Immunotherapy for Prostate Cancer

The human immune system is the body’s natural defense against potentially damaging foreign pathogens.

When functioning properly, it identifies and attacks a wide variety of threats to the body’s health, including viruses, bacteria, parasites, and cancerous growths, distinguishing them from the body’s healthy tissue and, hopefully, destroying them before they can have a harmful effect.

Cancer immunotherapy, also known as immuno-oncology, is a relatively new form of cancer treatment that uses the power of the body’s own immune system to attack various cancers by either activating or suppressing the immune response.

There are two types of immunotherapies. Those designed to create or amplify an immune response are classified as activation immunotherapies, while those that reduce the body’s immune response are classified as suppression immunotherapies. 

Activation immunotherapy is a fast-growing subspecialty of oncology designed to artificially stimulate the immune system to enhance its ′s natural ability to fight cancer.

The idea is to exploit the fact that cancer cells often have specific tumor antigens embedded in their surface that are detected by the immune system’s antibody proteins. These immune antibodies bind to the tumor′s antigens flagging the cancer cells for the immune system. Specialized killer cells in the immune system are then drawn to cancer and begin to destroy it. 

Suppression immunotherapy has long been used to treat allergies, to reduce the rejection of transplanted organs. It dampens autoimmunity to reduce inflammation in diseases such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis. 

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Castrate Resistant Prostate Cancer

Prostate cancer in some individuals is dependent on testosterone levels. The association between testosterone and prostate cancer growth was documented in 1941 by urologist Dr. Charles Huggins.

He performed surgical removal of the testicles (orchiectomy) on several men with advanced metastatic prostate cancer, depriving them of circulating testosterone. His finding was generally that cancer stopped progressing due to the testosterone deprivation. However, this is only true in some instances. 

Today, the practice of surgical castration has been essentially eliminated in favor of medical castration using androgen deprivation drugs, typically known as androgen deprivation therapy (ADT or hormone therapy). The current research indicates that only a small percentage of prostate cancer is naturally castrate-resistant. 

Due to the work of Huggins, many doctors still believe that testosterone fuels prostate cancer growth. Thus, they are reluctant to use any kind of testosterone supplementation, even for non-cancer patients, for fear of inducing prostate cancer. This supposition has been debunked for the past couple of decades, but entrenched ideas often become die-hard dogma. 

The body has an amazing ability to bring itself back into balance. The process of androgen deprivation for prostate cancer patients using pharmaceutical drugs often triggers the body to find new ways to produce what it needs to maintain cancer growth. Thus, the benefits of slowed cancer growth due to ADT treatment are typically only observed for a limited time and are generally used for extreme cases. 1 

Androgen deprivation drugs stop the testicles from making androgens like testosterone. Still, other cells in the body, such as the adrenal glands, can adapt to produce androgens, replacing those lost to the therapy. In addition, prostate cancer cells themselves can still make male hormones. This accounts for at least some of the failure of the androgen deprivation therapy over time. 

Unfortunately, once the patient’s prostate cancer has become resistant to testosterone level reduction via hormone therapy (castrate-resistant), treatment options are limited. Thus, ADT is typically used to treat severe metastatic prostate cancer, and therapy is alternated to try to avoid resistance.

Immunotherapy Therapy for Prostate Cancer

Immunotherapy is an option for prostate cancer that induces the body to attack cancer using the body′s own immune system. It is an artificial stimulation of the immune system attempting to improve the body’s natural ability to fight the disease. 

The human immune system is always on guard for things that look out of the ordinary. Immunotherapy is a way to use the power of the body’s own immune system to repel cancer.

Immunology for prostate cancer is a relatively new subspecialty of oncology that uses fundamental research and clinical trials to determine new ways of fighting various cancers. This field is rapidly expanding, with numerous practitioners proposing novel new or modified ways to treat advanced prostate disease

While several immunotherapies are FDA approved, there are only two currently FDA-approved immunotherapy options for prostate cancer; Provenge (Sipuleucel-T) and Pembrolizumab (Keytruda).

Provenge (Sipuleucel-T)

The most studied FDA and recently approved immunotherapy option. It is essentially a vaccine that is designed to train the immune system to recognize the patient′s specific cancer cells and help destroy them. The clinical trials for Provenge included men with metastatic castrate-resistant prostate cancer, some of whom failed chemotherapy and therefore had exhausted many other treatment options. 

Provenge is pioneering immunotherapy that is used in men with advanced, metastatic hormone-resistant prostate cancer. It targets a protein that is produced by the cancer and is approved for subsets of patients with advanced prostate cancer. Provenge is a personalized immunotherapy vaccine, composed of patients” own immune cells. 

Most prostate cancer cells express an antigen called prostatic acid phosphates, or PAP. Provenge enhances the ability of the immune system to recognize cancer cells with PAP and attack them. It has been shown to help specific prostate cancer patients live longer. In essence, Provenge activates immune cells to identify prostate cancer as abnormal cells better and destroy them. 

The treatment involves extracting the white blood cells (immune cells) from the patient and activating the T-cells to recognize and destroy the patient′s prostate cancer cells. The activated cells are then returned to the patient. Since the patient donates the blood cells, there is little chance of rejection. The most common side effects are flu-like symptoms that last about 24 hours. This infusion process is repeated three times on a bi-monthly basis.  

While the testing and use today has been on men with advanced prostate cancer, it is hoped that when Provenge is used on men with a smaller tumor burden, it will result in a much better overall survival benefit. 2.

Pembrolizumab (Keytruda)

The other approved immunotherapy for prostate cancer. It falls in the checkpoint inhibitors class and is approved for specific subsets of advanced prostate cancer patients. 

A significant player in the human immune system is known as a T-cell. Along with others, these cells are designed to help the body’s immune system attack and destroy cancer cells. A checkpoint inhibitor such as Keytruda blocks certain proteins made by the cancer cells from killing cancer cells. Blocking these inhibitors unleashes T cells, freeing them to interact more intensely and directly with the cancer cells to destroy them. 

The first checkpoint inhibitor was approved in 2011 for advanced melanoma. Keytruda targets a narrow set of immune pathways and is known as a T-cell-specific immune checkpoint inhibitor. Its goal is to elicit an immune response in the presence of tumor-associated antigens.

On May 23, 2017, Keytruda was granted accelerated approval by the (FDA) for the treatment of certain solid tumors, including prostate cancer. The drug is still under investigation for other types of prostate cancer. 3 

A relatively new drug, Ipilimumab (Yervoy), helps to down-regulate and reactivate a part of the immune system, thus reactivating the immune system to produce more cells that can attack the cancer; this reactivated immune response can then help the body to destroy cancer cells. Ipilimumab is currently approved by the European Medicines Agency to treat melanoma, lung cancer, and bladder cancer

Previous studies of Ipilimumab for prostate cancer did not show any significant survival advantage. However, a recently published long-term analysis of an international phase 3 clinical trial showed that overall survival was two to three times higher than in the placebo arm. This new data has resulted in several new studies being initiated for prostate cancer. 4

According to the American Cancer Society, a man diagnosed today with localized prostate cancer has a relative 10-year survival rate of about 98 percent. The survival rate for metastasized cancer is lower, but depending on the patient specifics, the level is near or greater than 90 percent for most men. 

Immunotherapy is one of the newer options that physicians are using to treat prostate and other cancers. Several immunotherapy options are currently in clinical trials for patients with advanced prostate cancer. As a result of the many options developed in the recent past to treat prostate cancer, it has become one of the most survivable cancers. 

However, while generally safe, immunotherapy should be carefully evaluated alongside other treatments whose outcome is more positive and studied. 5 

Clinical Trials for Prostate Cancer

Clinical trials for various drugs and techniques are ongoing, and new ones are proposed regularly. There are currently many trials related to prostate cancer treatment in progress in the United States alone. As of this article’s writing, there were 302 ongoing or proposed trials listed on the National Cancer Institute′s website. 6 

In addition, the Prostate Cancer Foundation has developed a tool to help prostate cancer patients easily find trials they may be eligible for. 7 

Clinical trials provide a valuable way for a man with prostate cancer to familiarize himself with the newest potential options for treating his disease. However, keep in mind that clinical trials are designed to discover new, novel ways to treat a disease. While they sometimes uncover valuable new drugs and techniques, some trials often fail completely. 

Before considering a clinical trial, every patient should thoroughly evaluate with his doctor whether his particular cancer can be treated effectively using a conventional, proven technique. Clinical trials are valuable, especially when conventional treatments have failed, but they also pose a significant risk that cancer may progress during a clinical trial that has little to no effect on it. 

Immunotherapy vs. Chemotherapy

Chemotherapy is the process of using strong chemical drugs to destroy cancer cells. Treatment requires a high degree of precision and monitoring due to the inevitable disturbance and destruction of healthy cells surrounding cancer. 

Chemotherapy is not usually used for prostate cancer but may help those with advanced or castration-resistant prostate cancer or those with newly diagnosed or hormone-sensitive metastatic prostate cancer. 

One of the major disadvantages of chemotherapy is that it can be toxic to healthy cells as well as cancerous ones. A major difference between chemotherapy and immunotherapy is that the latter does not normally harm healthy cells. Most chemotherapy treatments are cycled with a cycle’s length, depending on the cancer and the treatment drugs. Cycling helps minimize the effects on normal cells.

It is known that prostate cancer cells can induce tolerance for themselves within the immune system. Chemotherapy is sometimes used in conjunction with immunotherapy in such cases to treat advanced prostate cancers that have tumor-induced immune tolerance. 8 

Discussion

The human immune system is the body’s defense against all invaders. This includes bacteria, viruses, cancer, and minor infections. Its primary purpose is to detect and flag dangerous pathogens or growths for elimination. #

Cancer of any type represents a failure of the immune system. Theoretically, building the immune system can eliminate cancerous growths and restore the body to health.  

Vitamin C, also known as ascorbic acid, is a major immune support element and a potent antioxidant. As an essential cofactor in numerous chemical reactions in the body as well as in the regulation of various gene expressions, Vitamin C has a prominent role in human health. 

Studies in the 1970s and 1980s conducted by Linus Pauling, Ewan Cameron, and colleagues suggested that large doses of vitamin C (10 g/day) infused intravenously for 10 days helped increase the survival time of terminal cancer patients. Recent studies in mice have shown promise that vitamin C is a toxic agent against cancer cells.

Intravenous vitamin C has been used since the1970’ss for terminally ill cancer patients. Anecdotal reports have cited big increases in survival time. However, no randomized, controlled trials of Vitamin C’s efficacy on cancer patients’ survival have been conducted. As of this writing, some clinical trials are in progress, which may resolve this issue. 9 

Dr. Pauling′s experimentation showed that intravenous doses of Vitamin C increased the blood plasma concentration of the vitamin sufficiently to have an effect on terminal cancer. However, while there is a wealth of anecdotal evidence that supports this conclusion, no studies have ever conclusively proven that Vitamin C can cure cancer. Today, many institutions worldwide are using intravenous vitamin C as an adjunct treatment in the fight against COVID-19.

Note that the conventional medical community has questioned the efficacy of intravenous Vitamin C. Some of the reluctance to establish solid scientific testing of Vitamin C as a cancer therapy agent may be due to financial considerations.

Putting it simply, Vitamin C is a natural substance, not a patentable drug. Thus, a pharmaceutical company has a little financial incentive to devote expensive resources involved in creating and managing definitive studies on it. 

The Linus Pauling Institute in Washington provides an on-line micronutrient center with detailed, factual data on Vitamin C and many other vitamins and nutrients. 10  

Conclusion

Immunotherapy uses the patient’s own immune system to fight cancer. It is often employed on men with metastatic castrate-resistant prostate cancer when other standard, therapies, or treatment options have failed. 

Immunotherapies are generally safe and have few side effects. However, a downside is that the cancer may progress if the therapy used is ineffective. 

Prostate cancer is a curable disease for many men. Medical treatment is not really necessary for many men, but it is imperative to differentiate those men needing additional treatment after diagnosis. With prostate cancer, aggressive treatment can result in side effects that are far more debilitating than the disease. 

According to multiple studies published recently in respected peer-reviewed journals, overdiagnosis and overtreatment of prostate cancer have almost become a norm within our society. For example, the two most common treatments after a prostate cancer diagnosis are radical prostatectomy and radiation therapy. 

Both of these procedures commonly introduce severe side effects. In the case of the radical prostatectomy, side effects are immediate and with radiation therapy, delayed. However, any side effects are too many for a man whose cancer did not need medical intervention. 

Next Up

living with prostate cancer

Find out 10 Tips For Living with Prostate Cancer.

Sources

  1. Jeffrey Turner, MD, Is Testosterone the New Therapy for Prostate Cancer?, Prostate Cancer Research Institute blog, November 2015, Is. 18 Vol. 4
  2. Dendreon, PROvenge Treatment and Early Cancer Treatment (PROTECT), Clinical Trials.gov
  3.  Keytruda for Prostate Cancer, Prostate Cancer News Today, June 2017
  4. Victoria Forster, PhD, Ipilimumab May Help Some Patients With Prostate Cancer, Cancer Therapy Advisor, May 6, 2020
  5. Arthur N. Brodsky, Ph.D., Advances in Immunotherapy for Prostate Cancer with Dr. Sumit Subudhi, Cancer Research Institute blog, September 01, 2020
  6. Clinical Trials for Prostate Cancer, National Cancer Institute
  7. Prostate Cancer Clinical Trials, Prostate Cancer Foundation
  8. Susan Slovin, Chemotherapy and immunotherapy combination in advanced prostate cancer, Clin Adv Hematol Oncol, 2012 Feb;10(2):90-100.
  9. Vitamin C as an Anti-cancer Drug, U.S. National Library of Medicine, ClinicalTrials.gov
  10. Linus Pauling Institute, Micronutrient Information Center, lpi.oregonstate.edu/mic/vitamins/
Alternative Text

Dr. James Occhiogrosso

James Occhiogrosso is a qualified naturopathic doctor (N.D.) and health practitioner, as well as author of several books including “Your Prostate, Your Libido, Your Life,” He has authored hundreds of articles, and is a frequent guest on numerous radio and TV shows.

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