What Is Castration-Resistant Prostate Cancer and Is It Treatable?

Medically reviewed by Yamini Ranchod PhD, MS on December 5, 2017Written by Daniel Pendick

Overview

Castrate-resistant prostate cancer is prostate cancer that stops responding to hormone therapy. Hormone therapy, also called androgen deprivation therapy (ADT), dramatically lowers testosterone levels in the body. The testosterone levels are comparable to levels in men who have had their testicles surgically removed.

The surgical removal of the testes is sometimes called castration, but it’s more formally known as orchiectomy. The testicles produce androgens, so removing them causes hormone levels to plummet. Androgens are male sex hormones. Low testosterone levels usually slow the advance of prostate cancer. In men with castrate-resistant prostate cancer, the cancer still continues to progress, despite the decrease in testosterone.

If your prostate cancer advances and becomes castrate resistant, there are therapies that can help slow the advance of the disease, although they do not cure the cancer. One key goal is keeping the cancer from metastasizing. Metastasizing cancer is cancer that spreads from the prostate gland to more distant parts of the body like the spine, lungs, and brain.

Hormones and prostate cancer

Most prostate cancer today is diagnosed at an early stage when the cancer is still confined to the prostate gland. Men typically have surgery to remove the cancerous prostate gland or radiation treatment to destroy the cancerous cells in the gland.

If early-stage cancer comes back after surgery or radiation, or has begun to spread to more distant parts of the body (metastasize), treatment with hormone-blocking drugs can slow the advance of the cancer and reduce the size of tumors. This helps to prevent symptoms like urinary obstruction, which happens when tumors interrupt the normal flow of urine from the bladder. Hormone therapy can also enhance the effectiveness of radiation therapy and shrink a tumor before surgery.

Male sex hormones fuel prostate cancer. The main hormone that drives prostate cancer is testosterone, which is produced in the testicles.

ADT drastically lowers levels of testosterone and other androgens in the body, and stalls the advance of the cancer in many men — but only temporarily. For reasons that remain poorly understood, prostate cancer cells can adapt to lower levels of natural androgens and start to multiply again. The cancer is then said to be castrate resistant.

Androgen deprivation therapy

ADT reduces levels of testosterone and other androgens by 90 to 95 percent. Several different types of ADT medications interfere with or block the processes in the body that control the production of androgens that cause prostate cancer cells to multiply. The drugs are essentially a form of “chemical castration.” Some drugs are in pill form and others need to be injected anywhere from every month to every year.

Suppressing testosterone can trigger a wide range of side effects. They include:

  • anemia
  • fatigue
  • loss of libido or erectile dysfunction
  • “feminizing” effects like enlarged breasts, loss of body hair, and smaller penis or scrotum
  • hot flashes and mood swings, similar to the effect of menopause on women
  • impaired memory and depression
  • loss of lean body mass (muscle)
  • loss of bone strength (osteoporosis)
  • tenderness in the nipples
  • weight gain
  • changes in blood lipids
  • insulin resistance

Diagnosing castrate-resistant cancer

After you begin hormone treatment, your doctor will regularly measure levels of prostate-specific antigen (PSA) in your blood. PSA is a protein produced by prostate cancer cells. If PSA levels start to rise while you are on hormone therapy, this can be a sign that the treatment has stopped working and the cancer has become castrate resistant.

Another sign that hormone therapy has stopped working is the spread of cancer outside the prostate or the growth of existing tumors.

Treating castrate-resistant cancer

A combination of drugs and other treatments can slow the progression of castrate-resistant prostate cancer, even if it has metastasized.

Your doctor may suggest you stay on your existing hormone therapy. This prevents a rise in natural testosterone that could cause the cancer to get worse.

New hormone treatments

Two relatively new hormone therapies have shown promise for castrate-resistant and metastatic prostate cancer. In clinical trials, men lived longer while taking these drugs, even in men previously treated with chemotherapy.

  • Abiraterone (Zytiga). This medication is taken in pill form. It blocks the chemical production of testosterone throughout the body. Zytiga is taken with prednisone, a powerful anti-inflammatory medication.
  • Enzalutamide (Xtandi). This medication is also taken as a pill. Xtandi prevents androgens from promoting the growth of prostate cancer cells.

Chemotherapy

Some men with castrate-resistant prostate cancer are offered chemotherapy drugs, which kill cancer cells directly. Common chemotherapy medications for treating castrate-resistant prostate cancer include:

  • docetaxel (Docefrez, Taxotere) plus the corticosteroid (anti-inflammatory) drug prednisone
  • cabazitaxel (Jevtana) plus prednisone
  • mitoxantrone (Novantrone)

Immune therapy

In this approach, your doctor will harvest white blood cells from you and use them to create a vaccine unique to you. The vaccine is then injected into your bloodstream to help your immune system attack prostate cancer cells.

The anti-cancer vaccine is called sipuleucel-T (Provenge). The therapy requires several separate treatments. Immune therapy, for more advanced prostate cancer, may help to extend life.

Treating bone tumors

Metastatic prostate cancer frequently spreads to the bones. Bone tumors can cause fractures and severe pain. Treatment for bone tumors is palliative. That means it’s intended to minimize symptoms rather than to cure the disease. They include:

  • External-beam radiation. This involves radiation therapy being administered from outside the body.
  • Denosumab (Xgeva, Prolia). This drug helps reduce bone damage caused by prostate cancer.
  • Radium-233 (Xofigo). This unique form of radiation therapy is injected into the bloodstream and specifically targets prostate cancer tumors in bones. The radium accumulates in areas of bone where tumors are forming. The effect of the radioactivity acts over a very short distance, killing tumor cells with less damage to nearby healthy bone. In a clinical trial, men treated with radium-233 survived several months longer than men who got an inactive placebo injection.

Outlook

Treatment for advanced prostate cancer is an active field of research. New drugs, and new combinations of drugs and other treatments, are under development. The treatments both extend life and improve quality of life by reducing pain, urinary problems, and other complications of cancer that has spread outside the prostate gland. Doctors monitor the progression of the cancer and can offer new treatments when indicated.

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