Vesicourethral Anastomotic Stenosis Following Radical Prostatectomy: Risk Factors, Natural History, and Treatment Outcomes.

PURPOSE: Vesicourethral anastomotic stenosis after radical prostatectomy is a complication with significant adverse quality-of-life implications. Herein, we identify groups at risk for vesicourethral anastomotic stenosis and further characterize the natural history and treatment patterns. MATERIALS AND METHODS: Years 1987-2013 of a prospectively maintained radical prostatectomy registry were queried for patients with the diagnosis of vesicourethral anastomotic stenosis, defined as symptomatic and inability to pass a 17F cystoscope. Patients with follow-up less than 1 year, preoperative anterior urethral stricture, transurethral resection of prostate, prior pelvic radiotherapy, and metastatic disease were excluded. Logistic regression was performed to identify predictors of vesicourethral anastomotic stenosis. Functional outcomes were characterized. RESULTS: Out of 17,904 men, 851 (4.8%) developed vesicourethral anastomotic stenosis at a median of 3.4 months. Multivariable logistic regression identified associations with vesicourethral anastomotic stenosis including adjuvant radiation, BMI, prostate volume, urine leak, blood transfusion, and nonnerve-sparing techniques. Robotic approach (OR 0.39, P < .01) and complete nerve sparing (OR 0.63, P < .01) were associated with reduced vesicourethral anastomotic stenosis formation. Vesicourethral anastomotic stenosis was independently associated with 1 or more incontinence pads/d at 1 year (OR 1.76, P < .001). Of the patients treated for vesicourethral anastomotic stenosis, 82% underwent endoscopic dilation. The 1- and 5-year vesicourethral anastomotic stenosis retreatment rates were 34% and 42%, respectively. CONCLUSIONS: Patient-related factors, surgical technique, and perioperative morbidity influence the risk of vesicourethral anastomotic stenosis after radical prostatectomy. Ultimately, vesicourethral anastomotic stenosis is independently associated with increased risk of urinary incontinence. Endoscopic management is temporizing for most men, with a high rate of retreatment by 5 years.

Intraoperative Blood Transfusion Is Associated With Increased Risk of Venous Thromboembolism After Radical Cystectomy.

PURPOSE: Our objective was to examine whether perioperative blood transfusion is associated with venous thromboembolism following radical cystectomy adjusting for both patient- and disease-related factors. MATERIALS AND METHODS: Patients who underwent radical cystectomy for bladder cancer from 1980-2020 were identified in the Mayo Clinic cystectomy registry. Blood transfusion during the initial postoperative hospitalization was analyzed as a 3-tiered variable: no transfusion, postoperative transfusion alone, or intraoperative with or without postoperative transfusion. The primary outcome was venous thromboembolism within 90 days of radical cystectomy. Associations between clinicopathological variables and 90-day venous thromboembolism were assessed using multivariable logistic regression, with transfusion analyzed as both a categorical and a continuous variable. RESULTS: A total of 3,755 radical cystectomy patients were identified, of whom 162 (4.3%) experienced a venous thromboembolism within 90 days of radical cystectomy. Overall, 2,112 patients (56%) received a median of 1 (IQR: 0-3) unit of blood transfusion, including 811 (38%) with intraoperative transfusion only, 572 (27%) with postoperative transfusion only, and 729 (35%) with intraoperative and postoperative transfusion. On multivariable analysis, intraoperative with or without postoperative blood transfusion was associated with a significantly increased risk of venous thromboembolism (adjusted OR 1.73, 95% CI 1.17-2.56, P = .002). Moreover, when analyzed as a continuous variable, each unit of blood transfused intraoperatively was associated with 7% higher odds of venous thromboembolism (adjusted OR 1.07, 95% CI 1.01-1.13, P = .03). CONCLUSIONS: Intraoperative blood transfusion was significantly associated with venous thromboembolism within 90 days of radical cystectomy. To ensure optimal perioperative outcomes, continued effort to limit blood transfusion in radical cystectomy patients is warranted.

Impact of preferred surgical modality on surgeon wellness: a survey of workload, physical pain/discomfort, and neuromusculoskeletal disorders.

BACKGROUND: We compared surgeons' workload, physical discomfort, and neuromusculoskeletal disorders (NMSDs) across four surgical modalities: endoscopic, laparoscopic, open, and robot-assisted (da Vinci Surgical Systems). METHODS: An electronic survey was sent to the surgeons across an academic hospital system. The survey consisted of 47 questions including: (I) Demographics and anthropometrics; (II) The percentage of the procedural time that the surgeon spent on performing each surgical modality; (III) Physical and mental demand and physical discomfort; (IV) Neuromusculoskeletal symptoms including body part pain and NMSDs. RESULTS: Seventy-nine out of 245 surgeons completed the survey (32.2%) and 65 surgeons (82.2%) had a dominant surgical modality: 10 endoscopic, 15 laparoscopic, 26 open, and 14 robotic surgeons. Physical demand was the highest for open surgery and the lowest for endoscopic and robotic surgeries, (all p < 0.05). Open and robotic surgeries required the highest levels of mental workload followed by laparoscopic and endoscopic surgeries, respectively (all p < 0.05 except for the difference between robotic and laparoscopic that was not significant). Body part discomfort or pain (immediately after surgery) were lower in the shoulder for robotic surgeons compared to laparoscopic and open surgeons and in left fingers for robotic surgeons compared to endoscopic surgeons (all p < 0.05). The prevalence of NMSD was significantly lower in robotic surgeons (7%) compared to the other surgical modalities (between 60 and 67%) (all p < 0.05). CONCLUSIONS: The distribution of NMSDs, workload, and physical discomfort varied significantly based on preferred surgical approach. Although robotic surgeons had fewer overall complaints, improvement in ergonomics of surgery are still warranted.

Role of Lymphadenectomy during Radical Cystectomy for Nonmuscle-Invasive Bladder Cancer: Results from a Multi-Institutional Experience.

PURPOSE: While lymph node dissection (LND) at radical cystectomy (RC) for muscle-invasive bladder cancer has been studied extensively, the role of LND for nonmuscle-invasive bladder cancer (NMIBC) remains incompletely defined. Herein, we aim to assess the association between extent of LND during RC for NMIBC and local pelvic recurrence-free survival (LPRS), cancer-specific survival (CSS) and overall survival (OS). MATERIALS AND METHODS: A multi-institutional retrospective review was performed of patients with NMIBC undergoing RC at 3 large tertiary referral centers. To identify a threshold for lymph node yield (LNY) to optimize LPRS, CSS and OS, separate Cox regression models were developed for each possible LNY threshold. Model performance including Q-statistics and hazard ratios (HRs) were used to identify optimal LNY thresholds. RESULTS: A total of 1,647 patients underwent RC for NMIBC, with a median LNY of 15 (quartiles 9,23). Model performance curves suggested LNY of 10 and 20 to optimize LPRS and CSS/OS, respectively. On multivariable regression, LNY >10 was associated with lower risk of LPR compared to LNY ≤10 (HR 0.63, 95% CI 0.42-0.93, p=0.02). Similarly, LNY >20 was associated with improved CSS (HR 0.67, 95% CI 0.52-0.87, p=0.002) and OS (HR 0.75, 95% CI 0.64-0.88, p <0.001) compared to LNY ≤20. Similar results were observed in the cT1 and cTis subgroups. CONCLUSIONS: Greater extent of LND during RC for NMIBC is associated with improved LPRS, CSS and OS, supporting the inclusion of LND during RC for NMIBC, particularly among patients with cTis or cT1 disease. Future prospective studies are warranted to assess the ideal anatomical template of LND in NMIBC.

The Impact of Upper Tract Urothelial Carcinoma Diagnostic Modality on Intravesical Recurrence after Radical Nephroureterectomy: A Single Institution Series and Updated Meta-Analysis.

PURPOSE: Diagnostic ureteroscopic biopsy for upper tract urothelial carcinoma (UTUC) has been hypothesized to increase intravesical recurrence of urothelial carcinoma after radical nephroureterectomy (RNU). Moreover, the impact of ureteroscopy without biopsy or percutaneous biopsy on intravesical recurrence remains unknown. Herein, we compared post-RNU intravesical recurrences across UTUC diagnostic modalities. MATERIALS AND METHODS: Patients undergoing RNU at our institution between 1995 and 2019 were categorized by UTUC diagnostic modality: 1) no ureteroscopy or percutaneous biopsy; 2) percutaneous biopsy; 3) ureteroscopy without biopsy; 4) ureteroscopic biopsy. Intravesical recurrences were compared using Kaplan-Meier analyses and Cox-proportional hazard models. Results of group 4 vs 1 were pooled with the literature using a fixed effects meta-analysis. RESULTS: In a cohort of 834 RNU patients, 210 (25.2%) had undergone no ureteroscopy, 57 (6.6%) percutaneous biopsy, 125 (15.0%) ureteroscopy without biopsy, and 442 (53.0%) ureteroscopic biopsy. Two-year intravesical recurrence rates were 15.0%, 12.7%, 18.4%, and 21.9% for groups 1 through 4, respectively (p=0.09). Multivariable analysis found that group 4 had increased intravesical recurrences (HR 1.40, p=0.04) relative to group 1 while group 2 (HR 1.07, p=0.87) and group 3 (HR 1.15, p=0.54) did not. Group 4 remained associated with intravesical recurrence on subset analyses accounting for post-RNU surveillance cystoscopy frequency. On meta-analysis including 11 other series, ureteroscopic biopsy was associated with intravesical recurrence (HR 1.47, p <0.01). CONCLUSIONS: Ureteroscopic biopsy before RNU, but not percutaneous biopsy or ureteroscopy without biopsy, was associated with increased intravesical recurrence. Clinical trials of intravesical chemotherapy after ureteroscopic biopsy are warranted to reduce intravesical recurrences.

A Contemporary Analysis of Urethral Recurrence following Radical Cystectomy.

PURPOSE: Oncologic outcomes following urethral recurrence (UR) remain incompletely described, with reports limited by small cohort sizes. We evaluated risk factors for UR as well as cancer-specific survival (CSS) and overall survival (OS) among patients with UR. MATERIALS AND METHODS: We reviewed our institutional radical cystectomy (RC) registry to identify patients with UR. Cox proportional hazards regression was used to assess risk factors for UR. Kaplan-Meier and Cox models were used to assess the relationship between UR and CSS/OS as well as to compare outcomes following symptomatic vs asymptomatic presentation of UR. RESULTS: Overall, 2,930 patients underwent RC from 1980 to 2018, with a median postoperative followup of 7.1 years (IQR 2.8-13.1), of whom 144 (4.9%) were subsequently diagnosed with UR. Carcinoma in situ (HR 1.98, 95% CI 1.30-3.04), multifocal disease (HR 1.59, 95% CI 1.07-2.36) and prostatic urethral involvement at RC (HR 3.01, 95% CI 1.98-4.57) were associated with increased risk of UR. UR was associated with decreased CSS (HR 7.30, 95% CI 5.46-9.76) and OS (HR 1.86, 95% CI 1.54-2.24). A total of 63/144 patients were diagnosed with UR based on symptoms, while 104/144 patients with UR underwent urethrectomy. Patients with symptomatic UR had higher tumor stage at urethrectomy (≥pT2 in 13.1% vs 3.1%, p=0.007), while patients with asymptomatic UR experienced longer median CSS (12.1 vs 6.1 years) and OS (8.30 vs 4.82 years; p=0.05 for both). CONCLUSIONS: We identified pathological risk factors for UR after RC and report adverse subsequent survival outcomes for these patients. Presentation with symptomatic UR was associated with higher tumor stage and poorer prognosis, supporting a value to continued urethral surveillance after RC.

Cost-Effectiveness of Maintenance bacillus Calmette-Guérin for Intermediate and High Risk Nonmuscle Invasive Bladder Cancer.

PURPOSE: While guidelines support the use of maintenance bacillus Calmette-Guérin for patients with intermediate and high risk nonmuscle invasive bladder cancer, in an era of bacillus Calmette-Guérin shortage we explored the cost-effectiveness of maintenance bacillus Calmette-Guérin. MATERIALS AND METHODS: A Markov model compared the cost-effectiveness of maintenance bacillus Calmette-Guérin to surveillance after induction bacillus Calmette-Guérin for intermediate/high risk nonmuscle invasive bladder cancer from a U.S. Medicare perspective. Five-year oncologic outcomes, toxicity rates and utility values were extracted from the literature. Univariable and multivariable sensitivity analyses were conducted. A willingness to pay threshold of $100,000 per quality adjusted life year was considered cost-effective. RESULTS: At 5 years mean costs per patient were $14,858 and $13,973 for maintenance bacillus Calmette-Guérin and surveillance, respectively, with quality adjusted life years of 4.046 for both, making surveillance the dominant strategy. On sensitivity analysis full dose and 1/3 dose maintenance bacillus Calmette-Guérin became cost-effective if the absolute reduction in 5-year progression was greater than 2.1% and greater than 0.76%, respectively. On further sensitivity analysis full dose and 1/3 dose maintenance bacillus Calmette-Guérin became cost-effective when maintenance bacillus Calmette-Guérin toxicity equaled surveillance toxicity. In multivariable sensitivity analyses using 100,000 Monte-Carlo microsimulations, full dose and 1/3 dose maintenance bacillus Calmette-Guérin was cost-effective in 17% and 39% of microsimulations, respectively. CONCLUSIONS: Neither full dose nor 1/3 dose maintenance bacillus Calmette-Guérin appears cost-effective for the entire population of patients with intermediate/high risk nonmuscle invasive bladder cancer. These data support prioritizing maintenance bacillus Calmette-Guérin for the subset of patients with high risk nonmuscle invasive bladder cancer most likely to experience progression, in particular those who tolerated induction bacillus Calmette-Guérin well. Overall, our findings support the American Urological Association policy statement to allocate bacillus Calmette-Guérin for induction rather than maintenance therapy during times of bacillus Calmette-Guérin shortage.

A risk-stratified approach to neoadjuvant chemotherapy in muscle-invasive bladder cancer: implications for patients classified with low-risk disease.

PURPOSE: To validate published risk criteria for informing use of neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC), and to examine outcomes of low-risk (LR) patients treated with immediate radical cystectomy (RC). METHODS: We identified 1931 patients who underwent RC for MIBC from 1980 to 2016. Patients were considered high risk (HR) with hydronephrosis, lymphovascular invasion, variant histology and/or cT3/4 disease. Kaplan-Meier survival estimates were compared to patients classified as LR, and logistic regression was used to examine factors associated with pathologic downstaging. RESULTS: A total of 1025 LR and 906 HR patients were identified. Median follow-up was 6.3 years (IQR 2.6-12), during which time 1321 (68%) patients died, 753 (39%) from bladder cancer. HR patients had significantly lower 5-year CSS than LR patients (50% vs. 68%, p = 0.001). Of 561 cisplatin-eligible LR patients treated with RC without NAC, 293 (52%) had pathologic non-organ confined disease; of these, 81 (14%) received adjuvant chemotherapy; 78 (14%) did not due to a perioperative event, while 134 (24%) did not due to patient/provider choice. NAC in LR patients was associated with greater odds of pT0 (OR 3.05; p < 0.001) and < pT2 (OR 2.53; p < 0.001) disease, but was not significantly associated with CSS (p = 0.31). CONCLUSIONS: Our results validate the proposed risk groups. Among LR patients treated without NAC, 52% experienced pathologic upstaging, and 14% were unable to receive adjuvant chemotherapy due to a perioperative event. These data support offering NAC to both HR and LR MIBC patients, and may be useful for patient counseling.

Impact of time from biopsy to surgery on complications, functional and oncologic outcomes following radical prostatectomy.

INTRODUCTION: To determine the impact of time from biopsy to surgery on outcomes following radical prostatectomy (RP) as the optimal interval between prostate biopsy and RP is unknown. MATERIAL AND METHODS: We identified 7, 350 men who underwent RP at our institution between 1994 and 2012 and had a prostate biopsy within one year of surgery. Patients were grouped into five time intervals for analysis: ≤ 3 weeks, 4-6 weeks, 7-12 weeks, 12-26 weeks, and > 26 weeks. Oncologic outcomes were stratified by NCCN disease risk for comparison. The associations of time interval with clinicopathologic features and survival were evaluated using multivariate logistic and Cox regression analyses. RESULTS: Median time from biopsy to surgery was 61 days (IQR 37, 84). Median followup after RP was 7.1 years (IQR 4.2, 11.7) while the overall perioperative complication rate was 19.7% (1,448/7,350). Adjusting for pre-operative variables, men waiting 12-26 weeks until RP had the highest likelihood of nerve sparing (OR: 1.45, p = 0.02) while those in the 4-6 week group had higher overall complications (OR: 1.33, p = 0.01). High risk men waiting more than 6 months had higher rates of biochemical recurrence (HR: 3.38, p = 0.05). Limitations include the retrospective design. CONCLUSIONS: Surgery in the 4-6 week time period after biopsy is associated with higher complications. There appears to be increased biochemical recurrence rates in delaying RP after biopsy, for men with both low and high risk disease.

The Association of Aspirin Use with Survival Following Radical Cystectomy.

PURPOSE: Aspirin may have antineoplastic properties through the inhibition of inflammatory cytokines that regulate cell proliferation, angiogenesis and apoptosis. In patients with nonmuscle invasive bladder cancer aspirin use has been linked to a reduced risk of recurrence. We evaluated the association of aspirin with survival following radical cystectomy. MATERIALS AND METHODS: A total of 1,061 patients underwent radical cystectomy at our institution between 2007 and 2016, of whom 461 (43%) were aspirin users at the time of surgery. Survival estimates were assessed by the Kaplan-Meier method. The Cox proportional hazards model was applied to evaluate associations between patient features and survival. RESULTS: Median followup after radical cystectomy among survivors was 4.2 years (IQR 2-6.2). During this time 442 patients died, including 331 of bladder cancer. Aspirin users were significantly older, more likely to have a history of cardiovascular disease and diabetes, and more likely to use metformin or statin (each p <0.05). Nevertheless, we found that patients who ingested a daily aspirin had significantly higher 5-year cancer specific survival (68% vs 60%, p = 0.02) and overall survival (59% vs 52%, p = 0.03) compared to nonusers. Moreover, after multivariable adjustment aspirin use remained independently associated with lower cancer specific mortality (HR 0.64, 95% CI 0.45-0.89, p = 0.01) as well as all cause mortality (HR 0.70, 95% CI 0.53-0.93, p = 0.02) but not with distant metastasis (p >0.05). CONCLUSIONS: Daily aspirin use was associated with significantly improved survival outcomes following radical cystectomy. Further research is warranted to evaluate the potential underlying biological mechanisms and investigate causality.

Independent Validation of the American Joint Committee on Cancer 8th Edition Prostate Cancer Staging Classification.

PURPOSE: We sought to independently validate the AJCC (American Joint Committee on Cancer) 8th edition prostate cancer staging classification, which includes the elimination of pT2 subcategories and the reclassification of patients with prostate specific antigen 20 ng/ml or greater and Gleason Grade Group 5 as stage groups III-A and III-C, respectively. MATERIALS AND METHODS: We identified 13,839 men who underwent radical prostatectomy at Mayo Clinic between 1987 and 2011 from our institutional registry. Outcomes included biochemical recurrence-free, metastasis-free and cancer specific survival. Kaplan-Meier analyses and Cox regression models with the c-index were used. RESULTS: Median followup was 10.5 years (IQR 7.1-15.3). Among patients with pT2 prostate cancer the subclassification demonstrated limited discrimination for biochemical recurrence-free, metastasis-free and cancer specific survival (c-index 0.531, 0.545 and 0.525, respectively). At the same time patients with 7th edition stage group II prostate cancer and prostate specific antigen 20 ng/ml or greater had significantly worse 15-year biochemical recurrence-free survival (42.2% vs 58.8%), metastasis-free survival (78.2% vs 88.8%) and cancer specific survival (88.0% vs 94.4%, all p <0.001) than patients with 7th edition stage group II prostate cancer and prostate specific antigen less than 20 ng/ml. However, patients with 7th edition stage group II prostate cancer and prostate specific antigen 20 ng/ml or greater had significantly better 15-year biochemical recurrence-free survival (42.2% vs 31.3%, p = 0.007), metastasis-free survival (78.2% vs 68.0%, p <0.001) and cancer specific survival (88.0% vs 83.4%, p = 0.01) than patients with 7th edition stage group III. Also, patients with 7th edition stage group II prostate cancer and Gleason Grade Group 5 had significantly worse 15-year biochemical recurrence-free survival (37.1% vs 57.9%, p <0.001), metastasis-free survival (63.8% vs 88.5%, p <0.001) and cancer specific survival (73.0% vs 94.3%, p <0.001) than patients with 7th edition stage group II prostate cancer and Gleason Grade Group 1-4 as well as worse 15-year cancer specific survival (73.0% vs 83.4%, p = 0.005) than patients with 7th edition stage group III prostate cancer. CONCLUSIONS: Our data support the changes in the new AJCC classification.

Impact of Radical Prostatectomy on Long-Term Oncologic Outcomes in a Matched Cohort of Men with Pathological Node Positive Prostate Cancer Managed by Castration.

PURPOSE: Long-term data supporting the role of primary tumor resection in node positive prostate cancer are lacking. We evaluated the impact of adding radical retropubic prostatectomy to surgical castration on long-term oncologic outcomes in pathological node positive prostate cancer. MATERIALS AND METHODS: We identified men who underwent pelvic lymphadenectomy and orchiectomy within 90 days for pathological node positive prostate cancer from 1966 to 1995. Men treated with radical retropubic prostatectomy in addition to orchiectomy were matched 1:1 to men who underwent orchiectomy alone based on age, year of surgery, clinical grade, clinical T stage, number of positive nodes and preoperative serum prostate specific antigen, the latter from 1987 and thereafter. Kaplan-Meier and Cox regression analyses were done to compare cancer specific and overall survival. RESULTS: The matched cohort included 158 men with 79 in each group. Of men who underwent orchiectomy alone 76 died, including 60 of prostate cancer. Of patients treated with radical retropubic prostatectomy plus orchiectomy 70 died, including 28 of prostate cancer. On Kaplan-Meier analyses prostatectomy plus orchiectomy vs orchiectomy alone was associated with prolonged cancer specific survival (at 20 years 59% vs 18%, log rank p <0.001) and overall survival (at 20 years 22% vs 9%, log rank p <0.001). In Cox models prostatectomy plus orchiectomy vs orchiectomy alone was associated with improved cancer specific survival (HR 0.28, 95% CI 0.17-0.46, p <0.001) and overall survival (HR 0.48, 95% CI 0.34-0.66, p <0.001). Findings were similar in the subset with available preoperative prostate specific antigen values. CONCLUSIONS: With lifelong followup in nearly the entire cohort, this study demonstrates that adding radical retropubic prostatectomy to surgical castration for pathological node positive prostate cancer is associated with improved cancer specific and overall survival. When technically feasible in well selected patients, aggressive locoregional resection should be considered for node positive prostate cancer as part of a multimodal approach.

Severity of Preoperative Proteinuria is a Risk Factor for Overall Mortality in Patients Undergoing Nephrectomy.

PURPOSE: Chronic kidney disease may adversely affect survival following nephrectomy. Proteinuria is increasingly used as a marker of kidney disease. However, the relationship between preoperative proteinuria and survival after nephrectomy remains incompletely characterized. We evaluated the association of preoperative proteinuria with overall and cancer specific survival using our institutional nephrectomy registry. MATERIALS AND METHODS: We identified 1,846 patients with localized clear cell renal cell carcinoma treated with curative intent (radical or partial nephrectomy) between 1995 and 2010. Patients were categorized for analysis based on preoperative proteinuria severity (mild, moderate or severe). Overall and cancer specific survival was estimated by the Kaplan-Meier method. Cox proportional hazards regression models were used to assess for variables associated with overall and cancer specific mortality. RESULTS: Preoperative urine protein testing was available in 1,347 patients (73%). A total of 804 patients (60%) were classified with mild proteinuria (less than 150 mg per day), 332 (25%) were classified with moderate proteinuria (150 to 500 mg per day) and 211 (16%) were classified with severe proteinuria (greater than 500 mg per day). On multivariable analysis with mild proteinuria as the reference category the adjusted HR for all cause mortality was 1.18 (95% CI 0.95-1.48, p = 0.14) for moderate proteinuria and 1.61 (95% CI 1.26-2.07, p <0.001) for severe proteinuria. However, the proteinuria level was not associated with cancer specific survival. CONCLUSIONS: Severe preoperative proteinuria is associated with worse overall survival following radical or partial nephrectomy for localized clear cell renal cell carcinoma. Preoperative proteinuria should be evaluated in patients undergoing nephrectomy and considered when estimating overall patient health status.

Redefining and Contextualizing the Hospital Volume-Outcome Relationship for Robot-Assisted Radical Prostatectomy: Implications for Centralization of Care.

PURPOSE: Robot-assisted radical prostatectomy has undergone rapid dissemination driven in part by market forces to become the most frequently used surgical approach in the management of prostate cancer. Accordingly, a critical analysis of its volume-outcome relationship has important health policy implications. Therefore, we evaluated the association of hospital robot-assisted radical prostatectomy volume with perioperative outcomes, and examined the distribution of hospital procedure volume to contextualize the volume-outcome relationship. MATERIALS AND METHODS: We identified 140,671 men who underwent robot-assisted radical prostatectomy from 2009 to 2011 in NIS (Nationwide Inpatient Sample). The associations of hospital volume with perioperative outcomes and total hospital costs were evaluated using multivariable logistic regression and generalized linear models. RESULTS: In 2011, 70% of hospitals averaged 1 robot-assisted radical prostatectomy per week or less, accounting for 28% of surgeries. Compared to patients treated at the lowest quartile hospitals, those treated at the highest quartile hospitals had significantly lower rates of intraoperative complications (0.6% vs 1.4%), postoperative complications (4.8% vs 13.9%), perioperative blood transfusion (1.5% vs 4.0%), prolonged hospitalization (4.3% vs 13.8%) and mean total hospital costs ($12,647 vs $15,394, all ptrend <0.001). When modeled as a nonlinear continuous variable, increasing hospital volume was independently associated with improved rates of each perioperative end point up to approximately 100 robot-assisted radical prostatectomies per year, beyond which there appeared to be marginal improvement. CONCLUSIONS: Increasing hospital robot-assisted radical prostatectomy volume was associated with improved perioperative outcomes up to approximately 100 surgeries per year, beyond which there appeared to be marginal improvement. A substantial proportion of these procedures is performed at low volume hospitals.

Radical cystectomy for recurrent urothelial carcinoma after prior partial cystectomy: perioperative and oncologic outcomes.

PURPOSE: To evaluate perioperative and oncologic outcomes of patients undergoing radical cystectomy (RC) for recurrence of urothelial carcinoma (UC) after prior partial cystectomy (PC), and to compare these outcomes to patients undergoing primary RC. METHODS: Patients who underwent RC for recurrence of UC after prior PC were matched 1:3 to patients undergoing primary RC based on age, pathologic stage, and decade of surgery. Perioperative and oncologic outcomes were compared using Wilcoxon sign-rank test, McNemars test, the Kaplan-Meier method, and Cox proportional hazards regression analyses. RESULTS: Overall, the cohorts were well matched on clinical and pathological characteristics. No difference was noted in operative time (median 322 versus 303 min; p = 0.41), estimated blood loss (median 800 versus 700 cc, p = 0.10) or length of stay (median 9 versus 10 days; p = 0.09). Similarly, there were no differences in minor (51.7 versus 44.3%; p = 0.32) or major (10.3 versus 12.6%; p = 0.66) perioperative complications. Median follow-up after RC was 5.0 years (IQR 1.5, 13.1 years). Notably, CSS was significantly worse for patients who underwent RC after PC (10 year-46.8 versus 65.9%; p = 0.03). On multivariable analysis, prior PC remained independently associated with an increased risk of bladder cancer death (HR 2.28; 95% CI 1.17, 4.42). CONCLUSIONS: RC after PC is feasible, without significantly adverse perioperative outcomes compared to patients undergoing primary RC. However, the risk of death from bladder cancer may be higher, suggesting the need for careful patient counseling prior to PC and the consideration of such patients for adjuvant therapy after RC.

Oncologic surveillance following radical cystectomy: an individualized risk-based approach.

PURPOSE: To provide an alternative surveillance approach for bladder cancer (BC) following radical cystectomy (RC) according to more accurate predictions of a patient's projected BC course. METHODS: We identified 1797 patients who underwent RC for M0 BC between 1980 and 2007. Patients were stratified by pathologic stage (pT0Nx-0, pTa/CIS/1Nx-0, pT2Nx-0, pT3/4Nx-0, and pTanyN+), relapse location (urethra, upper tract, abdomen/pelvis, chest, and other), age (≤60, 61-70, 71-80, >80 years) and Charlson Co-morbidity Index (CCI ≤2 and CCI ≥3). Risks of disease recurrence and non-BC death were modeled using Weibull distributions. Recommended surveillance durations were estimated when the risk of non-BC death exceeded the risk of recurrence. RESULTS: At a median follow-up of 10.6 years (IQR 6.8,15.2), 713 patients developed recurrence. Vastly different recurrence patterns were appreciated. Specifically, among patients ≤60 years with pT2Nx-0, non-BC death risk exceeded the risk of recurrence in the abdomen at 7.5 years following surgery when CCI was ≥3, versus at year 10 after RC when CCI was ≤2. Meanwhile, for patients >80 years with pT2Nx-0, non-BC death risk exceeded the risk of abdominal recurrence at 1 year after RC, regardless of CCI. CONCLUSION: We present an alternative post-RC surveillance approach that incorporates a patient's changing risk profile with the influence of competing health factors. We believe this strategy provides more individualized recommendations than current guidelines, and may improve the benefit derived from surveillance while reducing resource misappropriation.

Risk Stratification of pN+ Prostate Cancer after Radical Prostatectomy from a Large Single Institutional Series with Long-Term Followup.

PURPOSE: Lymph node positive (pN+) prostate cancer after radical prostatectomy has wide variability in long-term oncologic outcomes. We present a large institutional series with extended followup to create an oncologic risk stratification system that clarifies the prognostic heterogeneity for patients with pN+ disease after radical prostatectomy. MATERIALS AND METHODS: Men with pN+ prostate cancer after radical prostatectomy during 1987 to 2012 were included in the study. Regression models were created to identify significant predictors of biochemical recurrence, metastasis, cancer specific mortality and overall mortality. A cancer specific mortality risk score was then created and internally validated to stratify patients in terms of risk of cancer specific mortality. RESULTS: For our cohort of 1,011 men with a median followup of 17.6 years the 20-year rate of cancer specific mortality was 31%. On multivariate Cox regression modeling 3 or more positive nodes (HR 1.75, p=0.003), pathological Gleason score 7 vs 6 (HR 1.74, p=0.04) and 8-10 vs 6 (HR 2.63, p=0.001), and positive surgical margins (HR 1.96, p=0.001) were significantly associated with increased cancer specific mortality, while adjuvant radiotherapy (HR 0.40, p=0.008) was associated with decreased cancer specific mortality. A cancer specific mortality risk score was then created using these 4 variables to stratify patients with markedly different prognoses, yielding 20-year cancer specific mortality rates of 19.1% vs 34% vs 46% (p <0.001) for low, intermediate and high risk categories, respectively. CONCLUSIONS: The prognosis of patients with pN+ prostate cancer varied significantly after radical prostatectomy. A risk score created using the number of positive nodes, pathological Gleason score, margin status and adjuvant radiotherapy status successfully separated patients into low, intermediate and high risk groups.

Decreased Skeletal Muscle Mass is Associated with an Increased Risk of Mortality after Radical Nephrectomy for Localized Renal Cell Cancer.

PURPOSE: We evaluate the association between severe skeletal muscle deficiency or sarcopenia, and disease progression, cancer specific mortality and all cause mortality in patients with localized renal cell carcinoma treated with radical nephrectomy. MATERIALS AND METHODS: The baseline lumbar skeletal muscle index of 387 patients treated with radical nephrectomy for nonmetastatic renal cell carcinoma between 2000 and 2010 was measured on preoperative computerized tomography. Sarcopenia was classified according to gender specific consensus definitions as male-skeletal muscle index less than 55 cm(2)/m(2) and female-skeletal muscle index less than 39 cm(2)/m(2). Progression-free, cancer specific and overall survival was estimated with the Kaplan-Meier method. Associations with progression, cancer specific mortality and all cause mortality were summarized with hazard ratios. RESULTS: Of 387 patients 180 (47%) had sarcopenia. Patients with sarcopenia were older, more likely to be male (77% vs 56%, p <0.001), to have a smoking history (67% vs 55%, p=0.02), and to have nuclear grade 3 or greater disease (67% vs 60%, p=0.05), but were otherwise similar to patients without sarcopenia. Median postoperative followup was 7.2 years. Patients with sarcopenia had inferior 5-year cancer specific survival (79% vs 85%, p=0.05) compared to those without sarcopenia, as well as significantly worse 5-year overall survival (65% vs 74%, p= 0.005). As a continuous variable, increasing skeletal muscle index was linearly associated with a decreased risk of cancer specific mortality and all cause mortality. Moreover, on multivariable analysis sarcopenia was associated with increased cancer specific mortality (HR 1.70, p=0.047) and all cause mortality (HR 1.48, p=0.039). CONCLUSIONS: Sarcopenia is independently associated with cancer specific mortality and all cause mortality after radical nephrectomy for renal cell carcinoma. These findings underscore the importance of assessing skeletal muscle index for risk stratification, patient counseling and treatment planning.

Standardizing the Definition of Biochemical Recurrence after Radical Prostatectomy-What Prostate Specific Antigen Cut Point Best Predicts a Durable Increase and Subsequent Systemic Progression?

PURPOSE: Multiple definitions of biochemical recurrence for prostate cancer exist after radical prostatectomy, and variation continues in prostate cancer outcome reporting and secondary treatment initiation. We reviewed long-term prostatectomy outcomes to assess the most appropriate prostate specific antigen cut point that predicts future disease progression. MATERIALS AND METHODS: We identified 13,512 patients with cT1-2N0M0 prostate cancer who underwent radical prostatectomy between 1987 and 2010. Single prostate specific antigen cut points of 0.2, 0.3, 0.4 and 0.5 ng/ml or greater, as well as confirmatory prostate specific antigen value definitions of 0.2 ng/ml or greater followed by prostate specific antigen greater than 0.2 ng/ml and 0.4 ng/ml or greater followed by prostate specific antigen greater than 0.4 ng/ml were tested. Continued prostate specific antigen increase after a designated cut point definition was estimated using cumulative incidence. The strength of association between biochemical recurrence definitions and subsequent systemic progression were analyzed using Cox proportional hazard models and the O'Quigley event based R(2) test. RESULTS: At a median postoperative followup of 9.1 years (IQR 4.9-14.3) a detectable prostate specific antigen developed in 5,041 patients and systemic progression developed in 512. After reaching the prostate specific antigen cut point of 0.2, 0.3 and 0.4 ng/ml, the percentage of patients experiencing a continued prostate specific antigen increase over 5 years was 61%, 67% and 74%, respectively, plateauing at 0.4 ng/ml. The strongest association between biochemical recurrence and systemic progression occurred using a single prostate specific antigen cut point of 0.4 ng/ml or greater (HR 36, R(2) 0.92). CONCLUSIONS: A prostate specific antigen cut point of 0.4 ng/ml or greater reflects the threshold at which a prostate specific antigen increase becomes durable and shows the strongest correlation with subsequent systemic progression. Consideration should be given to using a prostate specific antigen of 0.4 ng/ml or greater as the standard biochemical recurrence definition after radical prostatectomy.