A Th2-score in the tumor microenvironment as a predictive biomarker of response to Bacillus Calmette Guérin in patients with non-muscle invasive bladder carcinoma: A retrospective study.

Intravesical Bacillus Calmette Guerin (BCG) is the gold standard therapy for intermediate/high-risk non-muscle invasive bladder cancer (NMIBC). However, the response rate is ~60%, and 50% of non-responders will progress to muscle-invasive disease. BCG induces massive local infiltration of inflammatory cells (Th1) and ultimately cytotoxic tumor elimination. We searched for predictive biomarker of BCG response by analyzing tumor-infiltrating lymphocyte (TIL) polarization in the tumor microenvironment (TME) in pre-treatment biopsies. Pre-treatment biopsies from patients with NMIBC who received adequate intravesical instillation of BCG (n = 32) were evaluated retrospectively by immunohistochemistry. TME polarization was assessed by quantifying the T-Bet+ (Th1) and GATA-3+ (Th2) lymphocyte ratio (G/T), and the density and degranulation of EPX+ eosinophils. In addition, PD-1/PD-L1 staining was quantified. The results correlated with BCG response. In most non-responders, Th1/Th2 markers were compared in pre-and post-BCG biopsies. ORR was 65.6% in the study population. BCG responders had a higher G/T ratio and a greater number of degranulated EPX+ cells. Variables combined into a Th2-score showed a significant association with higher scores in responders (p = 0.027). A Th2-score cut-off value >48.1 allowed discrimination of responders with 91% sensitivity but lower specificity. Relapse-free survival was significantly associated with the Th2-score (p = 0.007). In post-BCG biopsies from recurring patients, TILs increased Th2-polarization, probably reflecting BCG failure to induce a pro-inflammatory status and, thus, a lack of response. PD-L1/PD-1 expression was not associated with the response to BCG. Our results support the hypothesis that a pre-existing Th2-polarized TME predicts a better response to BCG, assuming a reversion to Th1 polarization and antitumor activity.

Should continuous bladder irrigation be recommended when single instillation of intravesical chemotherapy cannot be used after transurethral resection in low-risk non-muscle invasive bladder cancer?

Reducing the recurrence rate in patients with low-risk non-muscle invasive bladder cancer patients is a critical concern in the urologic community. The gold standard treatment is single instillation (SI) of intravesical chemotherapy after transurethral resection of bladder tumor (TURBT), but unfortunately, it is underused. Continuous bladder irrigation (CBI) after TURBT is an alternative strategy to SI for the prevention of bladder tumor implantation and recurrence. The aim of this review was to present the evidence that supports CBI after TURBT when SI is not possible.

The Impact of Dose Reduction of Bacillus Calmette-Guerin on Oncological Outcomes and Toxicity in Non-Muscle Invasive Bladder Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Bacillus Calmette-Guerin (BCG) is the standard adjuvant treatment for intermediate and high-risk non-muscle invasive bladder cancer (NMIBC) following transurethral resection of the bladder (TURB). However, the optimal dose, strain, and schedule of BCG remain unclear. OBJECTIVE: To evaluate the impact of BCG dose reduction on oncological outcomes and toxicity in patients with non-muscle invasive bladder cancer. METHODS: We performed a systematic review of the literature in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases. Selected studies were analyzed for Meta Analysis using PRISMA criteria. The study focused on disease recurrence, progression, and toxicity. We also compared the oncological outcomes of the different BCG strains. RESULTS: A total of 2963 patients in 13 randomized controlled trials were included. In recurrence analysis, we found a non-significant difference between the full dose and any dose reduction of BCG (RR = 1.17, [1.06-1.28], I2 = 0%, p = 0.7). In terms of progression, the difference was also non-statistically significant (RR: 1.12 [0.89 - 1.41], I2 = 0%, p = 0.93). In the toxicity analysis, there were more local (RR: 0.81 [0.67-0.99] I2 = 76%; p < 0.01) and systemic (RR: 0.53 [0.34-0.82] I2 = 83%; p < 0.01) side effects in the full dose group than in the dose reduction group. There were no statistically significant differences in oncological outcomes between the analyzed BCG strains. CONCLUSIONS: Dose reduction did not affect the oncological outcomes of patients with NMIBC who received adjuvant therapy with BCG. On the other hand, dose reduction showed a significant trend towards fewer systemic and local side effects. Further studies comparing oncological and toxicity outcomes using different strains are needed.

Laparoscopic urinary undiversion due to recurrent neobladder vaginal fistula: from orthotopic neobladder to ileal conduit / Desderivación urinaria laparoscópica por fístula neo-vesico vaginal recurrente: de neovejiga ortotópica a conducto ileal

Objective: Describe our experience in laparoscopic urinary undiversion due to recurrent neobladder vaginal fistula (NBVF). Methods: Retrospective review of patients who underwent laparoscopic urinary undiversion. Complications were characterized according to the Clavien classification. The Patient Global Impression of Improvement (PGII) questionnaire was used at one year of follow-up to assess the quality of life (QOL). Results: Three laparoscopic urinary undiversions, from orthotopic neobladder to ileal conduit. Two patients underwent laparoscopic cystectomy due to bladder cancer, and one open pelvic exenteration due to cervical cancer. All patients had received previous pelvic radiotherapy. Complications during the first 2 months were Clavien II (two patients). According to the PGII score, two patients felt "much better" and one felt "very much better." Conclusion: Urinary undiversion is a last resort, complex procedure. Even though, it may be the only chance to improve QOL in patients with recurrent or unrepairable NBVF. A laparoscopic approach with neobladder resection, fistulectomy, and intracorporeal ileal conduit is feasible. Further studies are required to assess the best approach in the management of NBVF.

Objetivo: Describir nuestra experiencia en desderivación urinaria laparoscópica por fístula neo-vesico vaginal recurrente (NBVF). Métodos: Revisión retrospectiva de pacientes a los que se les realizó desderivación urinaria laparoscópica. Las complicaciones se caracterizaron según la clasificación de Clavien. El cuestionario de Impresión Global de Mejora del Paciente (PGII) se utilizó al año de seguimiento para evaluar la calidad de vida (QoL). Resultados: 3 desderivaciones urinarias laparoscópicas, de neovejiga ortotópica a conducto ileal. Dos pacientes se sometieron a cistectomía laparoscópica por cáncer de vejiga y una exenteración pélvica abierta por cáncer de cuello uterino. Todos los pacientes habían recibido radioterapia pélvica previa. Las complicaciones durante los primeros 2 meses fueron Clavien II (2 pacientes). Según la puntuación PGII, dos pacientes se sintieron «Mucho mejor¼ y uno se sintió «Muchísimo mejor.¼ Conclusión: La desderivación urinaria laparoscopica es un procedimiento complejo y de último recurso. Sin embargo, puede ser la única oportunidad para mejorar la calidad de vida en pacientes con NBVF recurrentes o irreparables. El abordaje laparoscópico con resección de neovejiga, fistulectomía y conducto ileal intracorpóreo es factible. Se requieren más estudios para evaluar el mejor enfoque en el manejo de NBVF.

Post-Transurethral Resection of Bladder Tumor Bladder Perforation Resulting in Mitomycin C Extravasation, Pudendal Neuralgia, and Ureterohydronephrosis.

Background: Mitomycin C (MMC) extravasation after transurethral resection of bladder tumor (TURBT) is a rare and highly morbid complication. Management of these cases may require a multidisciplinary approach with strategies ranging from conservative management to surgical intervention. Case Presentation: We present a 48-year-old woman who received a TURBT for a 5 mm bladder tumor. Procedure was uneventful and no bladder perforation was noticed. A single dose of instillation of MMC was performed after surgery resulting in extravasation, consequent ipsilateral pudendal neuralgia, and ureterohydronephrosis. Treatment included a second TURBT, Double-J stent placement, and multiple pain management schemes. After 8 months the patient had complete resolution of pain and ureterohydronephrosis. Conclusion: Perioperative chemotherapy is the standard of care in low-risk bladder cancer. Extravasation of MMC, although rare, can produce severe complications, sometimes irreversible. Other treatment options, such as gemcitabine, are less frequently used despite being less irritant and having similar efficacy. Further studies are needed to compare single-dose instillation regimens.