RECENT DEVELOPMENTS IN TREATMENT OF ADVANCED PROSTATE CANCER

Recent advancements in the treatment of advanced prostate cancer have allowed individuals to experience relief from pain and discomfort by slowing the growth and progression of cancer cells.

Cancer in the prostate can often remain confined to the prostate gland, grow slowly, and cause no symptoms. However, more advanced stages of prostate cancer can involve symptoms such as painful urination, blood in the urine and semen, bone pain, and fatigue. The prostate cancer cells can also become aggressive and metastasize to other parts of the body, such as the bones.

Prostate cancer is the second most common form of cancer in men, more prevalent in those over 65. In the US and the UK, research indicates that 1 in 8 men will be diagnosed with prostate cancer in their lifetime.

Different cancer treatment options have been developed to halt the progress of prostate cancer and relieve some of its symptoms, including hormone therapy, robotic prostatectomy, innovative radiation therapy, and ablative cancer treatments.

What Is Prostate Cancer?

Prostate cancer is a common type of cancer in men that develops in the prostate gland.

The prostate gland is a walnut-sized sex gland that is part of the male reproductive system and is crucial for male fertility. It is located just in front of the rectum between the bladder and the penis.

Prostate cells that have damaged DNA begin to divide and grow uncontrollably. As a result, the abnormal prostate cells continue to live while normal cells naturally die off. The buildup of abnormal cells eventually forms a tumor in the prostate.

Cancer in the prostate might grow slowly and remain confined to the prostate, or it might become more advanced and spread to the lymph nodes, bones, or other areas (metastatic prostate cancer).

Men with prostate cancer may not feel any signs or symptoms during the early stages of the disease. As the cancer advances, it could cause the following symptoms:

• Trouble urinating
• Weak urine flow
• Bloody urine
• Bloody semen
• Erectile dysfunction
• Unexplained weight loss
• Bone pain
• Fatigue

Recent Treatments of Advanced Prostate Cancer

Currently, no treatments can cure advanced or metastatic prostate cancer. However, there are several effective cancer treatment options that can help control cancer’s spread, relieve some of its symptoms, and prolong the life expectancy of prostate cancer patients.

Hormone therapy

Most prostate cancers depend on androgens (hormones such as testosterone) to maintain and grow.

Doctors use different types of hormone therapy, also known as androgen deprivation therapy (ADT), designed to cut off the testosterone supply to the advanced prostate cancer cells to shrink and slow their growth. This process is known as medical castration or chemical castration.

Options for hormone deprivation therapy include:

• Luteinizing hormone-releasing hormone (LHRH) agonists: The release of LHRH from the pituitary gland induces testosterone production in the testicles. LHRH agonists, also known as gonadotropin-releasing hormone (GnRH) agonists, lead to high levels of LHRH, which stop its production by the pituitary gland. As a result, the testicles will eventually stop receiving the signal to produce androgens leading to very low circulating testosterone levels. 
• Luteinizing hormone-releasing hormone (LHRH) antagonists: Antagonists of the luteinizing hormone block the pituitary gland from producing LHRH by binding to and blocking its receptors. Consequently, the testicles will stop producing androgens, and the levels of circulating testosterone will drop.
• Anti-androgens: Anti-androgens are prostate cancer drugs that can block the effect of testosterone in the body and prevent it from reaching the cancer cells in the prostate. Anti-androgen drugs are usually given with an LHRH agonist to further deprive the cancer cells of androgens.
• Orchiectomy: Surgery to remove the testicles, known as Orchiectomy, may be recommended to quickly and significantly decrease the testosterone level in your body. Testicle removal surgery is permanent and irreversible.

Clinical trials are underway to determine the efficacy of flooding the cancer cells with testosterone hormone rather than depriving them of it. Scientists believe that a short burst of high-dose testosterone after androgen deprivation would shock the prostate cancer cells and kill  them.

In case the prostate cancer has metastasized or doesn’t respond to hormone therapy, doctors might use chemotherapy drugs to kill rapidly growing cancer cells.

Radiation therapy

Radiation therapy uses high-powered energy to kill cancer cells and slow down or prevent the metastasis of prostate cancer.

Radiation treatment of advanced prostate cancer may include:

• External beam X-ray radiation: X-ray radiotherapy uses high-energy particles called photons to kill prostate cancer cells by destroying the genetic material that controls their growth and division. The radiation is delivered to a specific point where the prostate cancer is located. The machine moves around the patient while they are lying on a table or seated on a chair.
• Proton beam radiation: A more advanced and exact form of radiation treatment to precisely kill prostate tumor cells, Proton beam therapy works similarly to X-ray radiation, except that it delivers a positively charged particle, called a proton, that can accurately destroy cancer cells and reduce radiation delivered to normal tissue close to the tumor.

The use of external radiation for advanced prostate cancer treatment after cancer removal surgery can help to prevent cancer from spreading or coming back.

• Brachytherapy (internal radiation): This is a type of radiation that is placed inside the body. Surgeons strategically place radioactive sources in your prostate tissue which then deliver low doses of radiation over a long period of time.

In some cases, doctors may recommend both external and internal forms of cancer radiation therapy. Radiation therapy can also help reduce symptoms, such as pain, in areas of the body where cancer has spread, like the bones.

Surgery

The types of prostate removal surgeries include:

• Robotic 3D prostatectomy: Advances in 3D robotic laparoscopy enable most prostate removal cancer surgeries to be performed by robot-assisted prostatectomy. Surgeons will make several small incisions in your abdomen to gain access to and remove your prostate gland. A laparoscope, attached to a mechanical device (robot), is then carefully inserted through the incisions. The robot’s movement is then meticulously guided from a remote console using hand controls. The video feed from the laparoscope helps surgeons easily evaluate any technical issue during your surgery.
• Retropubic surgery: This type of prostate surgery is not commonly performed. In retropubic surgery, one long incision is made on your lower abdomen to access and remove your prostate gland. Although a less common surgical approach, it is sometimes necessary in certain cases.

Doctors often combine prostate removal surgery with other cancer treatment options to treat advanced prostate cancer that has spread to other regions of the body.

Ablative therapies

In advanced cases of prostate cancer, when other treatments like radiation have not worked, or for smaller prostate cancers when surgery isn’t possible, doctors may recommend ablation therapy. Ablation therapy works by destroying prostate tissue with cold or heat:

• Freezing prostate tissue: Cryotherapy or cryoablation for prostate cancer uses gas to freeze the prostate tissue. The tissue is then allowed to thaw, and the process is repeated. The continual thawing and freezing will kill the cancer cells and possibly some surrounding healthy tissue as well.
• Heating prostate tissue: Using high-intensity focused ultrasound (HIFU), concentrated ultrasound energy heats the prostate tissue, causing its death.

• Focal therapy: A type of targeted ablation therapy, focal therapy is being studied for treating one part of the prostate with HIFU or cryoablation. During the focal therapy, the areas of the prostate that contain the most aggressive cancer cells are identified and treated with heat or cold therapy. Studies have found that focal therapy can help reduce the side effects of ablative prostate cancer treatment by avoiding damage to surrounding healthy tissue.

Immunotherapy

For advanced prostate cancer that no longer responds to hormone therapy, immunotherapy is performed by manipulating the immune system to fight prostate cancer cells.

Cancer cells usually produce proteins that help them hide from the attack of your body’s disease-fighting immune system. Prostate cancer immunotherapy helps your body override cancer’s survival mechanism by: 

• Sipuleucel-T (Provenge) treatment: Experts take some of your own immune cells, then engineer them in a laboratory to fight prostate cancer, and finally inject them back into your body.
• Immunotherapy drugs: These drugs help the immune system precisely identify and attack cancer cells.

Targeted drug therapy

For advanced or recurrent prostate cancer that does not respond to hormone therapy, doctors may use targeted drug cancer therapy.

Many prostate cancer cells have specific abnormalities. Targeted drugs are designed to specifically block these abnormalities present within prostate cancer cells, causing their death.

Nevertheless, some targeted drug therapies can only work in certain patients whose cancer cells have certain mutations.

Summary

Advanced prostate cancer can become aggressive and cause uncomfortable symptoms. Recent advances and developments in treatment, such as minimally invasive robotic surgery, hormone therapy, targeted drug therapy, precise radiation therapy, and ablative methods, offer more options for patients in managing the disease, finding relief from associated pain, and slowing or stopping disease progression.

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Sources:

• https://pubmed.ncbi.nlm.nih.gov/34473525/
• https://pubmed.ncbi.nlm.nih.gov/29421921/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441973/
• https://www.ncbi.nlm.nih.gov/books/NBK470550/
• https://www.wcrf.org/cancer-trends/prostate-cancer-statistics/
• https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html
• https://prostatecanceruk.org/prostate-information/about-prostate-cancer

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