Transurethral Resection Of Tumor Research Articles

Preoperative oral treatment with cyclooxygenase‐2 inhibitor for cystitis glandularis

IntroductionA previous report has shown that cyclooxygenase‐2 inhibitors can prevent the recurrence of cystitis glandularis postoperatively. Herein, we present a case of cystitis glandularis in which the tumor volume was markedly reduced by preoperative oral administration of a cyclooxygenase‐2 inhibitor.Case presentationA 45‐year‐old man with voiding difficulty and lower abdominal pain during urination was referred to our hospital. Cystoscopy revealed multiple cystitis glandularis‐like edematous masses on the trigone and the neck of the bladder, completely involving the bilateral ureteral orifices. Cyclooxygenase‐2 inhibitor was orally administered at the patient's request. Six weeks later, the tumor volume was markedly reduced, bilateral ureteral orifices were identified, and the voiding difficulty and pain on urination disappeared. Complete transurethral resection of the residual tumor was performed, and the pathological diagnosis was intestinal‐type cystitis glandularis.ConclusionCyclooxygenase‐2 inhibition can be considered a useful therapeutic strategy for cystitis glandularis.

Correlation between Ki-67 or Profilin-1 Expression Levels, Clinicopathological Characteristics and Postoperative Prognosis in Patients with Bladder Cancer.

Bladder cancer is the most common malignancy of the urinary system, and the search for new and reliable biomarkers has important clinical significance for the personalized treatment of bladder cancer. This study aims to explore the correlation between nuclear proliferation antigen (Ki-67) or Profilin-1 (PFN1) levels, clinicopathological characteristics, and postoperative prognosis in patients with bladder cancer. Patients with bladder cancer who underwent transurethral resection of bladder cancer tumor in The Fourth Affiliated Hospital of Soochow University, hospital from January 2019 to January 2021 were selected as the study group (n = 60), and patients with benign lesions of bladder cancer during the same period were selected as the control group (n = 60). The expression of Ki-67 and PFN1 in tumor and bladder tissues of the two groups was analyzed. Ki-67 recorded the patient's pathological parameters and calculated the patient's postoperative prognosis. The correlation between Ki-67 and PFN1 expression levels, pathological parameters, and postoperative prognosis was analyzed. The positive expression rates of Ki-67 and PFN1 in the study group were 63.33% and 73.33%, respectively, which were significantly higher than the positive expression rates in the control group (χ2 = 14.803, 17.757, p < 0.001). The positive expression rates of Ki-67 and PFN1 were related to histological grade, clinical stage, infiltration, and lymph node metastasis, and the differences were statistically significant (p < 0.05). Bladder cancer patients with non muscle-invasive bladder cancer (NMIBC), high-grade histological grade, Ta~T1 clinical stage, invasive, and lymph node metastasis have a higher Ki-67 positive expression rate than bladder cancer patients with muscle-invasive bladder cancer (MIBC), low-grade histological grade, T2~T4, non-invasive, and no lymph node metastasis. The high expression level of Ki-67 has little relationship with gender, age, tumor diameter, and vascular invasion (p > 0.05). The survival time and three-year survival rate of the Ki-67 positive expression group were significantly lower than those of the Ki-67 negative expression group (p < 0.05). The survival time and three-year survival rate of the PFN1 positive expression group were significantly lower than those of the PFN1 negative expression group (p < 0.05). The positive expression rates of Ki-67 and PFN1 in bladder tumor tissue are significantly higher than those in bladder tissue, and pathological pattern, histological grade, clinical stage, infiltration, and lymph node metastasis are related to the positive expression rates of Ki-67 and PFN1, and different genders, ages, tumors diameter and vascular invasion are not related to the positive expression rates of Ki-67 and PFN1. The survival time and three-year survival rates of bladder cancer patients with Ki-67 positive and PFN1 positive expression are shorter.

The role of androgen response pathway in association with tumor biology and response to neoadjuvant immune-checkpoint inhibitors (ICI) in muscle-invasive urothelial bladder carcinoma (MIBC).

662 Background: Emerging findings from ICI trials are suggestive of differential outcomes in females compared with males. Sex-specific differences in tumor biology, microbiome, and outcomes in MIBC are well-established. Conversely, limited data are available regarding the role of the androgen response pathway in explaining subtype differences between males and females and, most importantly, response to ICI. Methods: We retrospectively evaluated the biomarker findings of the transurethral resection of the bladder tumors (TURBT) and baseline clinical characteristics of patients (pts) with cT2-4N0M0 MIBC who received neoadjuvant pembrolizumab and radical cystectomy (RC) in the PURE-01 study. Transcriptome-wide expression profiling was performed on 102 TURBT samples. We focused on androgen receptor (AR) gene expression and the hallmark androgen response pathway expression quantifying 117 different genes related to the androgen response pathway as previously reported (PMID: 26771021). Pt and tumor characteristics were compared between subgroups using χ2 tests and two-sided Wilcoxon rank-sum tests. Kaplan-Meier curves and log rank tests evaluated gene expression and signature scores in association with the event-free survival (EFS), calculated from start of pembrolizumab treatment. Signature scores were analyzed as continuous values and were split by median and quartile values. Results: Pts received pembrolizumab and RC from 2017 to 2022. There were 87 (85.3%) males and 15 (14.7%) females. AR gene expression was not significantly different between males and females (p = 0.5), whereas androgen response signature was significantly higher in male (p = 0.03). The AR gene expression and androgen response signature scores were more highly expressed in luminal tumors vs rest of molecular subtypes (p = 0.005 and p &lt; 0.001). Despite AR gene expression was not associated with ypT0N0 response (p = 0.425), hallmark androgen response signature scores were significantly lower in ypT0N0 responders (p = 0.033). Higher hallmark androgen response signature scores were statistically significantly associated with shorter EFS (p = 0.028), whereas AR gene expression was not (p = 0.152). Conclusions: For the first time to our knowledge, we reported the androgen response pathway expression to be a potential biomarker of ICI benefit in MIBC. This signature was also associated with a luminal subtype, linked to inferior responsiveness to ICI. If confirmed at a larger scale these analyses will strengthen the need for sex-specific approaches and potentially new combination therapies in MIBC.

Expression of Preferentially Expressed Antigen in Melanoma, a Cancer/Testis Antigen, in Carcinoma In Situ of the Urinary Tract.

Carcinoma in situ (CIS) of the urinary tract comprises 1-3% of all urothelial malignancies and is often a precursor to muscle-invasive urothelial carcinoma (UC). This study aimed to examine the expression profiles of preferentially expressed antigen in melanoma (PRAME), a cancer/testis antigen, and assess its diagnostic and therapeutic applications in CIS, given that its expression in UC has been minimally studied and has not yet been analyzed in CIS. We selected consecutive patients with CIS who underwent biopsy and/or transurethral tumor resection at the Osaka Medical and Pharmaceutical University Hospital. Immunohistochemical staining for PRAME and p53 was performed. Overall, 53 patients with CIS (6 females and 47 males) were included. Notably, PRAME expression was observed in 23 of the 53 patients (43.4%), whereas it was absent in the non-neoplastic urothelial epithelium. Furthermore, no correlation was found between PRAME expression and aberrant p53 expression. Therefore, PRAME expression may serve as a useful marker for CIS of the urinary tract. Furthermore, PRAME may be a candidate for the novel therapeutic target for standard treatment-refractory CIS patients.

Genomic Tumor Correlates of Clinical Outcomes Following Organ-Sparing Chemoradiation Therapy for Bladder Cancer.

There is an urgent need for biomarkers of radiation response in organ-sparing therapies. Bladder preservation with trimodality therapy (TMT), consisting of transurethral tumor resection followed by chemoradiation, is an alternative to radical cystectomy for muscle-invasive bladder cancer (MIBC), but molecular determinants of response are poorly understood. We characterized genomic and transcriptomic features correlated with long-term response in a single institution cohort of patients with MIBC homogeneously treated with TMT. Pretreatment tumors from 76 patients with MIBC underwent whole-exome sequencing; 67 underwent matched transcriptomic profiling. Molecular features were correlated with clinical outcomes including modified bladder-intact event-free survival (mBI-EFS), a composite endpoint that reflects long-term cancer control with bladder preservation. With a median follow-up of 74.6 months in alive patients, 37 patients had favorable long-term response to TMT while 39 had unfavorable long-term response. Tumor mutational burden was not associated with outcomes after TMT. DNA damage response gene alterations were associated with improved locoregional control and mBI-EFS. Of these alterations, somatic ERCC2 mutations stood out as significantly associated with favorable long-term outcomes; patients with ERCC2 mutations had significantly improved mBI-EFS [HR, 0.15; 95% confidence interval (CI), 0.06-0.37; P = 0.030] and improved BI-EFS, an endpoint that includes all-cause mortality (HR, 0.33; 95% CI, 0.15-0.68; P = 0.044). ERCC2 mutant bladder cancer cell lines were significantly more sensitive to concurrent cisplatin and radiation treatment in vitro than isogenic ERCC2 wild-type cells. Our data identify ERCC2 mutation as a candidate biomarker associated with sensitivity and long-term response to chemoradiation in MIBC. These findings warrant validation in independent cohorts.

Spectrum of Lesions in the Urinary Bladder: A Histopathological Study in a Tertiary Level Hospital

Background: Urinary Bladder cancer is the 7th most common cancer worldwide, with an estimated 260,000 new cases occurring each year in men and 76,000 in women. 90% of the bladder tumors are of urothelial origin. Cystoscopic examination has a limited role in staging process for which transurethral resection (TURBT) of visible tumor down to the base is required which can accurately assess depth of tumor invasion. Aim &amp; Objectives: The aim is to study the spectrum of urinary bladder lesions according to World Health Organization / International Society of Urological Pathology consensus classification and to determine age and sex distribution of urothelial tumors. Material &amp; Method: Study included 55 TURBT specimens, conducted over a period 12 months, extending from January 2022 to December 2022. Hematoxylin &amp; Eosin (H&amp;E) stained sections were examined for morphologic diagnosis of urothelial lesions. Results: In our study, there was male preponderance with ratio of 3.2:1. Among 55 cases studied, 34.55% cases were diagnosed as invasive urothelial carcinoma, 27.27% cases were of non-invasive urothelial carcinoma, 16.36% cases were of benign urothelial neoplasm and 16.36% cases were of non-neoplastic lesions in urinary bladder. There were also 1.82% cases of adenocarcinoma, metastasis and non-diagnostic each in our study. Amongst invasive carcinoma high grade were encountered most (30.91%) cases. Maximum numbers of urothelial neoplasms (25.45%) were seen in 71-80 years of age group. Conclusion: This study revealed that neoplastic lesions are more common than non-neoplastic lesions. Urothelial tumors are seen commonly in seventh decade with overall male predominance. Also this study, documents a high frequency of invasive than non-invasive type of urothelial neoplasm.

Plasmacytoid bladder cancer: a rare case report.

The authors report a case of a patient with locally advanced plasmacytoid urothelial carcinoma (PUC) of the bladder. A 71-year-old man with a history of chronic obstructive pulmonary disease presented with gross hematuria. The rectal examination revealed a fixed bladder base. A computed tomography scan showed a pedunculated lesion arising from the anterior and left lateral bladder wall and extended to the perivesical fat. The patient underwent transurethral resection of the tumor. The histologic examination revealed the presence of muscle-invasive PUC of the bladder. The decision of the multidisciplinary consultation meeting was to do palliative chemotherapy. Thus, the patient could not receive systemic chemotherapy and died 6 weeks after transurethral resection of the bladder tumor. A plasmacytoid variant of urothelial carcinoma is a rare subtype of urothelial carcinoma that has a poor prognosis with a high mortality rate. The disease is usually diagnosed at an advanced stage. Given the rarity of plasmacytoid bladder cancer, treatment guidelines are not clear; therefore, more aggressive treatment may be required. PUC of the bladder is characterized by high aggressiveness, an advanced stage at the time of diagnosis, and a poor prognosis.

Miliary Pulmonary Tuberculosis After Intravesical BCG Instillation in a Patient with High-Grade Bladder Cancer

Intravesical administration of Bacillus Calmette-Guerin (BCG) vaccine is used in the treatment of superficial bladder cancer. In clinical practice, intravesical BCG immunotherapy after transurethral tumor resection is a highly effective treatment option in preventing tumor recurrence and progression in medium and high risk superficial bladder tumors. Since patients are given live tuberculosis (TB) bacillus, serious side effects such as pneumonia, sepsis and even death can be seen. Lung involvement occurs in less than 1% of patients and most commonly presents as interstitial pneumonia or miliary TB. Miliary TB is difficult to diagnose and is usually based on high clinical suspicion, as Mycobacterium bovis is not isolated in most cases. Treatment is not completely standardized. However, in severe cases, a combination of antituberculosis drugs and corticosteroids is recommended. In this report, a case of miliary tuberculosis, a very rare complication after instillation of BCG into the bladder in a patient with a diagnosis of superficial bladder cancer, was presented. A 73-year-old male patient diagnosed with bladder tumor underwent transurethral resection of bladder tumor, and then weekly intravesical injection of BCG-MEDAC for six weeks had no adverse effects. Three weeks of intravesical BCG supplementation was planned for the patient who had no signs of recurrence when checked three months later by cystoscopy. Two hours after the first dose, the patient, who applied to the emergency department with the complaint of chills and shivering, was hospitalized for further follow-up and treatment. Afterwards, repeat cultures were taken from the patient whose fever continued on the seventh day of treatment with broad-spectrum antibiotics (meropenem and teicoplanin). In addition, when abdominal and thorax computed tomography (CT) were performed, multiple miliary nodular lesions were detected in both lungs and were evaluated in favor of miliary TB. With these findings, the patient was started on miliary TB therapy [isoniazid (INH), rifampicin (RIF), ethambutol (EMB) and streptomycin (STM)] targeting Mycobacterium bovis, since it was an infection that developed after BCG injection. In the third week of the treatment, the patient's fever was under control, and he was discharged on the 25th day of his hospitalization because of significant improvement in infection markers [C-reactive protein(CRP)-procalcitonin]. At the end of two months, there was clear regression of pulmonary abnormalities on control thorax CT. In conclusion, miliary TB developing after intravesical BCG instillation is a very rare condition, the cause of which is not fully understood, the etiology of fever can be easily missed, and the diagnosis is difficult. In addition, this case is presented to draw attention to a critical disease that requires long treatment and follow-up and requires attention.

Bladder Preservation With Transurethral Tumor Resection and Intravesical BCG Instillation in Superficial Muscle-Invasive Bladder Cancer: A 10-Year Follow-up

Purpose: The aim of this study was to evaluate the 10-year oncological outcomes of bladder preservation with transurethral resection of bladder tumor (TURBT) and intravesical bacillus Calmette-Guérin (BCG) instillation in selected patients with superficial muscle-invasive bladder cancer (MIBC).Materials and Methods: Patients diagnosed with superficial MIBC (stage T2a) by TURBT between 2001 and 2009 were included. Cystectomy-free survival, recurrence-free survival (RFS), progression-free survival (PFS), and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method. Cox regression analysis was used to identify predictors of each type of survival.Results: Of 145 patients, 135 underwent bladder preservation and 10 underwent immediate radical cystectomy (RC). Among the latter, 9 patients showed downstaging. During a median follow-up of 132 months (interquartile range, 96–161 months), 13 patients underwent RC, with a 10-year cystectomy-free survival rate of 83.9%. Seventy patients (48.3%) had recurrence, and the 10-year RFS rate was 48.9%. Progression occurred in 12 patients (8.3%), with a 10-year PFS rate of 90.1%. Death occurred only in patients who exhibited progression; 5 patients (3.4%) died of bladder cancer, and the 10-year CSS rate was 96.5%. Tumors greater than 3 cm were associated with RC, and a high tumor grade predicted recurrence. RC was related to progression and cancer-specific mortality.Conclusions: Although high-grade tumors require careful follow-up, bladder preservation with TURBT and intravesical BCG instillation can enable the successful management of selected patients with stage T2a MIBC less than 3 cm, without carcinoma in situ or tumor-associated hydronephrosis, in a nonmetastatic setting.

Re: Outpatient Photodynamic Diagnosis–guided Laser Destruction of Bladder Tumors Is as Good as Conventional Inpatient Photodynamic Diagnosis–guided Transurethral Tumor Resection in Patients with Recurrent Intermediate-risk Low-grade Ta Bladder Tumors. A Prospective Randomized Noninferiority Clinical Trial

Re: Outpatient Photodynamic Diagnosis–guided Laser Destruction of Bladder Tumors Is as Good as Conventional Inpatient Photodynamic Diagnosis–guided Transurethral Tumor Resection in Patients with Recurrent Intermediate-risk Low-grade Ta Bladder Tumors. A Prospective Randomized Noninferiority Clinical Trial

Outpatient Photodynamic Diagnosis–guided Laser Destruction of Bladder Tumors Is as Good as Conventional Inpatient Photodynamic Diagnosis–guided Transurethral Tumor Resection in Patients with Recurrent Intermediate-risk Low-grade Ta Bladder Tumors. A Prospective Randomized Noninferiority Clinical Trial

BackgroundTransurethral resection of recurrent low-grade intermediate-risk Ta bladder tumor (BT) in general anesthesia (GA) is burdensome to patients and health care system. Laser technologies enable treatment in office-based settings, reducing morbidity and costs. ObjectiveTo compare 4-mo recurrence-free survival after outpatient department (OPD) diode laser coagulation of BT in local anesthesia and gold standard transurethral resection of BT (TUR-BT) in GA in intermediate-risk Ta low-grade BT, and to evaluate treatment-related morbidity. Design, setting, and participantsA prospective randomized noninferiority trial with 4-mo follow-up, in the hospital setting, was conducted in Capital Region of Denmark from 2016 to 2020. Participants were patients with histologically verified Ta low-grade BT recurrence. A total of 206 patients were randomized; 176 finished treatment and follow-up as per protocol. InterventionLaser photocoagulation of bladder tumor (PC-BT) in OPD using a 980 nm diode laser compared with gold standard TUR-BT in GA, both performed with photodynamic diagnosis (PDD) guidance. Outcome measurements and statistical analysisFour-month recurrence-free survival was assessed; predefined inferiority criterion was set at 15%. The secondary outcomes were pain during PC-BT, postoperative morbidity, postoperative complications, and patient’s preference. Results and limitationsFour-month recurrence-free survival was 8% higher after PC-BT (95% confidence interval [CI]: –8% to 24%). The predefined noninferiority criterion was met. Pain score (1–10) during PC-BT was 2.4 (interquartile range 0.8–3.3). Postoperative lower urinary tract symptom score (0–100) was 13.9 points higher (95% CI: 6.9–21.0, p < 0.001) in the group with transurethral resection of the bladder. The frequency of minor complications was 8.1% higher after TUR-BT (95% CI: 1.0–14.6%, p = 0.026). Of the patients, 98% (95% CI: 92–100%) preferred PC-BT. ConclusionsPDD-guided PC-BT in OPD is as good as TUR-BT in GA to remove recurrent low-grade Ta BT. Postoperative quality of life is better after PC-BT and the frequency of minor complications was lower. Patient summaryThis study evaluates the efficacy of outpatient laser removal of low-grade noninvasive bladder tumor. Outpatient tumor removal with laser was as good as transurethral resection in general anesthesia and less burdensome to patients.

Pediatric urothelial bladder neoplasm

Urothelial bladder neoplasm (UBN) is an uncommon lesion in children and adolescents, without established follow-up protocol defined for this patient group. To report our experience and long-term follow-up data on pediatric patients with urothelial carcinoma of the urinary bladder. In this retrospective two center study, we analyzed the perioperative and long-term follow-up data of nine pediatric patients, who presented with neoplasms of urothelial origin within the urinary bladder between 2000 and 2021. Nine patients were identified with a mean age of 11.9 years (range 4-19 years) and median follow up of 48 months (range 12-160 month). 7 were male. Gross hematuria was the most common presenting symptom, occurring in 6 patients, followed by accidental finding on US, performed for other reasons. Cystoscopy was performed under general anesthesia, and transurethral resection of the bladder tumors was carried out in the same session. All patients had a solitary tumor with a mean size of 11mm (range 6-15mm). Pathology revealed 3 cases of papillary urothelial neoplasm of low malignant potential (PUNLMP), 5 cases of low grade (LG) noninvasive urothelial carcinoma (UC) and one case of high-grade (HG) UC invading lamina propria (pT1). All 8 patients with low grade tumor underwent follow up according to adult follow-up protocols without tumor recurrences to date. The single patient with HG pT1 UC, a 14-year-old female after renal transplantation, who was not eligible for intravesical bacillus Calmette-Guerin (BCG) installations due to immunosuppression, underwent 6 sessions of Radiofrequency-induced Thermo-chemotherapy with mitomycin, without complications. She had no recurrence to date, during a 4-year post treatment follow up. Pediatric non muscle invasive bladder cancer (NMIBC), seems to have a good prognosis with infrequent recurrences, which might be in favor of a more spacious follow up plan with less invasive diagnostic modalities as opposed to adult NMIBC population. To the best of our knowledge this is the single description of Heated Intravesical Chemotherapy efficacy for HG UC in the pediatric population.

A novel pathway to detect muscle-invasive bladder cancer based on integrated clinical features and VI-RADS score on MRI: results of a prospective multicenter study

PurposeTo determine the clinical, pathological, and radiological features, including the Vesical Imaging-Reporting and Data System (VI-RADS) score, independently correlating with muscle-invasive bladder cancer (BCa), in a multicentric national setting.Method and MaterialsPatients with BCa suspicion were offered magnetic resonance imaging (MRI) before trans-urethral resection of bladder tumor (TURBT). According to VI-RADS, a cutoff of ≥ 3 or ≥ 4 was assumed to define muscle-invasive bladder cancer (MIBC). Trans-urethral resection of the tumor (TURBT) and/or cystectomy reports were compared with preoperative VI-RADS scores to assess accuracy of MRI for discriminating between non-muscle-invasive versus MIBC. Performance was assessed by ROC curve analysis. Two univariable and multivariable logistic regression models were implemented including clinical, pathological, radiological data, and VI-RADS categories to determine the variables with an independent effect on MIBC.ResultsA final cohort of 139 patients was enrolled (median age 70 [IQR: 64, 76.5]). MRI showed sensitivity, specificity, PPV, NPV, and accuracy for MIBC diagnosis ranging from 83–93%, 80–92%, 67–81%, 93–96%, and 84–89% for the more experienced readers. The area under the curve (AUC) was 0.95 (0.91–0.99). In the multivariable logistic regression model, the VI-RADS score, using both a cutoff of 3 and 4 (P < .0001), hematuria (P = .007), tumor size (P = .013), and concomitant hydronephrosis (P = .027) were the variables correlating with a bladder cancer staged as ≥ T2. The inter-reader agreement was substantial (k = 0.814).ConclusionsVI-RADS assessment scoring proved to be an independent predictor of muscle-invasiveness, which might implicate a shift toward a more aggressive selection approach of patients’ at high risk of MIBC, according to a novel proposed predictive pathway.

En Bloc Resection of Bladder Tumor May be the best choice?

The quality of transurethral tumor resection plays an important role in histopathological assessment and treatment decision-making, which affects the prognosis of the disease. Piecemeal resection of tumor tissue leads to the dissemination

Multiple metastases of androgen indifferent prostate cancer in the urinary tract: two case reports and a literature review

BackgroundProstate cancer (PC) is mainly known to metastasize to bone, lung and liver, but isolated metastases of prostate cancer, including ductal carcinoma, in the urinary tract are very rare. We describe two patients with nodular masses in the urinary tract (the anterior urethra or the urinary bladder) that were found on cystoscopy during treatment of castration-resistant prostate cancer.Case presentationIn both cases, the pathological diagnosis from transurethral tumor resection showed that they were androgen indifferent prostate cancer (AIPC), including aggressive variant prostate cancer (AVPC) in Case 1 and treatment-induced neuroendocrine differentiation prostate cancer (NEPC) in Case 2. In Case 1, Loss of genetic heterozygosity (LOH) of BRCA2 and gene amplification of KRAS was identified from the urethra polyps. In Case 2, homozygous deletion was observed in PTEN, and LOH without mutation was observed in RB1.ConclusionThese are the first reports of two cases of urinary tract metastasis of AIPC.

MP54-05 EVALUATING INTRAVESICAL NADOFARAGENE FIRADENOVEC AND IMMUNE CHECKPOINT BLOCKADE COMBINATION THERAPY IN BCG-UNRESPONSIVE NON-MUSCLE-INVASIVE BLADDER CANCER: EVIDENCE FROM A PHASE 3 TRIAL

You have accessJournal of UrologyCME1 May 2022MP54-05 EVALUATING INTRAVESICAL NADOFARAGENE FIRADENOVEC AND IMMUNE CHECKPOINT BLOCKADE COMBINATION THERAPY IN BCG-UNRESPONSIVE NON-MUSCLE-INVASIVE BLADDER CANCER: EVIDENCE FROM A PHASE 3 TRIAL Anirban P. Mitra, Sharada Mokkapati, Tanner S. Miest, Vikram M. Narayan, Richard Philipson, Seppo Yla-Herttuala, David Sawutz, Nigel R. Parker, David J. McConkey, and Colin P.N. Dinney Anirban P. MitraAnirban P. Mitra More articles by this author , Sharada MokkapatiSharada Mokkapati More articles by this author , Tanner S. MiestTanner S. Miest More articles by this author , Vikram M. NarayanVikram M. Narayan More articles by this author , Richard PhilipsonRichard Philipson More articles by this author , Seppo Yla-HerttualaSeppo Yla-Herttuala More articles by this author , David SawutzDavid Sawutz More articles by this author , Nigel R. ParkerNigel R. Parker More articles by this author , David J. McConkeyDavid J. McConkey More articles by this author , and Colin P.N. DinneyColin P.N. Dinney More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002633.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: There are few efficacious bladder-preserving therapies for BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC). Pembrolizumab, an immune checkpoint inhibitor (ICI) targeting programmed cell death 1 (PD1) receptor, is approved in this setting. Nadofaragene firadenovec is an intravesical adenoviral vector-based therapy that delivers IFNA2 to urothelial cells, and has shown durable response in a multicenter phase 3 trial for BCG-unresponsive NMIBC. We evaluated the status of PD1 and its ligand (PD-L1) in transurethral resection (TUR) specimens from patients treated with nadofaragene, and examined the role for combining nadofaragene with anti-PD1 therapy in BCG-unresponsive NMIBC. METHODS: TUR specimens were available for 85 patients treated on a single-arm phase 3 trial with nadofaragene once every three months for up to four doses. Response was assessed at 12 months or disease recurrence, whichever was earlier. TUR of tumor was done at enrollment, and a templated biopsy at 12 months or study withdrawal. PD1/PD-L1 status were assayed per routine immunohistochemical protocols. PD1 (positive, >0% cells) and PD-L1 (positive, ≥1% cells) quantification were performed for urothelial and infiltrating lymphocyte compartments. Orthotopic tumors in C57Bl/6 mice were treated with intravesical adenoviral-IFN versus control, and PD1/PD-L1 status was assessed. RESULTS: Urothelial PD1 and PD-L1 status assessed on study-entry (Sin) and study-exit (Sout) TUR specimens were not associated with treatment response (all, p ≥0.26). Sin lymphocyte PD1+ was seen in 52% responders (R) and 57% nonresponders (NR) (p=0.72). Sin lymphocyte PD-L1+ was seen in 77% R and 92% NR (p=0.15). 62% NR had Sout lymphocyte PD1+ compared with 26% R (p=0.002). Sout lymphocyte PD-L1+ was also higher in NR compared with R (78% versus 50%, p=0.024). Differences in Sout lymphocyte positivity status between R and NR were evident as early as three months after therapy for PD1 (p=0.040) and PD-L1 (p=0.029). Co-expression assays on orthotopic bladder tumors showed PD1 overexpression on T lymphocytes in control mice compared with those that responded to intravesical adenoviral-IFN. CONCLUSIONS: Nadofaragene NR patients had relative PD1/PD-L1 overexpression in tumor-infiltrating lymphocytes, although this was not seen at baseline. In vivo models replicated these findings. Taken together, this suggests a role for ICI in BCG-unresponsive NMIBC who may have partial or short-term response to nadofaragene. Source of Funding: FKD Therapies. Clinical trial # NCT02773849 © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e927 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Anirban P. Mitra More articles by this author Sharada Mokkapati More articles by this author Tanner S. Miest More articles by this author Vikram M. Narayan More articles by this author Richard Philipson More articles by this author Seppo Yla-Herttuala More articles by this author David Sawutz More articles by this author Nigel R. Parker More articles by this author David J. McConkey More articles by this author Colin P.N. Dinney More articles by this author Expand All Advertisement PDF DownloadLoading ...

MP10-03 SURGICAL AUTONOMY OF UROLOGY RESIDENTS WITHIN THE VETERANS AFFAIRS HEALTHCARE SYSTEM

You have accessJournal of UrologyCME1 May 2022MP10-03 SURGICAL AUTONOMY OF UROLOGY RESIDENTS WITHIN THE VETERANS AFFAIRS HEALTHCARE SYSTEM Janmejay Hingu, Anh Nguyen, Kunj Jain, Devashish Anjaria, Joseph Oliver, and Hossein Sadeghi-Nejad Janmejay HinguJanmejay Hingu More articles by this author , Anh NguyenAnh Nguyen More articles by this author , Kunj JainKunj Jain More articles by this author , Devashish AnjariaDevashish Anjaria More articles by this author , Joseph OliverJoseph Oliver More articles by this author , and Hossein Sadeghi-NejadHossein Sadeghi-Nejad More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002532.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Surgical resident autonomy in procedures has been eroding over time due to factors such as duty hour restrictions, focus on operating time, complication rates, and trust among supervising physicians. This study examines whether urology residents at the Department of Veterans Affairs hospitals (VA) have experienced decreased surgical autonomy and what factors may contribute. METHODS: The VA Surgical Quality Improvement Program (VASQIP) was queried for the most common urologic procedures between 2004 to 2019 with resident involvement. The cases were stratified by resident involvement: attending as primary (AP), attending and resident (AR), resident as primary (RP). RESULTS: 127,757 urology cases were identified from 2004 to 2019. The most frequent surgeries were transurethral resection of prostate (TURP); transurethral resection of small, medium, or large tumor (TURBT); GreenLight laser of prostate (GLL); hydrocelectomy; and ureteral stent placement. These procedures accounted for 76.5% of all cases. The percentage of RP cases decreased from 31.3% of cases to 18.6%. Reduction in RP cases was seen in all seven top urology cases, particularly in ureteral stent placement which has declined from 44% RP in 2004 to 18% in 2019. Cases with resident involvement had patients with more cardiovascular, pulmonary, and infectious comorbidities. Mean operative times in all cases were not significantly different. The 30-day composite complications and 30-day return to operating room were greatest for AR. Postoperative complications of bleeding, infection, DVT, embolism, renal failure, wound dehiscence, and 30 day all-cause mortality were not significantly different. CONCLUSIONS: Urology resident autonomy has decreased within the VA healthcare system over the past 15 years. Mean operative times and postoperative complications are not inferior in cases that involve residents as the primary surgeon. Increased focus on resident education and surgical autonomy in the operating theater is vital for training the next generation of surgeons. Source of Funding: N/A © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e146 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Janmejay Hingu More articles by this author Anh Nguyen More articles by this author Kunj Jain More articles by this author Devashish Anjaria More articles by this author Joseph Oliver More articles by this author Hossein Sadeghi-Nejad More articles by this author Expand All Advertisement PDF DownloadLoading ...

Reduced Recurrence Rates Are Associated with Photodynamic Diagnostics Compared to White Light after Extended Transurethral Resection of Bladder Tumors.

One pillar in treating non-muscle-invasive bladder cancer (NMIBC) is the complete and high-quality transurethral resection of the primary tumor (TURBT). However, even after a high-quality primary resection, the residual tumor risk is considerable, thus requiring a re-TURBT. Resections performed with the aid of a photodynamic diagnostics report improved recurrence-free survival rates and increased detection rates of carcinoma in situ (CIS). This monocentric retrospective study reports on patients treated with an extended TURBT procedure using conventional white-light cystoscopy or photodynamic diagnostics (PDD). Only patients undergoing a TURBT resection for their primary tumor were included in the statistical analysis. Recurrence-free survival and overall survival were the clinical endpoints. Mann–Whitney U tests and chi-squared tests were used for descriptive intergroup comparisons. The associations with overall survival and recurrence-free survival were determined by univariate and multivariate analyses. The test results were considered significant when p was < 0.05. In comparison to conventional white-light cystoscopy, PDD increased the detection rates of CIS (p = 0.004) and tumor multifocality (p = 0.005) and led to reduced residual tumor incidence at the primary resection site (p < 0.001). Likewise, tumor recurrence rates were reduced in the PDD cohort (p < 0.001). Patient age and the presence of residual tumor at the primary resection site were identified as independent predictors of overall survival. For recurrence-free survival, only the PDD resection method was an independent predictor (HR = 0.43; p < 0.001). In summary, we demonstrated that the utilization of PDD techniques was associated with improved detection rates of CIS and multifocal tumors and with reduced recurrence rates. The extended resection protocol allowed us to determine that PDD resections lead to a reduced residual tumor rate at the initial resection site. This residual tumor state at the resection site, determined by extended TURBT, became an independent predictor of long-term survival. On the other hand, the PDD technique was confirmed as the only independent predictor of recurrence-free survival.

Collagen-targeted tumor-specific transepithelial penetration enhancer mediated intravesical chemoimmunotherapy for non-muscle-invasive bladder cancer

Intravesical instillation of chemotherapeutics or immune-stimulating agents could reduce the recurrence rate of non-muscle-invasive bladder cancer (NMIBC) after transurethral resection of the bladder tumors. Its efficacy, however, remains to be improved due to the bladder epithelial barrier. Although certain transmucosal delivery carriers are able to enhance the transepithelial penetration of intravesical agents, they could hardly differentiate carcinoma and adjacent normal tissues of the bladder wall. Here, we reported polyethylene glycol (PEG) & glutaraldehyde co-modified fluorinated chitosan (PGFCS) as a collagen-targeted transepithelial penetration enhancer, which could create a tumor-targeted adhesive interface by the aldehyde-selective reaction with collagen amines enriched in the tumor, thus opening the transepithelial-delivery barrier at the tumor site though the fluorinated-chitosan-mediated tight junction regulation. Interestingly, with the help of PGFCS pre-treatment, intravesical instillation of chemotherapeutics pirabucin (THP) combined with immune stimulating agent interleukin-12 could trigger potent antitumor chemoimmunotherapeutic responses in destructing orthotopic bladder tumors and inhibiting cancer recurrence. Our work presents a unique type of tumor-specific transepithelial penetration enhancer, which shows great potential for safe and effective intravesical instillation of NMIBC.

Clinical Efficacy and Quality of Life Assessment of Partial Cystectomy and Plasmakinetic Transurethral Resection of Tumor in Bladder Cancer Patients.

ObjectiveBladder cancer is a common malignant tumor of the urinary system, with an incidence ranking the first in the urinary system. Without timely and effective treatment, the tumor may spread to other parts of the body. Traditional partial cystectomy (PC) and plasmakinetic transurethral resection of bladder tumor (PKRBT) are common surgical methods for superficial bladder cancer (SBC). This study aims to clarify the clinical efficacy of bladder carcinoma (BC) patients treated by either PC or PKRBT and their effects on the quality of life (QOL) of patients.MethodsA total of 142 patients with SBC treated in Wenzhou Central Hospital and Bei da huang Industry Group General Hospital from March 2018 to June 2020 were analyzed retrospectively. According to the surgical method, patients undergoing PKRBT were included in the research group (n = 74) while those treated by PC were included in the control group (n = 69). Surgical indicators (intraoperative blood loss, IBL; operating time, OT; bladder irrigation time; catheter retention time; length of hospital stay, LOS), postoperative complication rate, and one-year recurrence rate were compared between the two groups. Besides, the levels of inflammatory factors [tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, IL-10], psychological and emotional scores (Self-Rating Anxiety Scale, SAS; Self-Rating Depression Scale, SDS), and living conditions (Pittsburgh Sleep Quality Index, PSQI) before and after treatment were compared.ResultsCompared with the control group, patients in the research group had 1) less IBL, less time of OT, bladder irrigation and indwelling catheter time, as well as shorter postoperative LOS; 2) lower contents of inflammatory factors TNF-α, IL-6 and IL-8, and higher IL-10; 3) lower SAS and SDS scores and higher PSQI; and 4) fewer postoperative complications and lower one-year recurrence rate.ConclusionCompared with PC, PKRBT contributes to higher efficacy and better postoperative QOL in patients SBC.