Immunotherapy in Urological Cancers

Introduction

Immunotherapy is an innovative and promising approach to treating urological cancers, leveraging the power of the immune system to fight against all types of cancer cells. Over the past few decades, understanding of the immune system and its role in cancer has grown humorously. This has led to significant advancements in immunotherapy treatments for various urological malignancies, including bladder, kidney, and prostate cancers.

What Is the Role of the Immune System Against Cancer?

The immune system is a very critical component in cancer prevention and treatment. It constantly scans the body, reads each cell, and detects the potential cancer cells and sites of infection. The immune system conducts a series of cellular interactions and checkpoints to avoid mistakenly attacking healthy cells and tissues. Cancer cells can exploit these checkpoints to evade the immune system's response, effectively hiding from detection.

Checkpoint inhibitors belong to a class of immunotherapy drugs that block these regulatory cellular interactions, unmasking cancer cells and allowing the immune system to attack them. These drugs have shown success in treating urological cancers, particularly urothelial cell carcinoma (UCC) of the bladder and upper tracts, and have significantly improved patient outcomes.

When Is the Best Time to Use an Immunotherapy?

• Patients with bladder cancer that is not muscle aggressive are mostly treated with BCG.

• Patients who are metastatic or in a late stage are currently provided checkpoint inhibitors.

• For individuals with bladder cancer in stages III or IV who are unable to undergo a major procedure, immunotherapy is a suitable choice.

• Immunotherapy may be helpful for patients whose other medical conditions prevent them from receiving chemotherapy.

• Immunotherapy is an option for patients with advanced bladder cancer who grow back or return after treatment.

• Patients receiving immunotherapy early in the process (during surgery, for instance) are part of several clinical trials.

What Are There Long-Term Side Effects of Immunotherapy?

• Weakness and Tiredness.

• Appetite decrease.

• High temperature.

• UTIs, or urinary tract infections.

• Irritation.

• Constipation.

Infusion Response: When receiving one of these medications, some patients may experience an infusion reaction. Similar to an allergic reaction, this can cause fever, chills, facial flushing, rash, itching skin, vertigo, asthma, and breathing difficulties. When taking one of these medications, it is critical to notify a physician or nurse straight away if experience any of these side effects.

Reactions on the Immune System: These medications function by essentially taking away one of the body's defenses. There are situations when the body's defense system attacks other organs, lungs, intestines, liver, hormone-producing glands, and other organs, posing a severe or even fatal risk.

What Are Immunotherapy for Bladder Cancer and Other Urologic Cancers?

The following are the different immunotherapy for urological cancer.

Bacillus Calmette-Guerin (BCG):

Bacillus Calmette-Guerin is a weak form of tuberculosis bacteria and has been used as an immunotherapy treatment for bladder cancer for over 40 years. Bacillus Calmette-Guerin is administered directly into the bladder as a liquid and stimulates the immune system to attack cancer cells in the bladder. This therapy has been beneficial in treating non-muscle invasive bladder cancer (before it has grown deep into the tissue) and is also being studied in other types of cancer.

Immune Checkpoint Inhibitors:

Immune checkpoint inhibitors are drugs that limit the checkpoints on the surface of cancer cells, preventing them from hiding from the immune system. By blocking these checkpoints, T cells (the immune system's killer cells) can find and attack cancer cells. Examples of checkpoint proteins found on T cells or cancer cells include PD-1 (Programmed cell death receptor 1), PD-L1 (Programmed cell death ligand 1), and CTLA-4 (Cytotoxic T lymphocyte-associated molecule 4).

Atezolizumab, Durvalumab, and Avelumab:

These drugs target PD-L1 on some cancer cells, preventing them from hiding and boosting the immune response to fight against the cancer cells. This leads to shrinkage of the tumors or slower tumor growth.

Nivolumab and Pembrolizumab:

These drugs target PD-1, another protein that helps regulate the immune system. By blocking PD-1, these drugs enable the immune system to attack cancer cells, which can shrink some tumors or slow their growth. Checkpoint inhibitors are used in various situations to treat bladder cancer, including as a first-line treatment for advanced bladder cancer, in combination with other therapies, and in patients who are not candidates for chemotherapy.

Antibody-Drug Conjugates:

Antibody-drug conjugates (ADCs) are monoclonal antibodies linked to chemotherapy drugs. The antibody portion of the antibody-drug conjugates acts as a homing device, bringing the chemotherapy directly to cancer cells, reducing side effects, and improving treatment efficacy. Antibody-drug conjugates (ADC) used in urological cancers include drugs like Enfortumab and Sacituzumab.

When Are the Indications of Immunotherapy for Urological Cancers?

• Immunotherapy treatments for urological cancers are typically used in specific situations, depending on the stage and type of cancer. Some examples include:

• BCG is primarily used for non-muscle invasive bladder cancer

• Checkpoint inhibitors are offered to late-stage or metastatic patients.

• Immunotherapy is suitable for stage III or IV bladder cancer patients who cannot undergo major surgery.

• Patients who cannot tolerate chemotherapy due to other health problems may benefit from immunotherapy.

• People with advanced bladder cancer that recurs or grows again after chemotherapy may consider immunotherapy.

• Clinical trials may provide immunotherapy to patients earlier in the treatment process (For example., during surgery).

What Are the Benefits of Immunotherapy?

Immunotherapy has shown promising results in treating urological cancers, with some patients experiencing extended survival rates compared to chemotherapy. Additionally, immunotherapy may help shrink tumors and alleviate pain caused by cancer. In many cases, immunotherapy has fewer side effects than traditional chemotherapy, making it a more tolerable treatment option for some patients.

What Are the Risks and Side Effects of Immunotherapy?

While immunotherapy can offer significant benefits, it is not without risks and side effects. Common side effects of immunotherapy for urological cancers include:

• Fatigue.

• Nausea.

• Diarrhea.

• Skin reactions.

In some patients, more severe side effects can occur, such as autoimmune reactions, inflammation in the lungs, liver, or colon, and the development of new autoimmune diseases.

It is crucial to discuss the potential benefits and risks of immunotherapy with the healthcare team to determine if it is the right treatment option for the patient.

Who Is a Good Candidate for Immunotherapy in Urological Cancers?

The best candidates for immunotherapy in urological cancers are those with specific types and stages of cancer, as well as a strong overall health profile. Some factors to consider when determining if a patient is a good candidate for immunotherapy include:

• The size and number of tumors.

• The aggressive nature of the tumor.

• The grade of the tumor (high grade is more aggressive).

• If tumors have recurred.

• The overall health of the patient.

What Is the Future of Immunotherapy in Urological Cancer?

Immunotherapy is a rapidly evolving field of cancer treatment, with ongoing research and clinical trials investigating new treatment options and combinations for urological cancers. As current treatment modalities, the immune system plays an important role in cancer continues to grow. It can be expected to see even more innovative and effective immunotherapy treatments for bladder cancer and other urologic malignancies in the future.

Conclusion

In conclusion, immunotherapy holds great promise in treating urological cancers, providing new and effective options for patients with limited choices as research and clinical trials continue to expand the understanding of the immune system's role in cancer. Looking forward to even more advancements in this promising treatment field. It is always recommended to consult the health care professional for the best treatment option available