) groups. The groups were compared in terms of perioperative outcomes, complications and adverse hemorrhagic events defined as the administration of 2 or more units of red blood cells, the need for vascular embolization or any procedures related to blood loss. RESULTS: There were no differences between the pharmacological prophylaxis and no pharmacological prophylaxis groups regarding mean operation time, median warm ischemia time and estimated blood loss. The rates of venous thromboembolism events were comparable between the groups (pharmacological prophylaxis 1.8% vs no pharmacological prophylaxis 2.1%, p=0.75). Overall 90% of venous thromboembolism events occurred within the first postoperative month. In the multivariable regression analysis encompassing pharmacological prophylaxis, perioperative aspirin intake, body mass index, operation time, Charlson comorbidity index, fellowship training and tumor complexity, operation time (OR 1.06, p=0.009) and Charlson comorbidity index (OR 1.28, p <0.0001) were associated with adverse hemorrhagic events. CONCLUSIONS: The administration of pharmacological prophylaxis did not increase the rate of adverse hemorrhagic events. Isolated inpatient administration of pharmacological prophylaxis after robotic partial nephrectomy does not appear to protect against venous thromboembolism postoperatively in that the majority of venous thromboembolism events occurred within the first 30 days after surgery. Longer duration of pharmacological prophylaxis for the prevention of venous thromboembolism after robotic partial nephrectomy should be considered.

A Multi-Institutional Analysis of Outcomes of Patients with Clinically Node Positive Urothelial Bladder Cancer Treated with Induction Chemotherapy and Radical Cystectomy.

PURPOSE: Selected patients with bladder cancer with pelvic lymphadenopathy (cN1-3) are treated with induction chemotherapy followed by radical cystectomy. However, the data on clinical outcomes in these patients are limited. In this study we assess pathological and survival outcomes in patients with cN1-3 disease treated with induction chemotherapy and radical cystectomy. MATERIALS AND METHODS: Data were collected on patients from 19 North American and European centers with cT1-4aN1-N3 urothelial carcinoma who received chemotherapy followed by radical cystectomy between 2000 and 2013. The primary end points were pathological complete (pT0N0) and partial (pT1N0 or less) response rates, with overall survival as a secondary end point. Logistic regression and Cox proportional hazard ratios were used for multivariate analysis of factors predicting these outcomes. RESULTS: The total of 304 patients had clinical evidence of lymph node involvement (cN1-N3). Methotrexate/vinblastine/doxorubicin/cisplatin was used in 128 (42%), gemcitabine/cisplatin in 132 (43%) and other regimens in 44 (15%) patients. The pN0 rate was 48% (cN1-56%, cN2-39%, cN3-39%, p=0.03). The complete and partial pathological response rates for the entire cohort were 14.5% and 27%, respectively. The estimated median overall survival time for the cohort was 22 months (IQR 8.0, 54). On Cox regression analysis overall survival was associated with pN0, negative surgical margins, removal of 15 or more pelvic nodes and cisplatin therapy. CONCLUSIONS: Complete pathological nodal response can be achieved in a proportion of patients with cN1-3 disease receiving induction chemotherapy. The best survival outcomes are observed in male patients on cisplatin regimens with subsequent negative radical cystectomy margins and complete nodal response (pN0) with excision of 15 or more pelvic nodes.

Robot-assisted partial nephrectomy with intracorporeal renal hypothermia using ice slush: step-by-step technique and matched comparison with warm ischaemia.

OBJECTIVES: To outline our step-by-step technique for intracorporeal renal cooling during robot-assisted partial nephrectomy (RAPN). PATIENTS AND METHODS: Patient selection was performed during a preoperative clinic visit. Cases where we estimated during preoperative assessment that warm ischaemia time would be >30 min, as determined by whether the patient had a complex renal mass, were selected. The special equipment required for this procedure includes an Ecolab Hush Slush machine (Microtek Medical Inc., Columbus, MS, USA) a Mon-a-therm needle thermocouple device (Covidien, Mansfield, MA, USA) and six modified 20-mL syringes. Patients are arranged in a 60° modified flank position with the operating table flexed slightly at the level of the anterior superior iliac spine. For the introduction of a temperature probe and ice slush, an additional 12-mm trocar is placed along the mid-axillary line beneath the costal margin. Modified 10/20 mL syringes are prefilled with ice slush for instillation via an accessory trocar. Peri-operative and 6-month functional outcomes in the cold ischaemia group were compared with those of a cohort of patients who underwent RAPN with warm ischaemia in a 2:1 matched fashion. Matching was performed based on preoperative estimated glomerular filtration rate (GFR), ischaemia time and RENAL nephrometry score. RESULTS: Strategies for successful intracorporeal renal cooling include: (i) placement of accessory port directly over the kidney; (ii) uniform ice consistency and modified syringes; (iii) sequential clamping of renal artery and vein; (iv) protection of the neighbouring intestine with a laparoscopic sponge; and (v) complete mobilization of the kidney. Kidney temperature is monitored via a needle thermocoupler device, while core body temperature is concurrently monitored via an oesophageal probe in real time. Renal function was assessed by serum creatinine level, estimated GFR (eGFR) and mercaptoacetyltriglycine (MAG-3) renal scan, peri-operatively and at 6-month follow-up. In the separate matched analysis, cold ischaemia during RAPN was found to be associated with a 12.9% improvement in preservation of postoperative eGFR. No difference was seen in either group at 6-month follow-up. CONCLUSIONS: We conclude that RAPN with intracorporeal renal hypothermia using ice slush is technically feasible and may improve postoperative renal function in the short term. Our technique for intracorporeal hypotheramia is cost-effective, simple and highly reproducible.

Multicentre outcomes of robot-assisted partial nephrectomy after major open abdominal surgery.

OBJECTIVE: To evaluate the outcomes of robot-assisted partial nephrectomy RAPN after major prior abdominal surgery (PAS) using a large multicentre database. PATIENTS AND METHODS: We identified 1 686 RAPN from five academic centres between 2006 and 2014. In all, 216 patients had previously undergone major PAS, defined as having an open upper midline/ipsilateral incision. Perioperative outcomes were compared with those 1 470 patients who had had no major PAS. The chi-squared test and Mann-Whitney U-test were used for categorical and continuous variables, respectively. RESULTS: There was no statistically significant difference in Charlson comorbidity index, tumour size, R.E.N.A.L. nephrometry score or preoperative estimated glomerular filtration rate (eGFR) between the groups. Age and body mass index were higher in patients with PAS. The PAS group had a higher estimated blood loss (EBL) but this did not lead to a higher transfusion rate. A retroperitoneal approach was used more often in patients with major PAS (11.2 vs 5.4%), although this group did not have a higher percentage of posterior tumours (38.8 vs 43.3%, P = 0.286). Operative time, warm ischaemia time, length of stay, positive surgical margin, percentage change in eGFR, and perioperative complications were not significantly different between the groups. CONCLUSIONS: RAPN in patients with major PAS is safe and feasible, with increased EBL but no increased rate of transfusion. Patients with major PAS had almost twice the likelihood of having a retroperitoneal approach.

Urinary fistula after robot-assisted partial nephrectomy: a multicentre analysis of 1 791 patients.

OBJECTIVE: To evaluate the incidence of and risk factors for a urine leak in a large multicentre, prospective database of robot-assisted partial nephrectomy (RPN). PATIENTS AND METHODS: A database of 1 791 RPN from five USA centres was reviewed for urine leak as a complication of RPN. Patient and tumour characteristics were compared between patients with and those without postoperative urine leaks. Fisher's exact test was used for qualitative variables and Wilcoxon sum-rank tests were used for quantitative variables. A review of the literature on PN and urine leak was conducted. RESULTS: Urine leak was noted in 14/1 791 (0.78%) patients who underwent RPN. The mean (sd) nephrometry score of the entire cohort was 7.2 (1.9), and 8.0 (1.9) in patients who developed urine leak. The median (range) postoperative day of presentation was 13 (3-32) days. Patients with urine leak presented in delayed fashion with fever (two of the 14 patients, 14%), gastrointestinal complaints (four patients, 29%), and pain (five patients, 36%). Eight of the 14 patients (57%) required admission, while eight (57%) and nine (64%) had a drain or stent placed, respectively. Drains and stents were removed after a median (range) of 8 (4-13) days and 21 (8-83) days, respectively. Variables associated with urine leak included tumour size (P = 0.021), hilar location (P = 0.025), operative time (P = 0.006), warm ischaemia time (P = 0.005), and pelvicalyceal repair (P = 0.018). Upon literature review, the historical incidence of urine leak ranged from 1.0% to 17.4% for open PN and 1.6-16.5% for laparoscopic PN. CONCLUSION: The incidence of urine leak after RPN is very low and may be predicted by some preoperative factors, affording better patient counselling of risks. The low urinary leak rate may be attributed to the enhanced visualisation and suturing technique that accompanies the robotic approach.

Achievement of trifecta in minimally invasive partial nephrectomy correlates with functional preservation of operated kidney: a multi-institutional assessment using MAG3 renal scan.

PURPOSE: To validate and compare the values of "MIC" and "trifecta" as predictors of operated kidney functional preservation in a multi-institutional cohort of patients undergoing minimally invasive PN. METHODS: We retrospectively reviewed records of consecutive cases of minimally invasive PN performed for cT1 renal masses in 4 centers from 2009 to 2013. Inclusion criteria consisted of availability of a renal scan obtained within 2 weeks prior to surgery and follow-up renal scan 3-6 months after the surgery. The primary endpoint of the study was to compare the degree of ipsilateral renal function preservation assessed by MAG3 renal scan in relation to achievement of MIC and trifecta. RESULTS: Total of 351 patients met our inclusion criteria. The rates of trifecta achievement for cT1a and cT1b tumors were 78.9 and 60.6 %, respectively. The rate of MIC achievement for cT1a tumors and cT1b tumors was 60.3 and 31.7 %, respectively. On multivariable linear regression model, only the degree of tumor complexity assessed by R.E.N.A.L nephrometry score [coefficient B -1.8 (-2.7, -0.9); p < 0.0001] and the achievement of trifecta [coefficient B 6.1 (2.4,9.8); p = 0.014] or MIC (coefficient B 7.2 (3.8,0.6); p < 0.0001) were significant clinical factors predicting ipsilateral split function preservation. CONCLUSIONS: Achievement of both MIC and "trifecta" is associated with higher proportion of split renal function preservation for cT1 tumors after minimally invasive PN. Thus, these outcome measures can be regarded not only as markers of surgical quality, but also as reliable surrogates for predicting functional outcome in the operated kidney.