Treatment of muscle-invasive and advanced bladder cancer in 2020.

Bladder cancer accounts for nearly 170,000 deaths worldwide annually. For over 4 decades, the systemic management of muscle-invasive and advanced bladder cancer has primarily consisted of platinum-based chemotherapy. Over the past 10 years, innovations in sequencing technologies have led to rapid genomic characterization of bladder cancer, deepening our understanding of bladder cancer pathogenesis and exposing potential therapeutic vulnerabilities. On the basis of its high mutational burden, immune checkpoint inhibitors were investigated in advanced bladder cancer, revealing durable responses in a subset of patients. These agents are now approved for several indications and highlight the changing treatment landscape of advanced bladder cancer. In addition, commonly expressed molecular targets were leveraged to develop targeted therapies, such as fibroblast growth factor receptor inhibitors and antibody-drug conjugates. The molecular characterization of bladder cancer and the development of novel therapies also have stimulated investigations into optimizing treatment approaches for muscle-invasive bladder cancer. Herein, the authors review the history of muscle-invasive and advanced bladder cancer management, highlight the important molecular characteristics of bladder cancer, describe the major advances in treatment, and offer future directions for therapeutic development.

A wireless, implantable bioelectronic system for monitoring urinary bladder function following surgical recovery.

Partial cystectomy procedures for urinary bladder-related dysfunction involve long recovery periods, during which urodynamic studies (UDS) intermittently assess lower urinary tract function. However, UDS are not patient-friendly, they exhibit user-to-user variability, and they amount to snapshots in time, limiting the ability to collect continuous, longitudinal data. These procedures also pose the risk of catheter-associated urinary tract infections, which can progress to ascending pyelonephritis due to prolonged lower tract manipulation in high-risk patients. Here, we introduce a fully bladder-implantable platform that allows for continuous, real-time measurements of changes in mechanical strain associated with bladder filling and emptying via wireless telemetry, including a wireless bioresorbable strain gauge validated in a benchtop partial cystectomy model. We demonstrate that this system can reproducibly measure real-time changes in a rodent model up to 30 d postimplantation with minimal foreign body response. Studies in a nonhuman primate partial cystectomy model demonstrate concordance of pressure measurements up to 8 wk compared with traditional UDS. These results suggest that our system can be used as a suitable alternative to UDS for long-term postoperative bladder recovery monitoring.

Prophylactic Use of Biologic Mesh in Ileal Conduit (PUBMIC): A Randomized Clinical Trial.

PURPOSE: We assessed the effect of prophylactic biologic mesh on parastomal hernia (PSH) development in patients undergoing cystectomy and ileal conduit (IC). MATERIALS AND METHODS: This phase 3, randomized, controlled trial (NCT02439060) included 146 patients who underwent cystectomy and IC at the University of Southern California between 2015 and 2021. Follow-ups were physical exam and CT every 4 to 6 months up to 2 years. Patients were randomized 1:1 to receive FlexHD prophylactic biological mesh using sublay intraperitoneal technique vs standard IC. The primary end point was time to radiological PSH, and secondary outcomes included clinical PSH with/without surgical intervention and mesh-related complications. RESULTS: The 2 arms were similar in terms of baseline clinical features. All surgeries and mesh placements were performed without any intraoperative complications. Median operative time was 31 minutes longer in patients who received mesh, yet with no statistically significant difference (363 vs 332 minutes, P = .16). With a median follow-up of 24 months, radiological and clinical PSHs were detected in 37 (18 mesh recipients vs 19 controls) and 16 (8 subjects in both arms) patients, with a median time to radiological and clinical PSH of 8.3 and 15.5 months, respectively. No definite mesh-related adverse events were reported. Five patients (3 in the mesh and 2 in the control arm) required surgical PSH repair. Radiological PSH-free survival rates in the mesh and control groups were 74% vs 75% at 1 year and 69% vs 62% at 2 years. CONCLUSIONS: Implementation of biologic mesh at the time of IC construction is safe without significant protective effects within 2 years following surgery.

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

PURPOSE: 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. METHODOLOGY/METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Impact of Divergent Differentiation and/or Histological Subtype of Urothelial Carcinoma on Patient Outcomes in the GETUG-AFU V05 VESPER Trial.

PURPOSE: Variant histology or divergent differentiation (VH/DD) of urothelial carcinoma (UC) may impact outcomes after neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer. Our aim was to assess the pathological response and progression-free survival (PFS) of patients with VH/DD in the prospective VESPER clinical trial. MATERIALS AND METHODS: This post hoc study included 300 NAC-treated patients with available transurethral diagnostic slides. Presence and percentage of VH/DDs were reviewed. For pathological response, logistic regression models were computed to measure association with VH/DD. For PFS, the associations were estimated in Cox proportional hazard regression model. All models were adjusted for randomization arm. RESULTS: VH/DD was identified in 177/300 patients (59%) and was predominant (≥50%) in 85/177. Compared to pure UC, VH/DD (≥10% or ≥50%) was not associated with a difference in proportion of complete pathological response (ypT0N0; OR adjusted: 0.79, 95% CI 0.49-1.29), downstaging (≤ypT1N0; OR adjusted: 0.62, 95% CI 0.37-1.02), or with an increased hazard of PFS (HR adjusted: 1.24, 95% CI 0.83-1.85). However, comparing specific VH/DD to pure UC, nested subtype was associated with decreased odds of complete pathological response (OR adjusted: 0.33, 95% CI 0.12-0.88) and downstaging (OR adjusted: 0.30, 95% CI 0.13-0.74), and an increased hazard of PFS was observed for UC with ≥ 50% squamous differentiation (HR adjusted: 2.11, 95% CI 1.01-4.38) or micropapillary subtype (HR adjusted: 2.03, 95% CI 0.98-4.22). CONCLUSIONS: In the VESPER trial, we did not observe evidence for association of VH/DD with outcomes after NAC, but the specific presence of a predominant squamous differentiation or micropapillary subtype may be associated with shorter PFS.

Feasibility, Acceptability, and Outcomes of a Mobile Health Tool for Radical Cystectomy Recovery.

PURPOSE: Postoperative education and symptom tracking are essential following cystectomy to reduce readmission rates and information overload. To address these issues, an internet-based tool was developed to provide education, alerts, and symptom tracking. We aimed to evaluate the tool's feasibility, acceptability, and impact on complication and readmission rates. MATERIALS AND METHODS: Thirty-three eligible patients over 18 years old scheduled for cystectomy were enrolled. Patients were asked to use the mobile health (mHealth) tool daily for the first 2 weeks, then less frequently up to 90 days after discharge. Descriptive statistics were used to summarize study variables. Feasibility was defined as at least 50% of patients using the tool once a week, and acceptability as patient satisfaction of > 75%. RESULTS: Use of the mHealth tool was feasible, with 90% of patients using it 1 week after discharge, but engagement declined over time to 50%, with technological difficulties being the main reason for nonengagement. Patient and provider acceptability was high, with satisfaction > 90%. Within 90 days, 36% experienced complications after discharge and 30% were readmitted. Engagement with the mHealth application varied but was not statistically associated with readmission (P = .21). CONCLUSIONS: The study showed that the electronic mobile health intervention for patients undergoing cystectomy was feasible, acceptable, and provided valuable educational content and symptom management. Future larger studies are needed to determine the tool's effectiveness in improving patient outcomes and its potential implementation into routine clinical care.

Temporal Trends in Urinary Diversion among Patients Undergoing Radical Cystectomy Between 1986 and 2022: Experience at the University Medical Center Mainz with 2224 Cases.

BACKGROUND: Analysis of temporal trends of urinary diversion (UD) and identification of predictive factors for continent urinary diversion (CUD) in patients with bladder cancer (BC) is scarce and data on large cohorts are missing. We aimed to describe longitudinal temporal trends and predictive factors for UD among patients with BC receiving radical cystectomy (RC). PATIENTS AND METHODS: We retrospectively analysed institutional data collected from patients undergoing RC from 1986 to 2022 to describe changes in patients' characteristics and UD. Primary end points were patients' characteristics associated with type of UD. Logistic regression analysis was used to determine predictive factors for CUD. RESULTS: In total, 2224 patients (77.16% male, 22.84% female) with a mean age of 66 years [standard deviation (SD), 10.64 years] were included. We observed an increase in mean age from 59.86 (10.8) years (1986-1990) to 69.85 (9.99) years (2016-2022) (p < 0.001). The proportion of CUD gradually declined from 43.72% (94/215; 1986-1990) to 18.38% (86/468; 2016-2022). Patients who were male [odds ratio (OR): 1.92, 95% confidence interval (CI): 1.43-2.57, p < 0.001), younger (OR: 0.88, 95% CI: 0.87-0.89, p < 0.001) and had no hydronephrosis prior to RC (OR: 2.2, 95% CI: 1.66-2.92, p < 0.001) were more likely to receive CUD. CONCLUSIONS: We report the largest European single-center cohort of UD after RC, demonstrating a significant shift from CUD to IUD, accompanied by an increasing age. Finally, our data mirrors the development and extensive experience with the Mainz Pouch-I in the 1980's and 1990's together with other colon pouches.

Role of Maximal Transurethral Resection Preceding Partial Cystectomy for Muscle-Invasive Bladder Cancer.

PURPOSE: We aimed to evaluate whether maximal transurethral resection (TUR) affects the oncological outcome of partial cystectomy (PC) performed in patients with muscle-invasive bladder cancer (MIBC), although radical cystectomy (RC) and trimodal therapy (TMT) are regarded as standard treatments for MIBC. METHODS: In this retrospective study, we evaluated the data of 98 patients who underwent PC due to MIBC between January 2006 and December 2018. Of the 98 patients, 71 underwent maximal TUR. We evaluated the recurrence-free survival (PFS), pelvic recurrence-free survival (pPFS), cancer-specific survival (CSS), and overall survival (OS) using the Kaplan-Meier method according to the maximal TUR status. Variables associated with survival were analyzed using Cox regression analyses. RESULTS: The 5-year PFS (42.5% vs. 20.3%, p = 0.008), pPFS (50.7% vs. 24.1%, p = 0.003), and CSS (74.0% vs. 51.0%, p = 0.016) were also higher in patients who underwent maximal TUR. The multivariable Cox regression analysis showed that maximal TUR was associated with PFS (hazard ratio [HR] = 0.500, p = 0.029), pPFS (HR = 0.353, p = 0.004), and CSS (HR = 0.416, p = 0.027). However, maximal TUR did not affect the OS (HR = 0.618, p = 0.132). CONCLUSION: PC resulted in acceptable oncological outcomes in patients with MIBC, while maximal TUR played an important role in improving the oncological outcomes. PC after maximal TUR can be suggested as a treatment option for MIBC patients who are unable to undergo RC and TMT.

A Proposal for Standardization of Early Outcomes Following Robot-Assisted Radical Cystectomy (RARC): RARC Tetrafecta.

BACKGROUND: Currently, there is no dedicated tool to record the early outcomes of robot-assisted radical cystectomy (RARC), and existing criteria for longer-term outcomes require a minimum of 3 months for assessment. However, early evaluation is essential to prevent future morbidity and mortality, especially in surgeries with a high risk of complications in the short term. We propose a comprehensive approach to report early RARC outcomes and investigate the influence of surgeon experience on these results. PATIENTS AND METHODS: We retrospectively analyzed the outcomes of patients who underwent RARC for bladder cancer between April 2009 and April 2020. The cohort was divided chronologically into three groups: patients 1-60 in group 1, 61-120 in group 2, and 121-192 in group 3. Patients with yields of ≥ 16 lymph nodes (LN), negative soft tissue surgical margins, absence of transfusion, and absence of major complications at 30 days were regarded as attaining the RARC tetrafecta. RESULTS: Of the 192 included patients, 93 (48.4%) achieved RARC tetrafecta, with the proportion increasing with surgical experience from 41.7% in group 1 to 55.6% in group 3. Age [odds ratio (OR) 0.947; 95% confidence interval (CI) 0.924-0.970; P = 0.021], LN yield (OR 1.432; 95% CI 1.139-1.867; P = 0.001), and greater surgical experience with RARC (> 120 patients; OR 2.740; 95% CI 1.231-6.100; P = 0.014) were significantly associated with the achievement of RARC tetrafecta. CONCLUSIONS: RARC tetrafecta could be a comprehensive method for reporting early outcomes in patients undergoing RARC, with improvements aligned with the surgeon's experience.

Long-Term Outcomes of Orthotopic Neobladder Versus Ileal Conduit Urinary Diversion in Robot-Assisted Radical Cystectomy (RARC): Multicenter Results from the Asian RARC Consortium.

PURPOSE: Robot-assisted radical cystectomy (RARC) has gained traction in the management of muscle invasive bladder cancer. Urinary diversion for RARC was achieved with orthotopic neobladder and ileal conduit. Evidence on the optimal method of urinary diversion was limited. Long-term outcomes were not reported before. This study was designed to compare the perioperative and oncological outcomes of ileal conduit versus orthotopic neobladder cases of nonmetastatic bladder cancer treated with RARC. PATIENTS AND METHODS: The Asian RARC consortium was a multicenter registry involving nine Asian centers. Consecutive patients receiving RARC were included. Cases were divided into the ileal conduit and neobladder groups. Background characteristics, operative details, perioperative outcomes, recurrence information, and survival outcomes were reviewed and compared. Primary outcomes include disease-free and overall survival. Secondary outcomes were perioperative results. Multivariate regression analyses were performed. RESULTS: From 2007 to 2020, 521 patients who underwent radical cystectomy were analyzed. Overall, 314 (60.3%) had ileal conduit and 207 (39.7%) had neobladder. The use of neobladder was found to be protective in terms of disease-free survival [Hazard ratio (HR) = 0.870, p = 0.037] and overall survival (HR = 0.670, p = 0.044) compared with ileal conduit. The difference became statistically nonsignificant after being adjusted in multivariate cox-regression analysis. Moreover, neobladder reconstruction was not associated with increased blood loss, nor additional risk of major complications. CONCLUSIONS: Orthotopic neobladder urinary diversion is not inferior to ileal conduit in terms of perioperative safety profile and long-term oncological outcomes. Further prospective studies are warranted for further investigation.

Vasohibin-1 Expression Can Predict Pathological Complete Remission of Advanced Bladder Cancer with Neoadjuvant Chemotherapy.

BACKGROUND AND PURPOSE: Neoadjuvant chemotherapy (NAC) is a well-established standard practice in invasive bladder cancer (BCa), however patient selection remains challenging. High expression of vasohibin-1 (VASH1), an endogenous regulator of angiogenesis, has been reported in high-grade and advanced BCa; however, its prognostic value for chemotherapy outcomes remains unexplored. In this study, we sought to identify biomarkers of chemotherapy response focusing on the relationship between angiogenesis and tissue hypoxia. METHODS: Forty Japanese patients with BCa who underwent NAC and radical cystectomy were included in the present analysis. We compared the immunohistochemical expression of CD34, VASH1, and carbonic anhydrase 9 (CA9) between patients who achieved tumor clearance at operation (ypT0) and those with residual disease after cystectomy. RESULTS: There were 19 patients in the ypT0 group, while the remaining 21 patients had residual tumors at operation. Patients in the ypT0 group had high microvessel density (p = 0.031), high VASH1 density (p < 0.001), and stronger CA9 staining (p = 0.046) than their counterparts. Multivariate analysis identified microvessel and VASH1 density as independent predictive factors for pathological ypT0 disease (p = 0.043 and 0.002, respectively). The 5-year recurrence-free survival rate was higher in the high VASH1 density group than in the low VASH1 density group (66.3% vs. 33.3%, p = 0.036). CONCLUSION: VASH1 density is a potential therapeutic biomarker for chemotherapy response in BCa.

Upper Urinary Tract Urothelial Cancer After Radical Cystectomy for Bladder Cancer: Survival Outcomes After Radical Nephroureterectomy.

BACKGROUND: Systemic and local recurrences of urothelial bladder cancer (UBC) significantly impair survival after radical cystectomy (RC), but little is known about the impact of the recurrence of urothelial cancer in the upper urinary tract (UTUC). This report describes survival outcomes and their predictors for patients who underwent RC followed by radical nephroureterectomy (RNU) for UTUC. METHODS: The Surveillance, Epidemiology, and End Results database was queried to identify patients who underwent RC for UBC and subsequent RNU for UTUC. The Kaplan-Meier method and competing-risk Cox regression (CRR) were used for the survival analysis. RESULTS: Overall, 102 patients have undergone RNU within a median of 49 months (interquartile range [IQR], 27-76 months) since RC. Muscle-invasive UTUCs were predominant at RNU (n = 58; 56.7%), but organ-confined bladder tumors were most frequent at RC (n = 42, 41.5%). After RNU, the estimated 5-year overall survival (OS) was 25.9%, the cancer-specific survival (CSS) was 35.6%, the median OS was 23 months (IQR, 11-63 months), and the CSS was 34 months (IQR, 13-132 months). In the multivariable CRR, the factors predictive for CSS after RNU included male gender (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.03-5.42; p < 0.05), muscle-invasive UTUC (HR, 2.20; 95% CI, 1.13-4.28; p < 0.05), and the presence of distant metastasis (HR,11.59; 95% CI, 5.33-25.2; p < 0.001). CONCLUSIONS: In conclusion, the patients who underwent RNU for UTUC after RC for UBC experienced poor OS and CSS. The majority of RNUs were performed for locally advanced tumors. The independent risk factors for worse OS and CSS after RNU were UTUC T stage, presence of metastasis, and male gender.

Recent Advances of Neoadjuvant Immunotherapy for Urothelial Bladder Cancer.

Urothelial bladder cancer is one of the most common malignant tumors of the urinary system, which accounts for 90~95% of urothelial carcinoma. Despite the current standard neoadjuvant management for localized urothelial MIBC (T2-4cN0M0) is cisplatin-based chemotherapy before radical cystectomy, there still had poor performances and less overall survival benefits in patients with localized urothelial MIBC. Moreover, nearly half of MIBC patients were ineligible for receiving cisplatin because of chronic kidney disease and performance status. Although immunotherapy, immune checkpoint inhibitors (ICIs) has been identified as first or second-line treatments for localized and metastasis bladder cancer based on less adverse reactions and favorable outcomes, neoadjuvant immunotherapy had rarely used for the treatment of these patients because of less large-scale clinical randomized studies and limited outcomes. Therefore, we reviewed the advances of efficacy and safety with neoadjuvant immunotherapy for urothelial bladder cancer depended on published articles and clinical studies, which could provide more theoretical evidences and promising strategy for clinical therapeutic development.

Paradigm Shifting Research: Key Studies in Urologic Oncology.

BACKGROUND: Genitourinary malignancies have a substantial impact on men and women in the USA as they include three of the ten most common cancers (prostate, renal, and bladder). Other urinary tract cancers are less common (testis and penile) but still have profound treatment implications related to potential deficits in sexual, urinary, and reproductive function. Evidenced-based practice remains the cornerstone of treatment for urologic malignancies. METHODS: The authors reviewed the literature in consideration of the four top articles influencing clinical practice in the prior calendar year, 2022. RESULTS: The PROTECT trial demonstrates favorable 15-years outcomes for active monitoring of localized prostate cancer. The SEMS trial establishes retroperitoneal lymph node dissection as a viable option for patients with seminoma of the testis with limited retroperitoneal lymph node metastases. CheckMate 274 supports adjuvant immunotherapy following radical cystectomy for muscle-invasive bladder cancer with a high risk of recurrence. Data reported from the IROCK consortium reinforce stereotactic ablative radiotherapy as an option for localized renal cell carcinoma. CONCLUSION: The care for patients with urologic cancers has been greatly improved through advances in surgical, medical, and radiation oncologic treatments realized through prospective randomized clinical trials and large multicenter collaborative groups.

Changes in the Urinary Microbiome After Transurethral Resection of Non-muscle-Invasive Bladder Cancer: Insights from a Prospective Observational Study.

BACKGROUND: This study aimed to characterize the urinary and tumor microbiomes in patients with non-muscle-invasive bladder cancer (NMIBC) before and after transurethral resection of the bladder tumor (TURBT). METHODS: This single-center prospective study included 26 samples from 11 patients with low-grade Ta papillary NMIBC. Urine samples were collected at the index TURBT and at a 1-year follow-up cystoscopy. The metagenomic analysis of bacterial and archaeal populations was performed based on the highly variable V3-V4 region of the 16S rRNA gene. RESULTS: Phylogenetic alpha diversity of the bladder microbiome detected in urine was found to be lower at the 1-year follow-up cystoscopy compared to the time of the index TURBT (p < 0.01). Actinomyces, Candidatus cloacimonas, Sphingobacterium, Sellimonas, Fusobacterium, and Roseobacter were more differentially enriched taxa in urine at the follow-up cystoscopy than at the index TURBT. Beta diversity of urine microbiome significantly changed over time (p < 0.05). Phylogenetic alpha diversity of the microbiome was greater in tumor tissues than in paired urine samples (p<0.01). Sphingomonas, Acinetobacter, Candidatus, and Kocuria were more differentially overrepresented in tumor tissues than in urine. The enrichment of the abundance of Corynebacterium and Anaerococcus species in urine collected at TURBT was observed in patients who experienced recurrence within the follow-up period. CONCLUSIONS: In patients with low-grade NMIBC, the urine microbiome undergoes changes over time after removal of the tumor. The microbiome detected in tumor tissues is more phylogenetically diverse than in paired urine samples collected at TURBT. The interplay between bladder microbiome, tumor microbiome, and their alterations requires further studies to elucidate their predictive value and perhaps therapeutic implications.

Prognostic value of micrometric substaging in pT1 bladder cancer patients treated with en-bloc transurethral resection.

AIMS: We aimed to assess the oncological impact of micrometric extent of invasion in patients with pT1 bladder cancer (BCa) who underwent en-bloc resection for bladder tumour (ERBT). METHODS AND RESULTS: We retrospectively analysed the records and specimens of 106 pT1 high-grade BCa patients who underwent ERBT. The extent of invasion, such as depth from basal membrane, number of invasive foci, maximum width of invasive focus, muscularis mucosae invasion and infiltration pattern (pattern A: solid sheet-like, nodular or nested growth, pattern B: trabecular, small cluster or single-cell pattern) were evaluated by a single genitourinary pathologist. The end-points were recurrence-free (RFS) and progression-free survival (PFS). Within a median follow-up of 23 months, overall, 36 patients experienced recurrence and 13 patients experienced disease progression. The 2-year PFS differed significantly depending on depth from basal membrane (< 1.3 mm: 94.8% versus ≧ 1.3 mm: 65.2%, P = 0.005), maximum width of invasive focus (< 4 mm: 91.7% versus ≧ 4 mm: 62.3%, P < 0.001), muscularis mucosae (MM) invasion (above MM = 96.1% versus into or beyond MM = 64.8%, P = 0.002) and infiltration pattern (pattern A: 100% versus pattern B: 83.3%, P = 0.037). In a multivariable analysis, MM invasion [hazard ratio (HR) = 4.54, 95% confidence interval (CI) = 1.25-16.5] and maximum width of invasive focus ≧ 4 mm (HR = 4.79, 95% CI = 1.25-16.5) were independent prognostic factors of progression. CONCLUSIONS: En-bloc resection facilitates the evaluation of pathologic variables that might be useful in predicting disease recurrence and progression. In particular, not only the MM invasion but also the maximum width of invasion focus, reflecting the invasive volume, appear to be reliable prognosticators for disease progression.

Carcinoma arising in ileal conduit or orthotopic ileal neobladder reconstruction: A 20-year single institute experience.

CONTEXT: Carcinomas found in urinary diversion specimens are uncommon, particularly new primary tumours. New primary tumours primarily occur when the large intestine is utilised, whereas the occurrence is infrequent with the use of the ileum. These tumours include both the recurrence of primary malignancy or the development of a new primary malignancy originating from the small intestine. DESIGN: A search was performed within the pathology laboratory system to identify cases of malignancies involving ileal conduit/reconstruction from 2002 to 2022. Data on demographics, clinical details, pathology and management was recorded. RESULTS: A total of 13 male patients, with a mean age of 67 years (range = 49-81 years) were included in the study. The initial procedure performed included cystoprostatectomy (n = 10, including one case with right nephroureterectomy) and cystectomy (n = 3, including one case for bladder exstrophy) for initial diagnoses including urothelial carcinoma (n = 11; conventional, 6; sarcomatoid, 1; glandular 1; plasmacytoid, 1; micropapillary, 2) and adenocarcinoma (n = 1). The initial management included radical surgery with neoadjuvant chemotherapy/immunotherapy (n = 1), adjuvant chemotherapy (n = 3), intravesical adjuvant BCG (n = 2) and intravesical adjuvant chemotherapy (n = 1). Malignancies in ileal conduit or orthotopic ileal neobladder included recurrent urothelial carcinoma (n = 10) and new secondary adenocarcinomas (n = 3), which developed as early as 3 months (usually recurrence) and up to 13, 33 and 45 years (new primary malignancy) following primary resection. CONCLUSIONS: Utilising the ileum as conduit/neobladder presents a viable alternative for urinary diversion with a reduced malignancy risk compared to using a segment of the large intestine. However, there remains a potential for malignancy, either tumour recurrence or a new primary malignancy. In our study, tumour recurrence occurred up to 4 years following the initial diagnosis and the development of a new primary malignancy occurred up to 45 years after the initial diagnosis. Consequently, it is crucial to prioritise long-term follow-up for these patients undergoing this procedure.

[68 Ga]Ga-FAPI-46 PET/CT for locoregional lymph node staging in urothelial carcinoma of the bladder prior to cystectomy: initial experiences from a pilot analysis.

INTRODUCTION: [68 Ga]Ga-FAPI-46 PET/CT is a novel hybrid imaging method that previously showed additional diagnostic value in the assessment of distant urothelial carcinoma lesions. We hypothesized that patients with bladder cancer benefit from [68 Ga]Ga-FAPI-46 PET/CT prior to radical cystectomy for locoregional lymph node staging. MATERIALS AND METHODS: Eighteen patients underwent [68 Ga]Ga-FAPI-46 PET/CT for evaluation of lymph node (LN) status in predefined LN regions. Two hundred twenty-nine intraoperatively removed LN served as histopathological reference standard. RESULTS: Urothelial carcinoma (UC) spread was found in ten LN in seven different regions (14.3%). Hereby, [68 Ga]Ga-FAPI-46 PET/CT was positive in four out of seven regions (57.1%) and showed significantly increased FAPI uptake compared to non-pathological regions. In the remaining three out of seven (42.9%) regions, [68 Ga]Ga-FAPI-46 PET/CT was rated negative since no pathological increased FAPI uptake was detected or the proximity of the urinary tract prevented a differentiation from physiological uptake. CT was inconspicuous in these three regions. In total, two FAP-positive LN regions were found without histopathological counterpart. Overall, sensitivity, specificity, positive predictive value, and negative predictive value were 57.1%, 95.2%, 66.7%, and 93.0% for PET imaging. CONCLUSION: In summary, this innovative [68 Ga]Ga-FAPI-46 PET/CT method showed high specificity and negative predictive value in patients with bladder UC with a future potential to optimize therapy planning.

Patients´ experiences of an exercise intervention in primary care following robot-assisted radical cystectomy due to bladder cancer: a qualitative study.

BACKGROUND: Physical activity is thought to be a key component in reducing postoperative complications following major abdominal surgery. The available literature on exercise interventions following radical cystectomy in patients with bladder cancer is scarce but suggests that physical activity and exercise might improve physical function and health-related quality of life, thus calling for further investigation. The CanMoRe-trial is a single-blinded randomised controlled trial (Clinicals Trials NCT03998579 25/06/2019), aimed at evaluating the impact of an exercise intervention in primary care following robot-assisted radical cystectomy. This study seeks to explore patients' experiences of the exercise intervention in the CanMoRe-trial to gain a better understanding of facilitating aspects and potential barriers. METHODS: A qualitative study was conducted involving 20 patients from the intervention group of the CanMoRe-trial who were interviewed individually between October 2020 and March 2023 using a semi-structured interview guide. The interviews were recorded and transcribed verbatim and reflexive thematic analysis was used to analyse the data. RESULTS: Four main themes were identified: Having to adapt to new circumstances, describing the challenges regarding physical activity patients face after discharge. Optimising conditions for rehabilitation, describing how practical conditions affect patients' ability to exercise. Motivated to get back to normal, describing patients´ desire to get back to normal life and factors influencing motivation. Importance of a supportive environment, describing the impact of social support, support from physiotherapists, and how the environment where exercise takes place impacts patients' ability to exercise. CONCLUSION: This study found that patients participating in the CanMoRe-trial are positive towards physical exercise in PC following radical RARC. They are motivated to get back to normal life but face major challenges when arriving home following surgery, which affect their ability to perform physical activity and engage in exercise. Conditions need to be optimised to support patients' ability to engage in exercise by providing an accessible PC location to perform exercise in. A supportive environment is also needed, including guidance from healthcare professionals regarding which type of exercise, intensity and amount of exercise that should be performed, enabling patients gradually to develop self-efficacy regarding exercise and focusing on goals related to patients' normal lives before surgery.

Effects of an exercise intervention in primary care after robot-assisted radical cystectomy for urinary bladder cancer: a randomised controlled trial.

INTRODUCTION: After radical cystectomy physical activity is important to reduce risk of complications, but patients with urinary bladder cancer have difficulties in achieving general recommendations on physical activity and exercise. The aim of this randomised controlled trial was therefore to evaluate the effects of a physical exercise programme in primary care, following discharge from hospital after robot-assisted radical cystectomy for urinary bladder cancer. MATERIALS AND METHODS: Patients with urinary bladder cancer scheduled for robot-assisted radical cystectomy at Karolinska University Hospital, Sweden between September 2019 and October 2022 were invited to join the study. At discharge, they were randomised to intervention or active control group. The intervention group was planned to start exercise with physiotherapist in primary care during the third week; the programme included aerobic and strengthening exercises, twice a week for 12 weeks, and daily walks. The control group received unsupervised home-based exercise with daily walks and a sit-to-stand exercise. Assessments were conducted before surgery, at discharge and after four months regarding the primary outcome physical function (Six-minute walk test), and secondary outcomes physical activity, pain, health-related quality of life, fatigue, and psychological wellbeing. RESULTS: Ninety patients were included, mean (sd) age 71.5 (8.5) years. An intention-to-treat analysis showed no intervention effect on the primary outcome physical function, or on pain or psychological wellbeing, but effect on physical activity with a difference from discharge to four months with a median (IQR) of 4790 (3000) and 2670 (4340) daily steps in the intervention and control group, respectively (p = 0.046), and for fatigue, and health-related quality of life, in favour of the intervention group. CONCLUSION: Both the intervention and control groups improved physical function, but the patients who exercised in primary care experienced additional positive effects on physical activity, fatigue, and health-related quality of life. Hence, exercise in primary care after discharge from hospital could be a promising method after radical cystectomy for urinary bladder cancer. TRIAL REGISTRATION: The study was registered in Clinical Trials with registration number NCT03998579, 20,190,607.