Oncolytic adenoviral therapy plus pembrolizumab in BCG-unresponsive non-muscle-invasive bladder cancer: the phase 2 CORE-001 trial.

Cretostimogene grenadenorepvec is a serotype-5 oncolytic adenovirus designed to selectively replicate in cancer cells with retinoblastoma pathway alterations, previously tested as monotherapy in bacillus Calmette-Guérin (BCG)-experienced non-muscle-invasive bladder cancer. In this phase 2 study, we assessed the potential synergistic efficacy between intravesical cretostimogene and systemic pembrolizumab in patients with BCG-unresponsive non-muscle-invasive bladder cancer with carcinoma in situ (CIS). Thirty-five patients were treated with intravesical cretostimogene with systemic pembrolizumab. Induction cretostimogene was administered weekly for 6 weeks followed by three weekly maintenance infusions at months 3, 6, 9, 12 and 18 in patients maintaining complete response (CR). Patients with persistent CIS/high-grade Ta at the 3-month assessment were eligible for re-induction. Pembrolizumab was administered for up to 24 months. The primary endpoint was CR at 12 months as assessed by cystoscopy, urine cytology, cross-sectional imaging and mandatory bladder mapping biopsies. Secondary endpoints included CR at any time, duration of response, progression-free survival and safety. The CR rate in the intention-to-treat population at 12 months was 57.1% (20 out of 35, 95% confidence interval (CI) 40.7-73.5%), meeting the primary endpoint. A total of 29 out of 35 patients (82.9%, 95% CI 70.4-95.3%) derived a CR at 3 months. With a median follow-up of 26.5 months, the median duration of response has not been reached (95% CI 15.7 to not reached). The CR rate at 24 months was 51.4% (18 out of 35) (95% CI 34.9-68.0%). No patient progressed to muscle-invasive bladder cancer in this trial. Adverse events attributed to cretostimogene were low grade, self-limiting and predominantly limited to bladder-related symptoms. A total of 5 out of 35 patients (14.3%) developed grade 3 treatment-related adverse effects. There was no evidence of overlapping or synergistic toxicities. Combination intravesical cretostimogene and systemic pembrolizumab demonstrated enduring efficacy. With a toxicity profile similar to its monotherapy components, this combination may shift the benefit-to-risk ratio for patients with BCG-unresponsive CIS. ClinicalTrials.gov Identifier: NCT04387461 .

Surgical Site Infections in Open and Laparoscopic Operations in Rooms With Open-floor Drainage Systems.

INTRODUCTION: Surgical site infections are common postoperative complications. Some operating rooms have open-floor drainage systems for fluid disposal during endourologic cases, although nonendoscopy cases are not always allowed in these rooms. We hypothesized that operating rooms with open-floor drainage systems would not materially affect risk of surgical site infections for patients undergoing open and laparoscopic procedures. METHODS: Patients who had surgical site infections from 2016 through 2020 were identified from data of the National Surgical Quality Improvement Program. Patients without surgical incisions, with open wounds, and with surgical site infections at surgery were excluded. The primary outcome was surgical site infection occurrence within 30 days of surgery. Multilevel multivariable logistic regression was used to estimate the observed-to-expected surgical site infection ratio for each operating room (2 with and 23 without open-floor drainage systems). RESULTS: We identified 8,419 surgical cases, of which 802 (9.5%) were performed in operating rooms with open-floor drainage systems; 166 patients (2.0%) had surgical site infections. Of the surgical site infections, 7 (4.2%) occurred in operating rooms with open-floor drainage systems. Surgical specialty, American Society of Anesthesiologists physical status, higher case acuity, dyspnea, immunosuppression, longer surgical duration, and wound classification were associated with surgical site infections (P < .05 for all). The observed-to-expected ratios of surgical site infections occurring in the 2 operating rooms with open-floor drainage systems were 0.85 and 1.15. The odds ratio of surgical site infections for urologic cases performed in room with vs without open-floor drainage systems was 1.30 (P = .65). CONCLUSIONS: Urology operating room designs often include open-floor drainage systems for water-based cases. These drainage systems were not associated with an increased risk of surgical site infections.

Perioperative and Oncologic Outcomes Associated with Simultaneous Radical Cystectomy and Nephroureterectomy.

OBJECTIVE: To compare the perioperative and oncologic outcomes associated with RCNU to a matched cohort undergoing RC alone. Simultaneous radical cystectomy and nephroureterectomy (RCNU) for synchronous upper tract and bladder urothelial carcinoma is an uncommon procedure. Sparse literature exists comparing outcomes in patients treated with radical cystectomy (RC) alone versus RCNU. METHODS: Adults treated with RCNU for urothelial carcinoma of the bladder (UCB) and upper tract urothelial carcinoma (UTUC) between 1980 and 2020 were identified. Patients were matched 2:1 to patients undergoing RC alone for UCB based on age (+/- 5 years), gender, BMI (+/- 5), Charlson Comorbidity Index, pathologic staging (stage ≤pT2 vs >pT2), and receipt of neoadjuvant chemotherapy. Outcomes included overall survival (OS), recurrence free survival (RFS), cancer specific survival (CSS), 30-day complications, length of stay (LOS), operative time, and estimated blood loss (EBL). RESULTS: A total of 39 patients undergoing RCNU were identified and matched to 74 patients undergoing RC. There were no significant differences in LOS, EBL, or 30-day complication rates. Operative time was significantly longer in the RC cohort. OS (HR 0.58, CI 0.35-0.97, P = .036) was significantly better for patients undergoing RC alone, while no significant difference was noted in RFS (HR 0.65, 0.34-1.24) and CSS (HR 0.58, CI 0.31-1.08, P = .08). CONCLUSIONS: Patients undergoing RCNU had significantly lower OS compared to a matched group of patients undergoing RC alone. Perioperative outcomes between the groups did not differ significantly. This data can inform patient counseling for treatment of this rare disease state.

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.

Collecting duct carcinoma: A single-institution retrospective study.

PURPOSE: Collecting duct carcinoma is a rare pathologic entity with a paucity of clinical data in the literature. We aim to evaluate our institutional experience with the management of this disease. MATERIALS AND METHODS: All renal tumors in the Mayo Clinic Nephrectomy Registry were re-reviewed retrospectively by an expert urologic pathologist. Cases of collecting duct carcinoma were identified. Descriptive statistics were used to characterize these cases. Overall survival and metastases-free survival were estimated using Kaplan-Meier methodology. RESULTS: Between 1970 and 2018, a total of 21 cases were identified with an incidence of 0.2%. Cases were seen predominantly in men (N = 17, 81%) with a median age at diagnosis of 57 years old. At the time of nephrectomy, high grade disease (grade 3 or 4) was noted in the majority of patients (90%). The median times to local recurrence and distant metastases were 5.6 and 5.1 months, respectively. Median overall survival occurred at 1.5 years. Median distant metastases-free survival among M0 patients occurred at 0.5 years. Four patients with localized disease and small tumor size who underwent nephrectomy lived longer than 10 years. No systemic therapies achieved a durable response in the metastatic setting. CONCLUSION: The Mayo Clinic nephrectomy registry contains 21 patients with collecting duct carcinoma over nearly 50 years. Early local recurrence and distant metastases were seen after nephrectomy. However, M0 patients with a small tumor may have long-term benefits from nephrectomy. Neither chemotherapy nor targeted therapy resulted in a durable response in the metastatic setting.

Development of a technique for evaluating the presence of malignant cells in prostatic fluid during robotic prostatectomy.

INTRODUCTION: To develop a technique to collect fluid expressed during robot-assisted radical prostatectomy (RARP) to assess whether malignant cells may have been inadvertently introduced into the surgical field. METHODS: Men with clinically localized grade group 2 to 5 prostate adenocarcinoma undergoing RARP were identified. Following bladder neck division, fluid expressed via prostatic urethra during seminal vesicle dissection was aspirated (specimen A). After specimen removal, an ex vivo seminal vesicle aspiration was performed as well (specimen B). Specimens were prepared with ThinPrep (Hologic, Marlborough, MA) and stained with 4 immunohistochemical markers: keratin-7, PAX-8, prostate-specific antigen (PSA), and prostatic acid phosphatase (PACP). RESULTS: Between December 2018 and May 2019, 15 men undergoing RARP were included. Median age was 60 years (range: 47-77), median PSA 8.5 ng/ml (range 5.1-24), and 7 (47%) had AUA high-risk disease. Specimen A had adequate cellularity in 13 patients (87%). Five patients were excluded from assessment of malignancy due to acellularity of specimen A (n = 2) or specimen B (n = 3). Three of the remaining 10 patients (30%) had cytologic features suspicious for malignancy on specimen A. Immunohistochemistry supported prostatic origin with positive PSA and PACP staining and negative PAX8 stains. Specimen B was not suspicious in any patient. CONCLUSION: We report a technique for intraoperative collection of fluid expressed during RARP. Three patients with adverse pathologic features had evidence of cancer cells within the operative field. Further work is needed to confirm this observation and to determine whether these cells are associated with adverse oncologic outcomes.

Association of intraoperative hypothermia with oncologic outcomes following radical cystectomy.

INTRODUCTION: Intraoperative hypothermia (IOH) has been suggested to adversely impact outcomes following surgery. The objective of this study was to evaluate the association between IOH and survival following radical cystectomy (RC). METHODS: Patients who underwent RC for bladder cancer from 2003 to 2018 were identified in our cystectomy registry. Intraoperative temperatures were extracted from the anesthesia record. IOH was defined as a median intraoperative temperature <36°C, and severe IOH as ≤ 35°C. Time under 36°C was assessed as a continuous variable. Recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were estimated using the Kaplan-Meier method. Associations between IOH and outcomes were assessed with multivariable Cox proportional hazards models. RESULTS: A total of 852 patients were identified, among whom 274 (32%) had IOH. Median follow up among survivors was 4.9 years (IQR 2.4-8.7), during which time 483 patients died, including 343 from bladder cancer. Two-year survival was not significantly different between patients with and without IOH (CSS: 74% vs. 71%, P= 0.31; OS: 68% vs. 67%, P= 0.13). Following multivariable adjustment, neither IOH nor time under 36°C was significantly associated with survival. A total of 37 patients (4.3%) had severe IOH. These patients were observed to have significantly lower 2-year OS (56% vs. 68%, P= 0.005); however, this association did not remain statistically significant after multivariable adjustment (P= 0.92). CONCLUSION: IOH was not independently associated with survival following RC. These data do not support IOH as a prognostic factor for cancer outcomes among patients undergoing RC.

Adding carboplatin to chemotherapy regimens for metastatic castrate-resistant prostate cancer in postsecond generation hormone therapy setting: Impact on treatment response and survival outcomes.

BACKGROUND: The clinical course in metastatic castrate-resistant prostate cancer (mCRPC) can be complicated when patients have disease progression after prior treatment with second generation hormone therapy (second HT), such as enzalutamide or abiraterone. Currently, limited data exist regarding the optimal choice of chemotherapy for mCRPC after failing second generation hormone therapy. We sought to evaluate three common chemotherapy regimens in this setting. METHODS: We retrospectively identified 150 mCRPC patients with disease progression on enzalutamide or abiraterone. Of these 150 patients, 92 patients were chemo-naïve while 58 patients had previously received docetaxel chemotherapy before being started on second HT. After failing second HT, 90 patients were assigned for docetaxel-alone (group A), 33 patients received carboplatin plus docetaxel (group B), while 27 patients received cabazitaxel-alone (Group C). A favorable response was defined by more than or equal to 50% reduction in prostate-specific antigen from the baseline level after a complete course of chemotherapy. Survival outcomes were assessed for 30-month overall survival. RESULTS: Patients in group (B) were 2.6 times as likely to have a favorable response compared to patients in group (A) (OR = 2.625, 95%CI: 1.15-5.99) and almost three times compared to patients in group (C) (OR = 2.975, 95%CI: 1.04-8.54) (P = .0442). 30-month overall survival was 70.7%, 38.9% and 30.3% for group (B), (A), and (C), respectively (P = .008). We report a Hazard Ratio of 3.1 (95% CI, 1.31-7.35; P = .0037) between patients in group (A) versus those in group (B) and a Hazard Ratio of 4.18 (95% CI, 1.58-11.06; P = .0037) between patients in group (C) compared to those in group (B) CONCLUSION: This data demonstrates improved response and overall survival in treatment-refractory mCRPC with a chemotherapy regimen of docetaxel plus carboplatin when compared to docetaxel alone or cabazitaxel alone. Further investigations are required.

Complete Surgical Metastasectomy of Renal Cell Carcinoma in the Post-Cytokine Era.

PURPOSE: Data supporting complete metastasectomy of metastatic renal cell carcinoma were derived primarily from the era of cytokine therapy. Whether complete metastasectomy remains beneficial in patients who receive more recently approved systemic therapies has not been well studied. The objective of this study was to examine survival outcomes among patients treated with complete metastasectomy in the era of targeted therapy and checkpoint blockade availability. MATERIALS AND METHODS: We queried our institutional nephrectomy registry and identified 586 patients who underwent partial or radical nephrectomy of unilateral, sporadic renal cell carcinoma with a first occurrence of metastasis between 2006 and 2017. Of these patients 158 were treated with complete metastasectomy. Associations of complete metastasectomy with cancer specific and overall survival were assessed using Cox proportional hazards models. RESULTS: Median followup after the diagnosis of metastasis was 3.9 years, during which 403 patients died, including 345 of renal cell carcinoma. Of the patients treated with complete metastasectomy 147 (93%) did not receive any systemic treatment of the index metastatic lesion(s). Two-year cancer specific survival was significantly greater in patients with vs without complete metastasectomy (84% vs 54%, p <0.001). After adjusting for age, gender, and the timing, number and location of metastases complete metastasectomy was associated with a significantly reduced likelihood of death from renal cell carcinoma (HR 0.47, 95% CI 0.34-0.65, p <0.001). CONCLUSIONS: Complete surgical resection of metastases of renal cell carcinoma was associated with improved cancer specific survival in the post-cytokine era. It may be considered in appropriate patients after a process of shared decision making.

Trends in Extended-Duration Venous Thromboembolism Prophylaxis Following Radical Cystectomy.

OBJECTIVE: To evaluate temporal trends in prescriptions for extended-duration pharmacologic prophylaxis (EDPP) intended to prevent venous thromboembolism following radical cystectomy (RC). MATERIALS AND METHODS: We used OptumLabs Data Warehouse, a national administrative claims database, to identify patients undergoing RC for bladder cancer from 2012 to 2017. Rates of outpatient prescriptions for EDPP following RC were assessed, and rate over time was evaluated using the Cochran-Armitage test for trend. Multivariable logistic regression was used to examine associations between clinical and practice-level characteristics with EDPP prescriptions. RESULTS: A total of 2054 patients were identified, including 386 (19%) who received an EDPP prescription. The rate of EDPP prescriptions increased significantly over the study period, from 9% of cases in 2012 to 26% of cases in 2017 (P <.001). On multivariable logistic regression, age <65 (OR 1.79, 95% CI 1.39-2.33; P <.001), receipt of neoadjuvant chemotherapy (OR 1.33, 95% CI 1.04-1.71; P = .02), more recent procedure year (OR 4.11, 95% CI 2.35-7.18; P <.001), treatment in a public as compared to a for-profit hospital (OR 3.38, 95% CI 1.31-8.74; P = .01), and treatment at a hospital with residency training (OR 4.45, 95% CI 1.26-15.7; P = .02) or a surgical robot (OR 3.44, 95% CI 1.31-9.08; P = .01) were significantly associated with increased odds of receiving EDPP. CONCLUSION: EDPP following RC has increased over time, but is still provided for only a minority of patients. These data may be useful for guiding quality improvement efforts given recent literature supporting the use of EDPP.

Sarcopenia and Response to Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer.

INTRODUCTION: The objective of the study was to determine whether sarcopenia is associated with pathologic and survival outcomes for patients with muscle-invasive bladder cancer (MIBC) treated with neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). PATIENTS AND METHODS: We identified MIBC patients treated with cisplatin-based NAC in our cystectomy registry from 2000 to 2016. Pre- and post-NAC computed tomography images were analyzed with BodyCompSlicer, a validated body composition assessment tool. Sarcopenia was defined as a skeletal muscle index (SMI) below sex-specific international consensus values. Associations of clinical features with pathologic downstaging ( .05). Meanwhile, only post-NAC sarcopenia (hazard ratio, 1.90; 95% confidence interval, 1.02-3.56; P = .04) was independently associated with an increased risk of CSM. CONCLUSION: Sarcopenia after NAC and before RC appeared to be prognostic. Although skeletal muscle mass declined significantly during NAC, neither the degree of muscle loss nor pretreatment SMI were significantly associated with downstaging after NAC and RC. These data do not support the use of sarcopenia as a risk stratification tool for selection of patients for or monitoring response to NAC.

Association of Partial versus Radical Nephrectomy with Subsequent Hypertension Risk Following Renal Tumor Resection.

PURPOSE: We investigated the risks of new onset and worsened hypertension after radical vs partial nephrectomy. MATERIALS AND METHODS: Using a national administrative database of privately and Medicare insured patients we performed a retrospective cohort study of 9,207 and 4,686 patients who underwent radical and partial nephrectomy, respectively, for a renal mass between January 1, 2007 and December 31, 2016. One-to-one propensity score matching was done to balance the surgical groups based on patient demographics, baseline comorbidities, current medications and surgery year. Primary outcomes included new onset hypertension among patients with no history of hypertension and worsened hypertension among patients with baseline hypertension. We performed subgroup analyses stratified by patient age (75 or greater vs less than 75 years) and the presence of baseline kidney disease. Incidence rates and Cox proportional hazards models were used to compare outcomes in matched cohorts. RESULTS: Among 3,106 propensity matched patients without preexisting hypertension radical nephrectomy was associated with a higher risk of new onset hypertension compared to partial nephrectomy (HR 1.40, 95% CI 1.22-1.60, p <0.001). Similarly among 6,250 propensity matched patients with hypertension prior to surgery radical nephrectomy was associated with a higher risk of worsening baseline hypertension (HR 1.18, 95% CI 1.10-1.26, p <0.001). Subgroup analyses were consistent with the main study findings of worsened hypertension (p for interaction ≥0.05). CONCLUSIONS: Radical nephrectomy was associated with a higher risk of new onset and worsened hypertension compared to partial nephrectomy, including among elderly patients and individuals with normal kidney function. Given prior noted associations between hypertension and noncancer related morbidity, our results further encourage the preferential use of partial nephrectomy to manage localized renal masses when technically feasible.

Comprehensive characterization of perioperative reoperation following radical cystectomy.

INTRODUCTION: To examine the nature, timing, and risk factors underlying return to the operating room (ROR) following radical cystectomy (RC). ROR has been proposed as a surgical quality metric based on data from the general surgery literature, but ROR has not been comprehensively characterized following RC. PATIENTS AND METHODS: We queried our institutional Cystectomy Registry from 2000 to 2016 to identify patients with ROR within 90 days of RC. Multivariable logistic regression was used to examine associations between patient features and ROR. Survival outcomes were studied based on whether ROR was necessary. RESULTS: Of 1968 patients treated with RC, 112 (5.7%) underwent 125 reoperations within 90 days of RC, of which 93% were unanticipated and due to postsurgical complications. The most common reasons for ROR were facial dehiscence (29%), bowel obstruction (21%), and enteric anastomotic leak (8%). On multivariable analysis, increasing body mass index (odds ratio 1.04, 95% confidence interval (CI) 1.01-1.08, P = 0.045) and albumin <3.5 g/dl (odds ratio 2.15, 95% CI 1.28-3.59, P = 0.004) were associated with greater odds of ROR. Patients with a ROR had significantly decreased 5-year overall survival compared to patients who did not undergo ROR (43% vs. 55%; P = 0.003), and ROR was associated with increased all-cause mortality after multivariable adjustment (hazard ratio 1.33, 95% CI 1.01-1.74, P = 0.04). CONCLUSION: ROR principally occurred due to unanticipated complications and was associated with increased mortality after RC. These data suggest ROR may be a useful metric by which urological programs can track the efficacy of interventions aimed at improving perioperative care for RC patients.

Implementation of multiparametric magnetic resonance imaging technology for evaluation of patients with suspicion for prostate cancer in the clinical practice setting.

OBJECTIVES: To investigate the impact of implementing magnetic resonance imaging (MRI) and ultrasonography fusion technology on biopsy and prostate cancer (PCa) detection rates in men presenting with clinical suspicion for PCa in the clinical practice setting. PATIENTS AND METHODS: We performed a review of 1 808 consecutive men referred for elevated prostate-specific antigen (PSA) level between 2011 and 2014. The study population was divided into two groups based on whether MRI was used as a risk stratification tool. Univariable and multivariable analyses of biopsy rates and overall and clinically significant PCa detection rates between groups were performed. RESULTS: The MRI and PSA-only groups consisted of 1 020 and 788 patients, respectively. A total of 465 patients (45.6%) in the MRI group and 442 (56.1%) in the PSA-only group underwent biopsy, corresponding to an 18.7% decrease in the proportion of patients receiving biopsy in the MRI group (P < 0.001). Overall PCa (56.8% vs 40.7%; P < 0.001) and clinically significant PCa detection (47.3% vs 31.0%; P < 0.001) was significantly higher in the MRI vs the PSA-only group. In logistic regression analyses, the odds of overall PCa detection (odds ratio [OR] 1.74, 95% confidence interval [CI] 1.29-2.35; P < 0.001) and clinically significant PCa detection (OR 2.04, 95% CI 1.48-2.80; P < 0.001) were higher in the MRI than in the PSA-only group after adjusting for clinically relevant PCa variables. CONCLUSION: Among men presenting with clinical suspicion for PCa, addition of MRI increases detection of clinically significant cancers while reducing prostate biopsy rates when implemented in a clinical practice setting.

Prognostic evaluation of perinephric fat, renal sinus fat, and renal vein invasion for patients with pathological stage T3a clear-cell renal cell carcinoma.

OBJECTIVE: To investigate the prognostic significance of various patterns of extrarenal extension that comprise pathological stage T3a clear-cell renal cell carcinoma (ccRCC) amongst patients undergoing nephrectomy for non-metastatic disease. PATIENTS AND METHODS: A retrospective review of 563 patients who underwent radical nephrectomy for pathologically confirmed T3aN0/NxM0 ccRCC between 1970 and 2011 was performed. All pathological slides were re-reviewed by one urological pathologist. Associations of patterns of extrarenal extension (perinephric fat [PF], renal sinus fat [SF], and renal vein [RV], in isolation or in any combination) with disease progression, cancer-specific mortality (CSM), and all-cause mortality were evaluated on multivariable analyses. RESULTS: Overall, PF invasion, renal SF invasion, and RV tumour thrombus were present in 144 (26%), 51 (9%), and 163 (29%) patients, respectively, with multiple patterns of extrarenal extension identified in 205 (36%) patients. There were no significant differences in survival outcomes for isolated involvement of PF, renal SF, or RV. However, patients with multiple patterns of extrarenal extension were at significantly increased risk of disease progression (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.04-1.65; P = 0.020), CSM (HR 1.64, 95% CI 1.27-2.12; P < 0.001), and all-cause mortality (HR 1.32, 95% CI 1.08-1.61; P = 0.008). CONCLUSIONS: The presence of multiple patterns of extrarenal extension is associated with a higher risk of disease progression and cancer-related death after radical nephrectomy compared to isolated involvement of the PF, renal SF, or RV, which carry similar prognostic weight. If validated, these findings may help refine risk stratification of non-metastatic T3a RCC by distinguishing patients with multiple vs one pattern of extrarenal extension.

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.