Non-metastatic Muscle-invasive Bladder Cancer Research Articles

Social Vulnerability and Receipt of Neoadjuvant Chemotherapy in Patients Undergoing Radical Cystectomy for Bladder Cancer.

To evaluate the association between a population-level measure of social determinants of health, the Centers for Disease Control and Prevention Social Vulnerability Index (SVI), and receipt of neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy. We queried our institutional database for patients with nonmetastatic MIBC treated with radical cystectomy between 2000 and 2022. Patients were assigned an SVI via ZIP code of residence and grouped into quintiles of SVI (i.e. least vulnerable to most vulnerable). Multivariable logistic regression was performed to evaluate the association between SVI and receipt of neoadjuvant chemotherapy, adjusting for age, race, gender, and cancer stage. A sub-analysis was performed to evaluate the association between subthemes of SVI (socioeconomic status, household composition/disability, race/ethnicity/language, and housing/transportation) and receipt of neoadjuvant chemotherapy. Of the 978 patients identified, 490 (50.1%) received neoadjuvant chemotherapy. Patients that received neoadjuvant chemotherapy had a lower SVI, were younger, and had >cT2 stage (all, p<0.05). The most vulnerable patients had lower odds of receiving neoadjuvant chemotherapy (OR 0.61, 0.39 - 0.95) compared to the least vulnerable patients. Analysis of subthemes of SVI demonstrated similar associations by socioeconomic status (OR 0.56, 0.36 - 0.86) and household composition/disability (OR 0.57, 0.33 - 0.99). Adverse social determinants of health, or social vulnerability, is associated with suboptimal and disparate utilization of neoadjuvant chemotherapy in patients with MIBC undergoing radical cystectomy. Strategies for identifying vulnerable populations may allow for more targeted interventions that would improve equity in bladder cancer care.

Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/SUO GUIDELINE (2017; Amended 2020, 2024).

Although representing approximately 25% of patients diagnosed with bladder cancer, muscle-invasive bladder cancer (MIBC) carries a significant risk of death that has not significantly changed in decades. Increasingly, clinicians and patients recognize the importance of multidisciplinary collaborative efforts that take into account survival and quality of life concerns. This guideline provides a risk-stratified, clinical framework for the management of muscle-invasive urothelial bladder cancer. In 2024, the MIBC guideline was updated through the AUA amendment process in which newly published literature is reviewed and integrated into previously published guidelines in an effort to maintain currency. The amendment allowed for the incorporation of additional literature released since the previous 2020 amendment. The updated search gathered literature from May 2020 to November 2023. This review identified 3739 abstracts, of which 46 met inclusion criteria.When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. Updates were made regarding neoadjuvant/adjuvant chemotherapy, radical cystectomy, pelvic lymphadenectomy, multi-modal bladder preserving therapy, and future directions. Further revisions were made to the methodology and reference sections as appropriate. This guideline seeks to improve clinicians' ability to evaluate and treat patients with MIBC based on currently available evidence. Future studies will be essential to further support or refine these statements to improve patient care.

Circulating Tumour DNA and Its Prognostic Role in Management of Muscle Invasive Bladder Cancer: A Narrative Review of the Literature.

Current management of non-metastatic muscle invasive bladder cancer (MIBC) includes radical cystectomy and cisplatin-based neoadjuvant chemotherapy (NAC), offers a 5-year survival rate of approximately 50% and is associated with significant toxicities. A growing body of evidence supports the role of liquid biopsies including circulating tumour DNA (ctDNA) as a prognostic and predictive marker that could stratify patients according to individualised risk of progression/recurrence. Detectable ctDNA levels prior to radical cystectomy have been shown to be correlated with higher risk of recurrence and worse overall prognosis after cystectomy. In addition, ctDNA status after NAC/neoadjuvant immunotherapy is predictive of the pathological response to these treatments, with persistently detectable ctDNA being associated with residual bladder tumour at cystectomy. Finally, detectable ctDNA levels post-cystectomy have been associated with disease relapse and worse disease-free (DFS) and overall survival (OS) and might identify a population with survival benefit from adjuvant immunotherapy.

The SUB-urothelial DUrvalumab InjEction-1 (SUBDUE-1) trial: first-in-human trial in patients with bladder cancer.

To assess the safety of sub-urothelial injection of durvalumab and examine the impact on tissue and circulating immune cell populations. The patients were chemotherapy and immunotherapy naïve (bacille Calmette-Guérin allowed) with non-metastatic muscle-invasive bladder cancer or non-muscle-invasive bladder cancer planned for radical cystectomy (RC). The study was a Phase Ib 3 + 3 dose-escalation design with sub-urothelial injection of durvalumab at three pre-determined doses (25, 75, 150 mg) diluted in 25 mL normal saline, injected at 25 locations (25 × 1 mL injections), at least 2 weeks before RC. A total of 11 patients were recruited (10 male, one female). No significant changes were reported on American Urological Association Symptom Score or O'Leary Interstitial Cystitis Scale. In all, 14 adverse events (AEs) were reported (10 Grade 1, three Grade 2, one Grade 3), none considered immune-related. No Grade 4 or 5 AEs were recorded. All the patients underwent RC. Tissue immune populations changed following durvalumab injection (P = 0.012), with a statistically significant increase in M2-macrophage (CD163) when comparing the 25-150 mg dose (P = 0.021). Basal/mixed cancers showed a larger CD163 increase than luminal cancers (P = 0.033). Sub-urothelial injection of durvalumab is feasible and safe without immune-related AEs and shows local immunological effects.

An in-depth analysis on the effects of body composition in patients receiving neoadjuvant chemotherapy for urothelial cell carcinoma

Introduction: Neoadjuvant chemotherapy (NAC) is the standard of care for patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC); however, NAC can be associated with significant side effects and morbidity in some patients. NAC may contribute to sarcopenia, obesity, and the combination of the two. Our study examined the effects of NAC on body composition and the association between body composition and adverse events. Methods: We created a retrospective database of patients with non-metastatic MIBC receiving NAC prior to RC. The change in skeletal muscle index (SMI) and fat mass index (FMI) was calculated using computed tomography (CT) scans done within three months prior to NAC and after the first two cycles. The association between body composition (sarcopenia, obesity, and sarcopenic obesity) and preoperative adverse events was investigated using a multivariable logistic regression. Changes in body composition were calculated using a paired Student’s t-test. Results: A total of 70 patients were included in our study. There was a mean decrease in SMI of 2.2±3.2 cm2/m2. Adiposity and FMI were unchanged by NAC. Sarcopenic obesity was found to be associated with adverse events among patients receiving NAC in the multivariable analysis. There were a total of 637 preoperative complications with grades 1–2 and 33 complications with grades 3–5. Conclusions: Based on our retrospective cohort study, NAC did not affect obesity and FMI, but there was a significant decrease in SMI. Sarcopenic obesity was associated with increased severity of NAC adverse events. As such, the presence of this factor may help predict tolerance of NAC.

Efficacy and safety of the combination of cisplatin plus nab-paclitaxel and nivolumab with radiotherapy after maximal tumor resection in non-metastatic muscle invasive bladder cancer (CNN-BC trial).

TPS723 Background: The therapeutic gold standard for muscle invasive bladder cancer (MIBC) is radical cystectomy (RC) preceded by neoadjuvant chemotherapy when appropriate. However, RC is a major surgery procedure with 13% rate of severe complication and a perioperative mortality rate of about 1.5 - 5 %. Trimodal therapy (TMT) is a “bladder sparing” option alternative to RC. TMT consists of complete transurethral bladder tumor resection (TURBT) followed by a combination of systemic chemotherapy and locoregional radiotherapy (RT), with the option of “salvage” cystectomy in case of local treatment failure. Immunotherapy with anti-PD1/PD-L1 monoclonal antibody significantly improves survival of metastatic BC patients, and it seems to potentiate the activity of RT without increased toxicity. Therefore, we investigate the role of a multimodal TMT strategy to increase the disease-free survival (DFS) and avoid or delay RC in non-metastatic MIBC pts. Methods: CNN-BC trial (NCT05203913) is a phase 2, open-label, mono-institutional study evaluating the activity and safety of TMT with cisplatin, nab-paclitaxel and nivolumab as systemic therapy in non-metastatic MIBC pts. Eligible pts should have undergone complete TURBT with diagnosis of T2-T3 N0M0 urothelial carcinoma, and no evidence of lymph nodes or metastatic disease at FDG-PET within 6 weeks from the start of treatments. TMT consists of nivolumab (480 mg IV every 4 weeks for a total of 13 doses), weekly nab-paclitaxel (60mg/m2) plus cisplatin (20mg/m2) administered concurrently with RT (60Gy in 25 fractions over 5 weeks on original bladder tumor, plus a concomitant boost of 50Gy in 25 fractions on whole bladder and pelvic nodes). The primary endpoint is the 1-year DFS rate, defined as the rate of survival free of recurrence in pelvic nodes or bladder, or appearance of distant metastases. Secondary endpoints include: the rate of pts who require salvage cystectomy, the rate of locoregional complete response (CR) and of locoregional DFS, median DFS, safety, and quality of life. Exploratory biomarkers analysis will be performed. The trial is actively recruiting. Clinical trial information: NCT05203913 .

Urinary microbiota signatures associated with different types of urinary diversion: a comparative study.

Radical cystectomy and urinary diversion (UD) are gold standards for non-metastatic muscle-invasive bladder cancer. Orthotopic neobladder (or Studer), ileal conduit (or Bricker) and cutaneous ureterostomy (CU) are mainstream UD types. Little is known about urinary microbiological changes after UD. In this study, urine samples were collected from healthy volunteers and patients with bladder cancer who had received aforementioned UD procedures. Microbiomes of samples were analyzed using 16S ribosomal RNA gene sequencing, and microbial diversities, distributions and functions were investigated and compared across groups. Highest urine microbial richness and diversity were observed in healthy controls, followed by Studer patients, especially those without hydronephrosis or residual urine, α-diversity indices of whom were remarkably higher than those of Bricker and CU groups. Studer UD type was the only independent factor favoring urine microbial diversity. The urine microflora structure of the Studer group was most similar to that of the healthy individuals while that of the CU group was least similar. Studer patients and healthy volunteers shared many similar urine microbial functions, while Bricker and CU groups exhibited opposite characteristics. Our study first presented urinary microbial landscapes of UD patients and demonstrated the microbiological advantage of orthotopic neobladder. Microbiota might be a potential tool for optimization of UD management.

Identifying Optimal Candidates for Trimodality Therapy among Nonmetastatic Muscle-Invasive Bladder Cancer Patients.

(1) Background: This research aims to identify candidates for trimodality therapy (TMT) or radical cystectomy (RC) by using a predictive model. (2) Methods: Patients with nonmetastatic muscle-invasive bladder cancer (MIBC) in the Surveillance, Epidemiology, and End Results (SEER) database were enrolled. The clinical data of 2174 eligible patients were extracted and separated into RC and TMT groups. To control for confounding bias, propensity score matching (PSM) was carried out. A nomogram was established via multivariable logistic regression. The area under the receiver operating characteristic curve (AUC) and calibration curves were used to assess the nomogram's prediction capacity. Decision curve analysis (DCA) was carried out to determine the nomogram's clinical applicability. (3) Results: After being processed with PSM, the OS of the RC group was significantly longer compared with the TMT group (p < 0.001). This remarkable capacity for discrimination was exhibited in the training (AUC: 0.717) and validation (AUC: 0.774) sets. The calibration curves suggested acceptable uniformity. Excellent clinical utility was shown in the DCA curve. The RC and RC-Beneficial group survived significantly longer than the RC and TMT-Beneficial group (p < 0.001) or the TMT group (p < 0.001). However, no significant difference was found between the RC and TMT-Beneficial group and the TMT group (p = 0.321). (4) Conclusions: A predictive model with excellent discrimination and clinical application value was established to identify the optimal patients for TMT among nonmetastatic MIBC patients.

Neoadjuvant Chemoradiotherapy Followed by Radical Cystectomy for Muscle-Invasive Bladder Cancer: Analysis of Efficacy and Safety in 119 Patients

IntroductionCisplatin-based systemic chemotherapy is recommended as neoadjuvant treatment for muscle-invasive bladder cancer (MIBC) before radical cystectomy (RC). However, clinical challenges include the possibility of primary chemoresistance and limited feasibility in patients with renal impairment. This study investigated the efficacy and safety profiles of neoadjuvant chemoradiotherapy (NCRT) followed by RC. Materials and MethodsWe retrospectively analyzed 119 patients with nonmetastatic MIBC, who were pathologically diagnosed with urothelial carcinoma and underwent NCRT before RC. The pathological response to NCRT was evaluated using RC specimens. Recurrence-free survival (RFS) and cancer-specific survival (CSS) were compared according to pathological responses to NCRT. ResultsOf the 119 patients, 111 (93%) underwent RC; ypT0 and downstaging to ≤ypT1 were observed in 42 (38%) and 76 (68%) patients, respectively. In the multivariable analysis, smaller tumor size was independently associated with ypT0. During a median follow-up of 5.2 years, 28 (25%) patients developed recurrence and 22 (20%) died of bladder cancer after RC. The 5-year RFS and CSS rates were 75% and 80%, respectively. The 5-year RFS rates in patients with ypT0, ypTa/is/1, and ≥ypT2 were 87%, 87%, and 46%, respectively. Similarly, patients with ypT0 and ypTa/is/1 had more favorable CSS (90% and 87% at 5 years, respectively) than those with ≥ypT2 (60%, P = .001). None of the patients experienced ≥grade 4 adverse events related to NCRT or ≥grade 4 complications of RC. ConclusionsThis study demonstrated sufficient efficacy and safety profile of NCRT followed by RC. Chemoradiotherapy may be a helpful alternative for neoadjuvant treatment before RC.

Pan-immune-inflammation value as a prognostic tool for overall survival and disease-free survival in non-metastatic muscle-invasive bladder cancer.

To evaluate the association between preoperative pan-immune inflammation value (PIV) and overall survival (OS) and disease-free survival (DFS) in patients who underwent radical cystectomy for non-metastatic muscle-invasive bladder cancer. A total of 119 patients with non-metastatic muscle-invasive bladder cancer who underwent radical cystectomy at our institution between January 2014 and January 2022 were included in this retrospective study. PIV was calculated using the formula (monocyte count × neutrophil count × platelet count)/lymphocyte count. Ideal cut-off values for PIV were determined using ROC curve analysis. Kaplan-Meier analysis was used to evaluate the impact of PIV on survival outcomes. The mean age of patients was 65 ± 14years, and the mean follow-up duration was 36months. The ideal cutoff value for PIV was determined to be 406.29, and a PIV above this value was associated with poorer OS (p < 0.001) (73months vs. 21months) and DFS (p = 0.002) (35months vs 19months). Higher neutrophil-to-lymphocyte ratio (NLR) values were also associated with poorer OS (p < 0.001) and DFS (p < 0.001), with similar effectiveness to PIV. PIV was found to be significantly more effective than platelet-to-lymphocyte ratio (PLR) and systemic immune inflammation index (SII) in predicting DFS. Preoperative PIV may serve as an independent prognostic factor for OS in patients who undergo radical cystectomy with non-metastatic muscle-invasive bladder cancer. A high PIV value was associated with poorer survival outcomes. Prospective multicenter studies are needed to further validate the relationship between PIV and histopathological features of bladder cancer.

Development of a Screening Nomogram for Regional Lymph Node Metastasis Development in Muscle Invasive Bladder Cancer after Multiagent Systemic Therapy

A reliable method of identifying clinically node negative bladder cancer patients at greater risk of developing lymph node metastasis and may require intensified therapy is needed. The purpose of this study was to create a nomogram to quantify the risk for regional lymphatic involvement in non-metastatic muscle invasive bladder cancer. Usingthe National Cancer Database, patients with clinical T2-4N0M0 urothelial carcinoma of the bladder between the years of 2004 - 2020 were selected. All patients completed multiagent chemotherapy followed by surgery for pathologic nodal staging to determine presence or absence of nodal disease. No neoadjuvant radiation therapy was allowed and patients with history of prior malignancies were excluded. Following a 70:30 training to testing data split, baseline variables were assessed using univariate logistic regression. Variables were selected for inclusion in the multivariate logistic regression model using a combination of previously reported findings in the literature and/or if found to have a p-value < 0.05 on univariate analysis. A nomogram was constructed using this final model with assessment using calibration plots and the area under the receiver operating characteristics curve (AUC), respectively. An empiric cut point was chosen at 95% sensitivity to identify patients at "high" and "low" risk for pathologic nodal disease with overall assessment in both cohorts using chi-square. A total of 6194patients were identified for study with a median age of 65 years (IQR = 58 - 71 years). Most patients were male (68.0%) with T2 disease (81.2%). The final multivariate model included age at time of diagnosis (OR = 0.99; 95% CI = 0.99 - 1.00; p = 0.172), time from diagnosis to initiation of chemotherapy (OR = 1.00; 95% CI = 1.00 - 1.01; p = 0.005), papillary histology (OR = 0.85; 95% CI = 0.72 - 1.01; p = 0.068), and clinical T stage (Table 1). Model calibration demonstrated excellent goodness-of-fit with good discrimination (AUC = 0.644). Within the training data, high risk patients were seen to have a twofold increase in pathologic nodal disease (N = 835/3924, 21.2%) when compared to those identified as low risk (N = 38/347, 9.9%) (p < 0.001). Validation within the testing data set demonstrated similar results with pathologic node rates of 22.8% and 7.8% for high- and low-risk patients, respectively (AUC = 0.645, p < 0.001). This study demonstrates a clinically applicable risk stratification tool for identifying patients at risk for developing lymphadenopathy in T2-4 bladder cancer and may help guide future research in selecting patients eligible for escalation of therapy. Future studies should aim to externally validate this tool within prospective cohorts, and seek to determine if this nomogram may provide further prognostic utility.

Radiotherapy vs. Cystectomy for Treatment of Muscle Invasive Bladder Cancer in Very Elderly Patients

Radical cystectomy (RC) has long remained the principal treatment of muscle invasive bladder cancer (MIBC). It is, however, associated with significant morbidity, long recovery, and reported worse overall and cancer specific survival, particularly for the very elderly (age > = 80). Bladder preservation with transurethral resection of bladder tumor (TURBT) followed by radiotherapy (RT) +/- concurrent chemotherapy (ChT) is regarded as a curative-intent alternative to RC in well-selected patients. The optimal treatment strategy remains unclear in very elderly patients. We hypothesize that outcomes following RT vs RC are clinically equivalent for treatment of MIBC in very elderly patients. Patients > = 80 years old with T2-T4 N0-N1 bladder cancer treated definitively with RT versus RC were included. Exclusion criteria included history of pelvic RT, prior cystectomy, or palliative treatment intent. Clinicopathologic and treatment-related details, as well as clinical outcomes and toxicities were retrospectively abstracted. Kaplan-Meier analyses were performed. At a median follow-up of 17 months (range 0.25-190), 47 patients received RT vs 83 patients who underwent RC with median age of 86 years (80-97) vs 83 years (range 80-91) (p<0.01), respectively. Median Charlson Comorbidity Index was similar between groups (p = 0.35) with median 7 for both cohorts, predicting 0% estimated 10y survival. Most patients had cT2 tumors (91% vs 99%, p = 0.06), cN0 nodal status (96% vs 100%, p = 0.06), and urothelial carcinoma histology (79% vs 90%, p = 0.22). Most RT patients received concurrent ChT (90%) and a minority of RC patients received neoadjuvant ChT (16%). 70% of RT pts had complete TURBTs prior to RT. Common RT regimens were 50-55 Gy in 20-25 fractions or 60-64.8 Gy in 30-36 fractions, using IMRT (89%) or 3D conformal (11%) technique. Overall survival for RT vs RC at 1- and 2- years was 79% vs 85% and 57% and 69%, respectively (p = 0.20). Locoregional control at 1- and 2-years was 73% vs 70% and 63% vs 66% (p = 0.59), respectively. Progression free survival at 1- and 2-years was 69% vs 66% and 52% vs 54% (p = 0.75), respectively. No RT patients went on to receive salvage cystectomy. Treatment complications are listed in Table 1; the Clavien Dindo classification system was used to describe acute surgical complications of RC and the Common Terminology Criteria for Adverse Events (CTCAE) Dictionary v5.0 was used for acute and late toxicity of RT. In the very elderly, RT (with or without concurrent ChT) offers survival and locoregional control rates comparable to RC, with a favorable side effect profile. RT should be offered for definitive management of non-metastatic MIBC as an alternative to RC in selected, well- informed, and compliant very elderly patients.

Comparison of sequential versus concurrent chemoradiation regimens in non-metastatic muscle-invasive bladder cancer.

The treatment approach for non-metastatic bladder cancer is guided by an invasion of the muscular layer of the bladder wall. Radical cystectomy is the recommended treatment for muscle-invasive disease. However, it has considerable morbidity and mortality and is not suited for many patients. Trimodality therapy consisting of chemoradiation after transurethral resection of bladder tumor offers a definitive approach with bladder-sparing potential. However, there is a lack of research defining the optimal combination of chemotherapy and radiation in this setting. We extracted patient data from the National Cancer Database to compare survival outcomes and demographic factors in 2,227 non-metastatic bladder cancer patients who were treated with chemotherapy sequential to or concurrently with radiation. Sequential treatment was defined as chemotherapy beginning >14 days before radiation, and concurrent was defined as beginning within 14 days of the first radiation. The sequential treatment group patients were younger (mean age, 74 vs. 78 years; p < 0.001) with more advanced disease. We found no difference in overall survival between patients who received chemotherapy sequential to radiation and those who received concurrent chemoradiation only (p = 0.533). Our data are concordant with a previous prospective study, and support that chemotherapy prior to radiation does not decrease survival outcomes relative to patients receiving only concurrent chemoradiation. Given that the sequential group had an overall higher stage but no difference in survival, downstaging chemotherapy prior to radiation may be helpful in these patients. Further studies including a larger, multi-institutional clinical trial are indicated to support clinical decision-making.

Neoadjuvant chemotherapy with dose-dense MVAC in muscle-invasive bladder cancer: a tertiary center experience.

Neoadjuvant chemotherapy in muscle-invasive bladder cancer (MIBC) patients has proven beneficial in overall survival. However, the optimal regimen is still a matter of debate. In this retrospective analysis, we evaluate the results obtained in 42 patients treated in our center with 4 cycles of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) followed by radical cystectomy from August 2015 to October 2020. All patients had cT2 or higher non-metastatic MIBC. Clinical and pathological outcomes are reported. Of the 42 patients, 90.5% were men (n = 38) and the mean age was 65years. All of them had ECOG 0-1 at diagnosis and most tumors had an initial clinical stage T2N0 (76%). Thirty-six patients (85.7%) completed 4 cycles of neoadjuvant treatment, and 21.4% required a dose reduction. The most frequent adverse event (AE) was grade 1-2 asthenia (81%), while neutropenia was the most frequent grade 3 or higher AE (38%). Complete pathological response (ypT0, ypN0) was achieved in 50% of patients (n = 21), and down-staging was observed in 57.1% (n = 24). Only one patient presented radiological progressive disease during neoadjuvant treatment (2.4%), and after a mean follow-up time of 31.5months, 33.3% of patients experienced disease recurrence. Neoadjuvant chemotherapy with 4 cycles of dd-MVAC is an effective regimen with high rates of pathological complete responses and down-staging along with an acceptable toxicity profile. DD-MVAC should be considered as an alternative to cisplatin and gemcitabine in patients with good clinical performance status.

Disease-Free Survival of Patients With Muscle-Invasive Bladder Cancer Treated With Radical Cystectomy Versus Bladder-Preserving Therapy: A Nationwide Study

Although level I evidence is lacking that radical cystectomy (RC) is superior to bladder-preserving therapy (BPT), RC is still advocated as the recommended treatment in patients with nonmetastatic muscle-invasive bladder cancer (MIBC). This study sought to compare the survival of patients with MIBC treated with BPT versus those treated with RC. All patients with nonmetastatic MIBC diagnoses were identified via the population-based Netherlands Cancer Registry. Only patients treated with BPT or RC were included. The primary endpoint was 2-year disease-free survival (DFS), defined as time from start of treatment until locoregional recurrence, distant metastasis, or death. The secondary endpoint was overall survival (OS). Inverse propensity treatment weighting (IPTW) was used based on propensity scores to adjust for baseline differences between treatment groups. Survival was analyzed with Kaplan-Meier and Cox proportional hazards models. A total of 1432 patients were included, of whom 1101 underwent RC and 331, BPT. Median follow-up was 39 months (range, 27-51 months). The IPTW-adjusted 2-year DFS was 61.5% (95% CI, 53.5%-69.6%) with BPT and 55.3% (95% CI, 51.6%-59.1%) with RC, with an adjusted hazard ratio of 0.84 (95% CI, 0.69-1.05). The adjusted 2-year OS for patients treated with BPT versus RC was 74.0% (95% CI, 67.0%-80.9%) versus 66.0% (95% CI, 62.7%-68.8%), respectively, with an adjusted hazard ratio of 0.80 (95% CI, 0.64-0.98). There was no statistically significant difference between the 2-year DFS of patients treated with BPT and RC. We propose that both RC and BPT should be offered as a curative treatment option to eligible patients with nonmetastatic MIBC.

Intravesical Gemcitabine Concomitant with Radiotherapy in Non-metastatic Muscle-invasive Urothelial Bladder Cancer

Intravesical Gemcitabine Concomitant with Radiotherapy in Non-metastatic Muscle-invasive Urothelial Bladder Cancer

Predictors of trimodality therapy in patients with muscle-invasive bladder cancer and effect on survival.

Due to its unique advantages over radical cystectomy (RC), trimodality therapy (TMT) is increasingly being utilized by patients diagnosed with muscle-invasive bladder cancer (MIBC) who are not suitable for or refuse RC. However, achieving a satisfactory oncological outcome with TMT requires strict patient selection criteria, and the comparative oncological outcomes of TMT versus RC remain controversial. Patients diagnosed with non-metastatic MIBC who underwent TMT or RC were identified from the SEER database during 2004-2015. Before one-to-one propensity score matching (PSM), logistic regression was utilized to identify predictors of TMT. After matching, K-M curves were generated to estimate cancer-specific survival (CSS) and overall survival (OS) with log-rank to test the significance. Finally, we conducted univariate and multivariate Cox analyses to identify independent prognostic factors for CSS and OS. The RC and TMT groups included 5812 and 1260 patients, respectively, and the TMT patients were significantly older than the RC patients. Patients with advanced age, separated, divorced, or widowed (SDW) or unmarried marital status (married as reference), and larger tumor size (< 40mm as reference) were more likely to be treated with TMT. After PSM, TMT was found to be associated with worse CSS and OS, and it was identified as an independent risk factor for both CSS and OS. MIBC patients may not be carefully evaluated prior to TMT, and some non-ideal candidates underwent TMT. TMT resulted in worse CSS and OS in the contemporary era, but these results may be biased. Strict TMT candidate criteria and TMT treatment modality should be required.

Robot-assisted radical cystectomy with intracorporeal reconstruction of urinary diversion by mechanical stapler: prospective evaluation of early and late complications.

Radical cystectomy with pelvic lymph node dissection is the gold standard treatment for non-metastatic muscle-invasive bladder cancer and high-risk non-muscle-invasive bladder cancer. For years, the traditional open surgery approach was the only viable option. The widespread of robotic surgery led to its employment also in radical cystectomy to reduce complication rates and improve functional outcomes. Regardless of the type of approach, radical cystectomy is a procedure with high morbidity and not negligible mortality. Data available in the literature show how the use of staplers can offer valid functional outcomes, with an acceptable rate of complications shortening the operative time. The aim of our study was to describe the perioperative outcomes and complications associated with robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) using a mechanical stapler. From January 2015 to May 2021, we enrolled patients who underwent RARC with pelvic node dissection and stapled ICUD (ileal conduit or ileal Y-shaped neobladder according to the Perugia ileal neobladder) in our high-volume center. Demographic features, perioperative outcomes and early (≤30 days) and late (>90 days) post-operative complications according to the Clavien-Dindo classification, were recorded for each patient. We also analyzed the potential linear correlation between demographic, pre-operative as well as operative features and the risk of post-operative complications. Overall, 112 patients who underwent RARC with ICUD were included with a minimum follow-up of 12 months. Intracorporeal Perugia ileal neobladder was performed in 74.1% of cases while ileal conduit was performed in 25.9%. The mean operative time, estimated intraoperative blood loss, and LOS were 289.1 ± 59.7 min, 390.6 ± 186.2 ml, and 17.5 ± 9.8 days, respectively. Early minor and major complications accounted for 26.7% and 10.8%, respectively. Overall late complications were 40.2%. The late most common complications were hydronephrosis (11.6%) and urinary tract infections (20.5%). Stone reservoir formation occurred in 2.7% of patients. Major complications occurred in 5.4%. In the sub-analysis, the mean operative time and the estimated blood loss improved significantly from the first 56 procedures to the last ones. RARC with ICUD performed by mechanical stapler is a safe and effective technique. Stapled Y-shaped neobladder did not increase the complication rate.

Identifying care fragmentation in the management of non-metastatic muscle-invasive bladder cancer.

e13527 Background: Measuring care fragmentation facilitates exploration of breakdowns in cancer care delivery that may impact quality of care and patient outcomes. Bladder cancer often requires a multimodal approach of surgery, chemotherapy and radiation, increasing the risk of fragmented care. This study assesses the extent of care fragmentation across different inpatient facilities and examines patient characteristics associated with inpatient care fragmentation. Methods: We adapt the modified Herfindahl-Hirschman market concentration index to construct a Fragmentation Index (FI) capturing the distribution of a patient’s care across inpatient facilities. We calculate FI for the 15 months following diagnosis for non-metastatic muscle-invasive bladder cancer (MIBC) patients who underwent radical cystectomy from 2010-2016 and had at least 2 admissions during the study period. We use Pennsylvania Cancer Registry data linked to statewide facility discharge records to estimate patient-level multivariable regression models of the relationship between FI and patient demographics, disease features, rurality, area deprivation index (ADI), payer, and Commission on Cancer hospital (CoC-H) accreditation status. Results: Of 965 patients, 87.3% (n = 842) lived in urban areas, 8.9% in large towns and 3.8% rural. Approximately 8% had Medicaid and 5.7% had uninsured or unknown payer status. A majority (64%; n = 614) were age 60-79; 76% were men and 92% non-Hispanic White; 19.5% (n = 188) had T4 disease and 25% (n = 239) received neoadjuvant chemotherapy. Almost half of patients (45.3%; n = 437) had an FI of 0, indicating all admissions were at the same hospital. The mean FI was 0.254 for the total cohort and 0.464 for patients with FI &gt; 0. Residency in a large town or rural area was associated with 0.59 (CI 0.003—0.114) and 0.14 (CI 0.060—0.220) higher FI relative to urban areas. T4 disease was associated with 0.063 higher FI (CI 0.019—0.107) relative to &lt;T2 disease. Factors associated with lower FI included Non-White race (-0.092, CI -0.151 – -0.033) and no admissions to CoC-H (-0.138, CI -0.182 – -0.095) relative to patients admitted to at least 1 CoC-H. Patients never admitted to a CoC-H (n = 134) mostly lived in urban areas (88%) and 49% had Medicare insurance: they were disproportionately from the most disadvantaged ADI quartile in the cohort (37.3%). Conclusions: Our findings highlight that many MIBC patients receive inpatient care across at least two different hospitals. Advanced disease and patient residence in non-urban areas are associated with greater fragmentation of inpatient care. Patients who never received care at a CoC hospital experienced less fragmentation but were more likely to be relatively economically disadvantaged. Future research will investigate relationships between fragmentation and clinical outcomes to inform policy and clinical strategies aimed at optimizing patterns of care.

Low adherence to recommended use of neoadjuvant chemotherapy for muscle-invasive bladder cancer

PurposeTo evaluate guideline adherence and variation in the recommended use of neoadjuvant chemotherapy (NAC) and the effects of this variation on survival in patients with non-metastatic muscle-invasive bladder cancer (MIBC).Patients and methodsIn this nationwide, Netherlands Cancer Registry-based study, we identified 1025 patients newly diagnosed with non-metastatic MIBC between November 2017 and November 2019 who underwent radical cystectomy. Patients with ECOG performance status 0–1 and creatinine clearance ≥ 50 mL/min/1.73 m2 were considered NAC-eligible. Interhospital variation was assessed using case-mix adjusted multilevel analysis. A Cox proportional hazards model was used to evaluate the association between hospital specific probability of using NAC and survival. All analyses were stratified by disease stage (cT2 versus cT3-4a).ResultsIn total, of 809 NAC-eligible patients, only 34% (n = 277) received NAC. Guideline adherence for NAC in cT2 was 26% versus 55% in cT3-4a disease. Interhospital variation was 7–57% and 31–62%, respectively. A higher hospital specific probability of NAC might be associated with a better survival, but results were not statistically significant (HRcT2 = 0.59, 95% CI 0.33–1.05 and HRcT3-4a = 0.71, 95% CI 0.25–2.04).ConclusionGuideline adherence regarding NAC use is low and interhospital variation is large, especially for patients with cT2-disease. Although not significant, our data suggest that survival of patients diagnosed in hospitals more inclined to give NAC might be better. Further research is warranted to elucidate the underlying mechanism. As literature clearly shows the potential survival benefit of NAC in patients with cT3-4a disease, better guideline adherence might be pursued.