BCG Instillation Research Articles

PD-L1/PD-1 expression as a predictor of response to BCG in patients with high-risk non–muscle invasive bladder cancer.

4550 Background: Intravesical BCG instillation (IBI) is the gold standard adjuvant treatment after transurethral resection of the bladder in high risk non muscle invasive bladder cancer (HR-NMIBC). IBI induce a type of Th1 immune response requiring a recruitment of cytotoxic cells. This response is downregulated by the PD-1/PD-L1 checkpoint inhibitors through an inhibition of the action of CD8+ T cells against their target. Our purpose was to assess whether PD-1/PD-L1 expression was associated with IBI response in HR-NMIBC. Methods: Histologically confirmed HR-NMBC from 5 academic French institutions which underwent maintenance IBI were retrospectively included. The following data were collected: pathological stage, grade, concomitant carcinoma in situ, number of lesions and size. From a paraffin embedded samples of initial resection, a unique dedicated uropathologist quantified immunochemistry expression of CD3, CD8, PD-L1 (antibody SP263/ SP142, E1L3N, 28 8) in both tumour cells and tumoral microenvironment. Univariate and multivariate analyses were performed using Cox proportional hazards model. Results: Overall 140 patients (median age 66.5 years, range:35-87; sex ratio male vs female:6:1) were included. The distribution of NMIBC tumour for stage and grade was: Ta 37.2% (n = 52), T1 62.8% (n = 88) and high grade 100% (n = 140) respectively. The median number of IBI which were delivered was 12 (range 7-36). The median length of follow-up was 54.24 mo (95% CI = 49.91-58.68). Overall, 25 patients (17.9%) had a recurrence/or progression. The 72mo Disease free survival (DFS) rate was 81.11% (95% CI = 72.20-87.41). Using univariate analysis, we found that Age (HR = 1.07; [1.02-1.12] p = 0.005), CD3/CD8 ratio (HR per 10 units = 3.43 [1.62-7.23] p = 0.014) and PD-L1(HR per 10 units = 1.65 [1.15-2.38] p = 0.046) were associated with DFS. In multivariate analysis, Age (HR = 1.07 [1.02-1.13] p = 0.009), CD3/CD8 ratio (HR per 10 units = 1.96 [1.28-3.00] p = 0.02) and PD-L1 expression in tumour cells (HR per 10 units = 3.38 [1.61-7.11] p = 0.01) remained significantly associated with DFS. Conclusions: PD-L1 expression in tumour cells and the T cells population in tumour microenvironment were both predictive factors of BCG response in HR-NMIBC. These results build a scientific rationale for pharmacological intervention on a molecular target using immuno-oncology.

MP63-19 IMMUNOGENICITY INVESTIGATION ON RECOMBINANT BCG CONTAINING NY-ESO-1 UPON VACCINATION

INTRODUCTION AND OBJECTIVES:Bladder cancer is one of the most common malignant tumors in the urinary system. Intravesical instillation of BCG has been proved to reduce the recurrence of bladder can...

Digital holography can differentiate between bladder cancer grades.

413 Background: Treatment of high grade non-muscle invasive bladder cancer (HG NMIBC) is controversial with BCG instillation and early cystectomy as viable options. However, accurate predictive markers for HG NMIBC are lacking. Refractive index (RI) is an optical feature of tissues and has been shown to be correlated with various oncologic outcomes in prostate and breast cancers. The role of RI in NMIBC has not been explored yet. The aim of this study is to measure and compare RI values of benign and malignant low and high grade NMIBC. Methods: After IRB approval, tissue samples were obtained from high and low grade NMIBC patients. Measurements were performed on non-stained slides using digital holography. Areas of benign and malignant tissues were marked by a fellowship trained GU pathologist. The average RI (RIavg) and RI variance (RIvar) over malignant and benign cell nuclei were measured. Comparison between benign and malignant tissue and between low and high grade tumors was performed with the Student's t-test. Results: Multiple nuclei of LG and HG patients were measured . Mean difference of RIavg between malignant and benign cells was 0.03 in HG patients (p < 0.001). Mean difference of RIvar between malignant and benign tissues was 0.016 in HG patients (p < 0.001). In LG tissues, there was no significant difference in RIavg or RIvar between benign and malignant cells. Finally, there was a significant difference in RIavg between HG and LG cells (p < 0.001). Conclusions: For the first time, RI was measured in bladder cancer tissue by digital holography. The RI values and variance were different between malignant and benign cells in HG tissues. Furtheremore, we found a significant difference in RI values between HG and LG cells. This technology may assist in the future in tissue diagnosis and classification of bladder tumor.

İntravezikal BCG Uygulaması Sonrası Gelişen BCG Sepsisi: Bir Olgu Sunumu

İntravezikal BCG Uygulaması Sonrası Gelişen BCG Sepsisi: Bir Olgu Sunumu

710 - Treatment of high grade non-muscle invasive bladder carcinoma by standard number and dose of intravesical BCG instillations versus reduced number and dose of intravesical BCG instillations. An initial report of the phase III clinical trial ‘NIMBUS’

710 - Treatment of high grade non-muscle invasive bladder carcinoma by standard number and dose of intravesical BCG instillations versus reduced number and dose of intravesical BCG instillations. An initial report of the phase III clinical trial ‘NIMBUS’

Short-term efficacy and predictive factors of BCG instillation in high risk non-muscle invasive bladder cancer

Objective To investigate the short-term efficacy, safety and factors affecting the efficacy of BCG intravesical therapy in high risk non-muscle-invasive bladder cancer (NMIBC) patients. Methods A total of 161 high-risk non-muscle invasive bladder cancer (NMIBC) patients were reviewed in our hospital from March 2014 to December 2017. They were all treated with BCG instillation after transurethral resection of bladder tumor (TURBT). There were 121 males (75.2%) and 40 females (24.8%). Median age was 65 years old, including 17 cases (10.6%) <50 years old, 23 cases (14.3%) within 50-59 years old, 72 cases (44.7%) within 60-69 years old, 49 cases ≥70 years old (30.4%). There were 112 patients (69.6%) with primary bladder cancer and 49 (30.4%) patients with recurrent bladder cancer. 56 cases (34.8%) had single tumor and 105 cases (65.2%) had multiple tumors. The tumors size in 106 cases (65.8%) was less than 3 cm, and tumor size in 55 cases (34.2%) was more than 3 cm. 43 patients (26.7%) suffered carcinoma in situ. 10 patients (6.2%) suffered urothelial carcinoma with variant types. According to the American Joint Commission for Cancer (AJCC) version 7 TNM staging system, 25 cases (15.5%) were classified into Ta stage, 129 cases (80.1%) were classified into T1 stage, and 7 cases (4.3%) were classified into Tis stage. There were 8 cases (5%) with low-grade cancer and 153 cases (95%) with high-grade cancer. 69 patients (42.9%) received chemo-instillation before. 43 cases were directly perfused without re-TURBT and 118 cases were perfused after re-TURBT. They were all treated with BCG instillation after transurethral resection of bladder tumor (TURBT). The 120 mg BCG were dissolved into 50 ml saline for instillation and were kept for 2 hours. Induction scheme of six-weekly and three fortnightly instillations started two weeks after the initial TUR or re-TUR. Maintenance instillations were then be offered in a scheme of ten monthly instillations. During treatment, patients were offered cystoscopy and cytology every three months, while CT and chest radiographs were reviewed every 6-12 months. Recurrence status and adverse effects were recorded. Univariate and multivariate regression analyses were performed to predict risk factors for failure of BCG instillation in bladder cancer. Results A total of 161 patients were followed up. The median follow-up time was 13 months, ranging 7-22 months. The overall recurrence rate was 26.1% (42/161) and the 1-year recurrence-free survival rate was 79.0%. On univariate analysis, recurrence history, history of instillation chemotherapy application and history of re-staging transurethral resection influenced recurrence. Multivariate regression analysis showed recurrence status was an independent prognostic factor regarding recurrence-free survival. The incidence of adverse events in all 161 instillation patients was 40.4% (26/65). Grade 1, grade 2 and grade 3 adverse events accounted for 53.8%(35/65), 40.0%(26/65) and 6.2%(4/65) respectively. 6 cases (3.7%) reduced the dose of BGC and 1 case stop the instillation due to the intolerance of BCG. Conclusion Short-term efficiency and safety were confirmed in BCG-treated high-risk NMIBC patients. And recurrence status was an independent prognostic factor for recurrence-free survival. Key words: Bacillus Calmette-Guerin; Bladder cancer; Intraversical instillation

Efficacy and complications of intravesical instillation of BCG for prevention of recurrence of moderate and high-risk non muscle invasive bladder cancer

Objective To assess the efficacy and side effects of intravesical instillation of BCG after transurethral resection of the bladder tumor (TURBT) in non-muscle invasive bladder cancer (NMIBC) patients. Methods The clinical data of patients treated with BCG 120 mg per course induced perfusion or more after TURBT from December 2013 to October 2016 in 18 hospitals of northeast China region, were analyzed retrospectively. The first part, data of 106 patients with moderate, high-risk NMIBC were collected. A total of 83 patients were male, while the other 23 patients were female. The average age was 66.7 years old.The clinical staging were T1 in 86(81.1%) cases, Ta in 20(18.9%) cases and carcinoma in situ in 6(5.7%)patients. Intravesical instillation of BCG was executed after transurethral resection of the bladder tumor. The incidence rate of recurrence and progression during more than 6 months’ follow-up time were observed. Multivariate analyses were done by using logistic analysis and Cox proportional hazards regression model with Kaplan-Meier method. The second part, treatment compliance of 276 patients with bladder cancer, including moderate/high-risk NMIBC in 263 cases, moderate/high-risk NMIBC followed with renal pelvis/ureteral carcinoma in 8 cases were and moderate/high-risk NMIBC with renal pelvis/ureteral carcinoma in 5 cases who treated with BCG after the surgeries, were observed. Patients consisted of 211 males and 65 females with average age of 68.3 years. Results With a median follow-up of 12 months, 9(8.5%) patients experienced tumor recurrence and 2(1.9%)patients were found progression in the first part. The one-year cancer free recurrence rate of the patients was 91.5%. Statistically significant prognostic factors for recurrence identified by multivariable analyses were prior recurrence of the tumors (OR=3.214, 95%CI 0.804-12.845, P=0.099). In the second port, an incidence rate of adverse effects was 64.1% (177/276). The Ⅲ/Ⅳ degree complications were occurred in 11 patients and satisfactory outcomes achieved with active treatment. A total of 36 patients withdrawal with the major causes were recurrence and progression of bladder tumor in 12 cases (4.4 %), 9 cases (3.3 %) with economic reasons and 11 cases(4.0%)with serious complications. Conclusions NMIBC patients treated with intravesical BCG therapy have approving cancer free recurrence rates and acceptable adverse effects. Prior recurrence may be prognostic factor of recurrence after intravesical BCG therapy. Key words: Non-muscle invasive bladder cancer; Bacillus Calmette Guerin; Recurrence; Adverse effects

A Single Case of Two Synchronous Metastatic Tumours

The incidence of multiple primary tumours increases with age and due to multiple other factors as environmental and genetic predisposition. The authors describe a case of a 77-year-old female patient with diagnosis in September 2009 of colon mucinous adenocarcinoma. She was submitted to surgery, considered R1 and adjuvant chemotherapy. Six months after treatment she had abdominal recurrence on a nodular lesion in peritoneal fat. The patient was submitted to surgery and did multiple courses of systemic treatment. She underwent cytoreductive surgery with hyperthermic chemotherapy, too. In December 2014 she presented a nodular lesion on the bladder and after excision, the histology confirmed a high-grade transitional cell carcinoma and she maintains treatment with endovesical BCG instillations. After that, she had no evidence of peritoneal disease progression. Besides the bad prognosis associated to peritoneal disease, our case report describes a long survival (5 years with no disease progression) in a patient with high risk at diagnosis to peritoneal recurrence. This case shows the importance of multimodal approach and the impact of locoregional treatment in localized metastatic disease.

A Case of PT1 Plasmacytoid Variant Bladder Cancer Treated by Bladder Conserving Therapy

Plasmacytoid variant bladder cancer is a highly malignant subtype associated with a high propensity for invasion, metastasis and poor prognosis. Among approximately 100 reported cases, most were diagnosed at an advanced stage and only 10 were diagnosed at a non-muscle-invasive stage. Due to the limited data on clinical features of non-muscle-invasive plasmacytoid variant bladder cancer, its treatment has not been established. We report a long-surviving patient with pT1 plasmacytoid variant bladder cancer in whom the bladder was conserved after detailed pathological examinations of the transurethral resection (TUR) specimen and intensive follow-up. A 65-year-old man presented with macroscopic hematuria. Cystoscopy revealed a nodular tumor 11 millimeters in diameter and no metastasis was observed on computed tomography. The histopathological diagnosis of the TUR specimen was pT1 plasmacytoid variant urothelial carcinoma of the bladder. Microvascular invasion was not found by immunohistochemical staining and histopathological examination of the specimen from the second TUR indicated no residual cancer. The patient strongly desired bladder conservation and additionally underwent intravesical instillation therapy with 40 mg of mitomycin C weekly for 6 consecutive weeks. Follow-up cystoscopy demonstrated 3 small papillary tumors 12 months after intravesical instillation therapy, but histopathologically, the recurrent tumors were pTa with pTis urothelial carcinomas without plasmacytoid components. To treat pTis disease, he subsequently underwent intravesical BCG instillation therapy. The plasmacytoid variant bladder cancer has not recurred for 26 months since the initial diagnosis. Non-muscle-invasive and localized plasmacytoid variant bladder cancer may be treated with bladder conserving therapy.

Results of Postoperative Instillation of Mitomycin C in Non Muscle Invasive Bladder Cancer after Complete Resection Versus BCG (Recurrence and Progression)

AbstractBackground: Intravesical immunotherapy or chemotherapy for non-muscle invasive bladder cancer is a well-established treatment for preventing or delaying tumour recurrence after tumour resection. However, up to 70% of patients may fail. New protocols and new intravesical agents with improved effectiveness are neededAim of Study: Is to evaluate the oncological outcome as regard progression, local recurrence and side effects of non-muscle invasive transitional cell carcinoma of the urinary bladder managed by complete resection followed by postop-erative intravesical instillation of Mitomycin C compared with BCG.Patients and Methods: This is a prospective study that included 51 patients with non-muscle invasive TCC bladder (Ta and T1) at Urology Department, Al-Azhar University hospitals between 2011 and 2015. Patients divided into two groups, the Mitomycin group received immediate MMC and periodic 6 doses of MMC and the other group, BCG received 6 doses of BCG one dose per week. Follow-up by cystoscope for two years at 3th, 6th, 9th, 12th, 18th, 24th month to detect the recurrence, progression and side effects.Results: The mean age of the patients was 60.58 (37 yrs. - 79 yrs.) in the MMC group and 61.76 (48 yrs-83 yrs) in the BCG group. The main comparison in this study is recurrence rate and progression rate of the tumor. Three patients (11.5%) had recurrence in the 1st year while four patients (15.4%) in the 2nd year with total recurrence seven patients (26.9%) in MMC group.In the BCG group, patients who had a recurrence in the 1st year were, two patients (8%) and three patients (12%) in the 2nd year with total recurrence, five patients (20%).The total progression in two years were 4 pts (15.38%) (One patient (3.8%) in the 1st year) (3 patients (11.5%) in the 2nd year) in the MMC group while were 4 pts (16%) (One patient (4%) in the 1st year) (year 3 patients (12%) in the 2nd year) in the BCG group.Conclusion: Our study confirmed the positive effect of immediate Mitomycin C intravesical instillation in patients who received periodic Mitomycin C instillation and either the positive effect of intravesical instillation of BCG in patients with non-muscle-invasive bladder tumors. Our present study showed that MMC and BCG equally reduced recurrence and progression in NMIBC patients while showed the superiority of MMC regarding to the adverse effects.

Analytical study of bladder tumor

Background: Treatment of bladder tumor still provides the romance in Urology. The purpose of this study is to study the prevalence of various types of bladder tumors, to compare various treatment modalities for bladder tumors, to study different presentations of patients with bladder tumor.Methods: The present study was a prospective analytical study of 30 patients of bladder tumor conducted at Dhiraj General Hospital attached to S.B.K.S Medical College from October 2011 to July 2013. All the details of patients in term of demography, risk factors, symptoms and sign, radiological, endoscopic, histopathological features, various treatment modalities offered, and follow-up of patients were studied and analysed using descriptive statistics.Results: Maximum number of patients was presented in sixth decade of life. Youngest patient was 30 years old and oldest patient was 77 years old. 80% patients were male, and 20% patients were female. History of smoking was present in 22 patients, history of exposure to occupational hazards was present in 4 patients and only 2 patients had positive family history. Majority 93.3% patients were presented with haematuria and 16 patients had anaemia. 15 patients had high grade muscle invasive TCC, followed by 10 patients with low grade non-muscle invasive TCC. 3 patients were having low grade non-muscle invasive SCC, 1 patient was having high grade muscle invasive SCC and 1 patient was having high grade non-muscle invasive TCC.Conclusions: The findings of the study conclude that TURBT followed by intravesical instillation of BCG gave good results in patients with low grade and high grade non-muscle invasive tumor. For muscle invasive tumor radical cystectomy with urinary diversion is the ideal treatment but TURBT followed by radiotherapy has also given good results with fewer side effects.

High-grade superficial bladder tumors (PT1G3): Prognostic factors of recidive and progression

PT1G3 High-grade bladder tumors are superficial, poorly differentiated, they are characterized by there architectural disorganization and marked cytologic abnormalities. These tumors pose a diagnostic problem for the pathologist and a therapeutic problem for the urologist. The aim of this work is to study the predictive factors for recurrence and progression of pT1G3 bladder tumors. Material and method We undertook in this work a retrospective descriptive study, including 100 patients who were treated in the urology department between January 2010 and December 2012 at the University Hospital of Rabat (Morocco) for urothelial carcinoma classified T1G3. Rates of recurrence, progression were studied, and specific survival was done by the Kaplan–Meier method. The prognostic factors associated with this type of tumor were then investigated by Cox regression. The overall mean decline in the study was 53.7 months about 4.5 years. The patients were 91 (91%) men and 9 (9%) women. The average age of our patients was 58 years old with extremes ranging from 25 to 71 years old. Of the 100 patients in the study, 66 (66%) were classified T1G3 from the outset, while 34 were classified T1G3 during a recurrence (T1G3 secondary). Initial treatment consisted of deep and complete transurethral resection (RTU) in all patients. Follow-up of a BCG protocol therapy in 56 patients, among 56 (56%) patients who received BCG therapy 15 (26%) recidivated including 5 in progression, for another 44 (44%) patient group 30 (68%) recidivated, 12 of which were under progression. In univariate analysis, the significantly identified risk factors for recurrence were: tumor size > 5 cm (P = 0.01), multifocality of lesions and the lack of the adjuvant treatment to the transurethral resection of the bladder (P = 0.001) including BCG therapy. In multi-varied analysis, the significantly identified risk factors for progression and recurrence were: the presence of carcinoma in situ and the failure of BCG therapy (P = 0.001). The primary or secondary character of the tumor was not significant (P = 0.4). Thus, the difference in overall survival as a function of the initial or secondary status of T1G3 tumors was not significant when the other prognostic factors were taken into consideration. The results of this retrospective study suggest that T1G3 tumors can be safely controlled by the RTU + BCG combination. These results justify a good deep resection followed by a second resection at 6-week intervals and intravesical BCG instillations. This study also identifies PT1G3 patients at high-risk of recurrence and progression and requires close monitoring.

Predictive factors of failure of BCG therapy in high-level superficial bladder tumors

Introduction High-grade bladder tumors are superficial, poorly differentiated, they are characterized by there architectural disorganization and marked cytologic abnormalities. The treatment of superficial tumors of the bladder has a twofold objective: the first one is to reduce the frequency of local recurrences and, on the second one is to prevent progression towards muscular infiltration. Hence, the indication of the adjuvant treatment to the transurethral resection of the bladder. The purpose of our work is to study the predictive factors for the failure of intravesical BCG instillations in the management of these tumors. Failure was defined by the progression or recurrence of superficial high-grade bladder tumors. Material and method We undertook in this work a retrospective descriptive study, including 80 patients who were treated in the urology department “A” at the RABAT CHU for high-grade urothelial carcinoma PTa and PT1 between January 2010 and June 2013. Rates of recurrence, progression after BCG therapy were studied. The prognostic factors associated with this type of tumor were then sought after by Cox regression. The overall average decline in the study was 50 months or about 4.5 years. Results The patients were 71 men and 9 women. The average age of our patients was 60 years old with extremes ranging from 38 to 71 years old. At 50 months, 60% of patients treated with BCG therapy are free from recurrence. This rate is 69% for PTa tumors and 53% for pT1 tumors ( P = 0.03); 22 (27%) patients had a recurrence under the same histological grade in the first 24 months, 11 (13%) patients had tumor progression, 4 of which were infiltrating cystectomy treated. In univariate analysis, the significantly identified risk factors for recurrence were: multifocal lesions ( P = 0.001), presence of associated in situ carcinoma, vascular invasion ( P P = 0.001), and the lack of maintenance therapy with BCG therapy. The risk factors for progression were: the presence of CIS, the crossing of the lamina propria especially in PT1G3 tumors, and the size greater than 5 cm. In multi-varied analysis, the presence of CIS, crossing the lamina propria and the tumor size in case of tumor PT1G3 are the significant factors of the failure of BCG therapy ( P = 0.001). The primary or secondary character of the high histological grade of tumor, patient age and multifocality ( P = 0.4) were not significant. This multi-varied study also showed a strong correlation between tumor size and invasion of the lamina propria. Conclusion The results of this retrospective study suggest that high-grade tumors must be compulsorily controlled by BCG therapy with a maintenance protocol. This study also made it possible to select patients with very high-risk of recurrence and progression after BCG therapy who should receive close monitoring and cystectomy if BCG therapy fails.

Immunotherapy in metastatic urothelial carcinoma: focus on immune checkpoint inhibition.

Immunotherapy has been used in localized urothelial carcinoma for decades, especially in the treatment of superficial disease, in which instillation of BCG is a commonly used treatment option. Clinical investigations based on new insights into the immunogenic potential of metastatic urothelial carcinoma have led to the accelerated FDA approval of the immune checkpoint inhibitors atezolizumab, nivolumab, durvalumab, avelumab, and pembrolizumab. Preliminary findings suggest additional benefits of combinations of immunotherapeutic agents as a future treatment approach in metastatic urothelial carcinoma. Treatment experience with immunotherapy suggests that these drugs are associated with a unique spectrum of immune-related adverse events and specific immune-related patterns of response, including cases of pseudoprogression, which could impede the optimal use of immune checkpoint inhibitors in the clinic. Appropriate management of immune-related adverse events and a greater awareness of immune-mediated response patterns will help to inform treatment decisions and improve patient outcomes; predictive biomarkers of response might facilitate selection of patients who are most likely to respond to and benefit from these exciting new treatments.

Availability and Patterns of Intravesical BCG Instillations.

Intravesical BCG instillations improve recurrence free survival in patients with non-muscle-invasive bladder cancer (NMIBC). This is a national survey study, covering 223 urological centres, aimed at reliable identification of BCG availability and implemented treatment patterns. Response rate was 93.7%. BCG was used in 56.5% of urological departments. Another 22.7% referred patients to other hospitals for instillations, while 20.8% did not recommend BCG at all. The most common indications for BCG instillations were as follows: T1 tumours (88.5%), carcinoma in situ (83.6%) and high grade tumours (73.8%). Maintenance therapy was routinely abandoned in 16.4% of centres or was scheduled for <1 year, 1 year, 3 years and 1-3 years in 6.6%, 19.7%, 21.3% and 31.2% of centres, respectively. Continuation of BCGdespite treatment failure in carcinoma in situ cases was considered in 21.3% of departments. Our findings indicate that BCG is underused, while patterns of maintenance and follow-up are suboptimal.

Outpatient photodynamic-guided diagnosis of carcinoma in situ with flexible cystoscopy: an alternative to conventional inpatient photodynamic-guided bladder biopsies in the operating theatre?

Objective: The aim of this prospective open comparative study was to establish whether conventional photodynamic-guided bladder biopsies using general anaesthesia and rigid resectoscopes (inpatient) can be replaced with less traumatic flexible cystoscopy in non-sedated patients (outpatient), without compromising the diagnosis of carcinoma in situ (CIS).Materials and methods: Thirty-one patients were included. After BCG instillation for CIS, bladder biopsies were obtained using photodynamic-guided flexible cystoscopy. Two weeks later, patients underwent the conventional inpatient procedure. An external pathologist reviewed the biopsy samples. Pain and quality of life (QoL) symptom score were recorded.Results: Post-BCG biopsies showed only CIS in 10 patients; high-grade Ta or T1 tumour in three patients, who were referred for cystectomy; and normal or low-grade tumour tissue in 18 patients. There was a high agreement of identification of high-grade disease in biopsies and cytology using the two methods (κ = 0.93, 95% confidence interval 0.8–1.0). The outpatient procedure identified four high-grade patients diagnosed as ‘normal/low-grade’ in the inpatient procedure. The opposite was observed in two patients. Quality of biopsies did not differ between the two procedures. Pain scores for outpatients were low, and median QoL symptom score was significantly lower than for inpatients (24 vs 33, p = 0.02). Hospital length of stay was significantly longer for inpatients.Conclusions: Outpatient photodynamic-guided flexible cystoscopy is less traumatic than the conventional inpatient procedure in the diagnosis of CIS. It is safe and cost-effective, and may be an alternative to conventional inpatient biopsy procedures in patients with malignant urine cytology and normal white-light cystoscopy.

Prognostic value of P53 nuclear overexpression in bladder cancer

Introduction: Urinary bladder cancer is one of the common genitourinary malignancy presenting to the urology department. Prognosis of these patients will depend upon the number of clinicopathological factors. Overexpression of p53 is associated with aggressive behaviour of bladder cancer. The purpose of the present study is to assess the role of p53 tumour suppressor gene as an independent prognostic marker. Materials & Methods: Thirty-three (33) consecutive cases of urinary bladder cancer attending Department of Urology between August 2006 to December 2008 were studied. In this study P53 protein, nuclear over expression was assessed in Formalin-fixed, paraffin-embedded tissue sections by the immunohistochemical method using monoclonal antibody. This p53 nuclear over expression was correlated with tumour grade and stage. Over all survival rate was assessed in p53 positive and negative patients. Results: Two patients with T1G1 tumours developed recurrence with initial TURBT and intravesical BCG instillation after 6 months and responded to Re TURBT and intravesical BCG instillation therapy. One patient of T1G3 developed recurrence after 1 year with initial TURBT and intravesical BCG instillation and responded to Re TURBT and intravesical BCG instillation therapy. One patient of T1G3 progressed to muscle invasive disease after 1 year and underwent Radical cystoprostatectomy with ileal conduit received adjuvant chemotherapy and radiotherapy. Two patients developed post-operative urinary leak and underwent bilateral cutaneous ureterostomy. Nine patients died in followup period. Conclusion: There was a strong positive correlation between the expression of mutant p53 and tumour grade, with none of the low-grade tumours were positive for mutant p53, in contrast to 60% of high-grade tumours. In this study, there was no significant difference in the mortality between p53 positive and negative patients.

Prognostic value of impaired estimated glomerular filtration rate in intravesical BCG-treated non\u2013muscle-invasive bladder cancer patients

To evaluate the influence of patient-associated parameters and comorbities, with a special focus on renal function after intravesical adjuvant bacillus Calmette-Gue´rin (BCG) immunotherapy in patients with non–muscle-invasive bladder cancer (NMIBC). We retrospectively reviewed the medical records of patients treated from October, 1991 to December, 2013 at Seoul National University who were diagnosed with NMIBC and treated with intravesical BCG. A total of 344 patients who were diagnosed with NMIBC and treated with intravesical BCG were enrolled in this study. Tumor recurrence was observed in 171 patients (49.3%); progression to higher pT category or grade was found in 68 patients (15.1%). Multivariate analysis demonstrated that recurrent tumors and the presence of multiple tumors increased the risk of recurrence. However, other factors also appeared to predict recurrence, such as impaired renal function (<60 ml/min), which was associated with recurrence in univariate and multivariate analyses (HR 1.879 p = 0.008). It is worthy of notice that impaired renal function was an independent predictor of tumor recurrence after BCG instillation in multivariate analysis. Therefore, we should consider not only the clinical or pathologic findings of a tumor but also renal function during decision-making for additional therapy.

Intratumoral Th2 predisposition combines with an increased Th1 functional phenotype in clinical response to intravesical BCG in bladder cancer

Th1-type immunity is considered to be required for efficient response to BCG in bladder cancer, although Th2 predisposition of BCG responders has recently been reported. The aim was to evaluate the relationship of Th1 and Th2 components in 23 patients undergoing BCG treatment. Peripheral blood, serum and urine samples were prospectively collected at baseline, during and after BCG. Th1 (neopterin, tryptophan, kynurenine, kynurenine-to-tryptophan ratio (KTR), IL-12, IFN-γ, soluble TNF-R75 and IL-2Rα) and Th2 (IL-4, IL-10) biomarkers as well as CD4 expression in T helper (Th), effector and regulatory T cells were determined. Local immune cell subsets were measured on formalin-fixed, paraffin-embedded cancer tissue by immunohistochemistry to examine expression of transcription factors that control Th1 (T-bet) and Th2-type (GATA3) immunity. We confirmed a Th2 predisposition with a mean GATA3/T-bet ratio of 5.51. BCG responders showed significantly higher levels of urinary (p = 0.003) and serum neopterin (p = 0.012), kynurenine (p = 0.015), KTR (p = 0.005), IFN-γ (p = 0.005) and IL-12 (p = 0.003) during therapy, whereas levels of IL-10 decreased significantly (p < 0.001) compared to non-responders. GATA3/T-bet ratio correlated positively with serum neopterin (p = 0.008), IFN-γ (p = 0.013) and KTR (p = 0.018) after the first BCG instillation. We observed a significant increase in CD4 expression in the Th cell population (p < 0.05), with only a modest tendency toward higher frequency in responders compared to non-responders (p = 0.303). The combined assessment of GATA3/T-bet ratio, neopterin and KTR may be a useful biomarker in predicting BCG response. Th2-promoting factors such as GATA3 may trigger Th1-type immune responses and thus contribute to the BCG success.

Recommandations en onco-urologie 2016-2018 du CCAFU : Tumeurs de la vessie

ObjectiveThe purpose of the guidelines national committee CCAFU on bladder cancer was to propose updated french guidelines for non-muscle invasive (NMIBC) and invasive (MIBC) bladder cancers. MethodsA Medline search was achieved between 2013 and 2016, as regards diagnosis, options of treatment and follow-up of bladder cancer, to evaluate different references with levels of evidence. ResultsDiagnosis of NMIBC (Ta, T1, CIS) is based on a complete deep resection of the tumour. The use of fluorescence and a second-look indication are essential to improve initial diagnosis. Risks of both recurrence and progression can be estimated using the EORTC score. A stratification of patients into low, intermediate and high risk groups is pivotal for recommending adjuvant treatment : instillation of chemotherapy (immediate post-operative, standard schedule) or intravesical BCG (standard schedule and maintenance). Cystectomy is recommended in BCG-refractory patients. Extension evaluation of MIBC is based on pelvic-abdominal and thoracic CT-scan; MRI and FDG-PET remain optional. Cystectomy associated with extensive pelvic lymph nodes resection is considered the gold standard for non metastatic MIBC. An orthotopic bladder substitution should be proposed to both male and female patients lacking any contraindications and in cases of negative frozen urethral samples. The interest of neoadjuvant chemotherapy is well known for all MIBC, wathever the stage. Thus, neoadjuvant chemotherapy is recommended for all eligible patients according PS (PS <2) and renal function (clearance > 60ml/mn). As regards metastatic MIBC, first-line chemotherapy using platin is recommended (GC or MVAC). In second line treatment, only chemotherapy using vinflunine has been validated to date, even if results of immunotherapy clinical trials are encouraging. ConclusionThese updated french guidelines will contribute to increase the level of urological care for the diagnosis and treatment for NMIBC and MIBC.© 2016 Elsevier Masson SAS. All rights reserved.