Prostate Cancer

Introduction – About the Prostate

The prostate is a walnut-sized gland located behind the base of the penis, in front of the rectum, and below the bladder.

The prostate continues to enlarge as people age. This can lead to a condition called benign prostatic hypertrophy (BPH), which is when the urethra becomes blocked. BPH is a common condition associated with growing older, and it has not been associated with a greater risk of having prostate cancer.

About the Prostate Cancer

Prostate cancer is somewhat unusual when compared with other types of cancer. This is because many prostate tumors do not spread quickly to other parts of the body. Some prostate cancers grow very slowly and may not cause symptoms or problems for years or ever.

Even when prostate cancer has spread to other parts of the body, it often can be managed for a long time. So people with prostate cancer, and even those with advanced prostate cancer, may live with good health and quality of life for many years.

An important part of managing prostate cancer is watching for growth over time to find out if it is growing slowly or quickly.

Prostate-specific antigen (PSA)

Prostate-specific antigen (PSA) is a protein produced by cells in the prostate gland and released into the bloodstream. PSA levels are measured using a blood test. Although there is no such thing as a “normal PSA” for anyone at any given age, a higher-than-normal level of PSA can be found in people with prostate cancer.
Other non-cancerous prostate conditions, such as BPH or prostatitis can also lead to an elevated PSA level.

Risk Factors

The following factors may raise a person’s risk of developing prostate cancer:
Age. The risk of prostate cancer increases with age, especially after age 50. Around 60% of prostate cancers are diagnosed in people who are 65 or older. Older adults who are diagnosed with prostate cancer can face unique challenges, specifically with regard to cancer treatment.

Race. Black men in the United States, and other men of African ancestry, are diagnosed with prostate cancer more than men of other races.

North American or northern European location. Prostate cancer occurs most often in North America and northern Europe.

Family history. Prostate cancer that runs in a family, called familial prostate cancer, makes up about 20% of all prostate cancers. This type of prostate cancer develops because of a combination of shared genes and shared environmental or lifestyle factors.
Hereditary prostate cancer, which is inheriting the risk from a relative, is rare and accounts for about 5% of all cases. Hereditary prostate cancer occurs when changes in genes, or mutations, are passed down within a family from 1 generation to the next.

Hereditary prostate cancer may be suspected if a family history includes any of the following characteristics:
3 or more first-degree relatives with prostate cancer
Prostate cancer in 3 generations on the same side of the family
2 or more close relatives, such as a parent, sibling, child, grandparent, uncle, or nephew, on the same side of the family diagnosed with prostate cancer before age.
Eating habits. Many studies that look at links between certain eating behaviours and cancer suggest there may be a connection. For example, obesity is associated with many cancers, including prostate cancer, and a healthy diet to avoid weight gain is recommended.

Screening

Screening is used to look for cancer before you have any symptoms or signs. When cancer is found earlier in its development, it is often at an earlier stage. This means that there is a better chance of successfully treating the cancer.
The overall goals of cancer screening are to:
Lower the number of people who die from the disease, or eliminate deaths from cancer altogether
Lower the number of people who develop the disease
Screening for prostate cancer is done to find evidence of cancer in otherwise healthy adults. Two tests are commonly used to screen for prostate cancer.

Digital Rectal Examination (DRE)

A DRE is a test in which the doctor inserts a gloved, lubricated finger into the rectum and feels the surface of the prostate through the bowel wall for any irregularities.

PSA Blood Test

There is controversy about using the PSA test to look for prostate cancer in people with no symptoms of the disease.
On the one hand, the PSA test is useful for detecting early-stage prostate cancer, especially in those with many risk factors, which helps some get the treatment they need before the cancer grows and spreads.

On the other hand, PSA screening may find very-slow-growing prostate cancers that would never threaten someone’s life. As a result, screening for prostate cancer using PSA may lead to treatments that are not needed, which can cause side effects and seriously affect a person’s quality of life.

Symptoms and Signs

While most prostate cancer does not cause any symptoms at all, the symptoms and signs of prostate cancer may include:

Frequent urination
Weak or interrupted urine flow or the need to strain to empty the bladder
The urge to urinate frequently at night
Blood in the urine
New onset of erectile dysfunction
Pain or burning during urination, which is much less common
Discomfort or pain when sitting, caused by an enlarged prostate

Other non-cancerous conditions of the prostate, such as BPH or an enlarged prostate, can cause similar symptoms. Or, the cause of a symptom or sign may be another medical condition that is also not related to cancer. Urinary symptoms also can be caused by an infection of the bladder or other conditions.
If cancer has spread outside the prostate gland, symptoms and signs may include:

Pain in the back, hips, thighs, shoulders, or other bones
Swelling or fluid build-up in the legs or feet
Unexplained weight loss
Fatigue
Change in bowel habit

Types of Treatment

How Prostate Cancer is Treated

Because most prostate cancers are found in the early stages when they are growing slowly, you usually do not have to rush to make treatment decisions. During this time, it is important to talk with your doctor about the risks and benefits of all your treatment options and when treatment should begin. This discussion should also address the current state of the cancer:

Whether you have symptoms or PSA levels are rising rapidly
Whether the cancer has spread to the bones
Your health history
Your quality of life
Your current urinary and sexual function
Any other medical conditions you may have

Although your treatment recommendations will depend on these factors, there are some general steps for treating prostate cancer by stage.

Active surveillance and watchful waiting

If prostate cancer is in an early stage, is growing slowly, and treating the cancer would cause more problems than the disease itself, a doctor may recommend active surveillance or watchful waiting.

Active surveillance. Prostate cancer treatments may seriously affect a person’s quality of life. These treatments can cause side effects, such as erectile dysfunction, and incontinence.

In addition, many prostate cancers grow slowly and cause no symptoms or problems. For this reason, many people may consider delaying cancer treatment rather than starting treatment right away. This is called active surveillance. During active surveillance, the cancer is closely monitored for signs that it is worsening. If the cancer is found to be worsening, treatment will begin.

Active surveillance is usually preferred for those with very-low-risk and low-risk prostate cancer that can be treated with surgery or radiation therapy if it shows signs of getting worse.

ASCO encourages the following testing schedule for active surveillance:
A PSA test every 3 to 6 months
A DRE at least once every year
Another prostate biopsy within 6 to 12 months, then a biopsy at least every 2 to 5 years

Treatment should begin if the results of the tests done during active surveillance show signs of the cancer becoming more aggressive or spreading, if the cancer causes pain, or if the cancer blocks the urinary tract.
Watchful waiting. Watchful waiting may be an option for older adults and those with other serious or life-threatening illnesses who are expected to live less than 5 years. With watchful waiting, routine PSA tests, DRE, and biopsies are not usually done.
If the prostate cancer causes symptoms, such as pain or blockage of the urinary tract, then treatment may be recommended to relieve those symptoms.

Local Treatments

Local treatments get rid of cancer from a specific, limited area of the body. Such treatments include surgery and radiation therapy. For early-stage prostate cancer, local treatments may get rid of the cancer completely.

Surgery

Surgery involves the removal of the prostate and some surrounding lymph nodes during an operation. The type of surgery depends on the stage of the disease, the patient’s overall health, and other factors.
Radical (open) prostatectomy.A radical prostatectomy is the surgical removal of the entire prostate and the seminal vesicles. Lymph nodes in the pelvic area may also be removed.

Robotic or laparoscopic This type of surgery is less invasive than a radical prostatectomy and may shorten recovery time. A camera and instruments are inserted through small keyhole incisions in the patient’s abdomen. The surgeon then directs the robotic instruments to remove the prostate gland

Bilateral orchiectomy.Bilateral orchiectomy is the surgical removal of both testicles.

Transurethral resection of the prostate (TURP).TURP is most often used to relieve symptoms of a urinary blockage, not to treat prostate cancer

Typically, younger or healthier patients may benefit more from a prostatectomy. Younger patients are also less likely to develop permanent erectile dysfunction and urinary incontinence after a prostatectomy than older patients.

Radiation Therapy

Radiation therapy is the use of high-energy rays to destroy cancer cells. A doctor who specializes in giving radiation therapy to treat cancer is called a radiation oncologist.

External-beam radiation therapy. External-beam radiation therapy is the most common type of radiation treatment. The radiation oncologist uses a machine located outside the body to focus a beam of x-rays on the area with the cancer.

One method of external-beam radiation therapy used to treat prostate cancer is called hypofractionated radiation therapy. This is when a person receives a higher daily dose of radiation therapy given over a shorter period, instead of lower doses given over a longer period.
Moderate hypofractionated radiation therapy regimens typically include 20 to 28 treatments.

Extreme hypofractionated radiation therapy is when the entire treatment is delivered in 5 or fewer treatments. This is also called stereotactic body radiation therapy (SBRT) or stereotactic ablative radiation therapy (SABR).

Brachytherapy. Brachytherapy, or internal radiation therapy, is the insertion of radioactive sources directly into the prostate. These sources, called seeds, give off radiation just around the area where they are inserted and may be left for a short time (high-dose rate) or for a longer time (low-dose rate).

Brachytherapy may be used with other treatments, such as external-beam radiation therapy and/or hormonal therapy.

Intensity-modulated radiation therapy (IMRT). IMRT is a type of external-beam radiation therapy that uses CT scans to form a 3D picture of the prostate before treatment.

With IMRT, high doses of radiation can be directed at the prostate without increasing the risk of damaging nearby organs.

Proton therapy. Proton therapy, also called proton beam therapy, is a type of external-beam radiation therapy that uses protons rather than x-rays. At high energy, protons can destroy cancer cells.

Side effects of Radiation Therapy

Radiation therapy may cause side effects during treatment, including increased urge to urinate or frequency of urination; problems with sexual function; problems with bowel function, including diarrhoea, rectal discomfort, or rectal bleeding; and fatigue. Most of these side effects usually go away after treatment.

Focal therapies

Focal therapies are less-invasive treatments that destroy small prostate tumors without treating the rest of the prostate gland. These treatments use heat, cold, and other methods to treat cancer, mostly for low-risk or intermediate-risk prostate cancer.

Cryosurgery, also called cryotherapy or cryoablation, involves freezing cancer cells with a metal probe inserted through a small incision in the area between the rectum and the scrotum, the skin sac that contains the testicles.

High-intensity focused ultrasound (HIFU) is a heat-based type of focal therapy. During HIFU treatment, an ultrasound probe is inserted into the rectum and then sound waves are directed at parts of the prostate gland with cancer.

Focal therapies are being studied in clinical trials. Most have not been approved as standard treatment options.

Hormonal Therapy

Because prostate cancer growth is driven by male sex hormones called androgens, lowering levels of these hormones can help slow the growth of the cancer. The most common androgen is testosterone.

Hormonal therapy is used to lower testosterone levels in the body, either by surgically removing the testicles, known as surgical castration, or by taking drugs that turn off the function of the testicles, called medical castration. Which hormonal therapy is used is less important than the main goal of lowering testosterone levels. This treatment can be referred to with other names, including androgen-deprivation therapy (ADT).

Another way to stop testosterone from driving the growth of prostate cancer is to treat it with a type of medication called an androgen axis inhibitor.

Treatment with hormonal therapy is used to treat prostate cancer in many different situations, including localized, locally advanced, and metastatic prostate cancer, as well as rising PSA level after surgery and/or radiation therapy for localized prostate cancer.

Types of hormonal therapy

Bilateral orchiectomy. Bilateral orchiectomy is the surgical removal of both testicles. Even though this is a surgical procedure, it is considered systemic, hormonal therapy because it removes the main source of testosterone production: the testicles.

LHRH agonists. LHRH stands for luteinizing hormone-releasing hormone. Medications known as LHRH agonists prevent the testicles from receiving messages sent by the body to make testosterone. By blocking these signals, LHRH agonists reduce the testosterone level just as well as removing the testicles.

LHRH agonists are injected or placed as small implants under the skin. Depending on the drug used, they may be given once a month or once a year.

LHRH antagonist. This class of drugs, also called a gonadotropin-releasing hormone (GnRH) antagonist, stops the testicles from producing testosterone like LHRH agonists, but they reduce testosterone levels more quickly and do not cause the flare associated with LHRH agonists.

Androgen receptor (AR) inhibitors. While LHRH agonists and antagonists lower testosterone levels in the blood, androgen receptor (AR) inhibitors block testosterone from binding to so-called “androgen receptors,” which are chemical structures in cancer cells that allow testosterone and other male hormones to enter the cells.

In effect, AR inhibitors stop testosterone from working.

Androgen synthesis inhibitors. Although the testicles produce most of the body’s testosterone, other cells in the body can still make small amounts of the hormone that may drive cancer growth. These include the adrenal glands and some prostate cancer cells. Androgen synthesis inhibitors target an enzyme called CYP17 and stop cells from making testosterone.

Combined androgen blockade. Sometimes, androgen receptor inhibitors are combined with bilateral orchiectomy or LHRH agonist treatment to maximize the blockade of male hormones or to prevent the flare associated with treatment with LHRH agonists.

Intermittent hormonal therapy. Traditionally, hormonal therapy was given for the patient’s lifetime. During the past 2 decades, researchers have studied the use of intermittent hormonal therapy, which is when therapy is given for specific times (most commonly 6 months) and then stopped temporarily to allow for testosterone levels to recover. For these patients, hormonal therapy is restarted when the PSA begins to rise again.

Targeted Therapy

Targeted therapy is a treatment that targets the cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. This type of treatment blocks the growth and spread of cancer cells and limits damage to healthy cells.

Not all tumours have the same targets. To find the most effective treatment, your doctor may run tests to identify the genes, proteins, and other factors in your tumour.

Targeted therapy for prostate cancer includes:
Olaparib (Lynparza).Olaparib is a type of targeted therapy called a PARP inhibitor.

Rucaparib (Rubraca).Rucaparib is another PARP inhibitor approved to treat metastatic castration-resistant prostate cancer.

One or more tests must be given to determine whether a patient may receive olaparib or rucaparib:
Testing for an inherited, or germline, mutation after discussion with a genetic counsellor

Genomic sequencing of tumour tissue

Genomic sequencing of the tumour DNA floating in the bloodstream

Genomic sequencing may be performed on tissue that was previously collected or on tissue from a new biopsy. Germline mutation testing alone identifies about half of the patients eligible for this treatment.

Chemotherapy

Chemotherapy is the use of drugs to destroy cancer cells, usually by keeping the cancer cells from growing, dividing, and making more cells. Chemotherapy may help those with advanced or castration-resistant prostate cancer and those with newly diagnosed or castration-sensitive metastatic prostate cancer.

There are several standard drugs used for prostate cancer. In general, standard chemotherapy begins with docetaxel combined with prednisone.

Cabazitaxel is approved to treat metastatic castration-resistant prostate cancer that has been previously treated with docetaxel. It is a microtubule inhibitor.

The side effects of chemotherapy depend on the individual, the type of chemotherapy received, the dose used, and the length of treatment.

Immunotherapy

Immunotherapy, also called biologic therapy, is designed to boost the body’s natural defenses to fight the cancer. It uses materials made either by the body or in a laboratory to improve, target, or restore immune system function.

For some people with castration-resistant metastatic prostate cancer who have no or very few cancer symptoms and generally have not had chemotherapy, vaccine therapy with sipuleucel-T (Provenge) may be an option.

Radiation Therapy by Infusion

Radium-223 is a radioactive substance used to treat castration-resistant prostate cancer that has spread to the bone. Radium-223 is an alpha-emitter radionucleotide that mimics calcium and targets areas in the bone where the cancer is causing changes. This treatment delivers radiation particles directly to tumors found in the bone, limiting damage to healthy tissue, including the bone marrow, where normal blood cells are made. Radium-223 is given by intravenous injection (IV) once a month for 6 months.

Bone-Modifying Drugs

Bone health is an important issue in the lives of people with prostate cancer. Osteopenia and osteoporosis are bone conditions that can be caused or worsened by hormonal therapy. Patients receiving hormonal therapy for non-metastatic prostate cancer should be evaluated for risk of fractures. Patients who are found to be at high risk for a fracture should receive treatment to lower the risk.

In patients with prostate cancer that has spread to the bone, there is always some risk of bone problems, such as fracture, pain, and spinal cord compression. These are called “skeletal-related events.”

When prostate cancer has spread to bone and has also become resistant to standard hormonal therapy, bone-modifying drugs may be recommended to reduce the risk of these problems. Specifically, denosumab or zoledronic acid can be given once per month to reduce that risk.

A rare but serious possible side effect of bone-modifying drugs is osteonecrosis of the jaw. The symptoms of osteonecrosis of the jaw include pain, swelling, and infection of the jaw; loose teeth; and exposed bone.

Physical, Emotional, and Social Effects of Cancer

Cancer and its treatment cause physical symptoms and side effects, as well as emotional, social, and financial effects. Managing all of these effects is called palliative care or supportive care. It is an important part of your care that is included along with treatments intended to slow, stop, or eliminate the cancer.

Any person, regardless of age or type and stage of cancer, may receive this type of care. And it often works best when it is started right after a cancer diagnosis. People who receive palliative care along with treatment for the cancer often have less severe symptoms, better quality of life, and report that they are more satisfied with treatment.

Palliative treatments vary widely and often include medication, nutritional changes, relaxation techniques, emotional and spiritual support, and other therapies. You may also receive palliative treatments similar to those meant to get rid of the cancer, such as chemotherapy, surgery, or radiation therapy.

Remission and the Chance of Recurrence

A remission is when cancer cannot be detected in the body and there are no symptoms. This may also be called having “no evidence of disease” or NED.

A remission can be temporary or permanent. This uncertainty causes many people to worry that the cancer will come back.

In general, following surgery or radiation therapy, the PSA level in the blood usually drops. If the PSA level starts to rise again, it may be a sign that the cancer has come back.

When this occurs, a new cycle of testing will begin again to learn as much as possible about the recurrence, including where the recurrence is located. Sometimes, the doctor cannot find a tumour even though the PSA level has increased. This is known as a PSA recurrence or biochemical recurrence.

The choice of treatment plan is based on the type of recurrence and the treatment(s) you have already received.