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.

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.

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.

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.

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.

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.

Symptomatic Venous Thromboembolism is Associated with Inferior Survival among Patients Undergoing Nephrectomy with Inferior Vena Cava Tumor Thrombectomy for Renal Cell Carcinoma.

PURPOSE: We investigated the incidence and survival impact of symptomatic venous thromboembolism after nephrectomy with inferior vena cava tumor thrombectomy. MATERIALS AND METHODS: We retrospectively reviewed the records of 183 patients who underwent nephrectomy with inferior vena cava tumor thrombectomy (level I-IV) for renal cell carcinoma between 2000 and 2010. Postoperative venous thromboembolism was defined as symptomatic bland thrombus or embolism confirmed on imaging. The cumulative incidence of venous thromboembolism was estimated by the Kaplan-Meier method. Associations of clinicopathological features with time to thromboembolism after surgery and all cause mortality were evaluated on multivariable analysis with Cox models. RESULTS: Symptomatic venous thromboembolism developed in 55 patients a median of 23 days (IQR 5-142) postoperatively, including pulmonary thrombosis in 24, deep venous thrombosis in 17, bland inferior vena cava thrombosis in 13 and portal vein thrombosis in 1. The cumulative incidence of thromboembolism 30, 90 and 365 days following surgery was 17%, 22% and 27%, respectively. A history of smoking (HR 2.15, 95% CI 1.09-4.24, p = 0.028), ECOG (Eastern Cooperative Oncology Group) performance status 1 or greater (HR 2.15, 95% CI 1.17-3.93, p = 0.013), hypercoagulability disorder (HR 5.12, 95% CI 1.93-13.59, p = 0.001) and bulky lymphadenopathy at surgery (HR 4.84, 95% CI 1.87-12.51, p = 0.001) was significantly associated with an increased risk of venous thromboembolism on multivariable analysis. Postoperative venous thromboembolism was significantly associated with an increased risk of all cause mortality (HR 1.53, 95% CI 1.04-2.23, p = 0.029). CONCLUSIONS: Venous thromboembolism after nephrectomy and tumor thrombectomy is common within 90 days of surgery. Symptomatic venous thromboembolism in this population is independently associated with a greater risk of mortality.

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.

The Temporal Association of Robotic Surgical Diffusion with Overtreatment of the Small Renal Mass.

PURPOSE: We evaluated contemporary practice patterns in the management of small renal masses. MATERIALS AND METHODS: We identified 52,804 patients in the NCDB (National Cancer Database) who were diagnosed with a small renal mass (4 cm or less) between 2010 and 2014. Utilization trends of active surveillance, ablation and robotic, laparoscopic and open surgical techniques were compared among all comers, elderly patients 75 years old or older and individuals with competing health risks, defined as a Charlson index of 2 or greater. Multivariable logistic regression models were used to assess factors associated with robotic renal surgery and active surveillance. RESULTS: Surgery remained the primary treatment modality across all years studied, performed in 75.0% and 74.2% of cases in 2010 and 2014, respectively. Although increases in active surveillance from 4.8% in 2010 to 6.0% in 2014 (p <0.001) and robotic renal surgery (22.1% in 2010 to 39.7% in 2014, p <0.001) were observed, the increase in the proportion of small renal masses treated with robotic partial and radical nephrectomy was greater than that of active surveillance (82.0% and 63.0%, respectively, vs 25.0%). Subgroup analyses in individuals 75 years old or older, or with a Charlson index of 2 or greater likewise revealed preferential increases in robotic surgery vs active surveillance. On multivariable analysis later year of diagnosis was associated with increased performance of robotic renal surgery compared to active surveillance (2014 vs 2010 OR 1.44, 95% CI 1.20-1.72, p <0.001) and nonrobotic procedural interventions (2014 vs 2010 OR 2.59, 95% CI 2.30-2.93, p <0.001). CONCLUSIONS: Robotic surgical extirpation has outpaced the adoption of active surveillance of small renal masses. This raises concern that the diffusion of robotic technology propagates overtreatment, particularly among elderly and comorbid individuals.

Partial Nephrectomy is Associated with Higher Risk of Relapse Compared with Radical Nephrectomy for Clinical Stage T1 Renal Cell Carcinoma Pathologically Up Staged to T3a.

PURPOSE: We studied recurrence-free survival after partial vs radical nephrectomy for clinical stage T1 renal cell carcinoma in all patients and in those up staged to pathological stage T3a. MATERIALS AND METHODS: We retrospectively reviewed the records of 1,250 patients who underwent partial or radical nephrectomy for clinically localized T1 renal cell carcinoma between 2006 and 2014. Recurrence-free survival was estimated using the Kaplan-Meier method and evaluated as a function of nephrectomy type with the log rank test and Cox models, adjusting for clinical, radiological and pathological characteristics. RESULTS: A total of 86 recurrences (7%) were observed during a median followup of 37 months. No difference in recurrence-free survival between partial and radical nephrectomy was found among all clinical stage T1 renal cell carcinomas. T3a up staging was noted in 140 patients (11%) and recurrent disease was observed in 44 (31.4%) during a median followup of 38 months. Among up staged T3a cases partial nephrectomy was associated with shorter recurrence-free survival compared to radical nephrectomy on univariable analysis (recurrence HR 2.04, 95% CI 1.12-3.68, p = 0.019) and multivariable analysis (recurrence HR 5.39, 95% CI 1.94-14.9, p = 0.001). CONCLUSIONS: In a subgroup of patients clinically staged T1 renal cell carcinoma will be pathologically up staged to T3a. Among these patients those who undergo partial nephrectomy appear to have inferior recurrence-free survival relative to those who undergo radical nephrectomy.

Active surveillance for incidental renal mass in the octogenarian.

OBJECTIVE: To evaluate the oncologic outcomes among a large cohort of octogenarian patients placed on active surveillance for a localized renal mass. METHODS: We retrospectively reviewed patients ≥80 years of age presenting for asymptomatic, incidentally detected clinically localized stage T1 renal mass between 2006 and 2013 who were followed by active surveillance (AS). The primary endpoint was development of metastatic renal cell carcinoma. Secondary outcomes included intervention-free survival, cancer-specific survival, and overall survival. RESULTS: Eighty-nine octogenarians (median age = 83.4 years) were placed on AS for a median 29.9 months. Median Charlson Comorbidity Index and Katz Index of Independence in Activities of Daily Living scores were 2 and 5, respectively. For all comers, median initial tumor size was 2.4 cm with median growth rate of 0.20 cm/year. Eight (9.0%) patients failed AS due to delayed intervention and three (1.1%) due to systemic progression after median follow-up of 27.8 and 39.9 months, respectively. Two (2.2%) patients in the delayed intervention cohort developed metastasis after treatment. Tumor growth rate was significantly higher among those undergoing intervention versus no intervention (0.60 vs. 0.15 cm/year, P = 0.05) and among patients with systemic progression versus no metastasis (1.28 vs. 0.18 cm/year, P = 0.001). Five-year intervention-free, metastasis-free, cancer-specific, and overall survivals were 90.6, 95.6, 95.6, and 85.7%, respectively. CONCLUSION: AS represents an effective management strategy in octogenarians given low overall risk of metastasis. Tumor growth kinetics may identify patients at risk of systemic progression in whom treatment should be considered.

Positive Surgical Margins Increase Risk of Recurrence after Partial Nephrectomy for High Risk Renal Tumors.

PURPOSE: The clinical significance of a positive surgical margin after partial nephrectomy remains controversial. The association between positive margin and risk of disease recurrence in patients with clinically localized renal neoplasms undergoing partial nephrectomy was evaluated. MATERIALS AND METHODS: A retrospective multi-institutional review of 1,240 patients undergoing partial nephrectomy for clinically localized renal cell carcinoma between 2006 and 2013 was performed. Recurrence-free survival was estimated using the Kaplan-Meier method and evaluated as a function of positive surgical margin with the log rank test and Cox models adjusting for tumor size, grade, histology, pathological stage, focality and laterality. The relationship between positive margin and risk of relapse was evaluated independently for pathological high risk (pT2-3a or Fuhrman grades III-IV) and low risk (pT1 and Fuhrman grades I-II) groups. RESULTS: A positive surgical margin was encountered in 97 (7.8%) patients. Recurrence developed in 69 (5.6%) patients during a median followup of 33 months, including 37 (10.3%) with high risk disease (eg pT2-pT3a or Fuhrman grade III-IV). A positive margin was associated with an increased risk of relapse on multivariable analysis (HR 2.08, 95% CI 1.09-3.97, p=0.03) but not with site of recurrence. In a stratified analysis based on pathological features, a positive surgical margin was significantly associated with a higher risk of recurrence in cases considered high risk (HR 7.48, 95% CI 2.75-20.34, p <0.001) but not low risk (HR 0.62, 95% CI 0.08-4.75, p=0.647). CONCLUSIONS: Positive surgical margins after partial nephrectomy increase the risk of disease recurrence, primarily in patients with adverse pathological features.

Outcomes of Laparoscopic Partial Nephrectomy in Patients Continuing Aspirin Therapy.

PURPOSE: A clinical dilemma surrounds the use of aspirin therapy during laparoscopic partial nephrectomy. Despite reduced cardiac morbidity with perioperative aspirin use, fear of bleeding related complications often prompts discontinuation of therapy before surgery. We evaluate perioperative outcomes among patients continuing aspirin and those in whom treatment is stopped preoperatively. MATERIALS AND METHODS: A total of 430 consecutive cases of laparoscopic partial nephrectomy performed between January 2012 and October 2014 were reviewed. Patients on chronic aspirin therapy were stratified into on aspirin and off aspirin groups based on perioperative status of aspirin use. Primary end points evaluated included estimated intraoperative blood loss and incidence of bleeding related complications, major postoperative complications, and thromboembolic events. Secondary outcomes included operative time, transfusion rate, length of hospital stay, rehospitalization rate and surgical margin status. RESULTS: Among 101 (23.4%) patients on chronic aspirin therapy, antiplatelet treatment was continued in 17 (16.8%). Bleeding developed in 1 patient in the on aspirin group postoperatively and required angioembolization. Conversely 1 myocardial infarction was observed in the off aspirin cohort. There was no significant difference in the incidence of major postoperative complications, intraoperative blood loss, transfusion rate, length of hospital stay and rehospitalization rate. Operative time was increased with continued aspirin use (181 vs 136 minutes, p=0.01). CONCLUSIONS: Laparoscopic partial nephrectomy is safe and effective in patients on chronic antiplatelet therapy who require perioperative aspirin for cardioprotection. Larger, prospective studies are necessary to discern the true cardiovascular benefit derived from continued aspirin therapy as well as better characterize associated bleeding risk.

To clamp or not to clamp? Long-term functional outcomes for elective off-clamp laparoscopic partial nephrectomy.

OBJECTIVE: To evaluate whether elective off-clamp laparoscopic partial nephrectomy (LPN) affords long-term renal functional benefit compared with the on-clamp approach. PATIENTS AND METHODS: This is a retrospective review of patients who underwent elective LPN between 2006 and 2011. Patients were followed longitudinally for up to 5 years. In all, 315 patients with radiographic evidence of a solitary renal mass and normal-appearing contralateral kidney underwent elective LPN; 209 were performed on-clamp vs 106 off-clamp. One patient who required conversion from LPN to open PN was excluded from the study. Additionally, four patients in the on-clamp cohort who underwent subsequent radical nephrectomy for local-regional recurrence were excluded from longitudinal functional evaluation after their procedure. The primary objective was to evaluate differences in postoperative estimated glomerular filtration rate (eGFR) between hilar clamping groups. Subgroup analyses were performed for patients with clamp times >30 min and those with baseline renal insufficiency (eGFR <60 mL/min/1.73m(2) ). Risk of developing worsened or new-onset renal insufficiency was also compared. RESULTS: The mean preoperative eGFR was similar between the on-clamp and off-clamp cohorts (80.7 vs 84.1 mL/min/1.73m(2) , P > 0.05). Univariable and multivariable analyses did not show significant differences in postoperative eGFR between both groups among all-comers, those with clamp times >30 min, and patients with baseline renal insufficiency. Risk of chronic kidney disease was not diminished by the off-clamp approach with up to 5 years of follow-up. CONCLUSIONS: Progressive recovery of renal function after hilar clamping in the elective setting eclipses short-term functional benefit achieved with off-clamp LPN by 6 months; there was no significant difference in eGFR or the percentage incidence of chronic kidney disease between the on-clamp and off-clamp cohorts with up to 5 years follow-up. As such, eliminating transient ischaemia during elective LPN does not confer clinical benefit.

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 .

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.

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.

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.