Prostate cancer

What is prostate cancer?

Prostate cancer is a malignant tumour in the prostate. There are several stages of prostate cancer. Your treatment and experience depend on the specific characteristics of the tumour and the expertise of your
medical team.

The sections in this series provide general information about prostate cancer, diagnosis, and various treatment options. Discuss with your doctor what is best in your individual situation.

Most prostate cancers develop slowly and do not cause symptoms. Fast-growing prostate cancer is less   common. The risk of getting prostate cancer increases with age. The average age for diagnosis of
prostate cancer is 69.

Because of the development in diagnostic tools and longer life expectancy, more prostate cancers are now detected. Prostate cancer is the most common cancer in elderly men in Europe. The survival rate for prostate cancer in Europe is relatively high and is still going up.

Stages of the disease

There are different stages of prostate cancer. If the tumour is limited to the prostate and has not spread, this is called localized prostate cancer. In locally advanced prostate cancer, the tumour has grown out of the prostate into surrounding tissue such as the seminal vesicles, the bladder neck, or lymph nodes around the prostate. Doctors speak of metastatic disease if the cancer has spread either to distant lymph nodes or other organs.

Risk factors for prostate cancer

There are different stages of prostate cancer. If the tumour is limited to the prostate and has not spread, this is called localized prostate cancer. In locally advanced prostate cancer, the tumour has grown out of the prostate into surrounding tissue such as the seminal vesicles, the bladder neck, or lymph nodes around the prostate. Doctors speak of metastatic disease if the cancer has spread either to distant lymph nodes or other organs.

Fig. 1a: A healthy prostate in the lower urinary tract.
Fig. 1a: A healthy prostate in the lower urinary tract.

What is the prostate?

The prostate is a gland located in the lower urinary tract, under the bladder and around the urethra (Fig. 1). Only men have a prostate. It produces part of the fluid which carries semen. The prostate contains smooth muscles which help to push out the semen during ejaculation.

A healthy prostate is about the size of a large walnut and has a volume of 15-25 millilitres.
The prostate slowly grows as men grow older.

The medical term for a prostate that has grown in size is benign prostatic enlargement (BPE).
Read more about this condition in EAU Patient Information on BPE.

Symptoms

Prostate cancer is generally asymptomatic, which means that there are no clear symptoms to indicate it. In most cases, symptoms are caused by benign prostatic enlargement (BPE), or an infection. If prostate cancer does cause symptoms it is usually a sign that the disease has advanced. Because of this it is important that you see a doctor to understand what causes the symptoms.

The symptoms may include:
• Urinary symptoms such as urinary frequency or a weak stream of urine
• Blood in the urine
• Erection problems
• Urinary incontinence
• Loss of bowel control
• Pain in the hips, back, chest, or legs
• Weak legs

Bone pain could be a sign that the cancer has spread through the body. This is known as metastatic disease.

Diagnostics

One of the most frequently used tools to diagnose prostate conditions is a blood test to check the level of prostate specific antigen (PSA). If the PSA level is too high, this suggests that the cells in the prostate are behaving unusually.
This could be because of a tumour in the prostate, but also because of an infection or a benign enlargement of the prostate.

Your doctor will do a rectal examination with a finger to feel the size, shape, and consistency of the prostate (Fig. 2).

This test is known as digital rectal examination (DRE).

Digital rectal examination (DRE)PSA Testing
Fig. 2: digital rectal examination male.
Fig. 2: digital rectal examination male.

In some cases your doctor may recommend to make a scan of the lower urinary tract. Different types of scans are available, such as ultrasound, CT scan, MRI scan, and bone scan.

None of these tools will provide a definite answer on whether or not you have prostate cancer. Your doctor will use the test results, together with your age and your family history, to estimate the risk of you having prostate cancer.

If the risk is high, you may need a biopsy of prostate tissue. This test is done to confirm if you have a tumour or not.

CT scanMRI scan

Classification

Prostate tumours are classified according to the tumour stage and the grade of aggressiveness of the tumour cells. These two elements are the basis for your possible treatment pathway.

The doctor does a series of tests to better understand your specific situation. Physical examination and imaging can be used to determine the stage of the disease. Prostate cancer is classified according to how advanced the tumour is, and whether or not the cancer has spread to the lymph nodes or other organs.
The other element of classification is the Gleason score. The Gleason score is determined by the pathologist, based on the tissue taken during biopsy. It gives information about the aggressiveness of the tumour. Based on the pattern that the cancer cells show, the pathologist can see how fast the tumour grows.

Staging

Prostate tumours are classified according to the tumour stage and the grade of aggressiveness of the tumour cells. These two elements are the basis for your possible treatment pathway.
The doctor does a series of tests to better understand your specific situation. Physical examination and imaging can be used to determine the stage of the disease. Prostate cancer is classified according to how advanced the tumour is, and whether or not the cancer has spread to the lymph nodes or other organs.
Prostate tumour stage is based on the TNM classification. The urologist looks at the size and invasiveness of the tumour (T) and determines how advanced it is, based on 4 stages. Your doctor will also assign an a, b, or c to the stage, depending on the size of the tumour.

Whether any lymph nodes around the prostate are affected (N) or if the cancer has spread to any other parts of your body (M) is also checked. If prostate tumours metastasize they generally spread to the bones, often the spine, or to the lungs, liver, or brain.

The Gleason score

The Gleason score ranges from 6 to 10. Tumours with a higher score are more aggressive and more difficult to cure.

The score is based on the pattern of the cancer cells. Each pattern gets a value between 1 and 5. The pathologist adds the scores of the two patterns that appear in most of the tissue samples.

For example: the most common pattern has a score of 3, and the second most common a score of 4. In this case, the Gleason score is 3 + 4 = 7.

Risk stratification

To form the risk stratification of your disease, the classification of the tumour is combined with your age, medical and family history, and general state of health.

Keep in mind that definitive classification of the tumour is only possible after you have had surgery to remove the entire prostate.

Treatment

This section describes the different treatment options which you should discuss with your doctor.

This is general information, which is not specified to your individual needs. Keep in mind that individual recommendations may depend on your country and health care system.
Each treatment has its own advantages and disadvantages. The choice depends on your individual situation.

Which treatment pathway is best for you depends on:

• The tumour characteristics
• Your medical history
• Your age
• The kind of treatment available at your hospital
• Your personal preferences and values
• The support network available to you

Localised Prostate Cancer

If you are diagnosed with localised prostate cancer, your doctor can recommend treating the cancer with conservative management, radical prostatectomy, radiation therapy, or new experimental techniques: ablation therapy.

Conservative management

Conservative management is a type of treatment where the progress of your disease is closely monitored. In prostate cancer, this can be done through active surveillance or watchful waiting.

Radical prostatectomy

Radical prostatectomy is a surgical treatment option for localized prostate cancer. The aim is to remove the entire prostate and the seminal vesicles.

Radiation therapy

Your doctor could also recommend radiation therapy. This therapy damages and kills cancer cells. You may be treated with external beam radiation therapy or brachytherapy.

Your doctor may suggest brachytherapy if you have a low Gleason score and no urinary symptoms.

New experimental techniques: Ablation therapy

New experimental techniques: Ablation therapy
Besides surgery, radiation, and conservative management there is also ablation therapy (also referred to as focal therapy) as treatment option for localized prostate cancer, such as:

  • Cryosurgical ablation of the prostate (CSAP)
  • High Intensity Focussed Ultrasound (HIFU)

Because the tumour cells are targeted directly, there is not much damage to other tissue in the prostate or the lower urinary tract.

Fig. 5: In focal therapy the prostate tumour cells are targeted directly so there is not much damage to other tissue.
Fig. 5: In focal therapy the prostate tumour cells are targeted directly so there is not much damage to other tissue.
Active surveillanceWatchful waitingRadiation therapyRadical prostatectomyAblation theapy

What is localised prostate cancer?

Localised prostate cancer refers to a tumour which is limited to the prostate and has not extended to other parts of your body. It may be a T1 or T2 tumour, depending on its size and where it is located in the prostate.

T1 means that the tumour is too small to be felt during a digital rectal examination (DRE) or seen on a scan. T1 tumours are confirmed with a biopsy and assigned an a, b, or c based on the analysis of the pathologist. A T2 tumour means that prostate cancer can be felt during a DRE, but is still limited to the prostate. Your doctor will also assign an a, b, or c to this stage, depending on the size of the tumour and whether it is in one or more lobes of the prostate (Fig. 3 and 4).

Fig. 3: A T1 prostate tumour is too small to be felt
Fig. 3: A T1 prostate tumour is too small to be felt during a digital rectal examination or seen on a scan.
Fig. 4: A T2 prostate tumour is limited to the prostate.
Fig. 4: A T2 prostate tumour is limited to the prostate.

Locally-advanced Prostate Cancer

If you are diagnosed with locally-advanced prostate cancer, your doctor can recommend treating the cancer with watchful waiting, radical prostatectomy, or a combination of radiation therapy and hormonal therapy.

Watchful waiting

In watchful waiting the doctor schedules regular visits to monitor your health and recommends further treatment when symptoms appear. This treatment is generally indicated when you are unfit for radical prostatectomy, radiation therapy or hormonal therapy. This may be related to your age or any medical conditions which make those treatments dangerous for you.

Radical prostatectomy

Radical prostatectomy is a surgical treatment option for locally-advanced prostate cancer. The aim is to remove as much of the tumour as possible. This is done by removing the entire prostate gland and both seminal  vesicles, as well as surrounding tissue affected by the tumour. The procedure also includes the removal of lymph nodes in the pelvic area.

 

Hormonal therapy and radiation therapy

As an alternative to surgery, your doctor may recommend radiation therapy to cure your cancer. This therapy damages and kills cancer cells. It is a common treatment option for locally-advanced tumours. In locally-advanced prostate cancer, radiation therapy is always combined with hormonal therapy.

Hormonal therapy affects the production of testosterone in the body. The aim is to stop the growth of the tumour. Another name for hormonal therapy is androgen deprivation therapy (ADT).

Watchful waitingRadical prostatectomyHormonal therapyRadiation therapy

What is locally-advanced prostate cancer?

Locally-advanced prostate cancer refers to a tumour which has spread outside of the prostate. It may be a T3 or T4 tumour, depending on where and how far outside of the prostate it has grown. T3 means that the tumour has grown just outside the prostate or to the seminal vesicles. A T4 tumour means that prostate cancer has invaded the bladder neck, the urinary sphincter, the rectum, or the pelvic floor (Fig.6 and 7).

Fig. 6: A T3 prostate tumour which has spread to the seminal vesicles.
Fig. 6: A T3 prostate tumour which has spread to the seminal vesicles.
Fig. 7: A T4 prostate tumour which has spread to the bladder neck, urinary sphincter, and rectum.
Fig. 7: A T4 prostate tumour which has spread to the bladder neck, urinary sphincter, and rectum.

Metastatic Prostate Cancer

Prostate cancer can spread to other organs or lymph nodes outside the pelvic area. This is called metastatic disease. The tumours in other organs or lymph nodes are called metastases. Your doctor may recommend treating metastatic disease with hormonal therapy.

It is important to realize that metastatic disease cannot be cured. Instead, your doctor will try to slow the growth of the tumour and the metastases. This will give you the chance to live longer and have fewer symptoms.

Hormonal therapy

If you have metastatic prostate cancer, your doctor will recommend hormonal therapy. This is part of a palliative care approach. The treatment will slow the growth of the primary tumour and the metastases, and help to manage the symptoms.

Bone metastases

See castration-resistant prostate cancer.

Hormonal therapy

What is metastatic prostate cancer?

If prostate cancer metastasizes, it usually spreads to the bones or the spine. At a later stage, prostate cancer may also spread to the lungs, the liver, distant lymph nodes, and the brain (Fig. 8). Most metastases cause a rise in the level of prostate-specific antigen (PSA) in your blood.

Metastases in the spine can cause symptoms like severe back pain, spontaneous fractures, or nerve or spinal cord compression. They can also be asymptomatic. In rare cases, lung metastases may cause a persistent cough.

Imaging can be used to detect metastases. Bone metastases can be seen on a bone scan. A CT scan may be recommended to get more detailed information about bone metastases, or to detect metastases in the liver, the lungs, or the brain.

Fig. 8: Metastatic prostate cancer can spread to the bones, spine, lungs, liver, or brain.
Fig. 8: Metastatic prostate cancer can spread to the bones, spine, lungs, liver, or brain.

Castration-resistant prostate cancer

Castration-resistant prostate cancer is a type of prostate cancer that usually develops during treatment for metastatic disease.

Hormonal therapy either stops the production or blocks the action of androgens. This is known as castration. When effective, hormonal therapy stops the growth of the tumour. This effect will not last and leads to castration-resistant prostate cancer. This generally happens 2-3 years after hormonal treatment started. Castration-resistant prostate cancer cannot be cured.

Castration-resistant prostate tumours need much lower levels of androgens to progress. This means that even when your body produces almost no androgens, the tumour and metastases continue to grow. These cancers are called castration-resistant, because they no longer respond to hormonal castration treatment.

In this type of cancer, the level of prostate-specific antigen (PSA) in the blood rises again. The doctor will diagnose castration-resistant prostate cancer if 3 tests in the space of 3 weeks show an increase in the PSA level in your blood. It can also be diagnosed if you experience symptoms caused by the growing tumour or metastases.

All treatments described here aim to slow the growth of the tumour and metastases. It may allow you to live longer and with fewer symptoms.

Castration-resistant prostate cancer can be managed with:

Additional treatment with anti-androgen therapy

Additional treatment with anti-androgen therapy
When you have been treated with either surgical or chemical castration, your doctor may recommend additional treatment with anti-androgen therapy. The most common anti-androgen drug to manage castration-resistant prostate cancer is bicalutamide.

Stopping anti-androgen treatment
If you have been treated with LHRH agonists or antagonists in combination with anti-androgen therapy, your doctor may recommend to stop taking the anti-androgen drugs. This approach may lower the level of PSA in your blood for a few months. The effect will be seen 4-6 weeks after you stop taking the drugs.

Radiation therapy

Castration-resistant prostate cancer can be managed with radiation therapy. The radiation damages and kills cancer cells.  Common side effects are a burning sensation when you urinate, urinary frequency, and anal irritation.

Oestrogen therapy

Drug therapy with the hormone oestrogen can slow down the growth of the tumour and lower the level of PSA in your blood, without affecting your bones. This treatment can cause cardiovascular disease, including blood clots and heart attacks. Because of these risks, oestrogen therapy is rarely recommended today.

Adrenolytic agents

After castration, the adrenal glands continue to produce small amounts of androgensAdrenolytic agents stop the adrenal gland from producing the hormones. Side effects of these drugs are diarrhoea, itching and skin rashes, fatigueerectile dysfunction, and liver damage. These drugs are not commonly used.

New hormonal agents

Castration-resistant prostate cancer can be managed with two new hormonal agents: abiraterone acetate and enzalutamide.

They both work differently.

Abiretarerone acetate stops the production of testosterone and ezalutamide blocks androgen receptors.

Immunotherapy

Immunotherapy is a type of treatment that uses your own immune system to fight the tumour cells. In prostate cancer the drug Sipuleucel-T is used as immunotherapy. Because your own blood is used to prepare the drug, you need to get blood drawn before the procedure.

Chemotherapy with docetaxel

Your doctor may recommend the chemotherapy docetaxel to manage castration-resistant prostate cancer. The drug relieves pain caused by the tumour or metastases. If effective, it allows you live longer and with fewer symptoms and side effects.

Treatment after chemotherapy

After you have been treated with docetaxel, your doctor can recommend treatment with hormonal therapy or another chemotherapy drug. The main hormonal treatments are abiraterone acetate and enzalutamide. Cabazitaxel is the chemotherapy drug most commonly used in these cases. You could also receive a second course of docetaxel. Your doctor will discuss the different treatment options to find the best one for you.

Discuss with your doctor which type of treatment after docetaxel is best for your individual situation.

Treatment of bone metastases

Prostate cancer cells can spread to the bones, generally to the spine. The treatment of bone metastases can have severe side effects. Your doctor will help to prevent and treat possible complications and side effects. This may allow you to live longer and with fewer symptoms.

Bone metastases can cause back pain. Your doctor will prescribe painkillers to manage the pain. In some cases your doctor may recommend a very strong painkiller, like morphine. When tumours in the spine grow, they may cause spinal cord compression. This is a rare complication, but it is an emergency situation because it can lead to paralysis of the legs.

The main signs of spinal cord compression are:

  • Pain in a specific spot in your spine that is different from your usual pain
  • New pain in the spine which gets worse and does not respond to painkillers
  • A tingling sensation down your spine, into your legs or arms
  • Pain in your spine which changes when you change position
  • Numbness in your legs
  • Stiffness or heaviness in your legs that make you lose your balance
  • Pain down your legs or arms
  • Weakness in your legs or arms

If you think your spinal cord may be compressed you should contact your medical team immediately.

Bones that are affected by tumours fracture more easily. If you are at risk of bone fractures, your doctor may recommend drugs to stabilize your bones. The most common are bisphosponates and denosumab. Your doctor may recommend a procedure to strengthen your bones by injecting material that helps harden your bone. This is known as cementoplasty. In rare cases, surgery is needed to stabilize your bones.

Bisphosphonates are administered with an IV every 4 weeks. They increase your bone mass, and can reduce pain and prevent fractures. Because bisphosphonates can damage your jaws, your doctor will advise you to see a dentist before you start treatment.

Denosumab is administered under the skin every 4 weeks. It also increases bone mass and generally causes fewer side effects than bisphosphonates. If the bone metastases cause symptoms while you receive drug treatment, radiation therapy may help to relieve them and prevent fractures. To keep your bones healthy you could exercise regularly, keep a healthy weight, stop smoking, and drink alcohol in moderation. The risk of bone complications increases with age. To prevent complications from bone metastases, you may need to take nutritional supplements like calcium or vitamin D3.

Treatment of recurrence

In localised prostate cancer or locally-advanced prostate cancer, it is possible that prostate cancer comes back after you have been treated. This is known as recurrence. The cancer may come back in the prostate, in tissue around the prostate or pelvic lymph nodes, or in other parts of the body. The follow-up treatment pathway depends on where the cancer is. Your doctor will recommend imaging tests such as CT, MRIPET scan or bone scans to locate the tumour, identify its characteristics, and determine treatment.

If you have been treated with radical prostatectomy and the PSA level in your blood rises, this could be a sign of recurrence. Your doctor may recommend salvage radiation therapy. In this procedure, the area where the prostate was located will be radiated to kill cancer cells. If your cancer was treated with radiation therapy, your doctor may recommend to treat recurrence with radical prostatectomy.

Localised prostate cancer
If you have been treated with experimental techniques, disucss with your doctor which treatment option is best for you.

Locally advanced prostate cancer
If radiation therapy is not the best option for you, your doctor can recommend hormonal therapy.

If the PSA level rises quickly, or you have symptoms, hormonal therapy will be recommended. In some countries, brachytherapy is available to treat recurrence as an alternative to hormonal therapy.

Authors

This information was produced by the European Association of Urology (EAU).

 

Contributors:
  • Dr. Roderick van den Bergh, Utrecht (NL)
  • Prof. Dr. Zoran Culig, Innsbruck (AT)
  • Prof. Dr. Louis Denis, Antwerp (BE)
  • Prof. Bob Djavan, Vienna (AT)
  • Mr. Enzo Federico, Trieste (IT)
  • Mr. Günter Feick, Pohlheim (DE)
  • Dr. Pirus Ghadjar, Berlin (DE)
  • Dr. Alexander Kretschmer, Munich (DE)
  • Prof. Dr. Feliksas Jankevičius, Vilnius (LTU)
  • Prof. Dr. Nicolas Mottet, Saint-Étienne (FR)
  • Dr. Bernardo Rocco, Milan (IT)
  • Ms. Maria Russo, Orbassano (IT)