Radical Cystectomy In Patients Research Articles

Discriminatory ability of perioperative heart rate variability in predicting postoperative complications in major urologic surgery: a prospective cohort study

We aimed to determine if continuous perioperative heart rate variability (HRV) monitoring could improve risk stratification compared to a short preoperative measurement in radical cystectomy patients. Electrocardiography (ECG) recordings were collected continuously preoperatively to discharge in 83 patients. Two, 5-min ECG signal segments (preoperative and at 24-h post ECG placement) were analyzed offline to extract HRV metrics. HRV metric discriminatory ability to identify patients with 30-day postoperative complications were analyzed using receiver operating characteristics curves. Sixty participants were included for analysis of which 27 (45%) developed a complication within 30 days postoperative. HRV was reduced in patients with complications. Postoperative standard deviation NN intervals and root mean square of successive differences had area under the curves (AUC) of 0.67 (95% CI 0.54 to 0.81) and 0.68 (95% CI 0.54 to 0.82), respectively. Significant discriminatory abilities were also reported for postoperative frequency metrics of absolute low frequency (LF) [AUC = 0.65 (95% CI 0.51 to 0.79)] and high frequency (HF) powers [AUC = 0.69 (95% CI 0.55 to 0.83)] and total power [AUC = 0.66 (95% CI 0.53 to 0.80)]. Postoperative acquired HRV metrics demonstrated improved discriminatory ability. Our findings suggest that longer-term perioperative HRV monitoring presents with superior ability to stratify complication risk.

Abstract A001: Urine-based liquid biopsy test for the detection of residual bladder cancer in radical cystectomy patients

Abstract One commonly employed management strategy for muscle-invasive bladder cancer (MIBC) is neoadjuvant chemotherapy followed by radical cystectomy (RC) and urinary diversion. Approximately 35% of patients achieve a pathologic complete response (pCR) when evaluated from RC specimens. RC with urinary diversion is a life-altering operation with high complication rates and therefore determining who are complete responders would improve quality of life and could decrease costs and still achieve a high cure rate via RC avoidance. Unfortunately, current methods cannot accurately identify complete responders. Our lab has developed a urine-based liquid biopsy test in which DNA isolated from urine and germline is isolated and subjected to panel exome sequencing for enumeration of somatic variants. This occurs under the premise that tumor DNA identified (as mutant alleles) is a marker of residual disease while the absence of tumor DNA (meaning the absence of mutant alleles) can indicate a pCR. A 60 gene panel was designed to be used for exonic sequencing of urinary DNA (uDNA) to identify mutations indicative of bladder cancer or therapeutic targets. We have shown that most mutations in tumor tissue (Mt) are detectable as mutations in urine (Mu). We also showed that the presence or absence of residual Mu after completion of chemotherapy strongly associates with residual disease or pCR at the time of RC, respectively. Therefore, this test could be used after neoadjuvant therapy to better identify patients for RC avoidance. We optimized this test by studying pre-analytical factors affecting the yield, purity, and integrity of uDNA and the quality of sequencing data using prospectively collected samples from patients with MIBC. We are also in the process of testing commercial and novel preservatives to optimize DNA integrity, yield, and mutation detection accuracy to enable temporary ambient temperature storage without compromising mutation detection, permitting shipping/centralized testing. Lastly, we are comparing two library preparation approaches. Study of these preanalytical factors has increased the number of Mu that can be detected and were applied to a cohort of patients who underwent bladder sparing curative-intent treatment in a prospective clinical trial. Studies described herein will enable liquid biopsy tests to accurately identify patients with pCR after neoadjuvant therapy and might safely avoid radical cystectomy. Citation Format: Philip H. Abbosh, Henkel Valentine, Rhea Arya. Urine-based liquid biopsy test for the detection of residual bladder cancer in radical cystectomy patients [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A001.

It's complicated: The relationship of non-narcotic medications and postoperative opioid use in radical cystectomy patients

IntroductionThe effect of individual non-narcotic analgesics in cystectomy enhanced recovery after surgery (ERAS) is unknown. Additionally, many non-narcotic medications are associated with side effects pertinent to the cystectomy population. To better understand the actual use and utility of these medications, we sought to characterize the association between non-narcotic medications and milligram morphine equivalent (MME) narcotic score during the postoperative inpatient stay. MethodsWe reviewed 260 consecutive ERAS cystectomy patients. The MME impact of non-narcotic compliance and cumulative dose of medication received was evaluated separately with general linear models. We also assessed relationship of non-narcotic compliance to patient reported pain score, length of stay (LOS), and time to return of bowel function (ROBF) and performed manual review of postoperative documentation to identify reasons for medication noncompliance. ResultsCompliance with postoperative acetaminophen, gabapentin, and ketorolac was low. There was an inverse relationship between ketorolac dose and MME on postoperative day 1 (−0.026 MME/mg; P = 0.004) and postoperative day 2 (−0.33 MME/mg; P < 0.001). Compliance with ketorolac was associated with lower MME on postoperative day 1 (26.1 MME v. 33.6 MME; P = 0.023). There were no such associations identified with gabapentin or acetaminophen. Gabapentin compliance was associated with earlier ROBF (3.7 days v. 4.3 days; P = 0.006). Ketorolac compliance was associated with lower pain score on POD1 (3.25 VAS v. 4.07 VAS; P = 0.019) and POD2 (3.05 VAS v. 3.85 VAS; P = 0.040) There was no association between medication compliance and LOS. The most common reasons identified for non-compliance with gabapentin and ketorolac were renal function concerns (38% and 40% respectively), bleeding concerns with ketorolac (20%) and concerns for neurologic adverse effect with gabapentin (16%). ConclusionCompliance with non-narcotic medications in our ERAS cystectomy protocol was poor. There was a modest association with ketorolac and postoperative MME but no association with gabapentin or acetaminophen. Further study will clarify the role of these medications for cystectomy patients. Component specific analysis of protocolized care is valuable and may alter care pathways.

Trimodal therapy vs radical cystectomy in patients with muscle-invasive bladder cancer: a systematic review and meta-analysis of comparative studies.

To perform a systematic review and meta-analysis of trials comparing trimodal therapy (TMT) and radical cystectomy (RC), evaluating differences in terms of oncological outcomes, quality of life, and costs. In July 2023, a literature search of multiple databases was conducted to identify studies analysing patients with cT2-4 N any M0 muscle-invasive bladder cancer (MIBC; Patients) receiving TMT (Intervention) compared to RC (Comparison), to evaluate survival outcomes, recurrence rates, costs, and quality of life (Outcomes). The primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS) and metastasis-free survival (MFS). Hazard ratios (HRs) were used to analyse survival outcomes according to different treatment modalities and odds ratios were used to evaluate the likelihood of receiving each type of treatment according to T stage. No significant difference in terms of OS was observed between RC and TMT (HR 1.07, 95% confidence interval [CI] 0.81-1.4; P = 0.6), even when analysing radiation therapy regimens ≥60 Gy (HR 1.02, 95% CI 0.69-1.52; P = 0.9). No significant difference was observed in CSS (HR 1.12, 95% CI 0.79-1.57, P = 0.5) or MFS (HR 0.88, 95% CI 0.66-1.16; P = 0.3). The mean cost of TMT was significantly higher than that of RC ($289 142 vs $148 757; P < 0.001), with greater effectiveness in terms of cost per quality-adjusted life-year. TMT ensured significantly higher general quality-of-life scores. Trimodal therapy appeared to yield comparable oncological outcomes to RC concerning OS, CSS and MFS, while providing superior patient quality of life and cost effectiveness.

Hyperthermic Intravesical Chemotherapy (HIVEC) Using Epirubicin in an Optimized Setting in Patients with NMIBC Recurrence after Failed BCG Therapy.

To evaluate hyperthermic intravesical chemotherapy (HIVEC) using conductive heating and epirubicin in an optimized setting as an alternative to radical cystectomy in patients with recurrent non-muscle invasive bladder cancer (NMIBC) who have failed bacillus Calmette-Guérin (BCG) therapy. We retrospectively analyzed our prospectively recorded database of patients who underwent HIVEC between 11/2017 and 11/2022 at two Swiss University Centers. Cox regression analysis was used for univariate/multivariate analysis, and the Kaplan-Meier method for survival analysis. Of the 39 patients with NMIBC recurrence after failed BCG therapy, 25 (64%) did not recur within the bladder after a median follow-up of 28 months. The 12- and 24-month intravesical RFS were 94.8% and 80%, respectively. Extravesical recurrence developed in 14/39 (36%) of patients. Only 7/39 (18%) patients had to undergo radical cystectomy. Seven patients (18%) progressed to metastatic disease, with five of these (71%) having previously developed extravesical disease. No adverse events > grade 2 occurred during HIVEC. Device-assisted HIVEC using epirubicin in an optimized setting achieved excellent RFS rates in this recurrent NMIBC population at highest risk for recurrence after previously failed intravesical BCG therapy. Extravesical disease during or after HIVEC, however, was frequent and associated with metastatic disease and consecutively poor outcomes.

Perioperative complications and in-hospital mortality in radical cystectomy patients with heart-valve replacement

PurposeTo assess in-hospital mortality and complication rates after radical cystectomy (RC) in patients with history of heart-valve replacement. Materials and methodsUsing the National Inpatient Sample (2000–2019), non-metastatic bladder cancer patients undergoing RC were stratified according to history of heart-valve replacement. Regression models (RM) predicted hospital outcomes. ResultsOf 25,535 RC patients, 250 (1.0%) harbored history of heart-valve replacement. Heart-valve replacement patients were older (median 74 vs. 70 years), more frequently male (87.2 vs. 80.6%), and more frequently had Charlson comorbidity index ≥3 (26.8 vs. 18.9%). In RC patients with history of heart-valve replacement vs. others, 62 vs. 2634 (24.8 vs. 10.4%) experienced cardiac complications, 28 vs. 3092 (11.2 vs. 12.2%) intraoperative complications, 11 vs. 1046 (4.4 vs. 4.1%) infections, <11 vs. 594 (<4.4 vs. 2.3%) perioperative bleeding, <11 vs. 699 (<4.4 vs. 2.8%) vascular complications, 74 vs. 6225 (29.6 vs. 24.7%) received blood transfusions, 37 vs. 3054 (14.8 vs. 12.1%) critical care therapy (CCT), and in-hospital mortality was recorded in <11 vs. 463 (<4.4 vs. 1.8%) patients. In multivariable RM, history of heart-valve replacement independently predicted cardiac complications (odds ratio 2.20, 95% confidence interval 1.62–2.99; p < 0.001). Conversely, no statically significant association was recorded between history of heart-valve replacement and length of stay, estimated hospital cost, intraoperative complications, perioperative bleeding, vascular complications, infections, blood transfusions, CCT use, and in-hospital mortality. ConclusionsRadical cystectomy patients with history of heart-valve replacement exhibited a 2.2-fold higher risk of cardiac complications, but no other complications, including no significantly higher in-hospital mortality.

Abstract 3701: Urine-based liquid biopsy test for the detection of residual bladder cancer in radical cystectomy patients

Abstract The gold standard therapy for muscle-invasive bladder cancer (MIBC) is neoadjuvant chemotherapy followed by radical cystectomy (RC) and urinary diversion. Some patients may have their disease completely eradicated by chemotherapy as ~35% of patients achieve a pathologic complete response (pCR) when evaluated from RC specimens. RC with urinary diversion is a life-altering operation with high complication rates and therefore determining who are complete responders would improve quality of life and could decrease costs and still achieve a high cure rate via RC avoidance. Unfortunately, current methods cannot accurately identify complete responders. Our lab has developed a urine-based liquid biopsy test in which DNA isolated from urine and germline is isolated and subjected to panel exome sequencing for enumeration of somatic variants. This occurs under the premise that tumor DNA identified (as mutant alleles) is a marker of residual disease while the absence of tumor DNA (meaning the absence of mutant alleles) can indicate a pCR. A 55 gene panel was designed to be used for exonic sequencing of urinary DNA (uDNA) to identify mutations indicative of bladder cancer or therapeutic targets. We have shown that most mutations in tumor tissue are detectable as mutations in urine (Mu). We also showed that the presence or absence of residual Mu after completion of chemotherapy strongly associates with residual disease or pCR at the time of RC, respectively. Therefore, this test could be used after neoadjuvant therapy to better identify patients for RC avoidance. To optimize this test, we are currently evaluating pre-analytical factors affecting the yield, purity, and integrity of uDNA and the quality of sequencing data using prospectively collected samples from patients with MIBC. We are also testing commercial and novel preservatives to identify one that maintains cell-free DNA integrity, yield, and mutation detection accuracy to enable temporary ambient temperature storage without compromising mutation detection, permitting shipping/centralized testing. Lastly, we are comparing two library preparation approaches: classical hybrid capture-based (Agilent SureSelect XTHS) and amplicon+hybrid capture-based (Agilent HaloPlexHS) to determine which performs the best for identifying the variants in a sample. Our results showed that both sequencing depth and the quality bases mapped was higher when utilizing the SureSelect XTHS kit as compared to HaloPlexHS using approximately the same number of reads. This improvement may also increase the power to detect rare alleles. Studies described herein will enable liquid biopsy tests to accurately identify patients with pCR after neoadjuvant therapy and might safely avoid radical cystectomy. Citation Format: Rhea Arya, Henkel Valentine, Uttam Satyal, Raju Chelluri, Mengmeng Li, Philip Abbosh. Urine-based liquid biopsy test for the detection of residual bladder cancer in radical cystectomy patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3701.

The effect of race/ethnicity on cancer-specific mortality after trimodal therapy.

Trimodal therapy (TMT) is the most validated bladder-sparing treatment for organ-confined urothelial carcinoma of the urinary bladder (OC UCUB, namely cT2N0M0). However, it is unknown if barriers to the use of TMT or cancer-specific mortality (CSM) differences exist according to race/ethnicity. We addressed this knowledge gap. Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified OC UCUB patients aged from 18 to 85 treated with radical cystectomy (RC) or TMT. Temporal trends described TMT versus RC use over time. Subsequently, in the subgroup of TMT-treated patients, survival analyses consisting of Kaplan-Meier plots and multivariable Cox regression (MCR) models addressed CSM according to race/ethnicity. Among 19,501 assessable patients, 15,336 (79%) underwent RC versus 4165 TMT (21%). Overall, of all races/ethnicities, 16,245 (83.3%) were White Americans, 1215 (6.3%) Hispanics, 1160 (5.9%) African Americans, and 881 (4.5%) Asian/Pacific Islanders. Among TMT-treated patients, 3460 (83.1%) were White Americans, 298 (7.1%) African Americans, 218 (5.3%) Hispanics, and 189 (4.5%) Asian/Pacific Islanders. The lowest rate of TMT use relative to RC and TMT patients was recorded in Hispanics (17.9%). Over time, TMT use increased in White Americans (EAPC: + 4.5%, p = 0.001) and Asians/Pacific Islanders (EAPC: + 5.2%, p = 0.003), but not in others. Kaplan-Meier analyses showed median CSM of 49months, 41months, and 34months and not reached in White Americans, Hispanics, African Americans, and Asian/Pacific Islanders, respectively (p = 0.02). In MCR models, two race/ethnicity subgroups independently predicted either worse (African Americans, HR: 1.20, p = 0.02) or better CSM (Asian/Pacific Islanders, HR: 0.75, p = 0.02). Race/ethnicity affects both access to TMT (lower access in Hispanics) as well as survival after TMT (better in Asians/Pacific Islanders and worse in African Americans).

Comparison of urological outcomes and quality of life after pelvic exenteration: partial vs radical cystectomy.

To compare perioperative morbidity, functional and quality-of-life (QoL) outcomes in patients with partial cystectomy vs radical cystectomy as part of pelvic exenteration. Retrospective analysis of a prospectively maintained database of pelvic exenteration patients (1998-2021) was conducted in a single centre. Study outcomes included postoperative complications, quality-of-life, functional and stoma-related outcomes. The 36-item Short-Form Health Survey Physical and Mental Health Components, Functional Assessment of Cancer Therapy-Colorectal questionnaires and Distress Thermometer were available pre- and postoperatively. QoL outcomes were compared at the various time points. Stoma embarrassment and care scores were compared between patients with a colostomy, urostomy, and both. Urological complications were similar between both groups, but patients with partial cystectomy experienced less wound-related complications. Overall, 34/81 (42%) partial cystectomy patients reported one or more long-term voiding complication (i.e., incontinence [17 patients], frequency [six], retention [three], high post-voiding residuals [10], permanent suprapubic catheter/indwelling catheter [14], recurrent urinary tract infection [nine], percutaneous nephrostomy [three], progression to urostomy [three]). The QoL improved following surgery in both the partial and radical cystectomy groups, differences between cohorts were not significant. Patients with two stomas reported higher embarrassment scores than patients with one stoma, although this did not result in more difficulties in stoma care. Partial cystectomy patients have fewer postoperative wound-related complications than radical cystectomy patients, but often experience long-term voiding issues. The QoL outcomes are similar for both cohorts, with significant improvement following surgery.

Role of thromboprophylaxis during neoadjuvant chemotherapy before radical cystectomy in patients with bladder cancer: Results of a multicenter retrospective cohort study.

598 Background: Patients undergoing radical cystectomy are at risk of developing venous thromboembolic events (VTE), with most VTEs occurring during neoadjuvant chemotherapy. The ASCO Clinical Practice Guideline Update recommends thromboprophylaxis in cancer patients with a high risk of VTE and a low risk of bleeding. However, the risks of VTE and bleeding with or without thromboprophylaxis in bladder cancer patients scheduled for radical cystectomy have not been well evaluated. Methods: We conducted a retrospective cohort study of patients with non-metastatic bladder cancer undergoing cystectomy across 28 centers in 13 countries between 1990 and 2021. Inverse probability weighting analyses were performed to estimate the effect of thromboprophylaxis during neoadjuvant chemotherapy on VTE and bleeding. Results: Of 4886 patients, 4631 (95%) received neither thromboprophylaxis nor anticoagulation during chemotherapy. Thromboprophylaxis during neoadjuvant chemotherapy was prescribed in 151 (3%) patients mainly being enoxaparin (80%) with a median duration of 94 (range 38 to 104) days. In inverse probability weighting analyses, patients with thromboprophylaxis compared to patients without thromboprophylaxis during chemotherapy had not only a lower VTE (HR 0.32 [95% CI, 0.12 to 0.81], p-value = 0.016) but also a lower bleeding risk (HR 0.03 [95% CI, 0.09 to 0.12], p-value: &lt;0.0001). Conclusions: In this retrospective analysis, the benefit of thromboprophylaxis during neoadjuvant chemotherapy before cystectomy is in line with data from randomized trials in other malignancies. Our data suggests thromboprophylaxis seems protective against VTEs during neoadjuvant chemotherapy in bladder cancer patients planned for cystectomy. The ASCO guidelines recommending thromboprophylaxis during chemotherapy should therefore also be regarded as a standard of care in patients treated with neoadjuvant chemotherapy before cystectomy.

The Association between Urinary Diversion Type and Other-Cause Mortality in Radical Cystectomy Patients.

It is unknown whether more complex UD, such as orthotopic neobladder and abdominal pouch, may be associated with higher OCM rates than ileal conduit. We addressed this knowledge gap within the SEER database 2004-2020. All T1-T4aN0M0 radical cystectomy (RC) patients were identified. After 1:1 propensity score matching (PSM), cumulative incidence plots, univariable and multivariable competing-risks regression (CRR) models were used to test differences in OCM rates according to UD type (orthotopic neobladder vs. abdominal pouch vs. ileal conduit). Of all 3008 RC patients, 2380 (79%) underwent ileal conduit vs. 628 (21%) who underwent continent UD (268 orthotopic neobladder and 360 abdominal pouch). After PSM relative to ileal conduit, neither continent UD (13 vs. 15%; p = 0.1) nor orthotopic neobladder (13 vs. 16%; p = 0.4) nor abdominal pouch (13 vs. 15%; p = 0.2) were associated with higher 10-year OCM rates. After PSM and after adjustment for cancer-specific mortality (CSM), as well as after multivariable adjustments relative to ileal conduit, neither continent UD (Hazard Ratio [HR]:0.73; p = 0.1), nor orthotopic neobladder (HR:0.84; p = 0.5) nor abdominal pouch (HR:0.77; p = 0.2) were associated with higher OCM. It appears that more complex UD types, such as orthotopic neobladder and abdominal pouch are not associated with higher OCM relative to ileal conduit.

Longer time to radical cystectomy in patients treated with neoadjuvant chemotherapy is associated with worse oncological outcomes

BackgroundCurrent muscle-invasive bladder cancer (MIBC) guidelines recommend not delaying radical cystectomy (RC) >3 months after diagnosis as it decreases overall survival (OS). However, literature investigating the impact of delay in RC in patients who receive NAC is limited, especially on a population-based level. ObjectiveTo investigate the association between time from diagnosis of MIBC to RC (TTRC) in patients with urothelial bladder cancer (UBC) treated with NAC and RC and 1) 2-year OS and 2) pathological lymph node status (pN+) in a population-based cohort. MethodsPatients were selected from the Netherlands Cancer Registry. The study included 237 patients with cT2-T4aN0M0 UBC, treated with NAC and RC between November 2017 and October 2019. Association between TTRC and OS was assessed using multivariable Cox regression analyses. Schoenfeld and Martingale residuals were used to investigate the proportional hazards assumption and whether a cut-off in the TTRC could be identified. Association between TTRC and pN+ was assessed using multivariable logistic regression analyses. ResultsMedian TTRC was 23 weeks (interquartile range (IQR) 19–26). 2-year OS was 67% (95%CI 59%–74%). Each week of delay in the TTRC was independently associated with 2-year OS (HR 1.06; P = 0.03) in the Cox regression analysis. The sensitivity analyses, defining TTRC as the time between last cycle of NAC and RC, revealed that each week of delay between NAC and RC was associated with 2-year OS (Hazard ratio (HR) 1.13; P < 0.0001), and with pN+ (Odds ratio (OR) 1.21; P = 0.01) in the Cox and logistic regression analyses, respectively. ConclusionsA longer TTRC is associated with worse oncological outcomes in patients treated with NAC and RC.

Comparative survival analysis of bladder preservation therapy versus radical cystectomy in muscle-invasive bladder cancer.

Bladder preservation therapy is an alternative to radical cystectomy in patients with muscle-invasive bladder cancer (MIBC). The purpose of this study is to compare survival outcomes between bladder preservation therapy and radical cystectomy in MIBC patients using an Asian nationwide cancer registry database. From the Taiwan Cancer Registry database and the Taiwan National Health Insurance Research Database, we identified bladder cancer patients from 2008 to 2018. The patients with urothelial carcinoma and clinical stage T2-T4aN0-1 M0 were included. Propensity score matching by age, gender, clinical stage, cT classification, and Charlson Comorbidity Index score was used between those receiving bladder preservation therapy or radical cystectomy. Overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) were compared using the Kaplan-Meier method. Multivariate Cox regression models were used to determine the predictive factors of OS, CSS, and DFS. Following the propensity score matching, 393 MIBC patients were analyzed, 131 (33.3%) receiving bladder preservation therapy and 262 (66.7%) receiving radical cystectomy. After 5 years of the follow-up period the overall duration was with a median of 15.6 months. The treatment groups did not differ significantly in OS, CSS, and DFS (p = 0.2681, 0.7208, and 0.3616, respectively). In multivariable Cox regression models, bladder preservation therapy remained non-inferior to radical cystectomy in OS (adjusted hazard ratio [aHR] 1.08; 95% confidence interval [CI], 0.77-1.50; p = 0.6689), CSS (aHR, 1.06; 95% CI, 0.72-1.57; p = 0.7728), and DFS (aHR, 0.76; 95% CI, 0.46-1.27; p = 0.2929). Additionally, among patients ≥80 years, the use of bladder preservation therapy compared with radical cystectomy resulted in an equivalent OS, CSS and DSS. In Asian populations, bladder preservation therapy yielded similar survival outcomes as radical cystectomy in MIBC patients. Based on the results, it is evident that a multidisciplinary approach and shared decision-making are recommended for bladder cancer treatment.

Efficiency of bladder-sparing strategies for bladder cancer: an umbrella review.

Bladder preservation (BP) has emerged as a clinical alternative to radical cystectomy (RC) for alleviating the substantial physical and psychological burden imposed on localized bladder cancer patients. Nevertheless, disparities persist in the comparative evaluations of BP and RC. We aimed to address the disparities between BP and RC. An umbrella review and meta-analysis were conducted to explore these disparities. We extracted data from meta-analyses and randomized controlled trials (RCTs) selected after searching PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews. Review Manager 5.4.0 and R x64 4.1.3 were used to evaluate the collected data. Our study included 11 meta-analyses and 3 RCTs. In terms of progression-free survival, all the meta-analyses reported that patients with localized bladder cancer who underwent BP exhibited outcomes comparable to those who underwent RC. Meta-analyses regarding the outcomes of cancer-specific survival (CSS) and overall survival (OS) are controversial. To solve these issues, we conducted a pooled analysis of CSS data, which supported the similarity of CSS between BP and RC with no significant heterogeneity [odds ratio (OR): 1.2; 95% confidence interval (CI): 0.71-2.02; I2 = 26%]. Similarly, the pooled OS results extracted from three RCTs indicated the comparability of OS between BP and RC with no significant heterogeneity (OR: 1.12; 95% CI: 0.41-3.07; I2 = 33%). A combination of umbrella review and meta-analysis results suggested that BP had survival rates comparable to those of RC. We suggest that BP may be a more eligible therapy than RC for patients with localized muscle-invasive bladder cancer. This conclusion warrants further validation through randomized controlled trials.

Comparative Effectiveness of Neoadjuvant Pembrolizumab Versus Cisplatin-based Chemotherapy or Upfront Radical Cystectomy in Patients with Muscle-invasive Urothelial Bladder Cancer

BackgroundRecent progresses in the use of immune checkpoint inhibitor (ICI) have challenged the therapeutic standards in patients with muscle-invasive urothelial bladder carcinoma (MIBC). ObjectiveTo compare neoadjuvant pembrolizumab followed by radical cystectomy (RC) versus neoadjuvant chemotherapy (NAC) and RC or upfront RC, according to cisplatin eligibility.Design, setting, and participants: We conducted two separate analyses for cisplatin-eligible and cisplatin-ineligible cT2-4N0M0 MIBC patients. We used a propensity score adjustment that relied on inverse probability of treatment-weighting (IPTW).Intervention: Pembrolizumab within the PURE-01 trial, and NAC and RC or upfront RC from a high-volume tertiary care referral single center.Outcome measurements and statistical analysis: The primary endpoint in both analyses was event-free survival (EFS), defined as freedom from recurrence, and/or death from any cause indexed from the date of treatment initiation or RC. The secondary endpoints included EFS in propensity score–matched patients, pathologic response rate, and recurrence-free survival (RFS) after RC. Resultsand limitations: A total of 458 patients who underwent RC, with or without NAC, at Moffitt Cancer Center between October 2005 and October 2020, and 146 patients enrolled in PURE-01 were analyzed. In cisplatin-ineligible patients, EFS was superior in those receiving pembrolizumab (p < 0.001). The estimated 3-yr EFS was 77.8% (95% confidence interval [CI]: 63.5–95.2) for pembrolizumab and RC, and 36.1% (95% CI: 28.6–45.5) for upfront RC. EFS remained superior in those receiving neoadjuvant ICI (NICI) following IPTW (p < 0.001). In cisplatin-eligible patients, EFS was superior in those receiving pembrolizumab and RC (p < 0.001). The estimated 3-yr EFS was 86.9% (95% CI: 80.9–93.3) for pembrolizumab and 63.5% (95% CI: 56.5–71.4) for NAC. EFS remained superior in those receiving NICI following IPTW (p < 0.001). Pathologic responses and RFS in pembrolizumab-treated patients were also superior to those in NAC-treated patients. Results are limited by the retrospective nature of the study. ConclusionsIn the first ever reported comprehensive comparison of outcomes between neoadjuvant ICI and NAC, followed by RC, or upfront RC, we report increased responses and improved oncologic outcomes with neoadjuvant ICI in patients with MIBC. Patient summaryWe compared the results obtained from the use of pembrolizumab and radical cystectomy with standard-of-care treatments in patients with a bladder carcinoma infiltrating the muscle layer. We reported increased survival and response possibilities with the use of immunotherapy, anticipating the possibility to set new therapeutic standards in these patients, pending the results of ongoing randomized studies.

Implementation of the enhanced recovery after surgery protocol for radical cystectomy patients: A single centre experience.

The enhanced recovery after surgery (ERAS) protocol for radical cystectomy aims to facilitate postoperative recovery and hasten a return to normal daily activities. This study aims to report on the perioperative outcomes of implementation of an ERAS protocol at a single Australian institution. We identified 73 patients with pT1-T4 bladder cancer who underwent open radical cystectomy at Western Health, Victoria between June 2016 and August 2021. A retrospective analysis of a prospectively maintained database was performed. Perioperative outcomes included length of hospital stay, nasogastric tube requirement and duration of postoperative ileus. The median age was 74 years (interquartile range [IQR] 66-78) for the ERAS group and 70 years (IQR 65-78) for the pre-ERAS group patients. All patients in each group underwent ileal conduit formation. The median length of hospital stay was 7.0 days (IQR 7.0-9.3) for the ERAS group and 12.0 days (IQR 8.0-16.0) for the pre-ERAS group (p=0.003). Within the ERAS group, 25.0% had a postoperative ileus, and 25.0% had a nasogastric tube inserted, compared with 64.9% (p=0.001) and 45.9% (p=0.063) respectively within pre-ERAS group. The median bowel function recovery time, defined as duration from surgery to first bowel action, was 5.0 days (IQR 4.0-7.0) in the ERAS group and 7.5 days (IQR 5.0-8.5) in the pre-ERAS group (p=0.016). Implementation of an ERAS protocol is associated with a reduction in hospital length of stay, postoperative ileus and bowel function recovery time.

Radiomics nomogram for predicting disease-free survival after partial resection or radical cystectomy in patients with bladder cancer.

To create a MRI-derived radiomics nomogram that combined clinicopathological factors and radiomics signature (Rad-score) for predicting disease-free survival (DFS) in patients with bladder cancer (BCa) following partial resection (PR) or radical cystectomy (RC), including lymphadenectomy (LAE). Finally, 80 patients with BCa after PR or RC with LAE were enrolled. Patients were randomly split into training (n = 56) and internal validation (n = 24) cohorts. Radiomic features were extracted from T2-weighted, dynamic contrast-enhanced, diffusion-weighted imaging, and apparent diffusion coefficient sequence. The least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was applied to choose the valuable features and construct the Rad-score. The DFS prediction model was built using the Cox proportional hazards model. The relationship between the Rad-score and DFS was assessed using Kaplan-Meier analysis. A radiomics nomogram that combined the Rad-score and clinicopathological factors was created for individualized DFS estimation. In both the training and validation cohorts, the Rad-score was positively correlated with DFS (P < .001). In the validation cohort, the radiomics nomogram combining the Rad-score, tumour pathologic stage (pT stage), and lymphovascular invasion (LVI) achieved better performance in DFS prediction (C-index, 0.807; 95% CI, 0.713-0.901) than either the clinicopathological (C-index, 0.654; 95% CI, 0.467-0.841) or Rad-score-only model (C-index, 0.770; 95% CI, 0.702-0.837). The Rad-score was an independent predictor of DFS for patients with BCa after PR or RC with LAE, and the radiomics nomogram that combined the Rad-score, pT stage, and LVI achieved better performance in individual DFS prediction. This study provided a non-invasive and simple method for personalized and accurate prediction of DFS in BCa patients after PR or RC.

Vesical imaging reporting and data system (VI-RADS) could predict the survival of bladder-cancer patients who received radical cystectomy

Vesical Imaging Reporting and Data System (VI-RADS) shows good potential in determining muscle-invasive bladder cancer (MIBC) patients. However, whether VI-RADS could predict the prognosis of radical cystectomy (RC) patients has not been reported. Our purpose is to determine whether VI-RADS contributed to predict oncologic outcomes. In this retrospective study, we analysed the information of bladder cancer patients who admitted to our centre from June 2012 to June 2022. All patients who underwent multiparametric magnetic resonance imaging (mpMRI) and underwent RC were included. VI-RADS scoring was performed by two radiologists blinded to the clinical data. Patients’ clinical features, pathology data, and imaging information were recorded. Kaplan–Meier method was used to estimate patients' overall survival (OS) and progression-free survival (PFS). Log-rank test was used to assess statistical differences. COX regression analysis was used to estimate risk factors. Ultimately, we included 219 patients, with 188 males and 31 females. The median age was 66 (IQR = 61–74.5) years. The VI-RADS scores were as follows: VI-RADS 1, 4 (1.8%); VI-RADS 2, 68 (31.1%); VI-RADS 3, 40 (18.3%); VI-RADS 4, 69 (31.5%); and VI-RADS 5, 38 (17.4%). Patients with VI-RADS ≥ 3 had poorer OS and PFS than those with VI-RADS < 3. The AUC of VI-RADS predicting 3-year OS was 0.804, with sensitivity of 0.824 and negative predictive value of 0.942. Multivariate COX analysis showed that VI-RADS ≥ 3 was risk factors for OS (HR = 3.517, P = 0.003) and PFS (HR = 4.175, P < 0.001). In the MIBC subgroup, patients with VI-RADS ≥ 4 had poorer OS and PFS. In the non-muscle invasive bladder cancer (NMIBC) subgroup, the prognosis of patients with VI-RADS ≥ 3 remained poorer. VI-RADS scores could effectively predict the survival of patients after RC.

Clinical Outcomes of Patients With Variant Histology of Urothelial Carcinoma After Radical Cystectomy

Purpose: The efficacy of standard chemotherapy or radical cystectomy in patients who have urothelial tumors with variant histology (VH) is very limited in terms of their prognosis. This study aimed to investigate the prognosis of bladder cancer (BC) patients with VH who underwent radical cystectomy (RC).Materials and Methods: We retrospectively evaluated 327 BC patients who underwent RC at Pusan National University Yangsan Hospital between February 2010 and June 2021. VH was categorized into less and more aggressive types according to the patient’s mortality risk relative to pure urothelial carcinoma (PUC). More aggressive types included micropapillary, plasmacytoid, and sarcomatoid variants. Less aggressive types comprised other variant types, including squamous differentiation, glandular differentiation, lipoid, and nested. Small cell carcinoma, pure adenocarcinoma, pure squamous cell carcinoma, and lymphoma BC were excluded from analysis. The progression-free survival (PFS) and overall survival (OS) rates were evaluated using Kaplan-Meier analysis and Cox regression.Results: After the exclusion of nonurothelial tumors, data from 299 patients were available for analysis. We identified 244 (74.6%) and 55 patients (16.8%) with PUC and urothelial carcinoma with VH, respectively. VH patients were categorized as having less aggressive (n=35) and more aggressive (n=20) types. Univariate analysis identified significant differences in PFS (p=0.031) between patients with PUC (n=244) and more aggressive VH (n=20). Multivariate analysis showed that more aggressive VH was significantly associated with OS and PFS. In the Kaplan-Meier analysis, a statistically significant difference was observed between PUC and more aggressive VH in OS and PFS.Conclusions: VH patients with more aggressive types showed more advanced TNM stages at presentation than PUC patients. Pathological upstaging after RC was more common in VH patients. Among VH patients, the presence of a more aggressive VH type can be an independent predictor of progression after RC, with a worse prognosis than that of PUC patients.

Preoperative optimization of the radical cystectomy patient: Current state and future directions.

Radical cystectomy (RC) is associated with high rates of morbidity and mortality despite adoption of robotics and implementation of enhanced recovery after surgery protocols. There have been increased efforts to investigate preoperative optimization through comprehensive nutritional evaluation, preoperative supplementation, and prehabilitation outside of previously described enhanced recovery after surgery protocols to reduce mortality and morbidity from RC. In this review, we summarize and evaluate the current literature on preoperative assessment and optimization in RC.