Initial Transurethral Resection Research Articles

Grade Heterogeneity in High-Grade Urothelial Carcinomas: Does It Have an Impact on the Survival of Patients With Intermediate/High-Risk Nonmuscle-Invasive Bladder Cancer Who Received Adequate Adjuvant Bacillus Calmette-Guérin Therapy?

We aimed to compare recurrence-free survival (RFS) and progression-free survival (PFS) of the patients with pure high-grade (HG) vs mixed-grade (MG) nonmuscle-invasive bladder cancer who received adequate bacillus Calmette-Guérin therapy. We conducted a retrospective cohort analysis using data from an institutional database. The study included patients diagnosed with HG nonmuscle-invasive bladder cancer at the initial transurethral resection specimen between 2010 and 2020. The initial transurethral resection specimens of all patients were reevaluated by a dedicated uropathologist. The percentage of low-grade tumor areas accompanying HG areas was determined for each case. Time-to-event analysis was performed using the Kaplan-Meier method. RFS and PFS rates were compared between groups. Of the 203 patients enrolled in the study, 69 (34%) had MG tumors. Recurrence was observed in 41 out of 134 patients (30.6%) in the HG group and in 19 out of 69 patients (27.5%) in the MG group. The 36-month RFS rates were 69% (CI: 62-77) and 72% (CI: 62-83) for the HG-urothelial carcinoma (UC) and MG-UC groups, respectively. The RFS rates were similar between groups (log-rank, P = .58). Progression was observed in 22 out of 134 patients (16.4%) in the HG group and in 4 out of 69 patients (5.8%) in the MG group. The 36-month PFS rates were 84% (CI: 77-90) and 94% (CI: 89-100) for the HG-UC and MG-UC groups, respectively. The pure HG-UC group had a worse PFS than the MG-UC group (log-rank, P = .042). Multivariate analysis demonstrated that age and tumor grade were significant risk factors for the development of progression. The indication of MG-UC category separately from pure HG carcinomas in the pathology report seems to be an important issue that can guide patient management. In this way, both more accurate risk classification and more accurate patient counseling can be performed. More importantly, the treatment plan can be made more accurately. For more precise conclusions, our results should be supported by prospective studies with larger sample size.

Routine Surveillance of Upper Urinary Tract Imaging for Diagnosing Upper Urinary Tract Urothelial Cancer Recurrence in Patients with Nonmuscle Invasive Bladder Cancer.

Although routine surveillance imaging to examine upper urinary tract urothelial cancer recurrence during follow-up of nonmuscle invasive bladder cancer is recommended, its necessity remains invalidated. A single-institute long-term follow-up cohort study to evaluate the clinical impact of routine surveillance imaging and identify risk factors for upper urinary tract urothelial cancer recurrence after nonmuscle invasive bladder cancer treatment was conducted. A retrospective chart review of 864 patients with primary nonmuscle invasive bladder cancer who underwent initial transurethral resection of bladder tumor between 1980 and 2020 was conducted. The opportunities to diagnose its recurrence were examined. Moreover, oncological outcomes included upper urinary tract urothelial cancer recurrence-free survival and overall survival. Of 864 patients, 19 (2.2%) experienced upper urinary tract urothelial cancer recurrence. Among 19 patients, recurrence was detected through routine imaging in 12 (63.2%), cystoscopy in 2 (10.5%), urine cytology in 2 (10.5%), and presence of gross hematuria in 1 (5.3%). All patients had high- or highest-risk NMIBC at diagnosis of primary nonmuscle invasive bladder cancer. On multivariate Fine-Gray proportional regression analyses, a tumor size of ≥30 mm and carcinoma in situ were independently associated with short upper urinary tract urothelial cancer recurrence-free survival (P=0.040 and 0.0089, respectively). Most patients experiencing upper urinary tract urothelial cancer recurrence were diagnosed by routine surveillance imaging, suggesting its clinical importance, especially for patients with nonmuscle invasive bladder cancer accompanied by a tumor size of ≥30 mm and carcinoma in situ.

Optimal timing for the first cystoscopic follow-up using time-to-treatment initiation analysis of oncologic outcomes in primary non-muscle invasive bladder cancer

Various guidelines recommend the first follow-up cystoscopy at 3 months; however, no data exist on the optimal timing for initial follow-up cystoscopy. We tried to provide evidence on the timing of the first cystoscopy after the initial transurethral resection of bladder tumor (TUR-BT) for patients with non-muscle invasive bladder cancer (NMIBC) using big data. This was a retrospective National Health Insurance Service database analysis. The following outcomes were considered: recurrence, progression, cancer-specific mortality, and all-cause mortality. Exposure was the time-to-treatment initiation (TTI), a continuous variable representing the time to the first cystoscopy from the first TUR-BT within 1 year. Additionally, we categorized TTI (TTIc) into five levels: < 2, 2–4, 4–6, 6–8, and 8–12 months. A landmark time of 1 year after the initial TUR-BT was described to address immortal-time bias. We identified the optimal time for the first cystoscopy using Cox regression models with and without restricted cubic splines (RCS) for TTI and TTIc, respectively. Among 26,660 patients, 16,880 (63.3%) underwent cystoscopy within 2–4 months. A U-shaped trend of the lowest risks at TTI was observed in the 2–4 months group for progression, cancer-specific mortality, and all-cause mortality. TTI within 0–2 months had a higher risk of progression (aHR 1.36; 95% confidence intervals [CI] 1.15–1.60; p < 0.001) and cancer-specific mortality (aHR 1.29; 95% CI 1.05–1.58; p = 0.010). Similarly, TTI within 8–12 months had a higher risk of progression (aHR 2.09; 95% CI 1.67–2.63; p < 0.001) and cancer-specific mortality (aHR 1.96; 95% CI 1.48–2.60; p < 0.001). Based on the RCS models, the risks of progression, cancer-specific mortality, and all-cause mortality were lowest at TTI of 4 months. The timing of the first cystoscopy follow-up was associated with oncologic prognosis. In our model, undergoing cystoscopy at 4 months has shown the best outcomes in clinical course. Therefore, patients who do not receive cystoscopy at approximately 4 months for any reason need more careful follow-up to predict a poor clinical course.

Prediction of recurrence risk in patients with non-muscle-invasive bladder cancer

ObjectiveNon-muscle-invasive bladder cancer (NMIBC) remains a common challenge in uro-oncology with conflicting reports on recurrence risk. This study aimed to elucidate the recurrence rate of NMIBC in the Cancer Clinic of Shahid Beheshti Hospital in Iran and to investigate related parameters affecting recurrence risk. MethodsThe data of 143 patients with NMIBC, who underwent treatment between January 2017 and January 2020 and were followed up from the initial transurethral resection of bladder tumor until November 30, 2020 in our institution, were retrospectively assessed. The Cox regression analysis and Kaplan–Meier plot of recurrence-free survival were used to determine independent contributing factors for tumor recurrence. ResultsAmong patients with NMIBC, 83.9% were male, and 16.1% were female, with a mean age of 64.4 (standard deviation [SD] 12.9) years. During the follow-up, 71 (49.7%) patients showed tumor recurrence, with a mean recurrence time of 11.5 (SD 6.9) months. In the Chi-square test or Fisher's exact test, the age (≥65 years) (p=0.037), obesity (body mass index ≥30 kg/m2) (p=0.004), no diabetes mellitus (p=0.005), smoking (current or former smoker) (p=0.001), immediate perfusion therapy (p=0.035), number of tumors (>3) (p<0.001), and tumor stage (Ta, T1, and Tis) (p=0.001) had independent significant effects on the recurrence of NMIBC. The multivariate Cox regression analysis indicated that preoperative obesity (hazards ratio [HR] 7.90; 95% confidential interval [CI] 4.01–15.55; p<0.001), current or former smoking (HR 1.85; 95% CI 1.07–3.20; p=0.027), and a high-grade tumor (HR 4.03; 95% CI 1.59–10.25; p=0.003) were significant predictors of tumor recurrence. The Kaplan–Meier plot of recurrence-free survival showed that obesity (log-rank p<0.001), current or former smoking (log-rank p=0.001), and a high-grade tumor (log-rank p=0.006) were associated with a shorter time interval until the first tumor recurrence. ConclusionThe study found a high recurrence rate of NMIBC in Iran from January 2017 to January 2020, with the obesity, smoking history, and the high-grade tumor as contributing factors.

High-Grade Urothelial Carcinoma with Divergent Prostatic Differentiation Mimicking a Collision Tumor

Abstract Introduction/Objective High-grade urothelial carcinoma (HGUC) shows marked morphologic plasticity with many recognized histologic subtypes that may coexist within the same tumor. These pose a diagnostic challenge and should be distinguished from collision tumors, defined by the coexistence of morphologically and genotypically distinct tumors at the same anatomic site. Herein, we present the first case of HGUC with malignant prostatic differentiation mimicking a collision tumor in a bladder diverticulum. Methods/Case Report 68 yo male presented with gross hematuria and was found to have a 2.2 cm tumor in a posterior bladder diverticulum. Initial transurethral resection (TUR) suggested HGUC, while re-TUR showed prostatic adenocarcinoma. Subsequent diverticulectomy specimen revealed two morphologically and immunohistochemically distinct tumor components: 1) a papillary component associated with urothelial carcinoma in situ, positive for CK903 and GATA3, and compatible with HGUC of the bladder, and 2) a distinct and intimately admixed malignant glandular component, which was GATA3 negative, but positive for markers of prostatic differentiation such as NKX3.1, PSA and PSAP and displayed prostatic duct adenocarcinoma features. Accurate diagnosis of this lesion is crucial, and a few possibilities exist: 1) a collision process between urothelial carcinoma of the bladder and a previously undiagnosed duct carcinoma of the prostate metastatic to the bladder diverticulum; 2) prostate cancer arising from an ectopic prostatic epithelium located in the bladder submucosa; 3) HGUC with malignant divergent prostatic differentiation. To this end, papillary and glandular tumor components were macrodissected and subjected to targeted massively parallel sequencing. Disease-associated variants in EGFR, DDR2, KMT2D, and RB1 were identified and were identical and shared among the two histologically distinct components. These findings suggest that the two components are part of the same neoplastic process and represent a urothelial carcinoma with divergent prostatic differentiation. Of note, the patient’s initial and subsequent PSA levels were within normal limits, and magnetic resonance imaging of the prostate was unremarkable. Results (if a Case Study enter NA) NA Conclusion Awareness of divergent differentiation in urothelial carcinomas has important diagnostic, prognostic and therapeutic implications and can be resolved with the use of ancillary and molecular studies.

HER2 overexpression predicts pathological T2 stage and improved survival in de novo muscle-invasive bladder cancer after immediate radical cystectomy: a retrospective cohort study.

Human epidermal growth factor receptor type 2 (HER2) overexpression is a prognostic factor and a therapeutic target for breast cancer; however, anti-HER2 therapies are ineffective in patients with bladder cancer. The authors investigated the effect of HER2 overexpression (HER2 + ) on the prognosis of muscle-invasive bladder cancer (MIBC). This retrospective cohort study included patients who underwent initial transurethral resection of bladder tumors between 2005 and 2013 and were registered in the Korea National Health Insurance Database, which provides data on overall survival (OS). Sixty-one patients with clinically nonmetastatic de novo MIBC were included in this study. As a subgroup, 33 patients who underwent immediate radical cystectomy (RC) were analyzed. Univariate and multivariate Cox proportional hazards models were used to identify prognostic factors for survival. A multivariable binary logistic regression model was used to identify the favorable T stage. Among the 61 patients with d-MIBC, 14 were HER2 + and 47 HER2 - . Age less than 70 years [hazard ratio (HR): 0.312, CI: 0.16-0.59, P <0.001] and HER2 + status (HR: 0.40, CI: 0.19-0.85, P =0.02) were favorable prognostic factors for OS after adjusting for clinical variables. In the RC subgroup, HER2 + status was a significant predictive factor for the pT2 stage (HR): 36.8, CI: 4.83-797.41, P <0.01). Age less than 70 years (HR: 0.15, CI: 0.05-0.42, P <0.001) and HER2 + status (HR: 0.11, CI: 0.02-0.54, P =0.01) were favorable prognostic factors for OS after adjusting for RC pathological variables. HER2 + status could be a marker for an indolent subset of MIBC and could predict favorable survival regardless of RC status. Moreover, HER2 + status not only consistently predicted a favorable T stage after RC, but also predicted better survival than pathological outcomes.

Repeat Transurethral Resection (TUR) + Bacillus Calmette-Guérin (BCG) Versus Upfront Induction BCG After TUR in High-risk Non–muscle-invasive Bladder Cancer: Feasibility Phase of a Randomized Controlled Study

BackgroundHigh-level evidence supporting the role of repeat transurethral resection (reTUR) in non–muscle-invasive bladder cancer (NMIBC) is lacking. A randomized controlled trial (RCT) assessing whether immediate reTUR has an impact on patient prognosis is essential. However, since such a RCT will require enrollment of a high number of patients, a preliminary feasibility study is appropriate. ObjectiveTo assess the feasibility of an RCT investigating the impact of immediate reTUR + adjuvant bacillus Calmette-Guérin (BCG) versus upfront induction BCG after initial TUR in NMIBC. Design, setting, and participantsEligible patients were randomly assigned to receive either reTUR + adjuvant BCG or upfront induction BCG after TUR. Patients with macroscopically completely resected high-grade T1 NMIBC, with or without concomitant carcinoma in situ, and with detrusor muscle (DM) present in the initial TUR specimen were considered eligible for inclusion. Exclusion criteria included lymphovascular invasion (LVI), histological subtypes, hydronephrosis, concomitant upper tract urothelial carcinoma (UTUC), or urothelial carcinoma within the prostatic urethra. The aim was to enroll 30 patients in this feasibility study. Outcome measurements and statistical analysisThe patient recruitment rate was the primary outcome. Oncological outcomes (recurrence-free and progression-free survival) were secondary endpoints. Results and limitationsOverall, 30 patients (15 per arm) were randomized over a period of 14 mo (August 2020–October 2021). Two eligible patients refused the randomization, resulting in a patient compliance rate of 93.3% for the study protocol. We excluded 49 ineligible patients before randomization because of histological subtypes (n = 16, 33%), LVI (n = 9, 18%), DM absence in the TUR specimen (n = 12, 24%), metastatic disease (n = 5, 10%), concomitant UTUC (n = 3, 6%), or hydronephrosis (n = 4, 8%). At reTUR, persistent disease was found in four patients (29%) and upstaging to muscle-invasive disease in one (7%). Over median follow-up of 17 mo, disease recurrence was detected in three patients (23%) in the reTUR arm and six patients (40%) in the upfront BCG arm. Progression to muscle-invasive disease was observed in one patient treated with upfront BCG. ConclusionsThe feasibility of conducting an RCT comparing upfront BCG versus reTUR + BCG in high-grade T1 NMIBC has been demonstrated. Our results underline the need to screen a large number of patients owing to characteristics meeting the exclusion criteria in a high percentage of cases. Patient summaryWe found that a clinical trial of the role of a repeat surgical procedure to remove bladder tumors through the urethra would be feasible among patients with high-grade non–muscle-invasive bladder cancer. These preliminary results may help in refining the role of this repeat procedure for patients in this category.

Occurrence of Distant Metastasis During Bladder Presevation in T1 high-grade Bladder Cancer: Report of Three Cases

We report three patients with T1 high-grade (HG) bladder cancer who suffered from distant metastasis during bladder preservation. The patients were a 48-year-old female (Case 1), a 75-year-old female (Case 2) and an 82-year-old male (Case 3) with the chief complaint of asymptomatic gross hematuria. The histopathological diagnoses of the initial transurethral resection of the bladder tumor (TURBT) and second TURBT were urothelial carcinoma, pT1, HG and no malignancy in all three patients. Bladder tumors of all patients revealed sessile growth pattern and no presence of carcinoma in situ. Case 2 and 3 did not receive BCG vesical instillation after the second TURBT. Lymph node metastases appeared in Case 1 and Case 2 and lung metastasis appeared in Case 3. Tumor budding (TB) was positive in Case 1 and Case 2. Variant histology (VH) of nested morphology was detected in Case 1 and VH of inverted morphology in Case 2 and Case 3. Twenty-four months after the initial TURBT, Case 1 died due to cancer progression after cisplatin-based chemotherapy and pembrolizumab therapy. Thirty-three and 11 months after the initial TURBT, Case 2 and Case 3 were alive without cancer progression after cisplatin-based chemotherapy and/or pembrolizumab therapy, respectively. The two patients with T1 HG bladder cancer with TB had lymphatic metastasis and the patient without TB had hematogenous metastasis. Nested morphology is reportedly categorized as high-risk disease and inverted morphology as low-risk disease. TB might be correlated with lymphatic metastasis in T1 HG bladder cancer, and TB should be considered in the management of T1 HG bladder cancer. In the case of VH, the guidelines should be followed during the treatment decision of T1 HG bladder cancer.

Does Repeating Transurethral Resection of Bladder Tumors Change Treatment Plan for All T1 Tumors?

Background: The main problem in the proper management of non-muscle invasive bladder cancer (NMIBC) is the under-staging of lesions after initial transurethral resection of bladder tumor (TUBRT). Under staging is much more evident in T1 tumors when the detrusor muscle is absent. So, we evaluated under-staging and residual tumors in patients with complete initial TURBT whose initial pathological samples revealed the presence of the detrusor muscle. Methods: In this prospective study performed in Bahonar hospital, Kerman, Iran, from August 2018 to April 2020, 51 patients with newly diagnosed T1 bladder tumors were enrolled according to our criteria and underwent standard Re-TURBT about eight weeks after the initial TURBT. Results: Of 51 patients who underwent Re-TURBT, 12 (23.5%) had tumors, of whom eight had microscopic, and four had macroscopic tumors. None of them were upstaged or upgraded. There was a statistically significant relationship between the presence of tumors in Re-TURBT and the size of the primary tumor (&gt;3 cm) and the number of tumors (&gt;1). No changes were observed in the stage and grade of the disease, besides, the treatment plan of patients did not change despite imposing financial burdens on patients and the healthcare system. Conclusion: Re-TURBT is not necessary for all superficial bladder tumors, especially in the case of complete initial TURBT, and also in the presence of the detrusor muscle in the pathological sample and when the tumor is single and less than three centimeters in size.

BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer: Current Treatment Landscape and Novel Emerging Molecular Targets.

Urothelial carcinoma (UC), the sixth most common cancer in Western countries, includes upper tract urothelial carcinoma (UTUC) and bladder carcinoma (BC) as the most common cancers among UCs (90-95%). BC is the most common cancer and can be a highly heterogeneous disease, including both non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) forms with different oncologic outcomes. Approximately 80% of new BC diagnoses are classified as NMIBC after the initial transurethral resection of the bladder tumor (TURBt). In this setting, intravesical instillation of Bacillus Calmette-Guerin (BCG) is the current standard treatment for intermediate- and high-risk patients. Unfortunately, recurrence occurs in 30% to 40% of patients despite adequate BCG treatment. Radical cystectomy (RC) is currently considered the standard treatment for NMIBC that does not respond to BCG. However, RC is a complex surgical procedure with a recognized high perioperative morbidity that is dependent on the patient, disease behaviors, and surgical factors and is associated with a significant impact on quality of life. Therefore, there is an unmet clinical need for alternative bladder-preserving treatments for patients who desire a bladder-sparing approach or are too frail for major surgery. In this review, we aim to present the strategies in BCG-unresponsive NMIBC, focusing on novel molecular therapeutic targets.

Socio-economic, education, and insurance-related factors associated with the treatment completion rates in patients with nonmetastatic urinary bladder cancer: A Retrospective cohort study.

Among urological malignancies, the diagnosis and treatment of urinary bladder cancer (UBC) incurs the highest cost per patient. Our objective was to broaden the current understanding of how demographic, socioeconomic, education, and insurance-related factors influence UBC management. Between January 2017 and December 2019, all patients with nonmetastatic bladder cancer were included. The demographic, treatment, and follow-up details were retrieved from a prospectively maintained database, and the Modified Kuppuswamy Index was used to evaluate the patients' socioeconomic level. Patients were divided into the completed treatment group, or the incomplete treatment group based on adherence to the initially intended treatment plan. Patients who presented with benign disease or metastases were not included. Eighty-nine patients did not complete the initially intended course of treatment out of 132 patients who needed additional management after the initial transurethral resection. Comparable risk factors and demographic profiles existed in both groups. Patients with intermediate-risk disease are more likely to fail to adhere to the initial intended treatment (odds ratio [OR] = 0.09; 95% confidence interval [CI]: 0.02-0.30). On logistic regression analysis, upper socioeconomic status (OR = 6.8; 95% CI: 0.35-132.1) patients and patients with higher educational status of graduation or above (OR = 3.62; 95% CI: 0.75-17.43) had higher chances of treatment completion. Education status significantly impacted treatment completion on multivariate analysis (P = 0.01). Patients who utilized employer-funded insurance had better treatment compliance (OR = 4.1; 95% CI: 0.90-18.7). The compliance was unaffected by smoking, occupation, or other demographic factors. Patients with low economic status, low levels of education, and who need adjuvant intravesical therapy had considerably greater treatment dropout rates.

Underutilization of intravesical chemotherapy and immunotherapy for high grade non-muscle invasive bladder cancer in California between 2006–2018: Effect of race, age and socioeconomic status on treatment disparities

ObjectiveAmong patients diagnosed with non-muscle invasive bladder cancer (NMIBC), those with high risk disease have the greatest risk of recurrence and disease progression. The underutilization of intravesical immunotherapy with Bacillus Calmette-Guérin (BCG) has been a longstanding concern in clinical practice. This study aimed to determine the disparities present in receipt of adjuvant intravesical chemotherapy and immunotherapy in treatment of patients with high grade NMIBC following initial transurethral resection of a bladder tumor (TURBT). MethodsThe California Cancer Registry data was used to identify 19,237 patients diagnosed with high grade NMIBC who underwent TURBT. Treatment variables include re-TURBT, re-TURBT and intravesical chemotherapy (IVC) and/or BCG. Independent variables include age, sex, race/ethnicity, neighborhood socioeconomic status (nSES), primary insurance payer and marital status at diagnosis. Multiple logistic regression and multinomial regression models were used to examine variation in the treatments received following TURBT. ResultsThe proportion of patients receiving TURBT followed by BCG was similar across all racial and ethnic groups (28%–32%). BCG therapy was higher in patients belonging to the highest nSES quintile (37% for highest vs. 23%–26% for the 2 lowest quintiles). In multiple variable analyses, receipt of any intravesical therapy (IVT) was influenced by nSES, age, marital status, race/ethnicity, and insurance type. Patients in the lowest nSES quintile had a 45% less likelihood of receiving IVT compared to the highest nSES group (OR [95%CI]: 0.55[0.49, 0.61]). Race/ethnicity differences in receipt of any adjuvant therapy were noted in the middle to lowest nSES quintile for Hispanic and Asian/Pacific Islander patients when compared to non-Hispanic White patients. When comparing variation in treatment by insurance type at diagnosis, those with Medicare or other insurance were 24% and 30% less likely to receive BCG after TURBT compared to those with private insurance, (OR [95%CI]: 0.76 [0.70, 0.82] and 0.70[0.62, 0.79]) respectively. ConclusionIn patients with a diagnosis of high risk NMIBC, disparities in utilization of BCG are seen based on SES, age, and insurance type.

Clinical practice of UroVysion® urine test in patients with bladder carcinoma in situ treated with intravesical Bacillus Calmette-Guerin.

In January 2019, the use of the UroVysion® urine test for surveillance of non-muscle invasive bladder cancer with carcinoma in situ (CIS) was approved in Japan. Clinical evidence of its use remains limited. Herein, we report the real-world clinical practice of the UroVysion test. Of 29 patients underwent at least one UroVysion test at our hospital from 2019 to 2022, only two (6.9%) tested positive without any visible tumor on the cystoscopy after the initial transurethral resection: a 77-year-old man with T1 high-grade tumor and concomitant CIS and a 76-year-old woman with CIS. The remaining 27 patients (93.1%) tested negative post-transurethral resection. This study was the first to report the Japanese real-world practice of the UroVysion test, demonstrating relatively low positive rate as compared to the previous reports from other countries. Further clinical evidence from other Japanese institutes needs to be accumulated to update the true value of this test.

The Japanese health care system-based cost-effectiveness of photodynamic diagnosis-assisted transurethral resection of bladder tumor for non-muscle invasive bladder cancer.

Photodynamic diagnosis-assisted transurethral resection of bladder tumor reduces the risk of intravesical recurrence compared with conventional white light-transurethral resection of bladder tumor. However, the patient burden of costs for photodynamic diagnosis-transurethral resection of bladder tumor is higher than that for white light-transurethral resection of bladder tumor per installment, and the impact of the medical economics of photodynamic diagnosis-transurethral resection of bladder tumor is unclear. Therefore, we evaluated the Japanese health care system-based cost-effectiveness of photodynamic diagnosis-transurethral resection of bladder tumor compared with that of white light-transurethral resection of bladder tumor. We conducted a retrospective chart review of 100 patients who underwent initial white light- or photodynamic diagnosis-transurethral resection of bladder tumor for non-muscle invasive bladder cancer from February 2012 to August 2019. Cumulative intravesical recurrences during 1000 post-operative days after the initial transurethral resection of bladder tumor were counted. Furthermore, the cumulative costs were calculated using the Diagnostic Procedure Combination and Per-Diem Payment System unique to Japan. The costs/year/person calculated using the person-year method was compared between the white light- and photodynamic diagnosis-transurethral resection of bladder tumor. Among the 100 patients, 40 (40%) and 60 (60%) underwent the initial white light- and photodynamic diagnosis-transurethral resection of bladder tumor, respectively. The cumulative incidence of bladder recurrence requiring hospitalization and transurethral resection of bladder tumor was 20 and 5% for the white light-transurethral resection of bladder tumor and photodynamic diagnosis-transurethral resection of bladder tumor, respectively. The costs for hospitalization and surgical procedures per white light- or photodynamic diagnosis-transurethral resection of bladder tumor were 348 228 and 481 820 Japanese yen, respectively. The cost/year/person by the person-year method was 8073 and 8557 Japanese yen for the white light- and photodynamic diagnosis-transurethral resection of bladder tumor, respectively. The cost/year/person for hospitalization and surgical procedures was slightly different between the white light- and photodynamic diagnosis-transurethral resection of bladder tumor. Furthermore, photodynamic diagnosis-transurethral resection of bladder tumor can reduce intravesical recurrence and is more cost-effective than white light-transurethral resection of bladder tumor.

Predictive molecular biomarkers for determining neoadjuvant chemosensitivity in muscle invasive bladder cancer.

Identifying neoadjuvant chemotherapy (NAC) response in patients with muscle invasive bladder cancer (MIBC) has had limited success based on clinicopathological features and molecular subtyping. Identification of chemotherapy responsive cohorts would facilitate delivery to those most likely to benefit. Develop a molecular signature that can identify MIBC NAC responders (R) and non-responders (NR) using a cohort of known NAC response phenotypes, and better understand differences in molecular pathways and subtype classifications between NAC R and NR. Presented are the messenger RNA (mRNA) and microRNA (miRNA) differential expression profiles from initial transurethral resection of bladder tumor (TURBT) specimens of a discovery cohort of MIBC patients consisting of 7 known NAC R and 11 NR, and a validation cohort consisting of 3 R and 5 NR. Pathological response at time of cystectomy after NAC was used to classify initial TURBT specimens as R (pT0) versus NR (≥pT2). RNA and miRNA from FFPE blocks were sequenced using RNAseq and qPCR, respectively. The discovery cohort had 2309 genes, while the validation cohort had 602 genes and 13 miRNA differentially expressed between R and NR. Gene set enrichment analysis identified mitochondrial gene expression, DNA replication initiation, DNA unwinding in the R discovery cohort and positive regulation of vascular associated smooth muscle cell proliferation in the NR discovery cohort. Canonical correlation (CC) analysis was applied to differentiate R versus NR. 3 CCs (CC13, CC16, and CC17) had an AUC &gt;0.65 in the discovery and validation dataset. Gene ontology enrichment showed CC13 as nucleoside triphosphate metabolic process, CC16 as cell cycle and cellular response to DNA damage, CC17 as DNA packaging complex. All patients were classified using established molecular subtypes: Baylor, UNC, CIT, Lund, MD Anderson, TCGA, and Consensus Class. The MD Anderson p53-like subtype, CIT MC4 subtype and Consensus Class stroma rich subtype had the strongest correlation with a NR phenotype, while no subtype had a strong correlation with the R phenotype. Our results identify molecular signatures that can be used to differentiate MIBC NAC R versus NR, salient molecular pathway differences, and highlight the utility of molecular subtyping in relation to NAC response.

Check Cystoscopy Follow-up Practice for Low-Risk (pTa) Non-muscle Invasive Bladder Cancer in the United Kingdom

Objectives: To identify the best practice policy and guideline for surveillance with check cystoscopies follow up for low-risk pTa urothelial bladder tumour and to identify the recurrence rate and the progression rate of low-risk urothelial bladder tumour and how safe is it to discharge them at 1- versus 5-years of follow up. Objectives: To identify the best practice policy and guideline for surveillance with check cystoscopies follow up for low-risk pTa urothelial bladder tumour and to identify the recurrence rate and the progression rate of low-risk urothelial bladder tumour and how safe is it to discharge them at 1- versus 5-years of follow up. Secondary outcome: To estimate the cost-effectiveness of a reduced follow-up scheme, if this is deemed a safe practice to follow. Methodology: It is a single centre, retrospective review of all low-risk NMIBC patients diagnosed with low-risk bladder tumors at our Trust between 2012 and 2014 from our local urological cancer multi-disciplinary team (MDT) registry and ensured a 5-year time-lapse from diagnosis. Histology grade and staging from the first TURBT, receiving of mitomycin within 24 hrs following the initial TURBT, the timing of cystoscopy follow-up, cystoscopy findings (evidence of recurrence), further procedures (bladder biopsy, fulguration or TURBT), histology of further procedures, recurrence rate and time from the first TURBT to discharge to primary care are reviewed and analysed. Result: Our initial review revealed a high likelihood of recurrence (33.9%) in the low-risk NMIBC patients after 12 months of being cancer free. It also demonstrated that there is further progression in (23.8%) of those who had a later recurrence despite being asymptomatic. Conclusion: We would recommend a 5-year follow-up surveillance and further national collaboration to audit this patient subgroup to define a safe period of cystoscopic follow-up for these patients and bring further evidence for NICE to build up their recommendations.

Trimodale Therapie des muskelinvasiven Blasenkarzinoms – eine äquivalente Alternative zur Operation im lokalisierten Tumorstadium?

BackgroundThe standard treatment of muscle-invasive bladder cancer is cystectomy with pelvic lymphadenectomy. Primary organ-preserving trimodal treatment is considered an alternative to radical surgery.ObjectiveThe concept and results of trimodal treatment, consisting of initial transurethral resection of the bladder tumor (TURBT) followed by simultaneous chemoradiotherapy (CRT), are presented.Material and methodsAn evaluation of retrospective case series and prospective treatment optimization studies on organ-preservation concepts was carried out. Comparative meta-analyses comparing cystectomy with trimodal treatment are presented.ResultsA complete TURBT including bladder mapping and tumor ground biopsy should be done before CRT. Radiosensitization should be with cisplatin-based chemotherapy or with a combination of 5‑fluorouracil and mitomycin C. Complete response rates after TURBT plus CRT are achieved by 60–90% of patients and 5‑year survival rates of 40–75%, with preservation of the bladder in approximately 80% of surviving patients.ConclusionTrimodal treatment is a viable alternative to radical cystectomy with curative intention for patients with muscle-invasive urinary bladder cancer. Patients with early tumors (cT2/3N0) are particularly suitable in whom the initial TURBT leads to complete tumor resection (R0). Older patients can also benefit from this approach.

The probability of residual tumor detection in the second transurethral resection of pT1 urothelial bladder cancer according to the risk factors

ObjectiveTo analyze the predictive factors for residual tumors in the second resection after the initial transurethral resection of bladder tumor (TUR-BT) in patients with pT1 tumors and to develop a simple method to predict the probability of residual tumor detection. Material and MethodsPatients with pT1 bladder cancer who underwent a second resection within two to six weeks after the initial TUR-BT were included in our retrospective study. The patients’ demographics and the tumor characteristics of the initial and second resections were recorded. ResultsA total of 144 patients were included in our analysis with a 53-month follow-up. In the univariate logistic regression analysis, tumor grade, concomitant carcinoma in situ (CIS), macroscopic appearance of the tumor (solid vs papillary), and presence of a variant histology, were significant risk factors for residual tumor. In the multivariate analysis, tumor grade was the only independent predictor of residual tumor at second TUR (OR: 5.62, 95% CI: 1.228–25.708, p = 0.026). According to our findings, the patients with the highest risk have a 90.9% residual tumor detection probability at the second resection, and the patients with the lowest risk have 25.4%. ConclusionsTumor grade, macroscopic appearance of the tumor (solid vs papillary), and concomitant CIS, were important predictors of residual tumors at second resection of primary pT1 NMIBC patients. We were able to calculate the probability of residual tumor which helped us determine risk adapted strategies according to these probabilities.

MP59-06 PD-L1 EXPRESSION AND BCG RESPONSE IN NON-MUSCLE INVASIVE BLADDER CANCER

You have accessJournal of UrologyCME1 May 2022MP59-06 PD-L1 EXPRESSION AND BCG RESPONSE IN NON-MUSCLE INVASIVE BLADDER CANCER Solomon Woldu, Thomas Gerald, Vitaly Margulis, Daniel Halstuch, Yaara Ber, Karin Lifshitz, David Margel, Yair Lotan, and Liwei Jia Solomon WolduSolomon Woldu More articles by this author , Thomas GeraldThomas Gerald More articles by this author , Vitaly MargulisVitaly Margulis More articles by this author , Daniel HalstuchDaniel Halstuch More articles by this author , Yaara BerYaara Ber More articles by this author , Karin LifshitzKarin Lifshitz More articles by this author , David MargelDavid Margel More articles by this author , Yair LotanYair Lotan More articles by this author , and Liwei JiaLiwei Jia More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002642.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Intravesical bacillus Calmette Guerin (BCG) is the standard of care adjuvant therapy for high risk non-muscle invasive bladder cancer (NMIBC), yet many patients experience recurrence or disease progression. The mechanism of BCG is thought to be related to stimulation of immune surveillance. Relatedly, systemic immune checkpoint inhibition is being utilized in advanced bladder cancer and approved for BCG unresponsive NMIBC. We sought to determine the association between PD-L1 expression and BCG treatment. METHODS: We identified 102 BCG-naïve patients with high grade (HG) NMIBC treated with BCG. All patients underwent initial transurethral resection (TUR). Dako 22c3 assay was used to determine PD-L1 expression. Patients were defined as PD-L1 positive if the combined positive score > 0. BCG unresponsiveness was defined by presence of HG disease at 6 months following adequate BCG (one induction and maintenance cycle or two induction cycles) for pT1 or 12 months for CIS or presence of pT1 at 3 months after induction. HG relapse was defined as HG disease after being followed for 6 months after BCG. RESULTS: The median follow-up was 57 months. Median number of BCG maintenance cycles was 1, and 17 (16.7%) patients underwent immediate reinduction BCG. PD-L1 expression was observed in 5.9% of pTa, 30.0% of pT1, and 3.6% of CIS. BCG unresponsiveness and HG relapse were observed in 32 (35.6%) and 29 (34.5%), respectively. On univariate analysis, PD-L1 expression was inversely associated with BCG unresponsiveness (OR=0.11; 95% CI 0.01-0.90) but not HG relapse (OR=0.30; 95% CI 0.06-1.44). The sensitivity, specificity, positive predictive value, and negative predictive value of PD-L1 expression for BCG responsiveness were 22%, 97%, 93%, and 41%, respectively. PD-L1 positive patients had a post-test probability of BCG responsiveness of 93%. On multivariate regression, pT1 (OR = 0.16; 95% CI 0.05-0.60), CIS (OR=0.25; 95% CI 0.07-0.86), and PD-L1 expression (OR=15.63; 95% CI 1.78-142.86) were associated with BCG responsiveness. CONCLUSIONS: PD-L1 expression in HG NMIBC was low, and those with PD-L1 expression at initial TUR were more likely to harbor invasive disease. Patients with PD-L1 expression were more likely to demonstrate BCG responsiveness. These findings suggest a role of PD-L1 in the immune surveillance mechanism of BCG at initial diagnosis and may assist in predicting response to BCG in patients with HG NMIBC. Further investigation is needed to determine if additional immune checkpoint markers have strong correlation with BCG response, particularly among patients without PD-L1 expression. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e1003 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Solomon Woldu More articles by this author Thomas Gerald More articles by this author Vitaly Margulis More articles by this author Daniel Halstuch More articles by this author Yaara Ber More articles by this author Karin Lifshitz More articles by this author David Margel More articles by this author Yair Lotan More articles by this author Liwei Jia More articles by this author Expand All Advertisement PDF DownloadLoading ...

MP54-16 IMMEDIATE RADICAL CYSTECTOMY VS. BCG IMMUNOTHERAPY FOR T1 HIGH GRADE NON-MUSCLE-INVASIVE BLADDER CANCER: AN INTERNATIONAL MULTICENTRE COLLABORATION

MP54-16 IMMEDIATE RADICAL CYSTECTOMY VS. BCG IMMUNOTHERAPY FOR T1 HIGH GRADE NON-MUSCLE-INVASIVE BLADDER CANCER: AN INTERNATIONAL MULTICENTRE COLLABORATION