Chap93N NMIBC management

• MMC 
• Epirubicin - used in europe

A single dose administered within 6 hours lessens recurrence rates, whereas a dose 24 hours later does not.

BCG can never be safely administered immediately after TUR because the risk of bacterial sepsis and death is high

• Induced expression of cytokines in the urine and bladder wall and by an influx of granulocytes, mononuclear, and dendritic cells.
• The initial step appears to be direct binding to fibronectin within the bladder wall, subsequently leading to direct stimulation of cell-based immunologic response and an antiangiogenic state. 
• The observed pattern of cytokine induction with preferential upregulation of interferon-γ, IL-2, and IL-12 reflects induction of a T-helper type-1 (Th1) response.

• In patients with intermediate- and high-risk tumours, intravesical BCG after TURB reduces the risk of tumour recurrence.
• It is more effective than TURB alone or TURB +intravesical chemotherapy. 
• Three-year maintenance is more effective than one year to prevent recurrence in patients with high-risk tumours, but not in patients with intermediate-risk tumours.

• Treatments begun 2 to 4 weeks after tumor resection, allowing time for reepithelialization, which minimizes the potential for intravasation of live bacteria. 
• For the same reason, a urinalysis is usually performed immediately before instillation to further ensure a diminished probability of systemic uptake of BCG.
• In the event of a traumatic catheterization, the treatment should be delayed for several days to 1 week, depending on the extent of injury.
• After instillation, the patient should retain the solution for at least 2 hours. Some clinicians have advocated the patient turn from side to side to bathe the entire urothelium, but there is no scientific support for this practice.
• Fluid, diuretic, and caffeine restriction before instillation is essential to limit dilution of the agent with urine and to facilitate retention of the agent for 2 hours

Induction phase: weekly for six weeks, followed by check cystoscopy ad cytology. 

Maintenance phase: on 3,6,12,18,24,30,36 months for 3 weeks on each phase.

Quinolones may affect the viability of BCG and should be avoided if possible during the course of BCG treatments

• Absolute Contraindications: 
• Immunosuppressed and immunocompromised patients
• Immediately after transurethral resection on the basis of the risk of intravasation and septic death
• Personal history of BCG sepsis
• Gross hematuria (intravasation risk)
• Traumatic catheterization (intravasation risk)
• Total incontinence (patient will not retain agent)

• Relative Contraindications
• Urinary tract infection (intravasation risk)
• Liver disease (precludes treatment with isoniazid if sepsis occurs)
• Personal history of tuberculosis (risk theorized but unknown)
• Poor overall performance status
• Advanced age
• No or Insufficient Data on Potential Need for Contraindications
• Patients with prosthetic materials
• Ureteral reflux
• Anti–tumor necrosis factor medications (theoretically predispose to BCG sepsis)

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Potential superiority of the combination or the possibility of decreasing the dosage of BCG, which may reduce side effects.

BCG refractory - nonimproving or worsening disease despite BCG

BCG resistant - recurrence or persistence of lesser degree, stage, or grade after an initial course, which then resolves with further BCG

BCG relapsing - recurrence after initial resolution with BCG

BCG-refractory patients in particular are an especially high-risk group and should be strongly considered for immediate cystectomy if young and in generally good health.

Declaring failure may take up to 6 months because the response rate for patients with high-grade bladder cancer treated with BCG rose from 57% to 80% between 3 and 6 months after therapy

• CIS cannot be cured by an endoscopic procedure alone.
• Compared to intravesical chemotherapy, BCG treatment of CIS increases the complete response rate, the overall percentage of patients who remain disease free, and reduces the risk of tumour progression.