What is the role of immunotherapy in urology?

From the Guidelines

Immunotherapy has become a crucial component in the treatment of urologic cancers, particularly for advanced bladder cancer, with immune checkpoint inhibitors like pembrolizumab, nivolumab, and atezolizumab being standard treatments after platinum-based chemotherapy failure, as supported by the most recent guideline from 2022 1.

Key Points

• Immunotherapy has revolutionized the treatment of advanced bladder cancer and renal cell carcinoma.
• Immune checkpoint inhibitors such as pembrolizumab, nivolumab, and atezolizumab are now standard treatments for metastatic bladder cancer after platinum-based chemotherapy failure, with some approved for first-line use in cisplatin-ineligible patients.
• These immunotherapies work by blocking proteins like PD-1, PD-L1, or CTLA-4, enhancing the immune system's ability to recognize and destroy tumors.
• Patients receiving these treatments require regular monitoring for immune-related adverse events, which can affect any organ system but commonly include fatigue, rash, colitis, hepatitis, and endocrinopathies.
• Early recognition and prompt management of these side effects with corticosteroids or other immunosuppressants is essential for optimal outcomes while maintaining treatment efficacy, as highlighted in recent studies 1.

Treatment Recommendations

• For metastatic bladder cancer, consider using immune checkpoint inhibitors like pembrolizumab (200mg IV every 3 weeks), nivolumab (240mg IV every 2 weeks), or atezolizumab (1200mg IV every 3 weeks) after platinum-based chemotherapy failure.
• In advanced renal cell carcinoma, combination therapies such as pembrolizumab plus axitinib or nivolumab plus ipilimumab may be considered, as they have demonstrated superior outcomes compared to traditional tyrosine kinase inhibitors alone 1.

Monitoring and Management

• Regularly monitor patients for immune-related adverse events, which can affect any organ system.
• Promptly manage side effects with corticosteroids or other immunosuppressants to maintain treatment efficacy and ensure optimal outcomes.
• Consider the latest guidelines and consensus statements, such as those from the European Society for Medical Oncology (ESMO) 1, when making treatment decisions.

From the FDA Drug Label

KEYTRUDA, in combination with enfortumab vedotin, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer KEYTRUDA, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma: who are not eligible for any platinum-containing chemotherapy, or who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy KEYTRUDA, as a single agent, is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

The role of immunotherapy in urology is to treat various types of urothelial cancer, including:

• Locally advanced or metastatic urothelial cancer in combination with enfortumab vedotin
• Locally advanced or metastatic urothelial carcinoma as a single agent in patients who are not eligible for platinum-containing chemotherapy or have disease progression during or following platinum-containing chemotherapy
• BCG-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) as a single agent in patients who are ineligible for or have elected not to undergo cystectomy 2, 2.

From the Research

Role of Immunotherapy in Urology

• Immunotherapy has played an essential role in treating urologic malignancies, with the development of immune checkpoint inhibitors (ICIs) being critical to urology 3
• Immunotherapeutic agents have been used to treat urothelial carcinoma, including BCG, interferon, anti-PD-1 (pembrolizumab, nivolumab), and anti-PD-L1 (atezolizumab, avelumab, durvalumab) 3, 4
• Renal cell carcinoma (RCC) has been known for its unique sensitivity to immunotherapies, with ICIs blocking PD-1/PD-L1 or CTLA4 signalling pathways being used as first-line treatment for metastatic RCC 3, 5
• Prostate cancer, considered an immunologically "cold" tumor, has seen the emergence of immunotherapeutic agents as an essential area in its treatment, particularly in castration-resistant prostate cancer 3
• Targeted and immunotherapy have been approved for the management of advanced urothelial carcinoma of the bladder, including pembrolizumab, avelumab, and nivolumab 4
• Immunotherapy based on tumor microenvironment has shown promise in clinical application for RCC, with the combination of targeted therapy and immunotherapy exhibiting a promising prospect 5
• Ongoing clinical trials are investigating the use of immunotherapy for bladder cancer, including novel approaches such as checkpoint inhibitor drugs 6

Types of Immunotherapies Used

• BCG (Bacillus Calmette-Guerin) for non-muscle invasive bladder cancer 3, 6
• Interleukin-2 for renal cell carcinoma 7
• Anti-PD-1 (pembrolizumab, nivolumab) for urothelial carcinoma and RCC 3, 4
• Anti-PD-L1 (atezolizumab, avelumab, durvalumab) for urothelial carcinoma and RCC 3, 4
• Ipilimumab for prostate cancer 3
• Sipuleucel T (vaccine-based) for prostate cancer 3

Future Directions

• Combination therapies, such as nivolumab/ipilimumab and pembrolizumab/axitinib, have become the standard first-line treatment for metastatic RCC 3
• Ongoing randomized clinical trials are investigating the use of immunotherapies in the adjuvant setting for urothelial carcinoma and RCC 3, 4
• Novel approaches, such as antitumoral monoclonal and bi-specific antibodies, manipulation of T-lymphocyte costimulatory molecules, and the administration of newly discovered cytokines, are being developed for the treatment of urological malignancies 7