Advanced Prostate Cancer

Next to lung cancer, prostate cancer is the second most common cancer among men. Currently, statistics indicate that one in eight American men will be diagnosed with prostate cancer at some point during their lifetime. Advanced prostate cancer is prostate cancer that has moved outside of the prostate.

There are two classifications of advanced prostate cancer: locally advanced prostate cancer, and metastatic prostate cancer. Locally advanced prostate cancer is cancer that has moved outside the prostate but remains close to the prostate gland. In this instance, cancer may have spread to adjoining tissue, the seminal vesicles, or pelvic lymph nodes. Generally, locally advanced prostate cancer can be treated surgically (prostatectomy – removal of the prostate), with Cryotherapy, or Radiation Therapy.

Metastatic prostate cancer is cancer that has moved to distant areas of the body and is no longer locally contained. Metastatic prostate cancer is diagnosed when cancer moves outside the prostate capsule into distant areas of the lymphatic system, bones, and organs, such as the lungs or brain.

Treatment options for advanced prostate cancer

With early detection, there are several options available to treat prostate cancer, especially if the cancer has remained inside the prostate. Currently, there are no cures for advanced prostate cancer. However, there are several treatment options to slow down the cancer’s progress, and to relieve symptoms.

Hormone Therapy for advanced prostate cancer

The growth and spread of prostate cancer is fueled by the hormone testosterone. The goal of hormone therapy, also known as androgen deprivation therapy (ADT), or androgen ablation, is to inhibit androgen production in the testicles, deplete testosterone levels in the body, and subsequently diminish the promotion of cancer growth by this hormone. At the same time, androgen therapy aims to reduce tumor size, and to lower prostate specific antigen (PSA) levels in the bloodstream. For advanced prostate cancer patients, hormone therapy is generally their first line of treatment.

There are several types of medications approved for hormone therapy treatment: Luteinizing hormone-releasing hormone (LHRH) analogues, Luteinizing hormone-releasing hormone (LHRH) antagonists, and Antiandrogens. The Urology Austin Pharmacy is now carrying Orgovyx (Relugolix).

Luteinizing hormone-releasing hormone analogues

Luteinizing hormone-releasing hormone analogs are commonly used by men to treat advanced prostate cancer. These medications work to reduce testosterone production in the body by affecting the pituitary gland’s ability to produce testosterone. Popular analog medications include Lupron and Eligard.

Luteinizing hormone-releasing hormone antagonists

Luteinizing hormone-releasing hormone antagonists are also indicated to treat advanced prostate cancer. Similar to LHRH analogs, antagonists are designed to lower testosterone levels. Firmagon is a common LHRH antagonist.

Antiandrogens

Antiandrogens are medications designed to mitigate the effects of testosterone by blocking androgen receptors in the body. Antiandrogens are oftentimes prescribed in conjunction with LHRH medications. Commonly prescribed antiandrogens include Erleada, Nubeqa, Xtandi , Yonsa and Zytiga.

While advanced prostate cancer is not cured by hormone therapy, progression of the disease can be slowed. During the course of treatment, the PSA level in some men may begin to rise. There may also be indications that the cancer is spreading. When prostate cancer becomes resistant to hormone therapy, the cancer may become identified as castration-resistant prostate cancer. When PSA levels rise and cancer has been found to spread far beyond the prostate, even with hormone therapy, the cancer will be identified as Metastatic castration-resistant prostate cancer.

Immunotherapy

Immunotherapy is a treatment option designed to use the patient’s own immune system to combat disease. This process is done by activating immune cells to target and destroy cancer cells. In simple terms, this is accomplished by harvesting dendritic immune cells, exposing them to a molecule engineered to target cancer cells, and injecting them back into the patient’s body. This molecule, and treatment option, is called Provenge. Immunotherapy is indicated for men with advanced prostate cancer who has seen cancer growth following androgen deprivation therapy. These men will also have little to no prostate cancer symptoms.

Provenge immunotherapy involves several minimally invasive steps that are performed in-office:

- Blood will be drawn from the patient to capture immune cells.
- The blood samples will be shipped, overnight, to Dendreon labs, the manufacturer of Provenge.
- At the laboratory, the immune cells will be exposed to Provenge molecules. Once completed, the modified “vaccine” will be shipped back to the provider for immediate infusion into the patient.
- Provenge is infused into the patient in three pre-determined doses. Each dose will be scheduled for infusion over the course of several weeks. Typically, the provider will allow one to two weeks between doses.

PARP and PDL-1 inhibitors

Human cells can replicate, repair and defend themselves thus, helping maintain a healthy body. Specific genes are responsible for replication, repair, defense and other functions needed by the cell. Gene alterations can affect this process and make the cell vulnerable to cell death. When gene alterations are identified we can attempt to capitalize on this vulnerability utilizing targeted cancer treatments, such as, PARP inhibitors and PDL-1 inhibitors.

PARP Inhibitors

PARPs are part of a family of proteins that are involved in DNA damage response. Cancer cells with certain gene alterations must rely only on PARPs to repair damaged DNA. PARP inhibitors block these proteins from repairing the cancer DNA therefore, leading to more DNA damage and eventually cancer cell death. These PARP inhibitors are delivered via an oral medication, such as, Lynparza and Rubraca.

PDL-1 Inhibitors

PDL-1 is a type of protein that helps keep immune cells from attacking normal cells in the body. Cancer cells can have a high level of this protein and thus not be detected by immune cells as needing to be destroyed. Cancer cells typically only possess one level of immune protection, in contrast, healthy cells have two levels of immune protection. PDL-1 inhibitors are a type of immunotherapy that block these proteins and remove the protective mechanism available to the cancer cells. The immune cells are now able to identify and destroy these cancer cells. This type of immunotherapy is delivered via an IV infusion, such as, Keytruda.

Watch Dr. David Phillips’ interview on KXAN TVs Studio 512 about Advanced Prostate Cancer, including how it differs from localized prostate cancer and treatment options. Air date: September 2021.

Video courtesy of Dendreon

Video courtesy of Dendreon.

When prostate cancer spreads into bone

For many patients, advanced prostate cancer can metastasize into bone. This will be verified through a bone scan or an Axumin PET scan. When prostate cancer moves into the bone, it is still termed ‘prostate cancer’ since this is where the cancer originated.

Xofigo is an IV injection indicated for patients whose cancer has moved into bone. These patients are also experiencing symptoms, and are no longer responding to androgen deprivation therapy. Because Xofigo is a radioactive medication, it is administered alone – without other treatment modalities. Due to the nature of this drug, patients will be advised of important steps and precautions before starting Xofigo.

Chemotherapy

Over time, some patients may no longer respond to androgen deprivation therapy. Chemotherapy is another viable treatment option that is designed to destroy cancer cells. There are several chemotherapy medications that have been FDA approved to specifically target advanced prostate cancer. These drugs work to prevent prostate cancer cells from dividing and multiplying. When this treatment is advised, a urologist will refer the patient to a qualified medical oncologist.

BRCA gene mutation

The BRCA gene mutation is most commonly associated with breast cancer. However, men can also have this gene mutation. In fact, men with this mutation are at a higher risk of developing prostate cancer than men without the mutation. Furthermore, men who have been diagnosed with prostate cancer and have the BRCA gene mutation may develop a more aggressive form of cancer.

We’ve included the following resources that expand on BRCA and men:

BRCA Blue – It Matters For Men

BRCA Fact Sheet

BRCA and Prostate Cancer – Your Genes Matter