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How to Prevent Prostate Cancer Recurrence: The Role of Immunotherapy and Focal Therapy

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Understanding Prostate Cancer Recurrence and Risk Factors

How Likely Is Prostate Cancer to Come Back?

“How likely will my prostate cancer return?” A question many patients ask themselves.

Prostate cancer recurrence occurs when cancer returns after treatment and a period of remission. The likelihood of recurrence varies depending on factors such as the stage of cancer at diagnosis, the type of treatment received, and individual patient characteristics.1 For many men, the fear of recurrence can be overwhelming, making it essential to understand the risk factors and potential strategies to prevent it.

The risk of recurrence is typically calculated for traditional therapies using the Han Tables, which consider factors like PSA levels and Gleason score. These tables are primarily based on treatment options like radiation therapy, hormone therapy, and surgery, which have been standard in managing prostate cancer. While these treatments can be effective, they come with significant side effects, and their ability to prevent long-term recurrence is limited. There is reason to believe that focal therapy might reduce recurrence risk by releasing cancer antigens that could train the immune system, but clinical studies are still lacking to confirm this.2 However, none of these approaches directly engage the immune system as effectively as immunotherapy, which offers a unique mechanism to prevent recurrence.

Leveraging Immunotherapy to Prevent Prostate Cancer Recurrence

What is Immunotherapy and How Does It Work for Prostate Cancer?

Immunotherapy is an innovative treatment approach that leverages the body’s immune system to fight cancer. Unlike traditional treatments like chemotherapy or radiation, which directly target cancer cells, immunotherapy works by enhancing the immune system’s ability to recognise and attack cancer cells.3 In prostate cancer, immunotherapy has shown promise, particularly in reducing the risk of recurrence.4,5

Can Immunotherapy Prevent Prostate Cancer Recurrence?

Studies suggest that immunotherapy can significantly reduce the risk of cancer recurrence by eliminating residual cancer cells that may persist after initial treatment.6 By boosting the immune system, immunotherapy helps to create a long-lasting defense against cancer, potentially preventing it from returning. However, while the results are promising, further research is needed to fully understand the long-term benefits of immunotherapy in preventing prostate cancer recurrence.

Combining Focal Therapy with Immunotherapy for Better Outcomes

How Focal Therapy Works to Target Prostate Cancer

Focal therapy refers to a range of treatments that target specific areas of the prostate affected by cancer, rather than treating the entire gland. The most common focal therapies include cryotherapy (freezing cancer cells), high-intensity focused ultrasound (HIFU), and laser ablation. More advanced focal therapies, such as irreversible electroporation (IRE) and electrochemotherapy (ECT) are now also employed for prostate cancer and can even be employed in advanced prostate cancer cases, precluding some traditional and other focal therapies. These treatments aim to destroy cancer cells while minimising damage to surrounding healthy tissue.2

The Synergy Between Focal Therapy and Immunotherapy

When focal therapy is used to treat prostate cancer, it not only destroys cancer cells but also releases cancer antigens—proteins that the immune system can recognise as targets.2 This process effectively “teaches” the immune system how to identify and attack prostate cancer cells. When combined with immunotherapy, this approach can be particularly effective in preventing recurrence. The focal therapy primes the immune system, while the immunotherapy boosts its ability to seek out and destroy any remaining cancer cells, reducing the likelihood of recurrence.2

Clinical Evidence Supporting Combination Therapy

Research has shown that combining focal therapy with immunotherapy can lead to better outcomes compared to using either treatment alone.2 For example, studies have indicated that patients receiving both treatments have lower rates of recurrence and improved survival rates. This combination therapy approach is an exciting development in the fight against prostate cancer, offering new hope for patients at risk of recurrence.

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The Effectiveness of Immunotherapy in Prostate Cancer: Beyond Initial Treatment

How Effective Is Immunotherapy for Prostate Cancer?

Immunotherapy has emerged as a promising treatment for prostate cancer, particularly in its ability to engage the body’s immune system in the fight against cancer. However, its effectiveness varies depending on the stage of the cancer and the specific characteristics of the tumor. For early-stage prostate cancer, immunotherapy alone may not be sufficient to eradicate the disease, but it has shown more promise in advanced or metastatic cases, particularly when combined with other therapies.11

One of the most well-known immunotherapies for prostate cancer is sipuleucel-T (Provenge), which has been approved for the treatment of metastatic prostate cancer. Clinical trials have shown that Provenge can extend overall survival in some patients by helping the immune system target and destroy cancer cells more effectively.12 However, it’s important to note that not all patients respond to immunotherapy in the same way, and ongoing research is crucial to identifying which patients are most likely to benefit from this treatment.

Keytruda (Pembrolizumab): A Promising Immune Checkpoint Inhibitor

Keytruda (pembrolizumab) is another type of immunotherapy that has garnered significant attention in recent years. Unlike Provenge, which is a form of active cellular immunotherapy, Keytruda is an immune checkpoint inhibitor. It works by blocking the PD-1 protein on the surface of immune cells. Under normal circumstances, PD-1 acts as a “brake” to prevent the immune system from attacking normal cells. However, many cancer cells exploit this pathway to evade immune detection. By inhibiting PD-1, Keytruda releases this brake, allowing the immune system to recognize and attack cancer cells more effectively.13

Keytruda has shown remarkable success in treating various types of cancers, including melanoma, lung cancer, and head and neck cancers and has also shown success in prostate cancer.14 Early studies have shown that Keytruda can be particularly effective in prostate cancer patients whose tumors have specific genetic mutations, such as those involving DNA mismatch repair (MMR) genes or high microsatellite instability (MSI-H). These mutations make cancer cells more recognizable to the immune system, which may explain the enhanced response to Keytruda in these cases.15

However, by combining immunotherapy with focal therapy, such as irreversible electroporation (IRE), we enhance the immune system’s ability to recognize and attack cancer cells. Focal therapies like IRE induce non-thermal cell death, preserving the cancer cell antigens, which are then released into the body. This antigen release is crucial because it primes the immune system, allowing treatments like Keytruda to more effectively target both the primary tumor and distant metastases. Unlike traditional therapies or even some focal therapies like HIFU, which can denature proteins and reduce antigen visibility, IRE ensures that these markers remain intact, thereby optimizing the immune response and improving overall treatment efficacy.

Other Emerging Immunotherapies

In addition to Provenge and Keytruda, several other immunotherapy approaches are being studied for their potential to treat prostate cancer. These include16:

  • CTLA-4 Inhibitors: Another class of immune checkpoint inhibitors targets the CTLA-4 protein, which also acts as a brake on the immune system. Ipilimumab (Yervoy) is one such drug that has shown promise in treating advanced melanoma and is currently being studied for use in prostate cancer. Although the results in prostate cancer have been mixed so far, combining CTLA-4 inhibitors with other therapies may enhance their effectiveness.
  • CAR T-Cell Therapy: Chimeric Antigen Receptor (CAR) T-cell therapy involves modifying a patient’s T-cells in the laboratory to express receptors that recognize specific proteins on cancer cells. These engineered T-cells are then infused back into the patient, where they seek out and destroy cancer cells. While CAR T-cell therapy has shown tremendous success in treating certain blood cancers, its application in solid tumors like prostate cancer is still in the experimental stages. Researchers are working on improving CAR T-cell therapy’s ability to penetrate solid tumors and persist in the body long enough to effectively combat the cancer.
  • Cancer Vaccines: Beyond Provenge, researchers are developing other types of cancer vaccines designed to stimulate the immune system to attack prostate cancer cells. These vaccines often contain tumor-associated antigens or peptides that are unique to prostate cancer cells. By presenting these antigens to the immune system, the vaccines aim to trigger a robust and sustained immune response against the cancer. Although still in the experimental stages, these vaccines represent a promising avenue for the treatment of prostate cancer, especially in combination with other immunotherapies.
  • Adoptive T-Cell Therapy: This approach involves extracting T-cells from a patient, expanding and activating them in a laboratory, and then infusing them back into the patient to fight the cancer. This technique is similar to CAR T-cell therapy but does not involve genetic modification. Instead, it relies on enhancing the patient’s existing immune response. Early trials have shown that adoptive T-cell therapy can lead to tumor regression in some prostate cancer patients, particularly when combined with other treatments.
  • Monoclonal Antibody Therapies: Monoclonal antibodies are lab-made proteins that can bind to specific targets on cancer cells. They can either directly attack cancer cells or mark them for destruction by the immune system. Researchers are investigating the potential of monoclonal antibodies in prostate cancer, particularly when combined with other immunotherapies. These therapies are being explored for their ability to target prostate cancer cells more precisely and stimulate a more effective immune response.

Additional Strategies to Prevent Prostate Cancer Recurrence

Monitoring and Early Detection

Preventing prostate cancer recurrence is not solely about treatment; it also involves vigilant monitoring and early detection. Regular PSA testing, imaging studies, and follow-up appointments with your healthcare provider are critical components of a proactive approach to managing prostate cancer after initial treatment. Early detection of a recurrence can lead to more effective interventions and better outcomes.

Lifestyle Modifications and Dietary Interventions

Beyond medical treatments, lifestyle factors play a significant role in preventing prostate cancer recurrence. Research has shown that maintaining a healthy weight, engaging in regular physical activity, and following a diet rich in fruits, vegetables, and whole grains can reduce the risk of recurrence. Specifically, diets low in red and processed meats and high in antioxidants and omega-3 fatty acids have been associated with better outcomes in prostate cancer survivors.1,18

The Importance of Mental Health and Stress Management

Mental health and stress management are often overlooked but are vital components of cancer care. Chronic stress has been shown to negatively impact immune function, potentially increasing the risk of cancer recurrence. Incorporating stress-reducing activities such as yoga, meditation, and counseling into a post-treatment plan can improve overall well-being and may contribute to a lower risk of recurrence.

Conclusion: The Road Ahead for Prostate Cancer Survivors

Optimising Treatment and Prevention Strategies

The future of prostate cancer treatment lies in personalised approaches that combine the best of medical innovation with proactive lifestyle strategies. Immunotherapy, particularly when used in combination with other treatments like focal therapy, offers a powerful tool in the fight against prostate cancer recurrence. As research continues to evolve, the potential for these therapies to improve survival rates and quality of life for prostate cancer survivors is becoming increasingly clear.

A Holistic Approach to Long-Term Health

Prostate cancer survivors should work closely with their healthcare providers to develop a comprehensive plan that includes regular monitoring, appropriate use of therapies, and lifestyle modifications. By taking a holistic approach to health, survivors can not only reduce their risk of recurrence but also enhance their overall well-being. The integration of advanced treatments like immunotherapy with everyday health practices represents the best strategy for long-term survival and quality of life.

Immunotherapy at Vitus private clinic

Grounded in our promise to advance patient care, we offer immunotherapy as part of our services. Not only that, but we employ it in different ways, we think could most benefit our patients. While ongoing research indicates that it can reduce the chance of recurrences, we have also seen the immediate (short-term) impacts of combining our focal therapies with immunotherapy. In one of our patients, a metastasised prostate cancer was completely eradicated after combined application of Electrochemotherapy and Immunotherapy with Pembrolizumab (Keytruda).

Find out more about Immunotherapy at Vitus Privatklinik

  1. WebMD. (n.d.). Can You Keep Prostate Cancer From Coming Back? Retrieved from WebMD ↩︎
  2. Jiang, M., Fiering, S., & Shao, Q. (2023). Combining energy-based focal ablation and immune checkpoint inhibitors: preclinical research and clinical trials. Frontiers in Oncology, 13, 1153066. doi:10.3389/fonc.2023.1153066. Retrieved from NCBI ↩︎ ↩︎
  3. Hopkins Medicine. (n.d.). Immunotherapy Precision Medicine in Action: Policy Brief. Retrieved from Hopkins Medicine ↩︎
  4. BCI Queen Mary University of London. (2022, February). New drug combination significantly reduces recurrence in aggressive breast cancer. Retrieved from BCI Queen Mary University of London  ↩︎
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  8. Jiang, M., Fiering, S., & Shao, Q. (2023). Combining energy-based focal ablation and immune checkpoint inhibitors: preclinical research and clinical trials. Frontiers in Oncology, 13, 1153066. doi:10.3389/fonc.2023.1153066. Retrieved from NCBI ↩︎ ↩︎
  9. Jiang, M., Fiering, S., & Shao, Q. (2023). Combining energy-based focal ablation and immune checkpoint inhibitors: preclinical research and clinical trials. Frontiers in Oncology, 13, 1153066. doi:10.3389/fonc.2023.1153066. Retrieved from NCBI ↩︎ ↩︎
  10. Jiang, M., Fiering, S., & Shao, Q. (2023). Combining energy-based focal ablation and immune checkpoint inhibitors: preclinical research and clinical trials. Frontiers in Oncology, 13, 1153066. doi:10.3389/fonc.2023.1153066. Retrieved from NCBI ↩︎ ↩︎
  11. Bilusic, M., Madan, R. A., & Gulley, J. L. (2017). Immunotherapy of prostate cancer: Facts and hopes. Clinical Cancer Research, 23(22), 6764–6770. doi:10.1158/1078-0432.CCR-17-0019. Retrieved from PMC ↩︎
  12. Anassi, E., & Ndefo, U. A. (2011). Sipuleucel-T (Provenge) injection: The first immunotherapy agent (vaccine) for hormone-refractory prostate cancer. P&T, 36(4), 197–202. Retrieved from PMC  ↩︎
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  18. Liu, V. N., Van Blarigan, E. L., Zhang, L., Graff, R. E., Loeb, S., Langlais, C. S., Cowan, J. E., Carroll, P. R., Chan, J. M., & Kenfield, S. A. (2024). Plant-based diets and disease progression in men with prostate cancer. JAMA Network Open, 7(5), e249053. doi:10.1001/jamanetworkopen.2024.9053. Retrieved from JAMA Network Open ↩︎