Search

Simple Summary: Intravesical instillations of BCG remain the standard of care for high-risk non-muscle-invasive bladder cancer (NMIBC). In the case of BCG failure, radical cystectomy is recommended. When patients refuse to undergo BCG or are ineligible due to comorbidities, bladder-sparing techniques can be discussed, the majority of which are still being evaluated. Hyperthermic IntraVEsical Chemotherapy (HIVEC) in patients with carcinoma in situ (CIS) of the bladder remains controversial in terms of its oncological efficacy. In this multicentric retrospective study, including BCG-failed patients treated with HIVEC, we did not find increased recurrence or progression rates in patients with CIS. These data encourage further evaluation of HIVEC for the treatment of non-muscle-invasive bladder carcinoma regardless of the presence of CIS. CIS of the bladder is associated with a high risk of progression. In the case of BCG failure, radical cystectomy should be performed. For patients who refuse or are ineligible, bladder-sparing alternatives are evaluated. This study aims to investigate the efficacy of Hyperthermic IntraVesical Chemotherapy (HIVEC) depending on the presence or absence of CIS. This retrospective, multicenter study was conducted between 2016 and 2021. Patients with non-muscle-invasive bladder cancer (NMIBC) with BCG failure received 6–8 adjuvant instillations of HIVEC. The co-primary endpoints were recurrence-free survival (RFS) and progression-free survival (PFS). A total of 116 consecutive patients met our inclusion criteria of whom 36 had concomitant CIS. The 2-year RFS rate was 19.9% and 43.7% in patients with and without CIS, respectively (p = 0.52). Fifteen patients (12.9%) experienced progression to muscle-invasive bladder cancer with no significant difference between patients with and without CIS (2-year PFS rate = 71.8% vs. 88.8%, p = 0.32). In multivariate analysis, CIS was not a significant prognostic factor in terms of recurrence or progression. In conclusion, CIS may not be considered a contraindication to HIVEC, as there is no significant association between CIS and the risk of progression or recurrence after treatment. [ABSTRACT FROM AUTHOR]

Purpose: Bacille Calmette-Guérin (BCG) is a well-established treatment for preventing or delaying tumour recurrence following high-grade nonmuscle invasive bladder cancer (NMIBC) resection. However, many patients will experience recurrence or progression during or following BCG. This scenario has been one of the most challenging in urologic oncology for several decades since BCG implementation. Finally, significant progress has occurred lately. The aim of this review was to summarize for the practising urologist the current treatment options available in 2020 or expected to be ready for routine use in the near future for patients with high-risk NMIBC who experience BCG failure. Methods: Narrative review using data through the end of 2020. Results: First, the definition of BCG unresponsive disease which is critical in counseling and managing patients has finally reached a consensus. Second, some promising options other than radical cystectomy are finally available and many other should be in a near future. The options can be categorized as chemotherapy, device-assisted therapy, check-point inhibitors, new intravesical and systemic agents and sequential combinations of these newer modalities with conventional therapy. Conclusions: Considering the options that are currently under scrutiny, many of which in phase III trials, clinicians should have at their disposal several new treatment options in the next five years. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate Hyperthermic-Intra-Vesical Chemotherapy (HIVEC) efficacy regarding 1-year disease-free survival (RFS) rate and bladder preservation rate in patients with High-risk Non-Muscle Invasive Bladder Cancer (NMIBC) who fail BCG therapy or are contraindicated to BCG. Methods: Between June 2016 and October 2019, patients treated with HIVEC for mostly high-risk NMIBC who failed BCG or BCG-naive if BCG contraindicated have been included in our study. These patients had a theoretical indication for cystectomy but were ineligible for surgery or refused it. Results: Fifty-three patients, median age 72 [39–93] years, were included in this study (n = 29 BCG-failure and n = 24 BCG-naive). The median follow-up was 18 months. The bladder preservation rate was 92.4%. The 12 months-RFS rate was 60.5%. The RFS rates for BCG-naive and BCG-failure groups were respectively 70% and 52.2% at 12 months. Three patients progressed to muscle infiltration, all in the BCG-failure group and all in the very high-risk EORTC group. Two of them developed metastatic disease and died from bladder cancer. Conclusion: Chemohyperthermia using HIVEC achieved a RFS rate of 60% at 1 year and enabled a bladder preservation rate of 92%. Given the low risk of progression in the BCG-naive group, HIVEC could be a good alternative. Conversely, for patients with very high-risk tumors that fail BCG, cystectomy should remain the standard of care and HIVEC may be discussed cautiously for patients who are not eligible for surgery and well informed of the risk of progression to muscle-invasive disease. [ABSTRACT FROM AUTHOR]

Objective: To assess PD-L1 expression in tumor (TC) and tumor infiltrating immune cells (IC) as a predictive factor of BCG therapy failure in high-risk NMIBC. Materials and methods: Patients treated with complete resection followed by bladder BCG instillation for high-risk NMIBC were included. Early recurrence (ER) was defined as tumor recurrence after BCG induction course. The association between ER and immuno-histochemistry PD-L1 (E1L3N clone) expression by tumors cells (TC) and tumor infiltrating immune cells (IC) was investigated using an exact Fisher test variant. Results: A total of 186 patients were included, of whom 38 (20.4%) were ER, 35 (18.8%) were positive for TC PD-L1 expression and 60 (32.3%) were positive for IC PD-L1. ER was not significantly (p = 0.97) more frequent in the TC PD-L1 ≥ 1% group (n = 7, 20.0%) than in the TC PD-L1-negative group (n = 31, 20.5%). Patients with IC PD-L1 negative had ER in 15 (19.2%) cases and patients with IC PD-L1 ≥ 1% had ER in 23 (21.3%) cases. PD-L1-positive expression for IC (threshold > 1%) was correlated with immune infiltrate density (95.2% dense immune infiltrate vs 47.2% low immune infiltrate, p < 0.05), with increased expression of PD-L1 by IC after BCG therapy (p = 0.006). Conclusion: No association was observed between immuno-histochemistry PD-L1 positivity and ER after BCG therapy. Nevertheless, the relationship between immune infiltrate and PD-L1 positivity confirmed the interest of assessing the immune infiltrate density to define tumor's profile. [ABSTRACT FROM AUTHOR]

Objectives To determine if a re-transurethral resection (TUR), in the presence or absence of muscle at the first TUR in patients with T1-high grade (HG)/Grade 3 (G3) bladder cancer, makes a difference in recurrence, progression, cancer specific (CSS) and overall survival (OS). Patients and methods In a large retrospective multicentre cohort of 2451 patients with T1-HG/G3 initially treated with bacille Calmette-Guérin, 935 (38%) had a re-TUR. According to the presence or absence of muscle in the specimen of the primary TUR, patients were divided in four groups: group 1 (no muscle, no re-TUR), group 2 (no muscle, re-TUR), group 3 (muscle, no re-TUR) and group 4 (muscle, re-TUR). Clinical outcomes were compared across the four groups. Results Re-TUR had a positive impact on recurrence, progression, CSS and OS only if muscle was not present in the primary TUR specimen. Adjusting for the most important prognostic factors, re-TUR in the absence of muscle had a borderline significant effect on time to recurrence [hazard ratio (HR) 0.67, P = 0.08], progression (HR 0.46, P = 0.06), CSS (HR 0.31, P = 0.07) and OS (HR 0.48, P = 0.05). Re-TUR in the presence of muscle in the primary TUR specimen did not improve the outcome for any of the endpoints. Conclusions Our retrospective analysis suggests that re-TUR may not be necessary in patients with T1-HG/G3, if muscle is present in the specimen of the primary TUR. [ABSTRACT FROM AUTHOR]

Objectives To assess bacillus Calmette- Guérin maintenance treatment schedule for non-muscle invasive bladder cancer at 2 years, using one-third of the full dose and fewer instillations every 3 months or 6 months. Methods This was a prospective, randomized, multicenter study. All patients had an intermediate- or high-risk non-muscle invasive bladder cancer. They received three weekly instillations of one-third dose bacillus Calmette- Guérin every 6 months (group I) and two weekly instillations every 3 months (group II) during 3 years. In the two schedules we assessed efficacy, tolerance, leukocyturia and prostate-specific antigen. Results No significant difference was observed between the two groups for recurrence at 6, 12 or 18 months. At 2 years, tumor recurrence was observed in 10.9% and muscle invasion in 2.9% of cases. Bacillus Calmette- Guérin tolerance was comparable - the adverse events score was 0.8 in group I and 1 in group II ( P = 0.242). No statistical correlation was observed between the adverse events score over 2 years, either for leukocyturia ( P = 0.8891) or prostate-specific antigen level ( P = 0.7155). Leukocyturia level was not significantly associated with tumor recurrence or progression. Conclusion One-third dose maintenance bacillus Calmette- Guérin is effective with no impact on tumor recurrence or muscle invasion. Furthermore, there seems to be no difference in tumor response or side-effects between patients receiving two or three maintenance instillations every 3 months or 6 months. In clinical practice, the use of leukocyturia or total prostate-specific antigen levels do not appear to be useful in predicting bacillus Calmette- Guérin toxicity. [ABSTRACT FROM AUTHOR]

Purpose: Predictive factors of T1 nonmuscle invasive bladder cancer evolution that could guide treatment decision making are lacking. We assessed the prognostic value of muscularis mucosa invasion in nonmuscle invasive bladder cancer. Materials and Methods: In a national multicenter study patients with primary T1 nonmuscle invasive bladder cancer were recruited from 6 French hospitals. All patients had undergone transurethral resection of bladder tumor. All T1 tumors were substaged according to muscularis mucosa invasion as T1a—no invasion beyond the muscularis mucosa or T1b—invasion beyond the muscularis mucosa with muscle preservation. Subsequent central pathology review was then done by a single referent uropathologist. Muscularis mucosa invasion was tested as a prognostic factor for survival on univariate and multivariate analysis. Results: A total of 587 patients were enrolled in the study, including 388 (66%) with T1a and 199 (34%) with T1b tumors. Median followup after transurethral resection of bladder tumor was 35 months (IQR 14-54). There was no significant difference between groups T1a and T1b except high tumor grade in T1b cases (p <0.0001). After central review, initial pathological substaging was confirmed in 84% of cases. On multivariate analysis muscularis mucosa invasion (T1b substage) was significantly associated with recurrence-free (p = 0.03), progression-free (p = 0.0002) and cancer specific (p = 0.02) survival. The main study limitation was absent systematic subsequent transurethral resection of bladder tumor. Conclusions: Muscularis mucosa invasion appears to be highly predictive of T1 nonmuscle invasive bladder cancer behavior. Consequently, systematic T1a vs T1b discrimination should be highly advocated by urologists and pathologists. We believe that it could aid in crucial decision making when choosing between conservative management and radical cystectomy remains a moot point. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: This paper discusses the most relevant new findings on bladder cancer (BCa) presented at the 2007 annual meetings of the European Association of Urology (EAU), American Urological Association (AUA), and American Society of Clinical Oncology (ASCO). Methods: The most relevant abstracts on BCa were selected by urological experts in the field of BCa, who are members of the Oncoforum group, and presented during the Oncoforum summary meeting in Brussels, Belgium. The abstracts were selected based on the following criteria: innovative data, relevance to clinical practice, and robust methodology (eg, multicentre trial, randomised, number of patients). Results: Major topics were the use of apoptotic biomarkers to enhance the diagnostic performance and the failure of 5-aminolevunilic acid-induced fluorescence cystoscopy to improve recurrence-free survival rates in patients with non–muscle-invasive disease. Regarding the management of non–muscle-invasive BCa, the efficacy of a maintenance adjuvant instillation therapy was demonstrated. Other studies showed that ofloxacin prophylaxis reduced the bacillus Calmette-Guérin (BCG)-induced side-effects and suggested a survival benefit with adjuvant BCG therapy among older patients. For patients with low-grade upper urinary tract transitional cell carcinoma (TCC), endoscopic treatment seems to be effective and safe, whereas for patients with high-grade upper urinary tract TCC, a laparoscopic nephroureterectomy might be a valid treatment option. Finally, laparoscopic radical cystectomy seems to offer potential for the treatment of patients with infiltrative/advanced BCa. Two studies suggested that in addition to a cystectomy, patients may benefit from a more extensive lymphadenectomy. Conclusions: New data presented at these meetings might contribute to an improved management of BCa. [Copyright &y& Elsevier]

Abstract: Objectives: This paper describes and discusses the most relevant new findings on bladder cancer (BCa) that were presented at the 2006 annual meetings from the European Association of Urology (EAU), American Urological Association (AUA) and the American Society of Clinical Oncology (ASCO). Methods: The most relevant abstracts on BCa were selected by experts in the field of BCa and discussed during a closed meeting. Results: The most relevant new data on BCa came from the EAU and AUA meetings. Major topic of the meetings was the development of the EORTC prognostic tables to calculate short- and long-term recurrence and progression rates of patients with superficial BCa. Many (controversial) studies discussed the diagnostic and prognostic potentials of the biomarkers survivin and NMP22. Two studies involved the treatment of patients with refractory superficial BCa. Intravesical therapy with Bacillus Calmette-Guérin+interferon-α was considered a promising therapy for patients who failed BCG therapy. With respect to invasive BCa, there were some controversial reports on the impact of delayed cystectomy or hospital volumes on (cancer-free) survival rates. The bladder cancer index was presented as a promising questionnaire to assess quality of life in patients with localised BCa. Finally, one study showed that extensive tumour necrosis in upper urinary tract tumours is a prognostic factor for poor patient outcome. Conclusions: There were many interesting studies about BCa at this year''s urologic meetings. Major headline was the introduction of the EORTC prognostic tables, which will probably lead to a major improvement in the evaluation and surveillance of patients with superficial BCa. [Copyright &y& Elsevier]

Background The impact of prognostic factors in T1G3 non–muscle-invasive bladder cancer (BCa) patients is critical for proper treatment decision making. Objective To assess prognostic factors in patients who received bacillus Calmette-Guérin (BCG) as initial intravesical treatment of T1G3 tumors and to identify a subgroup of high-risk patients who should be considered for more aggressive treatment. Design, setting, and participants Individual patient data were collected for 2451 T1G3 patients from 23 centers who received BCG between 1990 and 2011. Outcome measurements and statistical analysis Using Cox multivariable regression, the prognostic importance of several clinical variables was assessed for time to recurrence, progression, BCa-specific survival, and overall survival (OS). Results and limitations With a median follow-up of 5.2 yr, 465 patients (19%) progressed, 509 (21%) underwent cystectomy, and 221 (9%) died because of BCa. In multivariable analyses, the most important prognostic factors for progression were age, tumor size, and concomitant carcinoma in situ (CIS); the most important prognostic factors for BCa-specific survival and OS were age and tumor size. Patients were divided into four risk groups for progression according to the number of adverse factors among age ≥70 yr, size ≥3 cm, and presence of CIS. Progression rates at 10 yr ranged from 17% to 52%. BCa-specific death rates at 10 yr were 32% in patients ≥70 yr with tumor size ≥3 cm and 13% otherwise. Conclusions T1G3 patients ≥70 yr with tumors ≥3 cm and concomitant CIS should be treated more aggressively because of the high risk of progression. Patient summary Although the majority of T1G3 patients can be safely treated with intravesical bacillus Calmette-Guérin, there is a subgroup of T1G3 patients with age ≥70 yr, tumor size ≥3 cm, and concomitant CIS who have a high risk of progression and thus require aggressive treatment. [ABSTRACT FROM AUTHOR]

Background: Potential differences in efficacy of different bacillus Calmette-Guérin (BCG) strains are of importance for daily practice, especially in the era of BCG shortage.Objective: To retrospectively compare the outcome with BCG Connaught and BCG TICE in a large study cohort of pT1 high-grade non-muscle-invasive bladder cancer patients.Design, Setting, and Participants: Individual patient data were collected for 2,451 patients with primary T1G3 tumors from 23 centers who were treated with BCG for the first time between 1990 and 2011.Outcome Measurements and Statistical Analysis: Using Cox multivariable regression and adjusting for the most important prognostic factors in this nonrandomized comparison, BCG Connaught and TICE were compared for time to recurrence, progression, and the duration of cancer specific survival and overall survival.Results and Limitations: Information on the BCG strain was available for 2,099 patients: 957 on Connaught and 1,142 on TICE. Overall, 765 (36%) patients received some form of maintenance BCG, 560 (59%) on Connaught and 205 (18%) on TICE. Without maintenance, Connaught was more effective than TICE only for the time to first recurrence (hazard ratio [HR] = 1.48; 95% CI: 1.20-1.82; P<0.001). With maintenance, TICE was more effective than Connaught for the time to first recurrence (HR = 0.66; 95% CI: 0.47-0.93; P = 0.019) with a trend for cancer specific survival (HR = 0.36; 95% CI: 0.14-0.92; P = 0.033). For time to progression and overall survival, Connaught and TICE had a similar efficacy. Compared to no maintenance therapy, maintenance BCG significantly reduced the risk of recurrence, progression and death, both overall, and disease specific, for TICE, but not for Connaught.Conclusions: We found that BCG Connaught results in a lower recurrence rate as compared with BCG TICE when no maintenance is used. However, the opposite is true when maintenance is given.Patient Summary: As there is currently a BCG shortage, information on the efficacy of different BCG strains is important. In this nonrandomized retrospective comparison in over 2,000 patients, we found that BCG Connaught reduces the recurrence rate compared to BCG TICE when no maintenance is used, but the opposite is true when maintenance is given. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The objective of the study was to evaluate the effect of a history of bladder cancer (BC) or synchronous BC on the prognosis and survival of patients who have undergone radical nephroureterectomy (RNU). Methods and materials: Using a multi-institutional, retrospective database, we identified 662 patients with upper urinary tract urothelial carcinoma (UUT-UC) treated by radical nephroureterectomy, between 1995 and 2010. We analyzed clinicopathologic characteristics and outcomes according to the history of BC or concomitant BC or both, at the time of diagnosis. BC was evaluated as a prognostic factor for bladder recurrence and survival. Results: Overall, 83 (12.5%) patients had previous BC, 62 (9.4%) exhibited concomitant BC, and 75 (11.3%) presented with both previous and current BC. A history of BC was less seen in women and nonsmokers (P<0.0001 and P = 0.013, respectively). The patients with associated BC had more tumors located in the ureter (P<0.0001), as well as more multiple locations in the upper tract (P<0.0001). The tumors without concomitant BC were more likely to be associated with locally advanced stages (P = 0.024). At a median follow-up time of 37.3 months, 31.4% of patients experienced BC recurrence and 2.9% developed contralateral upper tract tumor. Using multivariate analyses, the previous or synchronous BC (P = 0.01) and positive surgical margins (P = 0.03) are independent prognostic factors for BC recurrence. The metastasis-free survival and cancer-specific survival rates did not significantly differ according to the associated BC status. Conclusions: In patients without previous or concomitant BC, the upper tract tumors are more frequently localized in the renal pelvis and are associated with a more invasive status at the time of diagnosis. Nevertheless, the presence of UUT-UC without previous or synchronous BC did not significantly affect the survival rates after nephroureterectomy. [Copyright &y& Elsevier]