Cumulative incidence of and risk factors for BCG infection after adjuvant BCG instillations.

OBJECTIVES: To investigate the cumulative incidence proportion of disseminated or local Bacillus Calmette-Guérin (BCG) infections after adjuvant BCG instillations in patients with non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: We analysed the timing and occurrence of BCG infections and absolute and relative risk in relation to patient characteristics available in the Swedish nationwide database 'BladderBaSe 2.0'. The cumulative incidence proportion of a BCG infection was indicated by a reported diagnosis of tuberculosis (TB) in the patient registry or filing a prescription for tuberculostatic drugs. RESULTS: The cumulative incidence proportion was 1.1% at the 5-year follow-up in 5033 patients exposed to adjuvant BCG instillations. The incidence rate was highest during the first 2 years after start of BCG instillations. Women had a lower risk than men (hazard ratio 0.23, 95% confidence interval 0.07-0.74). Age and calendar time at diagnosis, comorbidity, tumour risk group, previous medication with corticosteroids, immunosuppressive drugs, or time between transurethral resection of the bladder tumour and commencing the adjuvant BCG instillation were not associated with risk. CONCLUSIONS: These data further supports that the overall risk of a BCG infection after BCG-instillation treatment for NMIBC is low. The great majority of infections occur in the first 2 years, calling for an awareness of the diverse symptoms of BCG infection during this period. We provide evidence for male sex as a risk factor; however, the statistical precision is low and with a risk of selection bias, making it difficult to rule out the other suggested risk factors without further studies with different approaches.

[BCG strain shortage from 2012 to 2014: Evaluation of its impact on the management of patients with high-risk NMIBC]. / Pénurie en souche de BCG entre 2012 et 2014 : évaluation de son impact sur la prise en charge des patients présentant une TVNIM de haut risque.

INTRODUCTION: BCG instillations are the gold-standard treatment for high-risk non-muscle-invasive bladder cancer (NMIBC) with a decreased risk of tumor recurrence and muscle infiltration. From 2012 to 2014, a stock shortage of the Connaught strain has led to the cessation of supply for immucyst in France. The objective of this study was to evaluate the potential impact of BCG shortage on the management of patients with NMIBC. PATIENTS AND METHODS: We conducted a retrospective single-center study including patients followed from May 2005 to May 2015 with a high-risk NMIBC (primo-diagnosis). Patients were separated into two groups: not impacted by the shortage (NISG: 56 patients) and impacted by the shortage (ISG: 53 patients). Data on tumour recurrence (RFS), muscle progression (PFS) and overall and specific survival (OS and SS) were also analysed. RESULTS: The BCG induction schedule could not be carried out in 20.8% of cases in the ISG compared to only 5.3% of cases in NISG (P=0.02). Similarly, the maintenance treatment was incomplete for 56.6% of cases versus 37.5% in NISG (P=0.047). Nevertheless, it should be underlined that very high-risk NMIBC received a complete induction BCG schedule. The ISG seems to have benefited with the evolution of the guidelines with the use of diagnosis bladder fluorescence but without significant difference on the rate of second look bladder trans-uretral resection. The cystectomy rate was higher in ISG. No significant difference in RFS, PFS, OS, and SS between the two groups. CONCLUSION: In our experience, RFS, PFS, OS or SS were not impacted by the BCG shortage. These data may be explained by a better selection of very high-risk patients including the recommended BCG schedule and more frequently the use of diagnosis bladder fluorescence. LEVEL OF EVIDENCE: 3.

Management of high-grade papillary Ta or T1 bladder cancer after restaging transurethral resection: A retrospective study comparing Bacillus Calmette-Guerin therapy upfront versus a third resection.

PURPOSE: Performing restaging transurethral bladder resection (reTURB) for high-risk non-muscle invasive bladder cancer (NMIBC) reduces the risk of recurrence and tumour understaging. Management of residual high-grade papillary Ta or T1 after reTURB has changed this last 10years in international recommendations. This study aimed to compare the recurrence free survival according to the different management procedures performed. MATERIALS AND METHODS: Patients who underwent reTURB for initial high-risk NMIBC between 2011 and 2020 were included. Patients with residual high-grade papillary Ta or T1 tumour after reTURB were divided into two groups: BCG instillations upfront versus BCG following a third-look resection (3TURB). Patient and tumour characteristics, BCG instillations, recurrence-free survival were retrospectively analysed. RESULTS: A total of 162 high-risk patients were included. Sixty-one (37.7%) had residual high-grade papillary Ta or T1 at reTURB: 35 (21.6%) had BCG instillations upfront, 18 (11.2%) had a 3TURB and 8 (5%) had other management. The mean follow-up was 34.2weeks±20.2. Recurrence-free survival was significantly better in patients who underwent BCG instillations upfront (P<0.0043). Recurrence after BCG therapy following reTURB was significantly lower in patients with no residual NMIBC at 6 (92.5% vs. 72.4%, P<0.004) and 12months (85% vs. 67.3%, P<0.03). CONCLUSIONS: The efficacy of intravesical BCG is compromised in case of residual tumour following TURB. The role of a 3TURB following a positive reTURB is not yet determined. This study has confirmed that residual tumor following reTURB is a negative predictive factor but could not demonstrate the value of a 3TURB compared to upfront BCG.

Revolutionizing Treatment: Breakthrough Approaches for BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer.

Bladder cancer is the 10th most popular cancer in the world, and non-muscle-invasive bladder cancer (NMIBC) is diagnosed in ~80% of all cases. Treatments for NMIBC include transurethral resection of the bladder tumor (TURBT) and intravesical instillations of Bacillus Calmette-Guérin (BCG). Treatment of BCG-unresponsive tumors is scarce and usually leads to Radical Cystectomy. In this paper, we review recent advancements in conservative treatment of BCG-unresponsive tumors. The main focus of the paper is FDA-approved medications: Pembrolizumab and Nadofaragene Firadenovec (Adstiladrin). Other, less researched therapeutic possibilities are also included, namely: N-803 immunotherapy, TAR-200 and TAR-210 intravesical delivery systems and combined Cabazitaxel, Gemcitabine and Cisplatin chemotherapy. Conservative treatment and delaying radical cystectomy would greatly benefit patients' quality of life; it is undoubtedly the future of BCG-unresponsive NMIBC.

Mitomycin C vs. Bacillus Calmette-Guerin for treatment of intermediate-risk nonmuscle invasive bladder cancer patients-A comparative analysis from a single center.

BACKGROUND: Induction followed by 1 year maintenance instillation of intravesical Bacillus Calmette-Guerin (BCG) is the standard treatment for intermediate-risk (IR) nonmuscle invasive bladder cancer (NMIBC) patients. Few data exist on the efficacy of Mitomycin C (MMC) instillation in this setting. METHODS: We retrospectively analyzed 226 IR-NMIBC patients classified by the International Bladder Cancer Group (IBCG) and 250 IR-NMIBC intravescical treatment-naïve patients classified by the European Association of Urology (EAU). All patients received either a full induction course of BCG or 40 mg/40 ml MMC from 2012 to 2022. Optimal treatment was defined as 1-year maintenance for BCG and 11 monthly maintenance instillations for MMC. Kaplan-Meier analysis estimated recurrence-free survival (RFS) before and after inverse probability of treatment-weighting (IPTW) and progression-free survival (PFS). Multivariable Cox regression was used to evaluate difference in recurrence after adjustment for clinically relevant variables before and after IPTW. RESULTS: Optimal BCG and MMC courses were administered to 21% of IR-IBCG and 23% of IR-EAU patients. At 4-years, patients treated with optimal MMC and BCG treatment had similar RFS and PFS in both EAU and IBCG groups. Patients receiving nonoptimal BCG compared to optimal MMC exhibited lower 4-year RFS after IPTW (82% vs. 68% in EAU and 82% vs. 65% in IBCG). At 4-year optimal MMC had greater PFS non optimal BCG. Optimal MMC treatment predicted recurrence in EAU (adjusted and weighted HR 0.33, 95% CI, 0.11-0.98) and IBCG (adjusted and weighted HR 0.29, 95% CI, 0.08-0.97) groups compared to nonoptimal BCG. CONCLUSIONS: Optimal 40 mg/40 ml MMC treatment was as effective as optimal BCG in IR-IBCG and IR-EAU NMIBC patients, reducing both recurrence and progression compared to nonoptimal BCG. MMC could be a valid first line alternative to BCG for both IR-EAU and IR-IBCG intravescical treatment-naïve patients, during BCG shortages.

Sporotrichoid distributed tuberculous panniculitis as a late complication of intravesical bacillus Calmette-Guérin (BCG) immunotherapy.

An 82-year-old man presented with unilateral oedema of the right lower limb overlaid with multiple sporotrichoid distributed panniculitis lesions. These symptoms appeared in a context of immunodepression and were associated with significant weight loss and a deterioration in general condition. The patient's medical history, the histological findings, PCR testing, and bacterial culture led to a diagnosis of cutaneous tuberculosis due to Mycobacterium bovis. This infection occurred as a late complication of intravesical bacillus Calmette-Guérin (BCG) instillations that the patient had received as an adjunctive immunotherapy for bladder cancer. This is an unusual clinical presentation and aetiology of cutaneous tuberculosis. Indeed, the observed sporotrichoid pattern is uncommon for tuberculous mycobacteria. Moreover, the occurrence of tuberculous skin lesions after intravesical BCG instillations is extremely rare, with only a few cases described, and, to the authors' knowledge, none with such a clinical presentation. This case report suggests that a medical history of BCG immunotherapy should always be considered when assessing any infectious-type cutaneous lesions and that skin should be regarded as a possible late localization of infectious complications of this treatment.

Epidemiological study of granulomatous prostatitis in a tertiary hospital: Associated risk factors and relationship with prostate cancer.

OBJECTIVE: The primary objective was to estimate the incidence of granulomatous prostatitis (GP) in Son Espases University Hospital, a tertiary care hospital, in Palma de Mallorca (Spain). As secondary objectives, presence of concomitant PCa in the biopsy was analyzed, as well as the history of previous BCG instillations, biopsy origin, urinary symptoms, and cardiovascular risk (CV) factors. METHODS: A descriptive retrospective study of GP and the aforedescribed variables were carried out from 2010 to 2017. RESULTS: A total of 3651 histopathological prostate specimens were analyzed, 39 of which were diagnosed with GP (incidence of 1.06%). Lower urinary tract symptoms (LUTS) were present in a 48.7% and previous history of bladder tumor resection (TURBT) was present in 35.9% of the cases. Also, urinary tract infections were equally present. All cases with prior TURBT had intravesical instillations with BCG, although 5 (12.8%) and 4 (10.3%) cases had abnormal rectal examination and elevated PSA levels after instillations, respectively. Finally, in 14 cases (35.9%) there was also a diagnosis of concomitant PCa. The most common CV risk factor in these patients was smoking (79.5%) followed by hypertension (64.8%). CONCLUSIONS: The estimated incidence of GP in our center (1.06%)g is close to that described by other authors. About 14 cases were diagnosed with PCa (35.9%), a higher value than previously described in the literature, and most of these were found incidentally, especially in cystoprostatectomies. This high percentage of concomitant GP and PCa could be due to a rise in Transrectal Prostate biopsies (TRPB), as in recent years there has been a tendency to increase the use of PSA in routine clinical practice.