Theories behind Bacillus Calmette-Guerin failure in high-risk non-muscle-invasive bladder cancer and update on current management

Bladder cancer encapsulates a wide spectrum of disease severities,with non-muscle invasive bladder cancer(NMIBC)representing an entirely different entity from muscle-invasive disease.Bacillus Calmette-Guerin(BCG)is one of the most successful intravesical treatment methods for patients diagnosed.However,a considerable pro-portion of patients fail to respond to BCG treatment.Given the propensity for recurrence in patients with high-risk bladder cancer,these patients present with surgical dilemmas.There is currently no gold standard for salvage treatment post-BCG failure or unified definition as to what that means.In this review,we discuss the mechanisms of action and pathophysiology of BCG,potential theories behind BCG failure,and the scope of novel treatments forthis surgical conundrum.

Cryoablation techniques in bladder cancer: A review

Bladder cancer(BC)ranks as the tenth most common cancer globally.Histopathologically,BC is broadly categorized into urothelial and non-urothelial BC.Urothelial carcinoma represents over 90%of BC in most regions worldwide.The standard treatment procedure for diagnosing and treating non-muscle-invasive bladder cancer(NMIBC)is transurethral resection of bladder tumors(TURBT).Currently,the standard of care for muscle-invasive bladder cancer(MIBC)is neoadjuvant chemotherapy followed by radical cystectomy.Cryoablation therapy is a medical technique that uses extremely low temperatures to destroy diseased tissue.This treatment serves as a therapeutic tool for both benign and malignant diseases in organs such as the kidney,prostate gland,lung,liver,and breast,and is particularly effective for unresectable tumors,offering less trauma,quick recovery,good tolerability,and symptom control.However,cryoablation has its limitations.Over the past few years,cryoablation therapy has emerged as a new method for treating early BC.This treatment is minimally invasive,precise,and offers quick recovery,providing patients with a new treatment option.Although randomized studies are still limited,increasing evidence suggests its potential application in bladder cancer combined with transurethral resection(TURBT)or medication.Cryoablation is not standard therapy for bladder cancer.Treatment decisions should be discussed by a multidisciplinary team of urologists,oncologists,and interventional physicians and require more randomized controlled trials to define patient selection criteria and treatment approaches.

Clinical practice guideline on bladder cancer(PartⅡ)

Bladder cancer(BC)is an increasingly common malignancy in China,with an incidence rate of 5.80 per 100000 in 2015,making it the thirteenth most common cancer in the country.This trend underscores the urgent need for standardized diagnosis and treatment protocols.In terms of treatment,approaches for bladder cancer vary based on the cancer's stage and pathology,as well as the patient's overall health.Notably,non-muscleinvasive BC(NMIBC)confined to the mucosa(Ta)and lamina propria(T1)without invading the muscle represents about 75%of all BC cases.Succeeding the first part of the guideline,this part of the clinical practice guideline focuses on NMIBC.It details risk classifications and treatment options,including both surgical procedures and posttransurethral resection of the bladder tumor intravesical instillations.Special attention is given to the treatment strategies for carcinoma in situ.The guideline also covers the recommended follow-up procedures for patients with NMIBC,underscoring the need for thorough and continuous care management.

Holmium laser versus conventional transurethral resection of the bladder tumor

Background Transurethral resection of the bladder tumor （TURBT） remains the gold standard for non-muscle-invasive bladder cancer （NMIBC）. Laser techniques have been widely used in urology. This analysis aimed to assess the safety and efficacy of holmium resection of the bladder tumor （HoLRBT）vs. TURBT. Methods A systemic search of MEDLINE, Embase, Web of Science, and The Cochrane Library as well as manual bibliography searches were performed to identify the relevant studies. The pooled estimates of operation time, obturator nerve reflex rate, bladder perforation rate, bladder irrigation rate, catheterization time, hospital stay, and one- and two-year recurrence free survivals were calculated. Results Five studies were enrolled into our meta-analysis. No significant difference was observed in the operation time between groups （weighted mean difference （WMD） 1.01, 95% confidential interval （95% CI） -3.52-5.54, P=0.66）. The significant difference in the obturator nerve reflex （OR 0.05, 95% CI 0.01-0.04, P=0.004）, bladder perforation （OR 0.14, 95% CI 0.03-0.61, P=-0.009）, bladder irrigation （OR 0.13, 95% CI 0.04-0.45, P=0.001）, catheterization time （WMD -0.96, 95% C1-1.11 to-0.82, P 〈0.00001）, and hospital stay （WMD-1.46, 95% C1-1.65 to-1.27, P 〈0.00001）showed advantages of HoLRBT over TURBT. The 2-year recurrence free survival rate favors the HoLRBT group （OR 1.46, 95% CI 1.02-2.11, P=-0.04）. Conclusions As a promising technique, HoLRBT is safe and efficient, and showed several advantages over TURBT. HoLRBT can be used as an alternative procedure for TURBT in terms of low-grade papillary urothelial carcinoma or low-grade early TNM-stage urothelial carcinoma.

Efficacy of immediate instillation combined with regular instillations of pirarubicin for Ta and T1 transitional cell bladder cancer after transurethral resection： a prospective, randomized, multicenter study

Background Immediate intravesical instillation of chemotherapeutic agents after transurethral resection （TUR） of non- muscle invasive transitional cell bladder cancer has recently been suggested and has been proven to decrease the tumor recurrence rate significantly. This study is to evaluate the efficacy and safety of immediate intravesical instillation combined with regular instillations of Pirarubicin （THP~） as prophylaxis compared to regular instillations only after TUR operation. Methods This was a prospective, randomized, multi-center, clinical study. Patients diagnosed with non-muscle invasive bladder cancer （Ta and T1） pathologically and suitable for TUR were enrolled randomly into two groups. In the study group, the patients received intravesical instillation within 24-hour post TURBT, followed by regular intravesical therapy using 30 mg/50 ml of THP~ once a week for 8 weeks, and then once a month to 1 year postoperatively Among the patients. In the control group, patients received regular instillation only. Results A total of 403 patients were enrolled into this study from 26 institutions in China. Among the potients, 210 were enrolled into the study group and 193 were enrolled into the control group. At the median follow-up of 18 months, the recurrence rate was 7.8% in the study group, significantly lower than that in the control group （14.3%; P=0.042）. Subgroup analysis showed that the recurrence rate in low and intermediate-risk patients was significantly lower in the study group （6.8%） than in the control group （14.0%; P=0.047）, although no significant differences were found in high-risk patients. Conclusion One immediate dose of THP 30 mg after TURBT followed by regular intravesical therapy appears well tolerated and more effective than regular intravesical therapy for preventing tumor recurrence, especially in low and intermediate-risk patients.

Research progress in the off-target effects of Bacille Calmette-Guérin vaccine

Bacille Calmette-Guérin(BCG)vaccine is designed to provide protection against tuberculosis(TB).However,numerous epidemiological,clinical,and immunological studies have shown that BCG vaccination affects neonatal and infant mortality,which may be related to the reduction of TB-unrelated infections and diseases by BCG vaccine.We aimed to discuss the off-target effects of BCG vaccine on un-TB infections and diseases,as well as the potential mechanism and influencing factors.Literature was retrieved mainly from PubMed using medical subject headings"BCG,variations,and non-specific,heterologous or off-target".Studies have showed that BCG vaccination can prevent various heterologous infections,including respiratory tract infections,leprosy,and malaria,treat viral infections including human papillomavirus and herpes simplex virus infection as immunotherapy,and improve the immune responses as vaccine adjuvant.Besides,BCG vaccine can reduce the recurrence rate of non-muscle-invasive bladder cancer,and may provide protection against autoimmune diseases.These off-target effects of BCG vaccine are thought to be achieved by modulating heterologous lymphocyte responses or inducing trained immunity,which were found to be sex-differentiated and affected by the BCG vaccine strains,sequence or time of vaccination.