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To describe the most recent 7 year experience with 137 Indiana pouch patients at a single institution and provide data on complications with this type of urinary diversion during the first postoperative year.We queried our bladder cancer database to identify all patients who underwent cystectomy with continent catheterizable urinary reservoir between 2012 and 2018. Pre-, intra-, and postoperative data were collected. Complications were stratified into early (within 90 days) and midterm (90-365 days). The primary outcomes were postoperative complications, and overall and cancer-specific mortality.A total of 137 patients underwent open cystectomy with Indiana pouch creation. Of these, 93% were radical cystectomies. On average, the operation took 422 minutes. There were 53 (39%) patients who experienced any type of complication during the first postoperative year (Clavien II-V). Twenty-five patients (18.2%) readmitted in the early postoperative period vs 18 (13.1%) patients midterm. There were 10 (7.3%) patients that required early reoperation and 11 (8%) in the midterm period. The overall mortality rate was 1.5% early and 3.7% midterm, with the majority of the mortality rate attributed to cancer progression (85.7%).Patients undergoing continent catheterizable reservoir urinary diversion appear to have comparable complication rates to other urinary diversions published in the literature. At high-volume urologic institutions, Indiana Pouch creation is a suitable option for select patients desiring a continent diversion.

Supplementary Table S2: Cystectomy Pathologic Staging

Supplementary Figure Legends

Purpose: To assess the clinical and pharmacodynamic activity of dovitinib in a treatment-resistant, molecularly enriched non–muscle-invasive urothelial carcinoma of the bladder (NMIUC) population.Experimental Design: A multi-site pilot phase II trial was conducted. Key eligibility criteria included the following: Bacillus Calmette-Guerin (BCG)-unresponsive NMIUC (>2 prior intravesical regimens) with increased phosphorylated FGFR3 (pFGFR3) expression by centrally analyzed immunohistochemistry (IHC+) or FGFR3 mutations (Mut+) assessed in a CLIA-licensed laboratory. Patients received oral dovitinib 500 mg daily (5 days on/2 days off). The primary endpoint was 6-month TURBT-confirmed complete response (CR) rate.Results: Between 11/2013 and 10/2014, 13 patients enrolled (10 IHC+ Mut−, 3 IHC+ Mut+). Accrual ended prematurely due to cessation of dovitinib clinical development. Demographics included the following: median age 70 years; 85% male; carcinoma in situ (CIS; 3 patients), Ta/T1 (8 patients), and Ta/T1 + CIS (2 patients); median prior regimens 3. Toxicity was frequent with all patients experiencing at least one grade 3–4 event. Six-month CR rate was 8% (0% in IHC+ Mut−; 33% in IHC+ Mut+). The primary endpoint was not met. Pharmacodynamically active (94–5,812 nmol/L) dovitinib concentrations in urothelial tissue were observed in all evaluable patients. Reductions in pFGFR3 IHC staining were observed post-dovitinib treatment.Conclusions: Dovitinib consistently achieved biologically active concentrations within the urothelium and demonstrated pharmacodynamic pFGFR3 inhibition. These results support systemic administration as a viable approach to clinical trials in patients with NMIUC. Long-term dovitinib administration was not feasible due to frequent toxicity. Absent clinical activity suggests that patient selection by pFGFR3 IHC alone does not enrich for response to FGFR3 kinase inhibitors in urothelial carcinoma. Clin Cancer Res; 23(12); 3003–11. ©2016 AACR.

Objective To characterize the health-related quality of life reported by patients who received an ileal conduit (IC), Indiana pouch, or neobladder urinary diversion after radical cystectomy. Materials and Methods The Functional Assessment of Cancer Therapy-Vanderbilt Cystectomy Index survey was administered to patients with bladder cancer undergoing radical cystectomy and urinary diversion from 2015-2018. Surveys were completed prior to radical cystectomy and then longitudinally throughout the postoperative course. Results A total of 146 patients completed questionnaires over a median of 12.3 months, 83 (56.8%) received an IC, 31 (21.2%) an Indiana pouch, and 32 (21.9%) an orthotopic neobladder. There were no significant differences in health related quality of life among urinary diversion groups considering the Trial Outcome Index scores, general overall FACT-G assessment, or total Functional Assessment of Cancer Therapy-Vanderbilt Cystectomy Index instruments. Patients who received IC were older and had higher Charlson Comorbidity Index scores (p Conclusions To our knowledge this is the first and largest quality of life analysis comparing all three methods of urinary diversion in a longitudinal fashion utilizing a standardized, validated, treatment-specific health survey. Proper preoperative counseling is critical to ensure understanding of the benefits of available urinary diversion.

Objective: To compare peri-operative factors and renal function following open partial nephrectomy (OPN) and robotic partial nephrectomy (RPN) for intermediate and high complexity tumors when contr...

To determine the benefits of alvimopan and multimodal pain management strategies in men undergoing retroperitoneal lymph node dissection for testicular cancer.A retrospective cohort study was completed in men undergoing retroperitoneal lymph node dissection from January 2017 to May 2018. Patients were placed into the 3-drug, 2-drug, and control cohorts as a result of a prospectively determined protocol during the study period. Men in the 3-drug group were managed using alvimopan 12 mg PO the morning of surgery then BID until bowel movement, gabapentin 300 mg daily, and acetaminophen 1,000 mg q6H. The 2-drug group was managed with the above regimen excluding alvimopan. Controls were treated per our standard perioperative pathway. Primary outcomes were length of stay, IV narcotic consumption, bowel movement during hospitalization, and time to bowel movement and assessed in multivariate models controlling for operative time, concomitant surgery, chemotherapy receipt, and residual mass size.One-hundred and fifty-two consecutive patients underwent RPLND (42 3-drug, 38 2-drug, and 72 controls). Multivariable models indicated that the 3-drug (IRR 0.89, P0.0001) and 2-drug group (IRR 0.87, P = 0.0209) had shorter hospital stays than controls. Men in the 3-drug group required less narcotic pain medication than the 2-drug (β -8.16, P = 0.0405) and the control (β -8.16, P = 0.0302) group. Men receiving alvimopan (3-drug) were almost 6 times more likely than the 2-drug group (odds ratio 5.94, P0.0001) and 4 times more likely than the control group (odds ratio 3.86, P = 0.0017) to have a bowel movement during hospitalization. Men in the 3-drug group had the quickest return of bowel movements.Multimodal pain management improves length of stay in men undergoing retroperitoneal lymph node dissection for testis cancer. The addition of alvimopan allows for quicker return of bowel movements and reduces overall narcotic requirements.

Introduction and objective: Traditionally, patients with renal masses in solitary kidneys were managed with an open partial nephrectomy. With improving techniques, robotic-assisted partial nephrectomy in the setting of a solitary kidney is increasingly utilized. The objective of this study was to compare open partial nephrectomy and robotic-assisted partial nephrectomy outcomes in solitary kidney patients. Methods: A retrospective study of 536 total patients who underwent partial nephrectomy between 2004–2016 was performed. Of these patients, 23 had a renal mass in a solitary kidney. Patient demographics, perioperative values, and surgical outcomes were analyzed using descriptive statistics to compare open partial nephrectomy to robotic-assisted partial nephrectomy. Results: Of the 23 patients in the cohort, 52% ( n=12) underwent open partial nephrectomy and 48% ( n=11) underwent robotic-assisted partial nephrectomy. Patient characteristics were not significantly different. The mean (standard deviation) nephrometry score was 6.9 (1.8) for open partial nephrectomy and 6.1 (1.9) for robotic-assisted partial nephrectomy ( p=0.290). The mean (standard deviation) pre-operative creatinine was 1.2 (0.3) in open partial nephrectomy and 1.5 (0.4) in robotic-assisted partial nephrectomy, which did not reach statistical significance ( p=0.110). No difference in postoperative kidney function, Clavien grade 3 or higher complication rate, blood loss, or hospitalization length was noted. Conclusion: Although traditionally patients with a tumor in a solitary kidney are counseled to undergo open partial nephrectomy, robotic-assisted partial nephrectomy is a safe alternative with no decrease in postoperative renal function when compared with a similar cohort of patients undergoing open partial nephrectomy in a solitary kidney. Level of evidence: Level II

Residual retrocrural disease in testis cancer following chemotherapy is a surgical challenge. We sought to assess the outcomes and evolution with surgical management of residual retrocrural disease.We identified 2,788 testicular cancer patients from 1990 to 2010 who underwent retroperitoneal surgery for metastatic testicular cancer at our institution. Patients who also underwent postchemotherapy staged or concurrent retrocrural dissections were stratified for analysis. Surgical approach, clinical characteristics, additional procedures, complications and outcomes were evaluated.Retrocrural dissection was performed in 211 patients. Histology of retrocrural disease demonstrated teratoma in 72%, necrosis in 15.2%, active germ cell cancer in 8.1% and malignant transformation in 2.4%. Our preferred surgical approach to the retrocrural space has evolved over time. Earlier approaches from 1990 to 1995 favored a single thoracoabdominal incision (17, 25%), midline transabdominal incision (22, 32.4%), or with a concurrent or staged thoracotomy (29, 42.6%). A transabdominal/transdiaphragmatic approach at the time of midline retroperitoneal lymph node dissection has been used more frequently in 55% of contemporary cases, decreasing the need for thoracotomies. Patients undergoing a transabdominal/transdiaphragmatic approach had fewer complications (p=0.006) and required fewer associated procedures (p=0.001) and a shorter length of stay (5 vs 6 days, p=0.184).Metastatic testis cancer to the retrocrural space is surgically challenging however complete resection is needed to maintain an expected excellent oncologic outcome. Coordination between urological and thoracic surgeons for an individualized approach is important. We have found that a transabdominal/transdiaphragmatic approach where appropriate has resulted in fewer complications.

The purpose of this study was to evaluate the effect of neoadjuvant chemotherapy (NACT) on squamous variant (SV) bladder cancer by investigating patients presenting with SV histology at the time of transurethral resection (TUR), stratified by their receipt of NACT.The records of 71 patients with muscle-invasive bladder cancer and SV in the TUR specimen who underwent cystectomy between 2008 and 2018 were reviewed. Our primary outcome was pathologic response at time of cystectomy. Secondary outcomes included recurrence-free survival and overall survival stratified by receipt of NACT. A subgroup analysis was then conducted on the patients with defined SV% on TUR stratified by % involvement (50% SV vs. ≥ 50% SV).The median age of the NACT and no-NACT groups was 60.2 and 70 years, respectively (P = .003). The complete response rate at cystectomy was 60% versus 13.7% for the NACT and no-NACT groups, respectively (P .001). The non-organ-confined disease rate at time of radical cystectomy was 35% for the NACT group and 68.6% for the no-NACT group (P = .01). The NACT group had fewer recurrences than the no-NACT group (10% vs 47.1%; P = .003). In the subgroup analysis, the lower rate of non-organ-confined disease persisted for the patients who underwent NACT at the lower SV percentage but failed to remain significant at greater percentage involvement. This was also true for overall survival.The effect of NACT in variant histology bladder cancer is variable. In patients with SV, these results favor the recommendation in favor of NACT administration, particularly when the primary tumor has 50% involvement by the variant histology.

INTRODUCTION AND OBJECTIVE:Complication rates following cystectomy range from 40-80% with 75% of complications being related to the urinary diversion. Reported complication following continent cuta...

To evaluate the long-term (5 years) health-related quality of life (HRQOL) outcomes following radical cystectomy, comparing Indiana pouch (IP), neobladder (NB), and ileal conduit (IC).The departmental radical cystectomy database was queried to identify patients who underwent radical cystectomy and urinary diversion for bladder cancer between 1991 and 2009 and had not died. Three hundred patients were identified and sent the validated Bladder Cancer Index instrument.A total of 128 (43%) patients completed the survey. When adjusted for gender, age at surgery, surgeon, and time since surgery, IC and IP patients had significantly better urinary function than NB patients (P = .0013). Sexual bother was less in NB than IP (P = .0387). Among men ≥65 years of age, IC patients had significantly better urinary function (P = .0376) than NB patients (91.6 vs 49.4, respectively). Among men 65 years of age, IC and IP patients (76.0 and 82.8, respectively) had significantly better urinary function than NB patients (50.7) (P = .0199). Among women greater than 65 years, bowel bother was significantly better (P = .0095) for IC patients than IP patients (44.8 vs 69.5, respectively).Urinary diversion type after radical cystectomy affects HRQOL differently in long-term survivors. Age and gender at surgery influenced HRQOL based on diversion procedure. Urinary function but not urinary bother was significantly better in IC and IP compared to NB diversions. Prospective longitudinal studies using validated HRQOL tools will further help guide preoperative diversion choice decisions between patient and surgeon.

Background Carcinoma in situ (CIS) is a poor prognostic finding in urothelial carcinoma. However, its significance in muscle-invasive urothelial carcinoma (MIUC) treated with neoadjuvant chemotherapy (NAC) is uncertain. We assessed the effect of CIS found in pretreatment transurethral resection of bladder tumor (TURBT) biopsies on the pathologic and clinical outcomes. Materials and Methods Subjects with MIUC treated with NAC before cystectomy were identified. The pathologic complete response (pCR) rates stratified by TURBT CIS status were compared. The secondary analyses included tumor response, progression-free survival (PFS), overall survival (OS), and an exploratory post hoc analysis of patients with pathologic CIS only (pTisN0) at cystectomy. Results A total of 137 patients with MIUC were identified. TURBT CIS was noted in 30.7% of the patients. The absence of TURBT CIS was associated with a significantly increased pCR rate (23.2% vs. 9.5%; odds ratio, 4.08; 95% confidence interval, 1.19-13.98; P = .025). Stage pTisN0 disease was observed in 19.0% of the TURBT CIS patients. TURBT CIS status did not significantly affect the PFS or OS outcomes. Post hoc analysis of the pTisN0 patients revealed prolonged median PFS (104.5 vs. 139.9 months; P = .055) and OS (104.5 vs. 152.3 months; P = .091) outcomes similar to those for the pCR patients. Conclusion The absence of CIS on pretreatment TURBT in patients with MIUC undergoing NAC was associated with increased pCR rates, with no observed differences in PFS or OS. Isolated CIS at cystectomy was frequently observed, with lengthy PFS and OS durations similar to those for pCR patients. Further studies aimed at understanding the biology and clinical effect of CIS in MIUC are warranted.

Partial nephrectomy (PN) reduces the risk of postoperative chronic renal insufficiency (CRI). However, some patients still develop CRI after PN, and may eventually require dialysis. Being able to predict renal function before PN helps in counseling patients and managing expectations. We aimed to construct nomograms that predict estimated glomerular filtration rates (eGFRs), defined by the modification of diet in renal disease (MDRD) and the chronic kidney disease epidemiology collaboration (CKD-EPI) formulae, at 1 year after PN, using only preoperative covariates as predictors.We identified patients who underwent PN in our institution between 2004 and 2016, with known postoperative serum creatinine levels at 1 year. The preoperative covariates included patients' demographics, chronic comorbid conditions, tumor characteristics, and preoperative renal status. The endpoints were eGFRs at 1 year after PN, calculated using the MDRD and the CKD-EPI formulae. We first identified preoperative covariates with significant associations with the endpoints by Pearson correlation and independent samples t-test. Suitable covariates were then included in two multivariate linear regression models, for constructing and internally validating two nomograms.461 patients were eligible for analysis. The percentage of patients with eGFR below 60 mL/min/1.73 mWe constructed and internally validated two nomograms to predict eGFRs at 1 year after PN, using only preoperative covariates as predictors.

Primary choriocarcinoma of the urinary bladder is a rare entity, and should be distinguished from urothelial carcinoma with trophoblastic differentiation. The leading treatment modalities include surgical extirpation, chemotherapy, and radiation; however, survival remains poor. Herein we describe a rare case of choriocarcinoma of the bladder in a man who presented for evaluation with hematuria and subsequently underwent radical cystectomy with urinary diversion. Diagnosis of extragonadal germ cell tumor was confirmed using fluorescence in situ hybridization identification of isochromosome 12p.

Retroperitoneal lymph node dissection is an integral part of the management of testicular cancer. Surgical approach and outcomes have improved over the past decades. Several factors influence the complexity of the operation, including numerous patient characteristics and disease-related characteristics. An important consideration lies in the fact that this is largely a vascular operation, and techniques of vascular control should be comfortable for the urologic surgeon performing the procedure. This article discusses the known surgical complications related to this operation and their relative incidence reported throughout the literature.

INTRODUCTION AND OBJECTIVES:The use of Alvimopan and multi-modality pain management in enhanced recovery after surgery (ERAS) protocols has improved outcomes after numerous surgical procedures. We ...

Aim: We compared the efficacy of methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) versus gemcitabine/cisplatin in urothelial cancer and neoadjuvant chemotherapy (NACT) efficacy in variant histology (VH). Materials & methods: Radical cystectomy patients were retrospectively compared with those who received NACT. Factors associated with survival, pathologic complete response (pCR) and downstaging (pDS) were evaluated in multivariable models. Results: 9% of radical cystectomy patients (84/919) received NACT, with improved survival, pCR and pDS on both regimens. MVAC lead to higher pDS without an increase in pCR. On multivariable analysis, there was a nonsignificant increase in pDS with MVAC. NACT conferred similar responses in squamous and glandular differentiation VH. Conclusion: NACT was associated with improved survival, pCR and pDS. Furthermore, responses to NACT were not dependent on presence of VH.

Background Carcinoma in situ (CIS) is a poor prognostic finding in urothelial carcinoma. However, its significance in muscle-invasive urothelial carcinoma (MIUC) treated with neoadjuvant chemotherapy (NAC) is uncertain. We assessed the effect of CIS found in pretreatment transurethral resection of bladder tumor (TURBT) biopsies on the pathologic and clinical outcomes. Materials and methods Subjects with MIUC treated with NAC before cystectomy were identified. The pathologic complete response (pCR) rates stratified by TURBT CIS status were compared. The secondary analyses included tumor response, progression-free survival (PFS), overall survival (OS), and an exploratory post hoc analysis of patients with pathologic CIS only (pTisN0) at cystectomy. Results A total of 137 patients with MIUC were identified. TURBT CIS was noted in 30.7% of the patients. The absence of TURBT CIS was associated with a significantly increased pCR rate (23.2% vs. 9.5%; odds ratio = 4.08; 95% CI: 1.19–13.98; P = 0.025). Stage pTisN0 disease was observed in 19.0% of the TURBT CIS patients. TURBT CIS status did not significantly affect the PFS or OS outcomes. Post hoc analysis of the pTisN0 patients revealed prolonged median PFS (104.5 vs. 139.9 months; P = 0.055) and OS (104.5 vs. 152.3 months; P = 0.091) outcomes similar to those for the pCR patients. Conclusion The absence of CIS on pretreatment TURBT in patients with MIUC undergoing NAC was associated with increased pCR rates, with no observed differences in PFS or OS. Isolated CIS at cystectomy was frequently observed, with lengthy PFS and OS durations similar to those for pCR patients. Further studies aimed at understanding the biology and clinical effect of CIS in MIUC are warranted.

Radiation-induced ureteral stricture disease poses significant surgical challenges. Ureteral substitution with ileum has long been a versatile option for reconstruction. We evaluated outcomes in patients undergoing ileal ureter replacement for ureteral reconstruction due to radiation-induced ureteral stricture versus other causes. Between July 1989 and June 2013, 155 patients underwent consecutive ileal ureter creation. The study cohort included 104 patients with complete data sets and at least 7 months of follow up. Records were retrospectively reviewed with regard to demographics, indications, complications, and renal deterioration. Surgical indications included radiation-induced stricture in 23 (22%) and non-radiation-induced stricture in 81 (78%). Comparing ileal ureter substitution due to radiation versus other stricture etiologies, no statistical significance was observed in regard to age (45.6 vs. 51.2, p = 0.141), hospital length of stay in days (8.8 vs. 7.7, p = 0.216), percent GFR loss (MDRD-4 vs. -5%, p = 0.670 and CKD-EPI-7 vs. -6%, p = 0.914), 30-day surgical complications (26.1 vs. 30.1%, p = 0.658), metabolic acidosis (8.7 vs. 1.2%, p = 0.059), and renal failure requiring dialysis (4.3 vs. 1.2%, p = 0.337). Fistula formation (13.0 vs. 3.7%, p = 0.095), partial small bowel obstructions (21.7 vs. 7.4%, p = 0.063), and small bowel obstructions requiring reoperation (13.0 vs. 1.2%, p = 0.033) approached or reached statistical significance. Using Kaplan–Meier methodology, there was no difference in time to worsening renal outcome between the radiation and non-radiation groups (p > 0.05). Ureteral substitution with ileum is an effective reconstructive option for radiation-induced ureteral strictures in carefully selected patients.

Objective To evaluate the oncologic outcomes of patients with retroperitoneal teratoma only at primary retroperitoneal lymph node dissection (RPLND) who did not receive adjuvant chemotherapy. Materials and Methods Between 1979 and 2010, 23 patients with clinical stage (CS) I and II disease underwent primary RPLND at our institution with teratoma only in the retroperitoneum. No patient received adjuvant chemotherapy and the minimum follow-up was 2 years. Results At the initial diagnosis, 13 patients (56.5%) had CS I disease and 10 patients (43.5%) had CS II disease. Pathologic staging demonstrated IIA in 13 patients (56.5%), IIB in 8 patients (34.8%), and IIC in 2 patients (8.7%). The 5-year disease-free survival (DFS) was 100% with a median follow-up of 5.8 years (range, 2.1-25.4). DFS was not significantly different comparing pathologic stage IIA vs IIB/IIC disease ( P = .73). Two patients (14%) developed late relapses. One patient had a pelvic recurrence 11 years after primary RPLND. Final pathology from the pelvic resection demonstrated embryonal carcinoma. He remains disease free after his second surgery. The second patient had a contralateral retroperitoneal recurrence with yolk-sac tumor and teratoma 11 years after primary RPLND. He was treated with chemotherapy followed by postchemotherapy RPLND. Conclusion The relapse rate for patients with teratoma only at primary RPLND is low irrespective of PS. Adjuvant chemotherapy is therefore not recommended in the management of these patients.

Objectives To assess the effect of non-squamous differentiation (non-SQD) variant histology on survival in muscle-invasive bladder urothelial cancer (UC). Patients and Methods A cohort of 411 radical cystectomy (RC) cases performed with curative intent for muscle-invasive primary UC was identified between 2008 and June 2013. Survival analysis was evaluated using Kaplan–Meier methodology comparing non-variant (NV) + SQD histology to non-SQD variant histology (non-SQD variants). Multivariable cox proportional hazards regression assessed all-cause and disease-specific mortality. Results Of the 411 RC cases, 77 (19%) had non-SQD variant histology. The median overall survival (OS) for non-SQD variant histology was 28 months, whereas the NV+SQD group had not reached the median OS at 74 months (log-rank test P < 0.001). After adjusting for sex, age, pathological stage, and any systemic chemotherapy, patients with non-SQD variant histology at RC had a 1.57-times increased adjusted risk of all-cause mortality (P = 0.027) and 1.69-times increased risk of disease-specific mortality (P = 0.030) compared with NV+SQD patients. Conclusions While SQD behaves similarly to NV, non-SQD variant histology portends worse OS and disease-specific survival regardless of neoadjuvant or adjuvant chemotherapy and pathological stage. Non-SQD variants of UC could perhaps be considered a distinct clinical entity in UC with goals for developing new treatment algorithms through novel clinical trials.

ABSTRACT Aim: To evaluate a three-tiered prognostic stratification using one, two to five and >five positive lymph nodes (LNs) and this nodal staging system performs across different pelvic LN dissection (PLND) templates and adjuvant chemotherapy status. Methods: We evaluated 244 patients with positive LN urothelial cancer who underwent radical cystectomy and PLND between 2000 and 2011. Survival analyses utilizing the Kaplan-Meier method and log rank test were performed. Median follow-up was 55.3 months (range: 0.4–141). Multivariable Cox proportional hazards models were built to evaluate the prognostic stratification. Results: Extended PLND template was performed on 152 (62.3%) patients and standard on 92 (37.7%). The median number of LNs resected was 14 in the standard group vs 22 in the extended group (p < 0.01) and positive LNs was 2 vs 3 (p = 0.09), respectively. Stratification in patients with: one positive LN, two to five positive LNs or >five positive LNs lead to 5-year recurrence-free survival of: 48.6, 34.5 and 15.9% for each group, while the 5-year overall survival was: 43.0, 22.1 and 11.3%, respectively. Stratification in the three groups was also verified irrespective of PLND template and adjuvant chemotherapy. Two multivariable models confirmed the findings when controlling for demographic features and known pathologic risk factors. Conclusion: Three-tiered nodal classification system using the number of metastatic LNs (one, two to five and >five) stratifies patients with lymphatic disease into distinct prognostic groups.

Viable seminoma encountered at post-chemotherapy retroperitoneal lymph node dissection for pure testicular seminoma is rare due to the chemosensitivity of this germ cell tumor. In this study we define the natural history of viable seminoma at post-chemotherapy retroperitoneal lymph node dissection.The Indiana University testis cancer database was queried from 1988 to 2011 to identify all patients with primary testicular or retroperitoneal pure seminoma and who were found to have pure seminoma at post-chemotherapy retroperitoneal lymph node dissection. Clinical characteristics were reviewed and survival analysis was performed.A total of 36 patients met the study inclusion criteria. All patients received standard first line cisplatin based chemotherapy and 17 received salvage chemotherapy. The decision to proceed to retroperitoneal lymph node dissection was based on enlarging retroperitoneal mass and/or positron emission positivity in the majority of cases. Seven patients had undergone previous retroperitoneal lymph node dissection. Additional surgical procedures were required in 19 patients to achieve a complete resection. The 5-year cancer specific survival rate was 54%. However, only 9 of 36 patients remained continuously free of disease and of these patients 4 received adjuvant chemotherapy. Mean time from post-chemotherapy retroperitoneal lymph node dissection to death was 6.9 months. Second line chemotherapy, reoperative retroperitoneal lymph node dissection and earlier era of treatment were associated with poorer cancer specific survival.A total of 36 patients with pure seminoma were found to have viable pure seminoma at post-chemotherapy retroperitoneal lymph node dissection. While 5-year cancer specific survival was 54%, these surgeries are technically demanding and only a minority of patients achieves a durable cure from surgery alone.

Background Radical cystectomy (RC) for bladder cancer is frequently associated with delayed gastrointestinal (GI) recovery that prolongs hospital length of stay (LOS). Objective To assess the efficacy of alvimopan to accelerate GI recovery after RC. Design, setting, and participants We conducted a randomized double-blind placebo-controlled trial in patients undergoing RC and receiving postoperative intravenous patient-controlled opioid analgesics. Intervention Oral alvimopan 12mg (maximum: 15 inpatient doses) versus placebo. Outcome measurements and statistical analysis The two-component primary end point was time to upper (first tolerance of solid food) and lower (first bowel movement) GI recovery (GI-2). Time to discharge order written, postoperative LOS, postoperative ileus (POI)-related morbidity, opioid consumption, and adverse events (AEs) were evaluated. An independent adjudication of cardiovascular AEs was performed. Results and limitations Patients were randomized to alvimopan ( n =143) or placebo ( n =137); 277 patients were included in the modified intention-to-treat population. The alvimopan cohort experienced quicker GI-2 recovery (5.5 vs 6.8 d; hazard ratio: 1.8; p p =0.0051), and fewer episodes of POI-related morbidity (8.4% vs 29.1%; p p =0.09). Generalizability may be limited due to the exclusion of epidural analgesia and the inclusion of mostly high-volume centers utilizing open laparotomy. Conclusions Alvimopan is a useful addition to a standardized care pathway in patients undergoing RC by accelerating GI recovery and shortening LOS, with a safety profile similar to placebo. Patient summary This study examined the effects of alvimopan on bowel recovery in patients undergoing radical cystectomy for bladder cancer. Patients receiving alvimopan experienced quicker bowel recovery and had a shorter hospital stay compared with those who received placebo, with comparable safety. Trial registration ClinicalTrials.gov identifier NCT00708201

Objectives Plasmacytoid variant (PCV) urothelial cancer (UC) of the bladder is rare, with poor clinical outcomes. We sought to identify factors that may better inform expectations of tumor behavior and improve management options in patients with PCV UC. Materials and methods A retrospective analysis of the Indiana University Bladder Cancer Database between January 2008 and June 2013 was performed comparing 30 patients with PCV UC at cystectomy to 278 patients with nonvariant (NV) UC at cystectomy who underwent surgery for muscle-invasive disease. Multivariable logistic regression was used to assess precystectomy variables associated with non–organ-confined disease at cystectomy and Cox regression analysis to assess variables associated with mortality. Results Patients with PCV UC who were diagnosed with a higher stage at cystectomy (73% pT3-4 vs. 40%, P = 0.001) were more likely to have lymph node involvement (70% vs. 25%, P Conclusions PCV is an aggressive UC variant, predicting non–organ-confined disease and poor survival. Differentiating between non–muscle- and muscle-invasive disease in patients with PCV UC seems less important than the aggressive nature of this disease. Instead, any evidence of PCV on transurethral resection of bladder tumor may warrant aggressive therapy.

While reoperative retroperitoneal lymph node dissection results in durable long-term survival, outcomes are comparatively worse than in patients who undergo initial adequate resection. We identified predictors of cancer specific survival and correlated technical aspects of initial resection to local recurrence in patients treated with repeat retroperitoneal lymph node dissection.We reviewed subsequent data on 203 patients treated with reoperation for recurrent retroperitoneal germ cell tumor after initial retroperitoneal lymph node dissection with local relapse. We used multivariate Cox proportion hazard models for cancer specific survival and multivariate logistic regression for local recurrence.The only 2 factors associated with local recurrence at lymph node dissection were incomplete lumbar vessel division at initial resection (p0.01) and teratoma histology in the reoperative pathology specimen (p=0.01). Median followup was 73 months. Initial survival analysis including preoperative variables indicated that active cancer at initial operation (p=0.04), increased serum tumor markers (p=0.02), M1b stage (p0.01) and salvage chemotherapy (p=0.01) were independent predictors of worse cancer specific survival. After introducing the final pathological data from reoperation into the final multivariate model only active cancer at reoperation (p0.01), M1b stage (p=0.01) and salvage chemotherapy before reoperation (p=0.02) retained the association with worse oncologic outcomes.Tumor biology and inadequate surgical technique (incomplete lumbar ligation) are associated with local recurrence after initial retroperitoneal lymph node dissection. Decreased cancer specific survival is expected in this population, mostly driven by active cancer in the final pathology specimen.

Objective To examine differences in disease progression and nature of tumor invasion that may lead to more accurate expectations of tumor behavior and improved management options for plasmacytoid variant (PCV) histology urothelial bladder cancer patients. Methods Using the Indiana University Bladder Cancer Database, we conducted a retrospective analysis of patients undergoing radical cystectomy from 2008 to June 2013 to identify patients with PCV, micropapillary variant (MPV), or nonvariant (NV) histology and either positive ureteral margins (+UM), paravesical surgical margins (+PSM), or lymph node (+LN) involvement. Pearson's chi-squared test and analysis of variance were used for descriptive analysis. Results Of 510 patients who met inclusion criteria, 30 had +UM on final pathology. The incidence of +UM in NV patients was 17 of 457 (3.7%), in MPV 5 of 28 (17.9%), and in PCV 8 of 25 (32.0%) ( P Carcinoma in situ on the luminal margin was noted for all cases, except in 5 of the 8 PCV patients with +UM, in whom retrograde longitudinal invasion along the subserosal and adventitia was noted. +PSM and +LN were significantly higher for both PCV (28.0%, 72.0%) and MPV (10.7%, 64.3%) than NV (2.6%, 18.6%, P Conclusion PCV exhibits a unique pattern of spread along the ureter. This proposes a new mode of invasion along the fascial sheath. The incidence of +PSM and +LN liken PCV to the known aggressive MPV, and in conjunction with the increased incidence of +UM, may lead to a paradigm shift, with surgeons and pathologists being more vigilant with surgical margins.

We evaluate the incidence and risk factors of parastomal hernia formation in patients undergoing radical cystectomy and ileal conduit urinary diversion.We retrospectively reviewed the Indiana University cystectomy database between 2001 and 2011, and identified 516 patients who underwent radical cystectomy and ileal conduit diversion. Overall 199 patients had a clinical followup of at least 12 months and all underwent postoperative staging computerized tomography to confirm the presence of parastomal hernia. The incidence of parastomal hernia is reported with correlations made to demographic, patient level and perioperative risk factors.A parastomal hernia developed in 58 patients (29%) at a median followup of 27 months (range 12 to 125). Of these patients 26 (45%) underwent surgical repair due to abdominal discomfort (58%), acute strangulation or obstruction of the small bowel (15%), partial small bowel obstructions (15%) and elective repair for other intra-abdominal procedures (12%). Prior exploratory laparotomy (adjusted HR 1.98, 95% CI 1.97-3.36, p = 0.011) and severe obesity (adjusted HR 4.26, 95% CI 1.52-11.93, p = 0.006) were predictive of parastomal herniation. The cumulative risk of parastomal hernia formation at 1 and 2 years after cystectomy was 12.2% and 22.5%, respectively.We demonstrated that parastomal hernia will develop in nearly a third of patients after radical cystectomy with ileal conduit diversion. Prior laparotomy and severe obesity are independent risk factors. Preoperative counseling and preventative measures regarding parastomal hernia formation should be emphasized, particularly in these at risk patients.

Objective To report our experience, and to evaluate the long-term outcomes and complication profiles of ventral onlay buccal mucosal graft urethroplasty (BMU) after prior urological intervention. Methods We retrospectively reviewed 114 consecutive patients between February 2001 and April 2009 who underwent buccal mucosal graft urethroplasty for recurrent anterior urethral stricture disease. Seven patients were excluded for incomplete data. The remaining 107 patients comprised the study cohort. The mean follow-up time was 39.3 months (range 6.6–127.3 months). All patients had prior urological attempts at operative management. Results The mean stricture length was 3.14 cm (range 1.0–8.0 cm). Indications for buccal mucosal graft urethroplasty included: lichen sclerosis (2.8%), iatrogenic (24.3%), infection (4.7%) and perineal trauma/straddle injury (20.6%). Of these patients, 78 had bulbo-membranous stricture disease, 20 had penile involvement and nine were multifocal strictures. The average number of prior urological procedures was 2.83 (range 1–9). The overall graft failure rate was 6.5%. Importantly, the re-operation rate was 20.6%, primarily for stricture recurrence (18), meatal stenosis (3) and urethral diverticulum. The mean time to complication was 10.8 months. Conclusions Ventral onlay buccal mucosal graft urethroplasty offers satisfactory results in the setting of recurrent and complicated urethral stricture disease. Graft failures and complications generally occur within the first year after surgery. Bulbar strictures enjoy greater graft patency and lower complication rates than other stricture locations. In particular, guarded expectations should be given for stricture length >4 cm and multifocal disease.

We determined the clinical and pathological features associated with nephrectomy at post-chemotherapy retroperitoneal lymph node dissection.We retrospectively reviewed the testis cancer database from 1980 to 2007 to identify all patients treated with post-chemotherapy retroperitoneal lymph node dissection. Patients with pure seminoma and nongerm cell histology were excluded from study. A total of 1,807 patients were identified, of whom 17 without recorded mass size were excluded from further study. Pathological and clinical variables were assessed by bivariate analysis. Multivariate logistic regression was used to determine predictors of nephrectomy at post-chemotherapy retroperitoneal lymph node dissection.The overall incidence of nephrectomy at post-chemotherapy retroperitoneal lymph node dissection was 14.8% (265 of 1,790 cases). The incidence of nephrectomy was 17.0%, 18.9%, 13.6% and 8.0% in 1980 to 1988 (group 1), 1989 to 1997 (group 2), 1998 to 2002 (group 3) and 2002 to 2007 (group 4) (p = 0.0001). The nephrectomy rate for tumors less than 2, 2 to 5, 5 to 10 and greater than 10 cm was 6.0%, 5.8%, 13.9% and 31.9%, respectively (p = 0.0001). The incidence of nephrectomy based on retroperitoneal histology was 10.3% for fibrosis, 14.5% for teratoma and 20.4% for cancer (p = 0.0001). The strongest predictor of nephrectomy at post-chemotherapy retroperitoneal lymph node dissection was retroperitoneal mass size greater than 10 cm (OR 9.30, 95% CI 3.8-22.7).The incidence of nephrectomy at post-chemotherapy retroperitoneal lymph node dissection has decreased in the last 3 decades. A higher incidence was observed in patients with larger volume tumors, those who received salvage chemotherapy, those with a left primary testicular tumor and those with increased markers at post-chemotherapy surgery.

Purpose: To assess the clinical and pharmacodynamic activity of dovitinib in a treatment-resistant, molecularly enriched non–muscle-invasive urothelial carcinoma of the bladder (NMIUC) population. Experimental Design: A multi-site pilot phase II trial was conducted. Key eligibility criteria included the following: Bacillus Calmette-Guerin (BCG)-unresponsive NMIUC (>2 prior intravesical regimens) with increased phosphorylated FGFR3 (pFGFR3) expression by centrally analyzed immunohistochemistry (IHC+) or FGFR3 mutations (Mut+) assessed in a CLIA-licensed laboratory. Patients received oral dovitinib 500 mg daily (5 days on/2 days off). The primary endpoint was 6-month TURBT-confirmed complete response (CR) rate. Results: Between 11/2013 and 10/2014, 13 patients enrolled (10 IHC+ Mut−, 3 IHC+ Mut+). Accrual ended prematurely due to cessation of dovitinib clinical development. Demographics included the following: median age 70 years; 85% male; carcinoma in situ (CIS; 3 patients), Ta/T1 (8 patients), and Ta/T1 + CIS (2 patients); median prior regimens 3. Toxicity was frequent with all patients experiencing at least one grade 3–4 event. Six-month CR rate was 8% (0% in IHC+ Mut−; 33% in IHC+ Mut+). The primary endpoint was not met. Pharmacodynamically active (94–5,812 nmol/L) dovitinib concentrations in urothelial tissue were observed in all evaluable patients. Reductions in pFGFR3 IHC staining were observed post-dovitinib treatment. Conclusions: Dovitinib consistently achieved biologically active concentrations within the urothelium and demonstrated pharmacodynamic pFGFR3 inhibition. These results support systemic administration as a viable approach to clinical trials in patients with NMIUC. Long-term dovitinib administration was not feasible due to frequent toxicity. Absent clinical activity suggests that patient selection by pFGFR3 IHC alone does not enrich for response to FGFR3 kinase inhibitors in urothelial carcinoma. Clin Cancer Res; 23(12); 3003–11. ©2016 AACR.

To assess long-term renal preservation and surgical outcomes in patients undergoing ureteric substitution with ileum. This has been a mainstay of reconstruction options for lengthy ureteral defects.Consecutive patients aged 18 or older undergoing ileal ureters at our institution were retrospectively reviewed (from 1989 to June 2013). Patients with6 months of follow-up were excluded. Demographic, surgical, and renal functional outcomes were reviewed. Renal function was assessed by the Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease Study equations.Of the 108 patients meeting the inclusion criteria, 86 (79.6%) had single-renal unit reconstruction and 22 had bilateral reconstruction. Eighty-four (77.8%) had radiation-induced stricture and 24 had iatrogenic or trauma-induced strictures. The median follow-up was 51 months (interquartile range: 22-112). Short-term complications included Clavien grade I (16 [14.8%]), Clavien grade II (3 [2.8%]), Clavien grade III (9 [8.3%]), and Clavien grade IV (3 [2.8%]). Long-term complications included fistula in 6 patients (5.6%), renal failure requiring dialysis in 2 patients (1.9%), hyperchloremic metabolic acidosis in 4 patients (3.7%), and incisional hernia in 11 patients (10.2%). Nine patients (8.3%) had small-bowel obstructions; 3 (2.8%) required adhesiolysis. Four patients (3.7%) had an anastamotic stricture. Nineteen patients (17.6%) had worsening renal function. Cox proportional hazards regression found that those with bilateral repair were at 3.7 times increased risk of worsening renal function (P = .02).Ureteral substitution with ileum provides an effective and versatile long-term reconstructive option with minimal renal function compromise in properly selected patients. Bilateral reconstruction may contribute to worse long-term renal function.

To evaluate the clinicopathologic features and predictors of pelvic metastasis in patients with germ cell tumors.Between 1990 and 2009, 2722 patients undergoing retroperitoneal lymph node dissection (RPLND) were prospectively included in our institution's testis cancer database. Patients with pelvic disease were identified and clinicopathologic features were analyzed.Of the 134 patients, 14.5% had a history of prior groin surgery. At the time of referral, 98% had received prior chemotherapy, 19.4% had undergone prior RPLND, and 24% presented as late relapse. Surgery consisted of pelvic excision alone in 37 (27.6%) and pelvic excision with primary RPLND in 2 (1.5%) or with postchemotherapy RPLND in 95 (70.9%). Median pelvic mass size was 6.5 cm. Pathology of pelvic disease revealed teratoma in 74 (55%), nonseminomatous germ cell tumor in 28 (21%), sarcoma in 8 (6%), and necrosis in 22 (16.5%). Patients with pelvic metastases had a statistically higher initial stage of presentation (P .001) and had a higher incidence of prior groin surgeries (P .001).Pelvic metastasis in testicular cancer is uncommon and can be a site of late relapse. These patients tend to present with high-volume retroperitoneal disease or a history of prior groin surgeries. Surgery is curative in most patients, and pelvic pathology was teratoma in more than half.

INTRODUCTION AND OBJECTIVES: Bladder cancer (BCa), may present with variant morphologic features that deviate from the urothelial common aspect. These characteristics that can be defined as pure or mixed variants may have prognostic and therapeutic implications. METHODS: We retrospectively evaluated histopathological data from 1,067 BCa patients treated with radical cystectomy (RC) and PLND for BCa between 1990 and 2013 at a single tertiary care referral center. All specimen were evaluated by dedicated uropathologists. Uniand multivariate Cox regression analyses tested the impact of different histopathological variant CSM (cancer specific mortality) and OM (overall mortality) after accounting for age at surgery, pathological N stage, use of perioperative chemotherapy, number of positive nodes, number of removed nodes, positive surgical margin, pathological T stage, lymph vascular invasion, use of adjuvant chemotherapy. RESULTS: Of 1,067 patients, 756 (70.9%) harbored pure urothelial BCa while 311 (29.1%) were found to have a variant. Of these, 202 (64.9%) had a mixed variant and 109 (35.1%) a pure variant. Considering uncommon variants, 21 (6.8%) were sarcomatoid, 10 (3.2%) lymphoepitelial, 19 (6.1%) small cell, 4 (1.3%) plasmacitoid, 2 (0.6%) nested, 109 (35.0%) squamous, 89 (28.6%) micropapillary, 23 (7.4%) glandular and 34 (10.9%) multiple mixed. With a median follow up of 65 months, CSM and OM were recorded in 365 (34.2%), 451 (42.3%) patients, respectively. The OM was 47% vs. 53% vs. 59% for pure urothelial vs. mixed vs. pure variants, respectively (Log rank p1⁄40.011). The 5-years CSM was 44% vs. 47% vs. 53% for pure urothelial vs. mixed vs. pure variants, respectively (Log rank p1⁄40.019). At MVA Cox regression analyses, the presence of pure histological variant was associated with higher CSM (HR: 1.60, p 0.3). In details, neuroendocrine (HR 4.30, CI 2.02-9.13, p

e16525Background: Plasmacytoid urothelial carcinoma (PUC) is a rare variant histology where malignant cells resemble those of plasmacytoma. Majority of the patients (pts) are upstaged at the time o...

482 Background: Plasmacytoid urothelial carcinoma (PUC) is a rare variant histology with poor prognosis. We report clinical outcomes on patients with PUC. Methods: We retrospectively reviewed treatments and outcomes in patients with PUC seen at our institution from 1996 through 2016. The Kaplan-Meier method was used to calculate overall survival. Results: A total of 69 patients with a median age of 68 years were identified. Five patients presented with metastatic disease, whereas 64 were diagnosed with clinically localized PUC. Fifty-seven patients underwent radical cystectomy and the remainder elected for bladder preservation approaches. At time of cystectomy, 6 patients were found to have pathologically organ-confined disease (≤pT2 N0), and 51 had non-organ-confined disease (pT3,T4 or N+), 2 of which were noted to have diffuse peritoneal carcinomatosis. Twenty-eight patients had positive surgical margins, most of which had extensive infiltrative disease not amenable to complete excision. Of the 14 patients who received neoadjuvant cisplatin-based chemotherapy, 10 (71.4%) patients had lymph node involvement and 12 (85.7%) had pT3/4 disease at cystectomy. Only one patient had a pathologic complete response with pT0N0. Thirteen patients received adjuvant chemotherapy, 2 of which received neoadjuvant chemotherapy as well. Two patients received immunotherapy, with only a short-lived response. Median survival for all patients with PUC from time of initial diagnosis was 17.7 months (mo), and 14.0 mo from time of cystectomy for patients undergoing radical cystectomy. Patients with desmoplastic morphology tended to have the worst clinical outcomes (median survival 10.1 mo), whereas classic and pleomorphic subtypes had better survival (median survival 18.6 and 30.4 mo, respectively) (p = 0.083). Conclusions: PUC is an aggressive variant with overall poor outcomes. There appeared to be three morphologic subtypes of plasmacytoid disease; classic, desmoplastic and pleomorphic, with potentially distinct survival outcomes. Chemotherapy, whether in the neoadjuvant or adjuvant setting, or immunotherapy, appeared to have little effect on this cohort. Molecular markers/genomic analysis may provide insight to novel therapeutic approaches.

OBJECTIVE To report the long-term outcome of high-grade prostate cancer treated with radical prostatectomy (RP) as initial monotherapy, analyse the effect of clinical and pathological variables on survival, and report cancer-related symptoms. PATIENTS AND METHODS A retrospective chart review was conducted to identify patients with Gleason 8-10 prostate cancer found on pathological review in men undergoing RP as initial therapy for clinically localized disease between 1988 and 2005. Kaplan-Meier analysis was used to calculate event-free survival. Univariable and multivariable analyses were used to assess the effects of clinical and pathological variables on prostate-specific antigen (PSA) recurrence. RESULTS After excluding 20 patients, 119 were identified with pathologically confirmed high-grade cancers at the time of RP. The overall median (interquartile range) follow-up was 73 (41-113) months. Twenty-four (20%) patients had organ-confined cancer, 60 (50%) had specimen-confined cancer, and 14 (12%) had nodal metastasis. Kaplan-Meier analysis showed overall survival rates at 5 and 10 years, respectively, of 90% and 75%, cancer-specific survival of 92% and 82%, and a PSA recurrence-free follow-up at 5 years of 31%. Using univariable analysis, preoperative PSA level, pathological Gleason score, pathological stage, surgical margin status and tumour volume were found to significantly affect the PSA recurrence-free follow-up. No variables were significant on multivariable analysis. Cancer-related symptoms were reported by only 14 patients, with a median time from surgery to first symptom of 43 months. CONCLUSION High-grade prostate cancer can be treated with RP as initial monotherapy with an acceptable 10-year cancer-specific survival (82%). The PSA recurrence-free follow-up is poor (31% at 5 years). However, few patients progress to symptomatic recurrence after PSA relapse within the first 5 years.

Purpose: We determined outcomes in patients with testicular cancer with large volume (greater than 10 cm) retroperitoneal teratoma treated with post-chemotherapy retroperitoneal lymph node dissection.Materials and Methods: A retrospective review of our testicular cancer database was performed from 1995 to 2005 to identify patients undergoing post-chemotherapy retroperitoneal lymph node dissection for residual masses larger than 10 cm with final pathological examination revealing teratoma. A total of 99 patients met the study inclusion criteria.Results: A total of 27 patients presented with disease limited to the retroperitoneum, 46 had 2 or 3 disease sites and 26 had 4 or more disease sites. Mean and median hospital stay was 7.3 and 5.0 days, respectively. There were 23 recurrences in 27 locations with the most common being pulmonary in 5, mediastinal in 5 and retroperitoneal in 5. The 2 and 5-year disease-free survival was 86% and 75% with a mean followup of 42 months. The 2-year disease-free survival fo...

We reviewed indications and outcomes in patients undergoing ileal ureter replacement for ureteral reconstruction.Between December 1989 and September 2007, 105 patients underwent ileal ureter replacement, of whom 14 were excluded from study due to incomplete data. The remaining 91 patients (99 renal units) comprised the study cohort.Mean patient age was 46.8 years and mean followup was 36.0 months. Indications for an ileal ureter were stricture following genitourinary surgery in 29 cases (31.9%), radiation induced stricture in 17 (18.7%), nonurological surgery iatrogenic injury in 16 (17.6%) and retroperitoneal fibrosis in 11 (12.1%). Only 4 patients (4.4%) had primary ureteral cancer. Long-term complications included anastomotic stricture in 3 patients (3.3%) and fistula in 6 (6.6%). Serum creatinine decreased or remained stable in 68 patients (74.7%) and hyperchloremic metabolic acidosis developed in 3. No patient complained of excessive urinary mucous production.In 68.1% of patients indications for an ileal ureter included radiation induced stricture or iatrogenic injury. The ileal ureter is a reasonable option for long-term ureteral reconstruction with preserved renal function in carefully selected patients.

Preclinical urothelial carcinoma models suggest activity of dasatinib, an oral SRC-family kinase (SFK) inhibitor. We sought to determine the feasibility and biologic activity of neoadjuvant dasatinib (Neo-D) in patients with muscle-invasive urothelial carcinoma of the bladder (miUCB) preceding radical cystectomy (RC).A prospective multisite phase II trial was conducted. Key eligibility criteria included: resectable miUCB (T2-T4a, N0, M0), and Eastern Cooperative Oncology Group performance status 0 to 1. Patients received oral Neo-D 100mg once daily for 28±7 days followed by RC 8 to 24 hours after the last dose. The primary end point was feasibility, defined as≥60% of patients with miUCB completing therapy without treatment-related dose-limiting toxicity (DLT). Pre- and posttreatment tumor immunohistochemistry of phosphorylated SFK (pSFK), Ki-67, and cleaved caspase (Cas)-3 results were analyzed by paired t test.The study completed full accrual with enrollment of 25 patients of whom 23 were evaluable for feasibility. The study achieved its primary end point with 15 patients (65%) completing therapy without treatment-related DLTs. DLTs included: fatigue (n = 2), pulmonary embolism, abdominal pain, supraventricular tachycardia, enteric fistula, hematuria, and dyspnea (n = 1 each). At RC, 5 patients (23%) hadpT2 disease. Analysis of pre- and posttreatment tumors demonstrated significantly decreased pSFK (P = 0.003) but no overall significant changes in Ki-67 or Cas3. In total, 4 cases demonstrated a nonsignificant decrease in Ki-67, of which 3 cases also demonstrated a decrease in pSFK and 2 cases had marginal increase in Cas3.Neo-D in miUCB patients was feasible and safe. Overall, significant inhibition of pSFK was observed without overall reduction of cellular proliferation or increase of apoptosis, although biologic anti-tumor activity may exist in a small subset of patients. These results highlight the potential utility of the neoadjuvant trial paradigm and suggest that clinical benefit of single-agent SFK inhibition in unselected patients with miUCB is unlikely.