Impact of Preoperative Plasma Potassium Levels on Oncological Outcomes, Major Complications, and 30-Day Mortality in Bladder Cancer Patients Undergoing Radical Cystectomy.

INTRODUCTION AND OBJECTIVES: We examined the impact of preoperative plasma potassium levels (PPLs) on outcomes in patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB), hypothesizing that potassium imbalances might influence outcomes. PATIENTS AND METHODS: In this retrospective study, 501 UCB patients undergoing RC from 2009 to 2017 at a tertiary center were analyzed. Blood samples collected a week prior to surgery defined normal and abnormal PPL based on institutional standards. We assessed overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), postoperative complications, 30-day mortality, and non-organ confined disease. Kaplan-Meier estimates, Cox proportional hazards, logistic regression, and decision curve analyses (DCA) were employed. RESULTS: 63 (13%) patients had abnormal preoperative PPLs, with 50 (10%) elevated and 13 (2.5%) decreased. In a 59 months median follow-up, 152 (31%) had disease recurrence, 197 (39%) died from any cause, and 119 (24%) from UCB. Multivariable cox regression analyses adjusting for perioperative parameters demonstrated abnormal PPL was associated with worse OS (HR=1.9, P=0.009), CSS (HR=2.8, P<0.001) and RFS (HR=2.1; P=0.007). Elevated preoperative PPLs also demonstrated significant associations with adverse outcomes in OS, CSS, and RFS (all P<0.05). In multivariable logistic regression analyses, abnormal and elevated PPLs were not associated with 30-day mortality, major 30-day postoperative complications, positive nodal disease, pT3/4 stage, and non-organ confined disease (all P>0.05). CONCLUSION: Abnormal and elevated preoperative PPLs correlate with adverse oncologic outcomes in UCB patients treated with RC. Pending external validation, preoperative PPLs might be a cost-effective, easily obtainable supplemental biomarker for enriching accuracy of outcome prediction in this highly variable maladie.

Which Men Do or Do Not Achieve Long-Term Symptom Relief After Holmium Laser Enucleation of the Prostate (HoLEP): 11 Years of HoLEP Experience.

Purpose: Apart from the existing level-one evidence, few centers have reported on long-term outcomes after Holmium Laser Enucleation of the Prostate (HoLEP). Against this backdrop we aimed to report on our treatment experience and identify predictors of persistent/recurrent lower urinary tract symptoms (LUTS) after the procedure. Materials and Methods: From 2006 to 2017, 2566 men underwent HoLEP at our institution. Only patients with available, cross-sectional follow-up (F/u) ≥6 months were included. Perioperative and F/u characteristics were compared by duration of F/u in months (quartiles). Multivariable logistic regression models (MVAs) were used to identify predictors of persistent/recurring symptoms, defined as International Prostate Symptom Score (IPSS) >7 at F/u. Results: A total of 774 patients with a median age of 70 years (interquartile range [IQR] = 66-75), prostate volume of 80 mL (IQR = 60-105), American Society of Anesthesiologists score 2 (IQR = 2-3), IPSS of 19 (IQR = 14-24), and quality of life (QoL) of 4 (3-5) at the time of operation were analyzed. Median F/u was 52 months (IQR = 32-77), overall current median prostate-specific antigen was 0.91 mg/dL (0.5-1.8), median IPSS and QoL were 3 (IQR = 1-7) and 1 (IQR 0-2), respectively. LUTS medication was present in 20 patients (2.6%), 15 (2%) patients required reoperation, and permanent urinary incontinence was present in 17 (2.2%) patients. On MVA age at operation (odds ratio [OR] = 1.04; 95% confidence interval [CI], 1.01-1.1; p = 0.013), prostate volume (OR = 0.99 [95% CI, 0.98-0.99;], p = 0.003), body mass index (OR = 1.06 [95% CI, 1.0-1.1], p = 0.043), presence of indwelling catheter (OR = 0.51 [95% CI, 0.32-0.81], p = 0.004), and anticholinergics before procedure (OR = 1.74 [95% CI, 1.01-3.0], p = 0.046) were predictors of persistent/recurring symptoms. Conclusions: Our HoLEP experience confirms durable and profound symptom relief in the vast majority men. A small fraction of patients complained about subjective persistent/recurring LUTS stressing the need for proper patient selection and timing of surgical intervention.

Assessing the Outcome of Holmium Laser Enucleation of the Prostate by Age, Prostate Volume, and a History of Blood Thinning Agents: Report from a Single-Center Series of >1800 Consecutive Cases.

Purpose: To assess perioperative outcomes of holmium laser enucleation of the prostate (HoLEP) in a real-world scenario and with a focus on demanding patient factors, such as large prostate size, advanced patient age, and anticoagulation therapy (AT). Materials and Methods: We retrospectively analyzed HoLEP procedures at our institution between 2010 and 2016. After stratification by prostate volume, age, and AT, perioperative and early voiding characteristics were compared. A multivariable regression model was employed to identify predictors of prolonged time of catheterization (defined as being above group's median). Results: The study cohort consisted of 1816 men with a median age of 71 years (interquartile range [IQR]: 66-76), a median prostate volume of 80 mL (IQR: 58-105), and American Society of Anesthesiologists score ≥3 in 618 men (34%). Median time of enucleation and morcellation was 43 minutes (IQR: 31-60) and 10 minutes (IQR: 6-18), respectively. Perioperative blood transfusions were administered in 44 (2.4%) cases, severe postoperative complications (Clavien-Dindo grade ≥3b) occurred in 61 (3.3%) cases. The median time of catheterization was 2 days (IQR: 2-2), with prolonged catheterization occurring in 277 (15%) cases. After adjustment, large prostates (fourth volume quartile [106-280 mL]) (odds ratio [OR]: 1.8, 95% confidence interval [CI]: 1.3-2.6, p = 0.001), therapeutic low-molecular-weight heparin bridging regimen (OR: 2.2, 95% CI: 1.4-3.6, p = 0.037), low-dose acetylsalicylic acid (OR: 1.5, 95% CI: 1.0-2.2, p = 0.015), and a history of direct oral anticoagulation (OR: 2.3, 95% CI: 1.2-4.0, p = 0.022), but not patient age, were independently associated with prolonged catheterization. Conclusions: We confirm HoLEP as safe and efficient; however, patients with large prostates and patients with a history of AT are at risk of prolonged catheterization.

The impact of cytoreductive nephrectomy on survival outcomes in patients treated with tyrosine kinase inhibitors for metastatic renal cell carcinoma in a real-world cohort.

BACKGROUND: Tyrosine kinase inhibitor therapy (TKI) has changed the treatment paradigm of metastatic renal cell carcinoma (mRCC). The recent CARMENA and SURTIME trials challenged the role of the cytoreductive nephrectomy (CN). OBJECTIVE: To assess the impact of CN prior to TKI therapy in patients with mRCC in a real-world setting. METHODS: Overall, 262 consecutive patients with mRCC were treated with CN plus TKI or TKI only at our institution between 2000 and 2016. Patients with prior immunotherapy or metastasectomy were excluded. Multiple imputation and inverse probability of treatment weighting (IPTW) were performed to account for missing values and imbalances between the treatment groups, respectively. Unadjusted and adjusted Kaplan-Meier estimates were used to determine differences in progression-free (PFS), overall (OS), and cancer-specific survival (CSS). RESULTS: Overall, 104 (40%) patients received CN before TKI treatment. Most frequent first line therapy was Sunitinib (66%), followed by Sorafenib (20%) and Pazopanib (10%). After adjustment with IPTW, there was no difference in PFS, CSS, and OS (all P > 0.05) between the treatment groups. In subgroup analyses, CSS was improved when CN was performed in patients with sarcomatoid features and clear cell histology (P = 0.04 and P = 0.03) and PFS was improved in patients with clear cell histology when CN was performed [0.04]). CN did not improve OS in any subgroup analysis. CONCLUSION: The role of CN remains controversial. We found no difference in survival outcomes between patients treated with and without CN before TKI therapy. However, CN was associated with improved survival in specific patient subgroups. Tailored, individualized treatment is key to further improve oncological outcomes for mRCC.

Prospective analysis of artificial urinary sphincter AMS 800 implantation after buccal mucosa graft urethroplasty.

OBJECTIVES: To analyze functional outcomes and complication rates of artificial urinary sphincter (AUS) implantation in patients who had undergone buccal mucosa graft urethroplasty (BMGU) beforehand. PATIENTS AND METHODS: This prospectively maintained single-center database comprises data from 236 patients from 2009 to 2015 who underwent AUS implantation. A total of 17 patients after BMGU were available for analysis. Primary endpoints consisted of continence and complication rates. Continence was defined as no use of safety pads, social continence as < 2 pads per day. Stricture recurrence was defined as a decrease in uroflowmetry, a maximum flow rate < 10 ml/s or residual urine volume (> 100 ml). Kaplan-Meier analysis determined explantation-free survival. RESULTS: Median follow-up was 24 months (interquartile range [IQR] 6-31 months). Indication for AUS implantation was severe urinary incontinence with a history of radical prostatectomy (RRP) in 8 (47.1%), trauma in 1 (5.9%) and TUR-P in 8 (47.1%) patients. Pelvic irradiation was reported in 13 (76.5%) cases. The median length of buccal mucosa graft for urethroplasty was 4 cm (3-5 cm). A double cuff was implanted in 14 patients (82.4%), 3 patients received a single cuff. Complete and social continence was achieved in 76.5% and 100% of the patients, respectively. There was no significant difference in complications and explantation-free survival (log-rank, p = 0.191) between patients who had undergone BMGU before AUS compared to patients with no history of BMGU. CONCLUSIONS: According to the prospective follow-up data in a homogenous cohort, AUS implantation seems to be a viable, safe and effective therapeutic strategy for incontinence treatment despite previous BMGU.

Adherence to pelvic lymph node dissection recommendations according to the National Comprehensive Cancer Network pelvic lymph node dissection guideline and the D'Amico lymph node invasion risk stratification.

PURPOSE: To assess adherence rates to pelvic lymph node dissection (PLND) according to National Comprehensive Cancer Network (NCCN) PLND guideline (2% or higher risk) and D'Amico lymph node invasion (LNI) risk stratification (intermediate/high risk) in contemporary North American patients with prostate cancer treated with radical prostatectomy (RP). MATERIAL AND METHODS: We relied on 49,358 patients treated with RP and PLND (2010-2013) in SEER database. Adherence rates were quantified and multivariable (MVA) logistic regression analyses tested for independent predictors. RESULTS: According to NCCN PLND guideline and D'Amico LNI classification, PLND was recommended in 63.3% and 64.9% of patients, respectively. Corresponding adherence rates were 68.8% and 69.1%. Adherence rates improved from 67.3% to 71.6% and from 67.6% to 72.0%, respectively, over time. In MVA, more advanced clinical stage, higher biopsy Gleason score and higher number of positive biopsy cores predicted PLNDs that were performed below NCCN LNI nomogram risk threshold. Conversely, lower clinical stage, lower PSA and lower biopsy Gleason score predicted PLND omission in individuals with risk level above NCCN LNI nomogram risk threshold. MVA results for D'Amico classification were virtually identical. CONCLUSIONS: Adherence to NCCN PLND guideline and D'Amico LNI classification for purpose of PLND is suboptimal in SEER population-based patients treated with RP. However, adherence rates have improved over time. Patients, who did not undergo PLND despite elevated LNI risk, had more favorable PCa characteristics than the average. Conversely, patients, who underwent PLND despite low-risk, had worse PCa characteristics than the average.

Peri-operative allogeneic blood transfusion does not adversely affect oncological outcomes after radical cystectomy for urinary bladder cancer: a propensity score-weighted European multicentre study.

OBJECTIVES: To evaluate the effect of peri-operative blood transfusion (PBT) on recurrence-free survival, overall survival, cancer-specific mortality and other-cause mortality in patients undergoing radical cystectomy (RC), using a contemporary European multicentre cohort. PATIENTS AND METHODS: The Prospective Multicentre Radical Cystectomy Series (PROMETRICS) includes data on 679 patients who underwent RC at 18 European tertiary care centres in 2011. The association between PBT and oncological survival outcomes was assessed using Kaplan-Meier, Cox regression and competing-risks analyses. Imbalances in clinicopathological features between patients receiving PBT vs those not receiving PBT were mitigated using conventional multivariable adjusting as well as inverse probability of treatment weighting (IPTW). RESULTS: Overall, 611 patients had complete information on PBT, and 315 (51.6%) received PBT. The two groups (PBT vs no PBT) differed significantly with respect to most clinicopathological features, including peri-operative blood loss: median (interquartile range [IQR]) 1000 (600-1500) mL vs 500 (400-800) mL (P < 0.001). Independent predictors of receipt of PBT in multivariable logistic regression analysis were female gender (odds ratio [OR] 5.05, 95% confidence interval [CI] 2.62-9.71; P < 0.001), body mass index (OR 0.91, 95% CI 0.87-0.95; P < 0.001), type of urinary diversion (OR 0.38, 95% CI 0.18-0.82; P = 0.013), blood loss (OR 1.32, 95% CI 1.23-1.40; P < 0.001), neoadjuvant chemotherapy (OR 2.62, 95% CI 1.37-5.00; P = 0.004), and ≥pT3 tumours (OR 1.59, 95% CI 1.02-2.48; P = 0.041). In 531 patients with complete data on survival outcomes, unweighted and unadjusted survival analyses showed worse overall survival, cancer-specific mortality and other-cause mortality rates for patients receiving PBT(P < 0.001, P = 0.017 and P = 0.001, respectively). After IPTW adjustment, those differences no longer held true. PBT was not associated with recurrence-free survival (hazard ratio [HR] 0.92, 95% CI 0.53-1.58; P = 0.8), overall survival (HR 1.06, 95% CI 0.55-2.05; P = 0.9), cancer-specific mortality (sub-HR 1.09, 95% CI 0.62-1.92; P = 0.8) and other-cause mortality (sub-HR 1.00, 95% CI 0.26-3.85; P > 0.9) in IPTW-adjusted Cox regression and competing-risks analyses. The same held true in conventional multivariable Cox and competing-risks analyses, where PBT could not be confirmed as a predictor of any given endpoint (all P values >0.05). CONCLUSION: The present results did not show an adverse effect of PBT on oncological outcomes after adjusting for baseline differences in patient characteristics.

The T-plasty as therapy for recurrent bladder neck stenosis: success rate, functional outcome, and patient satisfaction.

PURPOSE: To determine success rate (SR), functional outcome, and patient satisfaction of a modified YV-plasty for reconstruction of the bladder neck in case of recurrent bladder neck stenosis (BNS) after transurethral surgery of the prostate: the T-plasty. PATIENTS AND METHODS: We identified all patients who underwent T-plasty at our center between December 2008 and July 2016. Patients' charts were reviewed. Patients were queried by telephone and by mail at time of follow-up (FU). Primary endpoint was SR. Secondary endpoints were complications, continence, satisfaction, and changes in quality of life measured by validated questionnaires. RESULTS: Thirty patients underwent the T-plasty. Median age at surgery was 69 (IQR 62-73) years. Most patients had BNS due to TUR-P [n = 25 (83.3%)]. No severe blood loss or severe complications occurred perioperatively. Median FU was 45 (IQR 18-64) months. Three patients were lost to FU. Success rate was 100%. Compared to pre-OP Q max, mean Q max post-OP improved significantly [pre-OP 6.79 (SD ± 4.76) ml/s vs post-OP was 24.42 (SD ± 12.61) ml/s; (t(5) = 4.12, p = 0.009)]. Mean post-void residual urine decreased significantly [pre-OP 140.77 (SD ± 105.41) ml vs post-OP 14.5 (SD ± 22.42) ml; (t(9) = -3.86, p = 0.004)]. One patient developed a de-novo-incontinence post-OP. Mean ICIQ-SF Score was 1.2 (SD ± 2.27). 88.5% of patients were pleased or delighted by surgery. 75% of patients claimed their quality of life has been (strongly) improved. CONCLUSIONS: The T-plasty is a valuable option as treatment of recurrent BNS. SR, rates of continence, and high patient satisfaction are very encouraging.

North American Population-Based Validation of the National Comprehensive Cancer Network Practice Guideline Recommendation of Pelvic Lymphadenectomy in Contemporary Prostate Cancer.

BACKGROUND: National Comprehensive Cancer Network (NCCN) guidelines recommend a pelvic lymph node dissection (PLND) in prostate cancer (PCa) patients treated with radical prostatectomy (RP) if a nomogram predicted risk of lymph node invasion (LNI) is ≥2%. We examined this and other thresholds, including nomogram validation. METHODS: We examined records of 26,713 patients treated with RP and PLND between 2010 and 2013, within the Surveillance, Epidemiology, and End Results database. Nomogram thresholds of 2-5% were tested and external validation was performed. RESULTS: LNI was recorded in 4.7% of patients. Nomogram accuracy was 80.4% and maintained minimum accuracy of 75.6% in subgroup analyses, according to age, race, and nodal yield >10. With the NCCN recommended 2% nomogram threshold, PLND could be avoided in 22.3% of patients at the expense of missing 3.0% of individuals with LNI. Alternative thresholds of 3%, 4%, and 5% yielded respective PLND avoidance rates of 60.4%, 71.0%, and 79.8% at the expense of missing 17.8%, 27.2%, and 36.6% of patients with LNI. NCCN cut-off recommendation was best satisfied with a threshold of <2.6%, at which PLND could be avoided in 13,234 patients (49.5%) versus missing 141 patients with LNI (11.2%). CONCLUSION: NCCN LNI nomogram remains accurate in contemporary patients. However, the 2% threshold appears to be too strict, since only 22.3% of PLNDs can be avoided, instead of the stipulated 47.7%. The optimal 2.6% threshold allows a higher rate of PLND avoidance (49.5%), at the cost of 11.2% missed instances of LNI, as recommended by NCCN guidelines. PATIENT SUMMARY. External validation in contemporary SEER prostate cancer patients showed that the NCCN nomogram remains accurate for predicting lymph node invasion and seems to be optimal at an alternative 2.6% threshold, with best ratio of avoided pelvic lymph node dissections (49.5%) and missed LNIs (11.2%), as recommended by NCCN guideline. Prostate 77:542-548, 2017. © 2017 Wiley Periodicals, Inc.

Risk stratification for locoregional recurrence after radical cystectomy for urothelial carcinoma of the bladder.

PURPOSE: To externally validate the Christodouleas risk model incorporating pathological tumor stage, lymph node (LN) count and soft tissue surgical margin (STSM) and stratifying patients who develop locoregional recurrence (LR) after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). In addition, we aimed to generate a new model including established clinicopathological features that were absent in the Christodouleas risk model. METHODS: Prospectively assessed multicenter data from 565 patients undergoing RC for UCB in 2011 qualified for final analysis. For the purpose of external validation, risk group stratification according to Christodouleas was performed. Competing-risk models were calculated to compare the cumulative incidences of LR after RC. RESULTS: After a median follow-up of 25 months (interquartile range 19-29), the LR-rate was 11.5 %. The Christodouleas model showed a predictive accuracy of 83.2 % in our cohort. In multivariable competing-risk analysis, tumor stage ≥pT3 (HR 4.32, p < 0.001), positive STSM (HR 2.93, p = 0.005), lymphovascular invasion (HR 3.41, p < 0.001), the number of removed LNs <10 (HR 2.62, p < 0.001) and the administration of adjuvant chemotherapy (HR 0.40, p = 0.008) independently predicted the LR-rate. The resulting risk groups revealed significant differences in LR-rates after 24 months with 4.8 % for low-risk patients, 14.7 % for intermediate-risk patients and 38.9 % for high-risk patients (p < 0.001 for all), with a predictive accuracy of 85.6 %, respectively. CONCLUSIONS: The Christodouleas risk model has been successfully externally validated in the present prospective series. However, this analysis finds that overall model performance may be improved by incorporating lymphovascular invasion. After external validation of the newly proposed risk model, it may be used to identify patients who benefit from an adjuvant therapy and suit for inclusion in clinical trials.

Impact of peri-operative blood transfusion on the outcomes of patients undergoing radical cystectomy for urothelial carcinoma of the bladder.

OBJECTIVE: To determine the association between peri-operative blood transfusion (PBT) and oncological outcomes in a large multi-institutional cohort of patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). PATIENTS AND METHODS: We conducted a retrospective analysis of 2895 patients treated with RC for UCB. Univariable and multivariable Cox regression models were used to analyse the effect of PBT administration on disease recurrence, cancer-specific mortality, and any-cause mortality. RESULTS: Patients' median (interquartile range [IQR]) age was 67 (60, 73) years and the median (IQR) follow-up was 36.1 (15, 84) months. Patients who received PBT were more likely to have advanced disease (P < 0.001), high grade tumours (P = 0.047) and nodal metastasis (P = 0.004). PBT was associated with a higher risk of disease recurrence (P = 0.003), cancer-specific mortality (P = 0.017), and any-cause mortality (P = 0.010) in univariable, but not multivariable, analyses (P > 0.05). In multivariable analyses, pathological tumour stage, pathological nodal stage, soft tissue surgical margin, lymphovascular invasion and administration of adjuvant chemotherapy were independent predictors of disease recurrence, cancer-specific mortality and any-cause mortality (all P values <0.002). CONCLUSIONS: Patients with UCB who underwent RC and received PBT had a greater risk of disease recurrence, cancer-specific mortality and any-cause mortality in univariable, but not multivariable, analysis. Although the greater need for PBT with more advanced disease is probably caused by a number of factors, including surgical and cancer-related factors, the present analysis showed that the disease characteristics rather than need for PBT led to worse outcomes.

Transurethral holmium laser enucleation versus transurethral resection of the prostate and simple open prostatectomy--which procedure is faster?

PURPOSE: The longer operative time of holmium laser enucleation of the prostate compared to transurethral resection of the prostate or simple open prostatectomy reported in the literature might have been biased by the unavailability of a soft tissue morcellator, limited surgical experience with holmium laser prostate enucleation or the fact that significantly more tissue was removed by enucleation than by resection. We objectively compared the resection speed of contemporary holmium laser enucleation vs transurethral resection of the prostate and of holmium laser enucleation vs simple open prostatectomy. MATERIALS AND METHODS: The study cohort consisted of 100 cases of transurethral prostate resection and 60 of simple open prostatectomy from our previous randomized, controlled trials. These cases were subjected to matched pair analysis with greater than 1,000 from our prospective contemporary database on holmium laser prostate enucleation. Exact matches were made for the same amount of resected tissue. In all contemporary holmium laser enucleation cases a mechanical soft tissue morcellator was used. We calculated and compared the specific resection speed in gm per minute and operative time for the same amount of resected tissue. RESULTS: In groups 1 and 2 we matched 99 exact laser enucleation-transurethral resection pairs and 53 exact laser enucleation-simple open prostatectomy pairs, respectively. Resection speed and operative time for laser enucleation were statistically significantly faster than for resection (0.61 vs 0.51 gm per minute and 62 vs 73 minutes, p <0.01) and similar to those of simple open prostatectomy (0.92 vs 1.0 gm per minute and 101 vs 90 minutes, respectively, p ≥0.21). CONCLUSIONS: Resection speed seems to be an objective criterion for comparing the efficacy of prostatic tissue removal. Based on resection speed holmium laser enucleation of the prostate is faster than transurethral resection of the prostate and similar to simple open prostatectomy.