Follow-up strategies after trimodal treatment for muscle-invasive bladder cancer: a systematic review.

PURPOSE: Optimal follow-up strategies following trimodal treatment for muscle invasive bladder cancer play a crucial role in detecting and managing relapse and side-effects. This article provides a comprehensive summary of the patterns and risk factors of relapse, functional outcomes, and follow-up protocols. METHODS: A systematic literature search on PubMed and review of current guidelines and institutional follow-up protocols after trimodal therapy were conducted. RESULTS: Out of 200 identified publications, 43 studies (28 retrospective, 15 prospective) were selected, encompassing 7447 patients (study sizes from 24 to 728 patients). Recurrence rates in the urinary bladder varied between 14-52%; 3-16% were muscle-invasive while 11-36% were non-muscle invasive. Nodal recurrence occurred at 13-16% and distant metastases at 15-35%. After 5 and 10 years of follow-up, around 60-85% and 45-75% of patients could preserve their bladder, respectively. Various prognostic risk factors associated with relapse and inferior survival were proposed, including higher disease stage (> c/pT2), presence of extensive/multifocal carcinoma in situ (CIS), hydronephrosis, multifocality, histological subtypes, incomplete transurethral resection of bladder tumor (TURBT) and incomplete response to radio-chemotherapy. The analyzed follow-up guidelines varied slightly in terms of the number, timing, and types of investigations, but overall, the recommendations were similar. CONCLUSION: Randomized prospective studies should focus on evaluating the impact of specific follow-up protocols on oncological and functional outcomes following trimodal treatment for muscle-invasive bladder cancer. It is crucial to evaluate personalized adaption of follow-up protocols based on established risk factors, as there is potential for improved patient outcomes and resource allocation.

Role of cytoreductive radical prostatectomy in men with oligometastatic prostate cancer on molecular imaging.

PURPOSE OF REVIEW: The implementation of PET with prostate-specific membrane antigen (PSMA) tracer as primary staging tool occurred recently. Since its introduction, a novel category of patients emerged, with negative staging at conventional imaging, and positive molecular imaging. Local treatment in these patients might be associated with improved oncological outcomes when combined with systemic therapy. However, its impact on oligometastatic prostate cancer (omPCa) remains unknown. In this review, we aimed at investigating the role of cytoreductive radical prostatectomy (cRP) in oligometastatic disease at molecular imaging. RECENT FINDINGS: After comprehensive review of literature, two retrospective studies highlighted the feasibility, safety, and potential benefits of surgery in omPCA patients at molecular imaging. They showed that 72% of patients achieved PSA less than 0.01 ng/ml following cRP as part of a multimodal approach, 17% experienced radiographic progression, and 7% died at 27-month median follow-up. Moreover, complications postcRP after PSMA PET were modest, with a 40% rate of any adverse event, and 5% of grade more than 3. The 1-year urinary continence after cRP rate was 82%. The oncological, functional outcomes and the complication rate aligned with those observed in series of cRP after conventional imaging. SUMMARY: cRP is feasible, well tolerated, and effective in selected patients with omPCa at PSMA PET.

Risks and benefits of partial nephrectomy performed with limited or with zero ischaemia time.

OBJECTIVE: To test the hypothesis that longer warm ischaemia time (WIT) might have a marginal impact on renal functional outcomes and might, in fact, reduce haemorrhagic risk intra-operatively. PATIENTS AND METHODS: Data from 1140 patients treated with elective partial nephrectomy (PN) for a cT1-2 cN0 cM0 renal mass were prospectively collected. WIT was defined as the duration of clamping of the main renal artery with no refrigeration and was tested as a continuous variable. The primary outcome of the study was evaluation of the effect of WIT on renal function (estimated glomerular filtration rate [eGFR]) postoperatively, at 6 months and in the long term (measured between 1 and 5 years after surgery). The secondary outcome of the study was haemorrhagic risk, defined as estimated blood loss (EBL) or peri-operative transfusions. Multivariable linear, logistic and Cox regression analyses, accounting for age, Charlson comorbidity index, clinical size, preoperative eGFR and year of surgery, were used and the potential nonlinear relationship between WIT and the study outcomes was modelled using restricted cubic splines. RESULTS: A total of 863 patients (76%) underwent PN with WIT and 277 (24%) without. The baseline median eGFR was 87.3 (68.8-99.2) mL/min/1.73m2 for the on-clamp population and 80.6 (63.2-95.2) mL/min/1.73m2  for the off-clamp population. The median duration of WIT was 17 (13-21) min. At multivariable analyses predicting renal function, longer WIT was associated with decreased postoperative eGFR (estimate: -0.21, 95% confidence interval [CI] -0.31; -0.11 [P < 0.001]). Conversely, no association between WIT and eGFR was recorded at 6-month or long-term follow-up (all P > 0.8). At multivariable analyses predicting haemorrhagic risk, clampless resection with no ischaemia time and PN with short WIT was associated with an increased EBL (estimate: -21.56, 95% CI -28.33; -14.79 [P < 0.001]) and peri-operative transfusion rate (estimate: -0.009, 95% CI -0.01; -0.003 [P = 0.002]). No association between WIT and positive surgical margin status was recorded (all P = 0.1). CONCLUSION: Patients and clinicians should be aware that performing PN with very limited or even with zero WIT might increase bleeding and the need for peri-operative transfusion while not improving long-term renal function outcomes.

Oncologic Surveillance for Variant Histology Bladder Cancer after Radical Cystectomy.

PURPOSE: Presently, major guidelines do not provide specific recommendations on oncologic surveillance for patients who harbor variant histology (VH) bladder cancer (BCa) at radical cystectomy. We aimed to create a personalized followup scheme that dynamically weighs other cause mortality (OCM) vs the risk of recurrence for VH BCa, and to compare it with a similar one for pure urothelial carcinoma (pUC). MATERIALS AND METHODS: Within a multi-institutional registry, 528 and 1,894 patients with VH BCa and pUC, respectively, were identified. The Weibull regression was used to detect the time points after which the risk of OCM exceeded the risk of recurrence during followup. The risk of OCM over time was stratified based on age and comorbidities, and the risk of recurrence on pathological stage and recurrence site. RESULTS: Individuals with VH had a higher risk of recurrence (recurrence-free survival 30% vs 51% at 10 years, p <0.001) and shorter median time to recurrence (88 vs 123 months, p <0.01) relative to pUC. Among VH, micropapillary variant conferred the greatest risk of recurrence on the abdomen and lungs, and mixed variants carried the greatest risk of metastasizing to bones and other sites compared to pUC. Overall, surveillance should be continued for a longer time for individuals with VH BCa. Notably, patients younger than 60 years with VH and pT0/Ta/T1/N0 at radical cystectomy should continue oncologic surveillance after 10 years vs 6.5 years for pUC individuals. CONCLUSIONS: VH BCa is associated with greater recurrence risk than pUC. A followup scheme that is valid for pUC should not be applied to individuals with VH. Herein, we present a personalized approach for surveillance that may allow an improved shared decision.

Protocol of the Italian Radical Cystectomy Registry (RIC): a non-randomized, 24-month, multicenter study comparing robotic-assisted, laparoscopic, and open surgery for radical cystectomy in bladder cancer.

BACKGROUND: Bladder cancer is the ninth most common type of cancer worldwide. In the past, radical cystectomy via open surgery has been considered the gold-standard treatment for muscle invasive bladder cancer. However, in recent years there has been a progressive increase in the use of robot-assisted laparoscopic radical cystectomy. The aim of the current project is to investigate the surgical, oncological, and functional outcomes of patients with bladder cancer who undergo radical cystectomy comparing three different surgical techniques (robotic-assisted, laparoscopic, and open surgery). Pre-, peri- and post-operative factors will be examined, and participants will be followed for a period of up to 24 months to identify risks of mortality, oncological outcomes, hospital readmission, sexual performance, and continence. METHODS: We describe a protocol for an observational, prospective, multicenter, cohort study to assess patients affected by bladder neoplasms undergoing radical cystectomy and urinary diversion. The Italian Radical Cystectomy Registry is an electronic registry to prospectively collect the data of patients undergoing radical cystectomy conducted with any technique (open, laparoscopic, robotic-assisted). Twenty-eight urology departments across Italy will provide data for the study, with the recruitment phase between 1st January 2017-31st October 2020. Information is collected from the patients at the moment of surgical intervention and during follow-up (3, 6, 12, and 24 months after radical cystectomy). Peri-operative variables include surgery time, type of urinary diversion, conversion to open surgery, bleeding, nerve sparing and lymphadenectomy. Follow-up data collection includes histological information (e.g., post-op staging, grading, and tumor histology), short- and long-term outcomes (e.g., mortality, post-op complications, hospital readmission, sexual potency, continence etc). DISCUSSION: The current protocol aims to contribute additional data to the field concerning the short- and long-term outcomes of three different radical cystectomy surgical techniques for patients with bladder cancer, including open, laparoscopic, and robot-assisted. This is a comparative-effectiveness trial that takes into account a complex range of factors and decision making by both physicians and patients that affect their choice of surgical technique. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04228198 . Registered 14th January 2020- Retrospectively registered.

Optimal pathological response after neoadjuvant chemotherapy for muscle-invasive bladder cancer: results from a global, multicentre collaboration.

OBJECTIVES: To evaluate outcomes of patients achieving a post-treatment pathological stage of

Adjuvant chemotherapy is ineffective in patients with bladder cancer and variant histology treated with radical cystectomy with curative intent.

OBJECTIVES: Adjuvant chemotherapy (ACT) is recommended for non-organ-confined bladder cancer (BCa) after radical cystectomy (RC) and pelvic lymph node dissection (PLND), but there are sparse data regarding its specific efficacy in patients with histological variants. The aim of our study was to evaluate the role of ACT on survival outcomes in patients with variant histology in a large multicenter cohort. MATERIALS AND METHODS: We retrospectively evaluated data of 3963 patients with BCa treated with RC and bilateral PLND with curative intent at several institutions between 1999 and 2018. The histological type was classified into six groups: pure urothelial carcinoma (PUC) or squamous, sarcomatoid, micropapillary, glandular and neuroendocrine differentiation. Multivariable competing risk analysis was applied to assess the role of ACT on recurrence and cancer-specific mortality (CSM) in each histological subtype. RESULTS: Of the 3963 patients included in the study, 23% had variant histology at RC specimen and 723 (18%) patients received ACT. ACT was found to be significantly associated with reduced risk of recurrence (sub-hazard ratio [SHR]: 0.55, confidence interval [CI] 0.42-0.71, p < 0.001) and CSM (SHR: 0.58, CI 0.44-0.78, p < 0.001) in the PUC only, while no histological subtype received a significant benefit on survival outcomes (all p > 0.05) from administration of ACT. The limitation of the study includes the retrospective design, the lack of a central pathology review and the number of ACT cycles. CONCLUSION: In our study, the administration of ACT was associated with improved survival outcomes in PUC only. No histological subtype found a benefit in overall recurrence and CSM from ACT.

The impact of treatment modality on survival in patients with clinical node-positive bladder cancer: results from a multicenter collaboration.

PURPOSE: To assess the impact of perioperative chemotherapy on survival in cN+ BCa patients and analyze it according to the pN status. METHODS: A retrospective analysis was conducted on 639 BCa patients with cTanyN1-3M0 BCa treated with radical cystectomy (RC) and bilateral lymph node dissection (LND) with or without perioperative chemotherapy in ten tertiary referral centers from 1990 to 2017. Selected cN+ patients received induction chemotherapy (IC), whereas adjuvant chemotherapy (ACT) was delivered to selected pN+ patients. Univariable and multivariable Cox regression analyses were used to predict overall mortality (OM) after surgery, adjusting for clinicopathological confounders. Kaplan-Meier analyses assessed OM according to the treatment modality. RESULTS: Overall, 356 (56%) patients were treated with surgery alone, 155 (24%) with IC followed by surgery, and 128 (20%) with ACT following surgery. Over a median follow-up of 25 months, 316 deaths were recorded. At univariable analysis, patients treated with IC and surgery had lower OM both considering cN+ [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.87, p = 0.004] and cN+pN- patients (HR 0.61, 95% CI 0.37-0.99, p = 0.05) compared to those treated with surgery alone. cN+pN+ patients treated with ACT experienced lower OM compared to those treated with IC or surgery alone at multivariable analysis (HR 0.40, 95% CI 0.22-0.74, p = 0.003). CONCLUSION: Patients with cTany cN+ cM0 BCa benefit more in terms of OS when treated with IC followed by RC + LND compared to RC + LND alone, regardless of LNMs at final histopathology examination. More data are needed to assess the role of ACT in the management of cN+ patients.

Sex- and age-related differences in the distribution of bladder cancer metastases.

OBJECTIVE: Our objective was to investigate age- and sex-related differences in the distribution of metastases in patients with metastatic bladder cancer. METHODS: Within the National Inpatient Sample database (2008-2015), we identified 7040 patients with metastatic bladder cancer. Trend test and Chi-square test analyses were used to evaluate the relationship between age and site of metastases, according to sex. RESULTS: Of 7040 patients with metastatic bladder cancer, 5226 (74.2%) were men and 1814 (25.8%) were women. Thoracic, abdominal, bone and brain metastases were present in 19.5 vs. 23.0%, 43.6 vs. 46.9%, 23.9 vs. 18.7% and 2.4 vs. 2.9% of men vs. women, respectively. Bone was the most common metastatic site in men (23.9%) vs. lung in women (22.4%). Increasing age was associated with decreasing rates of abdominal (from 44.9 to 40.2%) and brain (from 3.2 to 1.4%) metastases in men vs. decreasing rates of bone (from 21.0 to 13.3%) and brain (from 5.1 to 2.0%) metastases in women (all P < 0.05). Finally, rates of metastases in multiple organs also decreased with age, in both men and women. CONCLUSIONS: The distribution of metastases in bladder cancer varies according to sex. Moreover, differences exist according to patient age and these differences are also sex-specific. In consequence, patient age and sex should be considered in the interpretation of imaging, especially when findings are indeterminate.

How to improve patient selection for neoadjuvant chemotherapy in bladder cancer patients candidate for radical cystectomy and pelvic lymph node dissection.

PURPOSE: To improve patient selection for neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) in bladder cancer patients (BCa). METHODS: Retrospective evaluation of 1057 patients with cT2-4N0M0 BCa treated with RC and pelvic lymph node dissection between 1990 and 2018 at 3 referral centers. Adverse pathologic features (APF) were defined as pT3-pT4/pN + disease at RC. A regression tree model (CART) was used to assess preoperative risk group classes. A multivariable logistic regression (MVA) was performed to identify predictors of APF at RC. RESULTS: Median age was 70 years and most of the patients were men (83%). Of the 1057 patients included in our study, 688 (65%) had APF. CART analysis was able to stratify patients into 3 risk groups: low (cT2 and single disease, odds ratio [OR] 0.62), intermediate (cT2 and multiple disease, OR 1.08), and high (cT3-cT4, OR 1.28). On MVA APF were associated with variant histology (odds ratio [OR] 3.97, 95% confidence interval [CI] 1.46-10.83, p = 0.007), multifocality at TUR (OR 2.56, CI 1.27-5.17, p = 0.09), completeness of resection (OR 0.47, CI 0.23-0.96, p = 0.04) and clinical extravesical disease (OR 3.42, CI 1.63-7.14, p = 0.001). CONCLUSION: We defined three pre-operative risk classes. Our results indicate that patients with a cT3-T4 disease are those who might benefit more from NAC whereas those with T2 single disease should be those to whom NAC probably shouldn't be proposed. Given the high rate of understaging in BCa patients, NAC can be proposed in selected cases of cT2/multifocal disease.

Rates of other-cause mortality after radical cystectomy are decreasing over time-A population-based analysis over two decades.

BACKGROUND AND OBJECTIVES: To investigate other-cause mortality (OCM) rates over time according to several baseline characteristics in bladder cancer (BCa) patients treated with radical cystectomy (RC). METHODS: Within the Surveillance, Epidemiology, and End Results database (1988-2011), we identified 7702 T1-2 N0 M0 urothelial BCa patients treated with RC. Temporal trends and multivariable Cox regression (MCR) analyses assessed 5-year OCM. Data were stratified according to the year of diagnosis (1988-1995 vs 1996-2000 vs 2001-2004 vs 2005-2008 vs 2009-2011), age group (<60 vs 60-75 vs >75 years), sex, race, marital status, and socioeconomic status. RESULTS: Overall, OCM rates decreased from 13.9% in 1988-1995 to 8.6% in 2009-2011. The greatest decrease was recorded in elderly (>75) patients (32%-16%, slope: -0.55% per year; P = .01), followed by patients aged 60 to 75 (21%-5%, slope: -0.35% per year; P = .01), unmarried patients (16%-10%, slope: -0.26% per year; P < .001), male patients (14%-8.9%, slope: -0.23% per year), and African Americans (16%-11%, slope: -0.27% per year; P < .001). MCR models corroborated these results. CONCLUSIONS: Most important decrease in OCM after RC over the last decades was recorded in the elderly, unmarried, and male patients. Nonetheless, these three patient groups still represent ideal targets for efforts aimed at minimizing the morbidity and mortality after RC, as their risk of OCM is higher than in others.

Contemporary conditional cancer-specific survival after radical nephroureterectomy in patients with nonmetastatic urothelial carcinoma of upper urinary tract.

BACKGROUND AND OBJECTIVES: To examine the effect of conditional survival on 5-year cancer-specific survival (CSS) probability after radical nephroureterectomy (RNU) in a contemporary cohort of patients with non-metastatic urothelial carcinoma of the upper urinary tract (UTUC). METHODS: Within the Surveillance, Epidemiology and End Results database (2004-2015), 6826 patients were identified. Conditional 5-year CSS estimates were assessed after event-free follow-up duration. Multivariable Cox regression (MCR) models predicted cancer-specific mortality (CSM) according to event-free follow-up length. RESULTS: Overall, 956 (14.0%) were T1 low grade(LG)N0 , 1305 (19.1%) T1 high grade(HG)N0 , 1215 (17.8%) T2 N0 , 2249 (32.9%) T3 N0 and 1101 (16.1%) T4 N0 /Tany N1-3 . From baseline, 93.4% to 94.2% in T1 LGN0 provided 5-year CSS and, respectively, 86.2% to 95.3% in T1 HGN0 , 77.5% to 87.8% in T2 N0 , 63.0% to 91.1% in T3 N0 , and 38.8% to 88.2% in T4 N0 /Tany N1-3 . In MCR models, relative to T1 LGN0 , T1 HGN0 (Hazard ratio [HR] 1.7), T2 N0 (HR 3.0), T3 N0 (HR: 5.2), and T4 N0 /Tany N1-3 (HR 11.9) were independent predictors of higher CSM. Conditional HRs decreased to levels equivalent to T1 LGN0 at 3 years vs 5 years of event-free survival for T1 HGN0 and all other groups, respectively. CONCLUSIONS: A direct relationship exists between event-free follow-up and survival probability after RNU. From a clinical perspective, such survival estimates may have particular importance during preoperative counseling.

The Impact of Experience on the Risk of Surgical Margins and Biochemical Recurrence after Robot-Assisted Radical Prostatectomy: A Learning Curve Study.

PURPOSE: Improved cancer control with increasing surgical experience (the learning curve) has been demonstrated for open and laparoscopic prostatectomy. We assessed the relationship between surgical experience and oncologic outcomes of robot-assisted radical prostatectomy. MATERIALS AND METHODS: We analyzed the records of 1,827 patients in whom prostate cancer was treated with robot-assisted radical prostatectomy. Surgical experience was coded as the total number of robotic prostatectomies performed by the surgeon before the patient operation. We evaluated the relationship of prior surgeon experience to the probability of positive margins and biochemical recurrence in regression models adjusting for stage, grade and prostate specific antigen. RESULTS: After adjusting for case mix, greater surgeon experience was associated with a lower probability of positive surgical margins (p = 0.035). The risk of positive margins decreased from 16.7% to 9.6% in patients treated by a surgeon with 10 and 250 prior procedures, respectively (risk difference 7.1%, 95% CI 1.7-12.2). In patients with nonorgan confined disease the predicted probability of positive margins was 38.4% in those treated by surgeons with 10 prior operations and 24.9% in those treated by surgeons with 250 prior operations (absolute risk reduction 13.5%, 95% CI -3.4-22.5). The relationship between surgical experience and the risk of biochemical recurrence after surgery was not significant (p = 0.8). CONCLUSIONS: Specific techniques used by experienced surgeons which are associated with improved margin rates need further research. The impact of experience on cancer control after robotic prostatectomy differed from that in the prior literature on open and laparoscopic radical prostatectomy, and should be investigated in larger multi-institutional studies.

Development of a New Comorbidity Assessment Tool for Specific Prediction of Perioperative Mortality in Contemporary Patients Treated with Radical Cystectomy.

PURPOSE: The Deyo adaptation of the Charlson comorbidity index (DaCCI), which relies on 17 comorbid condition groupings defined with 200 ICD-9-CM diagnostic codes, lacks specificity in the context of radical cystectomy (RC) for bladder cancer (BCa). We attempted to develop a new comorbidity assessment tool based on individual comorbid conditions and/or BCa manifestations for specific prediction of perioperative mortality after RC. METHODS: We relied on 7076 T1-T4 nonmetastatic BCa patients treated with RC between 2000 and 2009 in the SEER-Medicare linked database. Within the development cohort (n = 6076), simulated annealing (SA) was used to identify (1) individual comorbid conditions, (2) individual BCa manifestations, and (3) the combination of both, that satisfy the criteria of maximal accuracy and parsimony for prediction of 90-day mortality after RC, after adjusting for several confounders. The accuracy of the newly identified groups of individual comorbid conditions and/or BCa manifestations and of the original DaCCI was tested in a 1000-patient external validation cohort. RESULTS: The combination of six individual comorbid conditions and two individual BCa disease manifestations (type II diabetes without complications, anemia, chronic obstructive pulmonary disease, congestive heart failure, aortocoronary bypass, cardiomegaly, urinary tract infection, and hydronephrosis), and seven individual comorbid conditions (type II diabetes without complications, anemia, chronic obstructive pulmonary disease, congestive heart failure, aortocoronary bypass, osteoarthrosis, and cardiomegaly) respectively showed 71.1 and 70.2% accuracy versus 68.0% for the original DaCCI. CONCLUSIONS: These new approaches are specific to contemporary RC patients and represent simpler methods compared with the original DaCCI, without any compromise in accuracy.

Long-term incidence of secondary bladder and rectal cancer in patients treated with brachytherapy for localized prostate cancer: a large-scale population-based analysis.

OBJECTIVE: To examine the incidence and time trends of secondary bladder cancer (BCa) and rectal cancer (RCa) after brachytherapy (BT) relative to radical prostatectomy (RP). MATERIALS AND METHODS: Within the Surveillance, Epidemiology and End Results (SEER) database (1988-2015), we identified patients with localized PCa as an only or first primary cancer, who underwent BT or RP. Cumulative incidence plots and multivariable competing-risks regression (CRR) models were used. Sensitivity analyses focused on patients' age and year of diagnosis intervals and tested the effect of an unmeasured confounder. RESULTS: Of 318 058 patients with localized prostate cancer (PCa), 55 566 (18.4%) underwent BT. After propensity score-matching, 20-year secondary BCa incidence was 6.0% in patients who had undergone BT vs 2.4% in those who had undergone RP (P < 0.001) and the respective 20-year secondary RCa incidence was 1.1% vs 0.5% (P < 0.001). In multivariable CRR models, BT predicted higher secondary BCa (hazard ratio [HR] 1.58; P < 0.001) and RCa rates (HR 1.59; P < 0.001) vs RP. Sensitivity analyses replicated the same results after stratification according to age and showed HRs of decreasing magnitude for historical, intermediate and contemporary years of diagnosis. An unmeasured confounder with an HR of 2 would render the effect of BT statistically insignificant if it affected patients in the RP group with a ratio of 2 relative to those in the BT group. Finally, temporal trends showed a decrease of secondary 5-year BCa and RCa rates.> CONCLUSIONS: Brachytherapy predominantly increases the risk of secondary BCa and, to a lesser extent, that of RCa. Follow-up of such patients is therefore required. It is encouraging that both secondary BCa, and RCa rates, in particular, have recently decreased, RCa.

Differences in trends in the use of robot-assisted and open radical cystectomy and changes over time in peri-operative outcomes among selected centres in North America and Europe: an international multicentre collaboration.

OBJECTIVES: To compare trends in the use of robot-assisted radical cystectomy (RARC) and changes over time in peri-operative outcomes in selected North American and European centres. MATERIALS AND METHODS: We conducted a retrospective evaluation of 2401 patients treated with open radical cystectomy (ORC) or RARC for bladder cancer at 12 centres in North America and Europe between 2006 and 2018. We used the Kruskal-Wallis and chi-squared test to evaluate differences between continuous and categorical variables. RESULTS: Overall, 49.5% of patients underwent RARC and 51.5% ORC. RARC became the most commonly performed procedure in contemporary patients, with an increase from 29% in 2006-2008 to 54% in 2015-2018 (P < 0.001). In the North American centres the use of RARC was higher than that of ORC from 2006, and remained stable over time, whereas in the European centres its use increased exponentially from 2% to 50%. In both groups patients who underwent RARC had less advanced T stages (P < 0.001), lower American Society of Anesthesiologists scores (P < 0.05), lower blood loss (P = 0.001) and shorter length of hospital stay (P < 0.05). No differences were found in early complications. Early readmission and re-operation rates were worse for patients treated with RARC in the European centres; however, when contemporary patients only were considered, the statistical significance was lost. CONCLUSION: The present study shows that the use of RARC has constantly increased since its introduction, overtaking ORC in the most contemporary series. While RARC was more frequently performed than ORC since its introduction in the North American centres and its use remained substantially stable over time, its use increased exponentially in the European centres. The different trends in use of RARC/ORC and changes over time in peri-operative outcomes between the North American and European centres can be attributed to the earlier introduction and spread of RARC in the former compared with the latter.

Trends and Social Barriers for Inpatient Palliative Care in Patients With Metastatic Bladder Cancer Receiving Critical Care Therapies.

BACKGROUND: Use of inpatient palliative care (IPC) in the treatment of advanced cancer represents a well-established guideline recommendation. A recent analysis showed that patients with genitourinary cancer benefit from IPC at the second lowest rate among 4 examined primary cancers, namely lung, breast, colorectal, and genitourinary. Based on this observation, temporal trends and predictors of IPC use were examined in patients with metastatic urothelial carcinoma of the bladder (mUCB) receiving critical care therapies (CCTs). PATIENTS AND METHODS: Patients with mUCB receiving CCTs were identified within the Nationwide Inpatient Sample database (2004-2015). IPC use rates were evaluated in estimated annual percentage change (EAPC) analyses. Multivariable logistic regression models with adjustment for clustering at the hospital level were used. RESULTS: Of 1,944 patients with mUCB receiving CCTs, 191 (9.8%) received IPC. From 2004 through 2015, IPC use increased from 0.7% to 25.0%, respectively (EAPC, +23.9%; P<.001). In analyses stratified according to regions, the highest increase in IPC use was recorded in the Northeast (EAPC, +44.0%), followed by the West (EAPC, +26.8%), South (EAPC, +22.9%), and Midwest (EAPC, +15.5%). Moreover, the lowest rate of IPC adoption in 2015 was recorded in the Midwest (14.3%). In multivariable logistic regression models, teaching status (odds ratio [OR], 1.97; P<.001), more recent diagnosis (2010-2015; OR, 3.89; P<.001), and presence of liver metastases (OR, 1.77; P=.02) were associated with higher IPC rates. Conversely, Hispanic race (OR, 0.42; P=.03) and being hospitalized in the Northeast (OR, 0.36; P=.01) were associated with lower rate of IPC adoption. Finally, patients with a primary admission diagnosis that consisted of infection (OR, 2.05; P=.002), cardiovascular disorders (OR, 2.10; P=.03), or pulmonary disorders (OR, 2.81; P=.005) were more likely to receive IPC. CONCLUSIONS: The rate of IPC use in patients with mUCB receiving CCTs sharply increased between 2004 and 2015. The presence of liver metastases, infections, or cardiopulmonary disorders as admission diagnoses represented independent predictors of higher IPC use. Conversely, Hispanic race, nonteaching hospital status, and hospitalization in the Midwest were identified as independent predictors of lower IPC use and represent targets for efforts to improve IPC delivery in patients with mUCB receiving CCT.

The impact of completeness of last transurethral resection of bladder tumors on the outcomes of radical cystectomy.

PURPOSE: To evaluate the role of a complete transurethral resection of bladder tumors (c-TURBT) on oncological outcomes after radical cystectomy (RC) and its relationship with adverse pathological features. METHODS: We retrospectively analyzed data of 727 patients treated with RC and bilateral pelvic lymph node dissection at three tertiary referral centers. Possible c-TURBT was reported by the treating surgeon. Multivariable Cox regression analyses were used to assess the relationship of c-TURBT and survival outcomes after surgery in 1:1 propensity score-matched cohort adjusted for age and gender. Moreover, multivariable logistic regression (MVA) was built to predict the relationship between c-TURBT and pT3-T4 stages at RC, lymph node invasion (LNI) and positive soft tissue surgical margin (STSM). RESULTS: A total of 433 (60%) patients received a c-TURBT. 3.0% of patients with a c-TURBT achieved a pT0-pTa-pTis status vs. 2.0% of patients with incomplete TURBT. At multivariable Cox regression analyses, c-TURBT was not associated with survival outcomes. At MVA, incompleteness of TURBT was significantly associated with a pT3-T4 stage [odds ratio (OR) 8.04, 95% confidence interval (CI) 2.33-27.67, p = 0.001]. No significant association was found between c-TURBT, LNI and STSM. CONCLUSION: We found a low rate of achievement of pT0 stage at RC. An incomplete TURBT before RC represented a predictor of pT3-T4 stages, but no effect of a c-TURBT was shown on survival outcomes. Given the current inadequacy of clinical staging strategies with more than 50% of extravesical disease being under-staged, our results could improve patients selection for NAC, driving the decision-making in doubtful cases.

Radical Cystectomy in Pathological T4a and T4b Bladder Cancer Patients: Is There Any Space for Sub Stratification?

INTRODUCTION: According to TNM staging, pathological T4ab are comprehensive of the invasion of prostate, seminal vesicles, uterus or vagina and pelvic or abdominal wall. However, few data are available on the perioperative and oncological outcomes of specific organ invasion. MATERIALS AND METHODS: A total of 917 consecutive bladder cancer (BCa) patients treated with radical cystectomy (RC) at a single institution between 1990 and 2015 were studies. Cox regression analyses were used to stratify pT4ab according to the site of invasion and survival. RESULTS: Overall, 176 (19.2%) and 40 (4.4%) patients harbored pT4a or pT4b disease. Specifically, 84 (9.2%) patients reported prostate and/or SVI invasion, 62 (6.8%) prostate only, 16 (1.7%) uterus, 14 (1.5%) vaginal, 24 (2.6%) pelvic wall, and 16 (1.7%) abdominal wall invasion. The median follow-up in pT4 patients was 48 months. The 1-year cancer-specific mortality (CSM) rates were 71, 65, 24, 50, 50, and 72%, for vaginal, uterus, prostate only, prostate and/or seminal vesicles, pelvic wall, and abdominal wall invasions, respectively. At multivariable Cox regression, the invasion of prostate only (hazard ratio [HR] 3.53), prostate and/or SVI (HR 4.98), uterus (HR 7.16), vagina (HR 6.12), pelvic (HR 11.81), abdominal (8.36) were associated with adverse CSM. CONCLUSIONS: Our study described the differences in survival related to invasion site in pT4 patients, confirming poor survival expectancies in this subgroup. Patients with prostate invasion only seem to be associated with better survival than those affected by concomitant invasion of seminal vesicles. Uterus and vaginal invasions were associated with poor survival outcomes. Patients Summary: In this study, we looked at the outcome of locally advanced invasive BCa (stage pT4) in patients treated with RC at a tertiary referral hospital. We analyzed the differences in survival related to the specific organ invasion. We confirmed poor survival in this subgroup of patients. Only patients who had prostate invasion only seem to have a better survival.

Surgical treatment for clinical node-positive bladder cancer patients treated with radical cystectomy without neoadjuvant chemotherapy.

OBJECTIVE: Growing literature supports good survival expectancies in bladder cancer (BCa) patients affected by clinical node metastases (cN+) treated with multimodal therapy. We evaluated the role of adjuvant chemotherapy in cN+BCa patients treated with radical cystectomy (RC) and pelvic lymph node dissection (PLND) without neoadjuvant chemotherapy (NAC). METHODS: We evaluated a total of 192 patients with BCa and cN+. All patients were treated with RC and PLND without NAC between 2001 and 2013. Kaplan-Meier analyses and Cox regression analyses were used to assess the impact of adjuvant chemotherapy (ACT) on recurrence, cancer-specific mortality (CSM) and overall mortality (OM) after surgery. RESULTS: Overall, 99 patients (51.6%) were found without node metastases at RC, while 18 (9.4%), 58 (30.2%) and 17 (8.9%) patients were found pN1, pN2 and pN3, respectively. With a median follow-up of 48 months, in cN+ patients we recorded 5-year recurrence, CSM and OM of 55, 53 and 51%, respectively. Overall, 36 (18.8%) patients were treated with adjuvant chemotherapy. At univariable analyses, ACT was associated with improved overall survival [Hazard ratio (HR): 0.42, confidence interval (CI) 0.20-0.86, p = 0.02) in pN+ subgroup only. These results were confirmed at multivariable analyses, where ACT was associated with improved CSS (HR: 0.45, CI 0.21-0.89, p = 0.03) and OS (HR: 0.37, CI 0.17-0.81, p = 0.01). CONCLUSIONS: We report good survival outcomes in cN+ patients treated with RC. The use of ACT after surgery increases survival expectancies, especially in those patients with pathological node disease. Our data need to be further evaluated in prospective setting.