What are the adjuvant therapies for bladder cancer post-tumor resection?

From the Guidelines

Intravesical BCG therapy is the recommended adjuvant treatment for high-risk non-muscle-invasive bladder cancer after tumor resection, as it has been shown to decrease the risk of recurrence and is superior to TURBT alone or TURBT and chemotherapy in preventing recurrences of high-grade Ta and T1 tumors 1. The choice of adjuvant therapy for bladder cancer post-tumor resection depends on the cancer stage, grade, and individual patient factors.

Adjuvant Therapies

• Intravesical chemotherapy: Drugs like mitomycin C or gemcitabine are instilled directly into the bladder, typically within 24 hours after surgery. This is often done as a single dose to kill any remaining cancer cells.
• Intravesical immunotherapy: Bacillus Calmette-Guerin (BCG) is instilled into the bladder weekly for 6 weeks, starting 2-4 weeks after surgery. This stimulates the immune system to attack cancer cells.
• Systemic chemotherapy: For more advanced cases, drugs like cisplatin and gemcitabine may be given intravenously.
• Radiation therapy: External beam radiation may be used, especially if surgery isn't an option.
• Ongoing surveillance: Regular cystoscopies and urine cytology tests are crucial to monitor for recurrence. According to the most recent guidelines, BCG therapy is commonly given once a week for 6 weeks, followed by a rest period of 4 to 6 weeks, with a full reevaluation at week 12 (ie, 3 months) after the start of therapy 1. Several meta-analyses demonstrate that BCG after TURBT is superior to TURBT alone or TURBT and chemotherapy in preventing recurrences of high-grade Ta and T1 tumors 1. It's essential to follow the prescribed regimen closely and attend all follow-up appointments to ensure the best possible outcome. In patients with extensive comorbid disease or poor performance status who are noncystectomy candidates, treatment options include concurrent chemoRT, RT alone, or TURBT alone, with chemoRT with cisplatin alone or 5-FU and mitomycin C being the recommended option 1.

From the FDA Drug Label

Cisplatin Injection is indicated as therapy to be employed as follows: ... Advanced Bladder Cancer Cisplatin Injection is indicated as a single agent for patients with transitional cell bladder cancer which is no longer amenable to local treatments, such as surgery and/or radiotherapy. The adjuvant therapies for bladder cancer post-tumor resection are not explicitly stated in the provided drug label. However, it can be inferred that cisplatin may be used as a single agent in patients with advanced bladder cancer that is no longer amenable to local treatments such as surgery.

• Key points:
  • Cisplatin is indicated for advanced bladder cancer
  • Cisplatin is used as a single agent
  • The label does not explicitly address adjuvant therapies post-tumor resection 2

From the Research

Adjuvant Therapies for Bladder Cancer Post-Tumor Resection

Adjuvant therapies for bladder cancer post-tumor resection include:

• Intravesical Bacillus Calmette-Guérin (BCG) therapy, which remains the standard of care in the treatment of bladder carcinoma in situ and as adjuvant therapy after thorough transurethral resection of high-grade non-muscle-invasive bladder cancer 3
• Intravesical chemotherapy, such as mitomycin C, gemcitabine, and docetaxel, which can be used as salvage options for patients who are unresponsive to BCG therapy 4, 5
• Device-assisted chemotherapy, which is currently being investigated as a potential treatment option 3
• Radiation-based treatment, which is also being explored as a possible therapy 3
• Checkpoint inhibitors, such as programmed death-1/programmed death ligand-1, which are being studied as novel therapies for bladder cancer 3, 6

Treatment Options After BCG Failure

For patients who experience disease recurrence after BCG failure, treatment options include:

• Radical cystectomy, which is the recommended treatment for high-risk patients failing BCG 4
• Intravesical therapy with gemcitabine, mitomycin combined with thermo-chemotherapy, docetaxel, nab-paclitaxel, photodynamic therapy (PDT), BCG with interferon (IFN), and combination sequentially administered chemotherapy 4
• Emerging treatments, such as novel agents and bladder-sparing strategies, which are currently being tested in clinical trials 6

Role of Mitomycin C in Intermediate-Risk Non-Muscle-Invasive Bladder Cancer

Mitomycin C (MMC) instillations are recommended to prevent recurrence of intermediate-risk non-muscle-invasive bladder cancer (IR-NMIBC) 7

• The optimal regimen and dose of MMC are uncertain, but estimates suggest that MMC induction plus maintenance can provide short-term recurrence-free survival (RFS) rates equivalent to those for BCG maintenance in IR-NMIBC 7
• A dose of 40 mg MMC appears to be more effective in preventing recurrence than 30 mg MMC 7