Holmium laser enucleation of the prostate in men on active surveillance for prostate cancer with refractory lower urinary tract symptoms secondary to enlarged prostates.

INTRODUCTION: The surgical treatment of men with lower urinary tract symptoms (LUTS) and significantly enlarged symptomatic prostates on active surveillance (AS) for low-risk prostate cancer (PCa) is not well defined. We report our single-institution initial experience with holmium laser enucleation of the prostate (HoLEP) for LUTS in men with low-risk PCa being managed with AS. MATERIALS AND METHODS: Men on AS who underwent HoLEP between 2013 and 2019 were identified. Data regarding preoperative cancer workup, prostate-specific antigen (PSA), perioperative outcomes, and voiding parameters were analyzed. Postoperative surveillance for PCa including PSA nadir, prostate magnetic resonance imaging, prostate biopsy (PBx), and PSA at last follow-up were evaluated. RESULTS: Twenty men met the inclusion criteria. Preoperative mean max flow 7.9 ml/s, median postvoid residual 101 cc, and mean transrectal ultrasound prostate size 99 cc. Patients had a median adjusted preoperative PSA of 8.5 (interquartile range [IQR]: 4.8-13.2) ng/ml. Mean resected tissue weight was 65.5 g with improved postoperative flow rate and significantly decreased residual. A total of 5/20 men had PCa in the specimen (all Gleason Grade Group 1). The median postoperative PSA nadir was 1.2 (IQR: 0.5-1.8) ng/ml at median of 5 months. At the last follow-up (median 18.5 months, IQR: 10.5-37.8), the median postoperative PSA was 1.4 (IQR: 0.63-2.48) ng/ml. Nine men underwent postoperative multiparametric magnetic resonance imaging (mpMRI) with the identification of a new prostate imaging reporting and data system 5 lesion in one patient who underwent negative fusion biopsy. Five men underwent post-HoLEP PBx with progression in two patients, who both successfully underwent radical prostatectomy. CONCLUSIONS: Men on AS for low-risk PCa can safely undergo HoLEP with significantly improved voiding parameters. Postoperative monitoring with PSA, mpMRI, and PBx can detect disease progression requiring definitive treatment. Further research is needed to optimize surveillance strategies and long-term cancer-specific outcomes.

Outcomes after definitive radiation therapy for localized prostate cancer in a national health care delivery system.

PURPOSE: Accurate information regarding real-world outcomes after contemporary radiation therapy for localized prostate cancer is important for shared decision-making. Clinically relevant end points at 10 years among men treated within a national health care delivery system were examined. METHODS: National administrative, cancer registry, and electronic health record data were used for patients undergoing definitive radiation therapy with or without concurrent androgen deprivation therapy within the Veterans Health Administration from 2005 to 2015. National Death Index data were used through 2019 for overall and prostate cancer-specific survival and identified date of incident metastatic prostate cancer using a validated natural language processing algorithm. Metastasis-free, prostate cancer-specific, and overall survival using Kaplan-Meier methods were estimated. RESULTS: Among 41,735 men treated with definitive radiation therapy, the median age at diagnosis was 65 years and median follow-up was 8.7 years. Most had intermediate (42%) and high-risk (33%) disease, with 40% receiving androgen deprivation therapy as part of initial therapy. Unadjusted 10-year metastasis-free survival was 96%, 92%, and 80% for low-, intermediate-, and high-risk disease. Similarly, unadjusted 10-year prostate cancer-specific survival was 98%, 97%, and 90% for low-, intermediate-, and high-risk disease. The unadjusted overall survival was lower across increasing disease risk categories at 77%, 71%, and 62% for low-, intermediate-, and high-risk disease (p < .001). CONCLUSIONS: These data provide population-based 10-year benchmarks for clinically relevant end points, including metastasis-free survival, among patients with localized prostate cancer undergoing radiation therapy using contemporary techniques. The survival rates for high-risk disease in particular suggest that outcomes have recently improved.

Preoperative MRI PI-RADS scores are associated with prostate cancer upstaging on surgical pathology.

INTRODUCTION: Prostate Imaging Reporting and Data System (PI-RADS) scores can help identify clinically significant prostate cancer and improve patient selection for prostate biopsies. However, the role of PI-RADS scores in patients already diagnosed with prostate cancer remains unclear. The purpose of this study was to evaluate the association of PI-RADS scores with prostate cancer upstaging. Upstaging on final pathology harbors a higher risk for biochemical recurrence with important implications for additional treatments, morbidity, and mortality. METHODS: All patients from a single high-volume institution who underwent a prostate multiparametric magnetic resonance imaging and radical prostatectomy between 2016 and 2020 were included in this retrospective analysis. Univariable and multivariable analyses were conducted to investigate potential associations with upstaging events, defined by pT3, pT4, or N1 on final pathology. A logistic regression model was constructed for the prediction of upstaging events based on PI-RADS score, prostate-specific antigen density (PSA-D), and biopsy Gleason grade groups. We built receiver operative characteristic (ROC) curves to measure the area under the curve of different predictive models. RESULTS: Two hundred and ninety-four patients were included in the final analysis. Upstaging events occurred in 137 (46.5%) of patients. On univariable analysis, patients who were upstaged on final pathology had significantly higher PI-RADS scores (odds ratio [OR] 2.34 95% confidence interval [CI] 1.64-3.40, p < 0.001) but similar PSA-D (OR 2.70 95% 0.94-8.43, p = 0.188) compared with patients who remained pT1 or pT2 on final pathology. On multivariable analysis, PI-RADS remained independently significantly associated with upstaging, suggesting it is an independent risk predictor for upstaging. Lymph node metastasis only occurred in patients with PI-RADS 4 or 5 lesions (n = 15). Our model using PSA-D, biopsy Gleason grade, and PI-RADS had a predictive AUC of 0.69 for upstaging events, an improvement from 0.59 using biopsy Gleason grade alone. CONCLUSION: PI-RADS scores are independent predictors for upstaging events and may play an important role in forecasting biochemical recurrence and lymph node metastasis. Modern nomograms should be updated to include PI-RADS to predict lymph node metastases and the likelihood of biochemical recurrence more accurately.

Envisioning clinical trials as complex interventions.

Clinical trials are critical components of modern health care and infrastructure. Trials benefit society through scientific advancement and individual patients through trial participation. In fact, billions of dollars are spent annually in support of these benefits. Despite the massive investments, clinical trials often fail to accomplish their primary aims and trial enrollment rates remain low. Prior efforts to improve trial conduct and enrollment have had limited success, perhaps due to oversimplification of the complex, multilevel nature of trials. For these reasons, the authors propose applying implementation science to the clinical trials context. In this commentary, the authors posit clinical trials as complex, multilevel evidence-based interventions with significant societal and individual benefits yet with persistent gaps in implementation. An application of implementation science concepts to the clinical trials context as means to build common vocabulary and establish a platform for applying implementation science and practice to improve clinical trial conduct is introduced. Applying implementation science to the clinical trials context can augment improvement efforts and build capacity for better and more efficient evidence-based care for all patients and trial stakeholders throughout the clinical trials enterprise.

The effect of day of discharge on hospital readmission after minimally invasive partial nephrectomy.

INTRODUCTION: To assess the association between postoperative discharge day after minimally invasive partial nephrectomy with 30-day readmission rates, and specifically compare postoperative day 1 to postoperative day 2 discharge. We hypothesized that discharge on earlier postoperative days would be associated with higher rates of readmission after partial nephrectomy. MATERIALS AND METHODS: The National Cancer Database was queried for patients undergoing minimally invasive partial nephrectomy for non-metastatic disease without chemo or radiation therapy from 2010-2014. Readmission rates were compared between postoperative discharge days. Multivariable logistic regression was used to analyze variables associated with 30-day readmission. RESULTS: A total of 19,300 patients undergoing minimally invasive partial nephrectomy were included, comprising patients discharged on postoperative day 0 (POD0) (n = 601, 3%), POD1 (n = 2,999, 16%), POD2 (n = 6,866, 36%), POD3 (n = 4,568, 24%), POD4 (n = 2,068, 11%), and POD5 or later (n = 2,198, 11%). Rates of 30-day readmission were similar between POD0, POD1 and POD2 discharges (1.8%, 1.9%, 2.2%, respectively), but were higher for discharges on POD3 or later (POD3 3.0%, POD4 4.9%, POD5 or greater 5.5%). On multivariable analysis, odds of 30-day readmission were similar between POD0 (OR 0.83 [95%CI 0.45-1.55], p = 0.56) and POD1 (OR 0.84 [95%CI 0.62-1.15], p = 0.28) compared to discharge on POD2. CONCLUSIONS: Patients discharged on POD2 are not readmitted any less frequently than patients discharged on POD0 or POD1. Implementing protocols with POD1 as the default discharge day after partial nephrectomy should be considered. Future studies designing and evaluating safe and acceptable implementation strategies for these protocols are necessary.

Initial transperineal prostate biopsy experience at a high-volume center.

INTRODUCTION: Transperineal prostate biopsy (TPBx) allows for prostate cancer detection with fewer infectious complications when compared to transrectal prostate biopsy (TRUSBx). We evaluated the initial experience of a single physician with no prior TPBx exposure, compared to TRUSBx and MRI/US fusion biopsy (MRIBx) performed by experienced physicians. MATERIALS AND METHODS: All consecutive patients undergoing prostate biopsy (June 2019-March 2020) were included. Patient discomfort, procedural time, clinically significant cancer detection rates (csCDR) and 30-day complications were compared between TPBx, TRUSBx and MRIBx. RESULTS: A total of 303 patients underwent biopsy. Comparing TPBx to TRUSBx to MRIBx, median pain scores during the anesthetic block were 4 versus 2 versus 3 (p = 0.007) respectively, and not statistically different during the rest of the procedure. Median time of biopsy was 11, 7.5 and 12 minutes respectively. csCDR were 38%, 29.8%, and 43.6% (p = 0.12) respectively. The combined transrectal groups (n = 211) had nine complications including two sepsis events. The TPBx group (n = 92) had no 30-day complications. CONCLUSIONS: TPBx was well tolerated in the office setting with similar levels of discomfort for all aspects of the procedure compared to transrectal approach. Learning curve for TPBx showed rapid improvement in procedural time within the first 15 cases with an average procedure time of 9 minutes thereafter. Similar rates of csCDR were found between the groups and TPBx had significantly fewer infectious complications than standard transrectal technique.

Reducing postoperative opioid pill prescribing via a quality improvement approach.

BACKGROUND: The opioid epidemic has been fueled by prescribing unnecessary quantities of opioid pills for postoperative use. While evidence mounts that postoperative opioids can be reduced or eliminated, implementing such changes within various institutions can be met with many barriers to adoption. OBJECTIVE: To address excess opioid prescribing within our institutions, we applied a plan-do-study-act (PDSA)-like quality improvement strategy to assess local opioid prescribing and use, modify our institutional protocols, and assess the impacts of the change. The opioid epidemic has been fueled by prescribing unnecessary quantities of opioid pills for postoperative use. While evidence mounts that postoperative opioids can be reduced or eliminated, implementing such changes within various institutions can be met with many barriers to adoption. We describe our approach, findings, and lessons learned from our quality improvement approach. METHODS: We prospectively recorded home pain pill usage after robotic-assisted laparoscopic prostatectomy (RALP) and robotic-assisted partial nephrectomy (RAPN) at two academic institutions from July 2016 to July 2019. Patients prospectively recorded their home pain pill use on a take-home log. Other factors, including numeric pain rating scale on the day of discharge, were extracted from patient records. We analyzed our data and modified opioid prescription protocols to meet the reported use data of 80% of patients. We continued collecting data after the protocol change. We also used our prospectively collected data to assess the accuracy of a retrospective phone survey designed to measure postdischarge opioid use. Our primary outcomes were the proportion of patients taking zero opioid pills postdischarge, median pills taken after discharge and the number of excess pills prescribed but not taken. We compared these outcomes before and after protocol change. RESULTS: A total of 266 patients (193 RALP, 73 RAPN) were included. Reducing the standard number of prescribed pills did not increase the percentage of patients taking zero pills postdischarge in either group (RALP: 47% vs. 41%; RAPN 48% vs. 34%). The patients in either group reporting postoperative Day 1 pain score of 0 or 1 were much more likely to use zero postdischarge opioid pills. Our reduction in prescribing protocol resulted in an estimated reduction in excess pills from 1555 excess pills in the prior protocol to just 155 excess pills in the new protocol. CONCLUSION: Our PDSA-like approach led to an acceptable protocol revision resulting in significant reductions in excess pills released into the community. Reducing the quantity of opioids prescribed postoperatively does not increase the percentage of patients taking zero pills postdischarge. To eliminate opioid use may require no-opioid pathways. Our approach can be used in implementing zero opioid discharge plans and can be applied to opioid reduction interventions at other institutions where barriers to reduced prescribing exist.

The role of perioperative medications in urinary retention following midurethral sling.

AIMS: Postoperative urinary retention (PUR) is a known complication of midurethral sling (MUS) placement. The use of certain perioperative medications may influence the risk of this complication. This study aimed to investigate the association of perioperative medications with urinary retention after MUS. METHODS: This was a retrospective study of women undergoing MUS placement for stress urinary incontinence by a fellowship-trained urologic surgeon between 2015 and 2018, under approval by the Institutional Review Board. Both retropubic and transobturator approaches were included. All patients underwent an active void trial following surgery. Intraoperative medications given by the anesthesia team were retrospectively noted. The Fisher's exact test was used to compare the association of PUR with categorical variables. RESULTS: A total of 82 patients were included, 17 (21%) of whom failed postoperative void trial due to urinary retention. Of 25 patients receiving perioperative scopolamine, 40% failed the postoperative void trial, compared to 12% of patients not receiving scopolamine (p = .048). Groups were then stratified based on scopolamine use due to the observed independent association with PUR. Subgroup analysis revealed a stronger association of postoperative retention with scopolamine in patients undergoing concomitant prolapse surgery. Notably, retention rate and scopolamine use were similar whether patients underwent sling placement alone or in combination with prolapse surgery. Rate of retention was also higher for retropubic versus transobturator slings (36% vs. 9%; p = .005). CONCLUSIONS: Perioperative scopolamine may be associated with an increased risk of postoperative urinary retention following MUS, especially in the setting of a concomitant prolapse surgery.

Effect of Urethroplasty on Anxiety and Depression.

PURPOSE: To our knowledge anxiety and depression in patients with urethral stricture disease and the impact of urethroplasty on mental health has never been explored. We hypothesized that patients with urethral stricture disease would have higher than normal anxiety and depression levels, and urethroplasty would improve mental health. MATERIALS AND METHODS: We retrospectively reviewed the records of patients in a multi-institutional reconstructive urology database who underwent anterior urethroplasty. Preoperative and postoperative evaluation of anxiety and depression, and overall health was recorded using the validated EQ-5D™-3L Questionnaire. Sexual function was evaluated with the IIEF (International Index of Erectile Function) and the Men's Sexual Health Questionnaire. Stricture recurrence was defined as the need for a subsequent procedure. RESULTS: Median followup in the 298 patients who met study inclusion criteria was 4.2 months. Preoperative anxiety and depression was reported by 86 patients (29%). Those with anxiety and depression reported higher rates of marijuana use, a worse preoperative IIEF score (17.5 vs 19.6, p = 0.01) and a lower image of overall health (66 vs 79, p ≤0.001). Improvement or resolution of anxiety and depression was experienced by 56% of patients treated with urethroplasty while de novo postoperative anxiety and depression were reported by 10%. These men reported a decreased flow rate (16 vs 25 ml per second, p = 0.01). Clinical failure in 8 patients (2.7%) had no effect on the development, improvement or resolution of anxiety and depression. CONCLUSIONS: Of patients with preoperative anxiety and depression 56% reported improvement or resolution after urethroplasty. Although new onset anxiety and depression was rare, these patients had a significantly lower postoperative maximum flow rate, possibly representing a group with a perceived suboptimal surgical outcome. A urethral stricture disease specific questionnaire is needed to further elucidate the interplay of urethral stricture disease with anxiety and depression.

Is measurement of renal function necessary for all trauma patients before iodinated contrast administration?

PURPOSE: The purpose of this study was to identify factors at the time of presentation which could quickly exclude or identify renal dysfunction in blunt trauma patients, thus negating serum measurement of renal function prior to contrast-enhanced imaging and expediting care. METHODS: Patients, >18 years old, without renal failure, presenting after blunt trauma, with serum creatinine measured at presentation, were retrospectively studied at a single center. Variables recorded at presentation including vitals, mechanism, and past medical history were analyzed using multivariate regression analysis to identify independent predictors of abnormal renal function. RESULTS: From 2009 to 2015, a total of 1099 patients met the inclusion criteria. Of those, 75 (6.8%) had renal dysfunction at presentation. Patients with renal dysfunction had a mean age of 74.3 (SD 15.5) years old, and 57.3% were male. Multivariate analysis identified independent predictors of renal dysfunction at presentation as age ≥ 61 (p < 0.001), hypotension (p = 0.02), and diabetes (p = 0.02). The presence of a single identified factor had an 85% sensitivity for renal dysfunction and a 98.5% negative predictive value. CONCLUSIONS: Impaired renal function at presentation was infrequent in our trauma cohort. Trauma patients who were normotensive, under the age of 61, and without diabetes were unlikely to have impaired renal function at presentation. In the urgent setting of trauma, patients without these comorbidities are likely safe to forgo screening of renal function prior to contrast-enhanced imaging.

The Impact of Regionalization of Cystectomy on Racial Disparities in Bladder Cancer Care.

PURPOSE: Regionalization of surgical care has improved the quality of care for patients with bladder cancer. We explored whether regionalization has benefited white and black patients equally. MATERIALS AND METHODS: We used a New York State inpatient database to identify all patients who underwent cystectomy for bladder cancer from 1997 to 2011. Hospital volume was classified in quintiles based on the number of cystectomies performed in the first 5 years of the study. Logistic regression was done to assess the association between race and low volume/very low volume hospitals. Racial disparities were further characterized using stratification by time and by the racial composition of the patient community. RESULTS: A total of 8,168 patients treated with cystectomy for bladder cancer were included in analysis. Compared with white race, black race was associated with a higher likelihood of low volume/very low volume hospital use (OR 1.59, 95% CI 1.26-2.02). The disparity was most prominent in 2002 to 2006 (OR 2.51, 95% CI 1.64-3.85) but it did not persist in 2007 to 2011 (OR 1.46, 95% CI 0.92-2.32). Black patients living in a black community had the highest likelihood of low volume/very low volume hospitalization during all periods of increased regionalization (2002 to 2006 OR 4.14, 95% CI 1.84-9.34 and 2007 to 2011 OR 2.40, 95% CI 1.07-5.39). CONCLUSIONS: Regionalization of cystectomy transiently worsened the racial disparity in bladder cancer care, although the disparity did not persist with time. Specific efforts may be needed to address the consequences of regionalization in particularly vulnerable subpopulations, such as black patients who live in a black community where disparities have persisted.

Pathological T0 following radical cystectomy with or without neoadjuvant chemotherapy: a useful surrogate.

PURPOSE: Several large, randomized, controlled trials provide evidence that neoadjuvant chemotherapy improves the outcome of radical cystectomy for muscle invasive urothelial bladder cancer. We analyzed the designs, methods and observations of these trials to identify patient subgroups that appeared most likely to benefit. We also identified distinguishing features compared to groups that did not achieve improved outcomes. MATERIALS AND METHODS: We analyzed initial and updated methods and results of the 4 main prospective trials of neoadjuvant chemotherapy (SWOG, Medical Research Council, and Nordic I and II) and subsequent meta-analyses. These series are the basis for advocating neoadjuvant chemotherapy in all patients with muscle invasive urothelial bladder cancer who undergo radical cystectomy. RESULTS: The greatest apparent benefit was seen in patients free of cancer at radical cystectomy (pT0). They had markedly improved overall and disease specific survival compared to patients with residual disease. However, improvements occurred regardless of whether there was down-staging from muscle invasive urothelial bladder cancer to pT0 after transurethral resection alone (controls) or after resection plus neoadjuvant chemotherapy. Thus, the major benefit of chemotherapy appeared to be that more patients achieved pT0. We also explored the study limitations that may have influenced outcomes and considered the potential for overtreatment in patients not likely to benefit from chemotherapy. Finally, we used risk stratification to create a decision tree model for selecting patients for neoadjuvant chemotherapy that could conceivably maximize oncologic outcome and minimize overtreatment. CONCLUSIONS: Patients with pT0 in the 4 main neoadjuvant chemotherapy trials and their subsequent meta-analyses experienced similar survival, far exceeding that in groups that did not achieve pT0. The benefit of neoadjuvant chemotherapy appears to be the larger number of cases than in the transurethral resection only group that were down-staged to pT0, suggesting that variables other than chemotherapy may have influenced outcomes. Therefore, strategies to selectively administer neoadjuvant chemotherapy to certain patients at risk have the potential to maintain improved bladder cancer outcomes while reducing overtreatment and its associated toxicity.