Prostate Cancer

Factsheet

Definition of prostate cancer

  • Prostate cancer forms in the tissue of the prostate, a gland of the male reproductive system found below the bladder and in front of the rectum. The prostate gland is made of 2 symmetric lobes.
  • It is not to be confused with benign prostatic hyperplasia which is a non-cancerous enlargement of the prostate gland.

 

Diagnosis

  • Symptoms such as increase in urination frequency, difficulties in starting to urinate, getting up multiple times to urinate at night, urgency or sensation of necessity to urinate immediately may be an indication of prostate cancer.
  • A physical examination and the measurement of a protein produced by the prostate (PSA) in the blood will guide the diagnosis.
  • The diagnosis can only be confirmed by the analysis of pieces of the prostatic tissue (biopsy) under a microscope.

 

Treatment according to the extension of the disease (classified into different stages)

  • Stage I and stage II prostate cancers are called localized or early stage cancers as the tumour is confined to the prostate:
    • When the cancer is diagnosed at a very early stage and it is considered that the risks of treatment may outweigh the benefits, a “watch and wait” approach can be discussed. It consists of regular check-ups with no intervention unless a check-up indicates the tumour is growing.
    • In all other cases, surgery or radiotherapy are similarly effective. They however cause different side effects, so risks and benefits of both should be discussed with all patients. In addition, hormone therapy will be given.
    • Hormone therapy alone could be proposed to elderly patients and patients unsuitable or unwilling to be treated by radiotherapy or surgery.
  • Stage III prostate cancers are called locally advanced cancers as the tumour has spread through the outside layer of the prostate called the capsule:
    • Radiotherapy and additional hormone therapy is the standard of care.
    • In selected cases, surgery could also be an option.
  • Stage IV prostate cancers are called advanced or metastatic cancers as the tumour has spread further:
    • Hormone therapy is the standard of care.
    • Surgery and radiotherapy can also help to relieve symptoms related to cancer.

 

Follow-up

  • To detect if the cancer has come back, PSA is measured regularly. An increase of the PSA level is not sufficient to confirm that the cancer has come back and therefore results have to be combined with other findings such as positive biopsy or abnormal CT-scan results.

The follow-up also aims to evaluate adverse effects of the treatment and to provide psychological support and information to enhance return to normal life.

 

PATIENT INFORMATION BASED ON ESMO CLINICAL PRACTICE GUIDELINES
As treatments are becoming more personalized due to the advances in cancer care, we would kindly ask you to contact info@anticancerfund [dot] org for a more appropriate guidance according to the most recent guidelines on this cancer type. This guide for patients is a service to patients and their families, to help them understand the nature of the disease and the existing treatment choices. We recommend that patients ask their doctors about what tests or types of treatments are needed for their type and stage of disease. This Guide for Patients in particular has been produced in collaboration with the European Society for Medical Oncology (ESMO) and is disseminated with its permission. It has been written by a medical doctor and reviewed by two oncologists from ESMO including the lead author of the clinical practice guidelines for professionals. It has also been reviewed by patients’ representatives from ESMO’s Cancer Patient Working Group.

Introduction

PATIENT INFORMATION BASED ON ESMO CLINICAL PRACTICE GUIDELINES
As treatments are becoming more personalized due to the advances in cancer care, we would kindly ask you to contact info@anticancerfund [dot] org for a more appropriate guidance according to the most recent guidelines on this cancer type. This guide for patients is a service to patients and their families, to help them understand the nature of the disease and the existing treatment choices. 

 

Definition of prostate cancer

 

Prostate cancer is a cancer that forms in tissues of the prostate (a gland in the male reproductive system found below the bladder and in front of the rectum). Prostate cancer usually occurs in older men. It is not to be confused with benign prostatic hyperplasia which is the enlargement of the prostate gland due to an increase in the number of cells but that does not spread to other parts of the body, and for which symptoms are associated with the compression of adjacent structures, i.e. the urethra.

 

Anatomy of the male reproductive and urinary systems, showing the prostate, testicles, bladder, and other organs.

 

 

Frequency

PATIENT INFORMATION BASED ON ESMO CLINICAL PRACTICE GUIDELINES
As treatments are becoming more personalized due to the advances in cancer care, we would kindly ask you to contact info@anticancerfund [dot] org for a more appropriate guidance according to the most recent guidelines on this cancer type. This guide for patients is a service to patients and their families, to help them understand the nature of the disease and the existing treatment choices. 

 

Is prostate cancer frequent?

 

Prostate cancer is the most common cancer amongst men. In Europe, about one in every 10 men will develop prostate cancer at some point in their life. This probability is lower in some Nordic countries and in Mediterranean Europe.

In Europe, in 2008 it was estimated that 382000 in total or 65 men out of 100000 were diagnosed with prostate cancer, ranging from 18 in Greece to 126 in Ireland. This difference depends on the frequency of the use of prostate cancer screening by country.

In its initial phases, prostate cancer may not cause symptoms and in otherwise healthy men aged between 55 and 69 years it is commonly detected by a blood screening test called prostate specific antigen (PSA). It has been suggested that screening with PSA test reduces death rate due to prostate cancer in 20%, but this is controversial. However, prostate cancer develops relatively slowly and symptoms at diagnosis indicate an advanced stage. The utility of this screening method has been widely studied and it is believed that although it certainly decreases slightly the rate of deaths due to prostate cancer, many patients could be being over treated, reducing their quality of life unnecessarily.
 

Causes

PATIENT INFORMATION BASED ON ESMO CLINICAL PRACTICE GUIDELINES
As treatments are becoming more personalized due to the advances in cancer care, we would kindly ask you to contact info@anticancerfund [dot] org for a more appropriate guidance according to the most recent guidelines on this cancer type. This guide for patients is a service to patients and their families, to help them understand the nature of the disease and the existing treatment choices. 

 

What causes prostate cancer?

 

Today, it is not clear why prostate cancer occurs. Some risk factors have been identified. A risk factor increases the risk of cancer occurring, but is neither necessary nor sufficient to cause cancer. A risk factor is not a cause in itself.

Some men with these risk factors will never develop prostate cancer and some without any of these risk factors will nonetheless develop prostate cancer.

The main risk factors of prostate cancer are:

  • Aging: The risk of prostate cancer is largely influenced by age. After 50 years of age the risk increases exponentially every year. The exact mechanism is unclear, but aging of the cells and the consecutive changes in their DNA have been pointed out.
  • Ethnicity: In developed countries, black men are at higher risk of developing prostate cancer than white and Asian men. The reasons are unclear.
  • Genes: Recent research has shown that there are several inherited genes related to higher risk of developing prostate cancer, but apparently they account for a small amount of cases. Currently, studies are being developed to see if tests looking for those genes are useful to predict prostate cancer risk.
  • Family history of prostate cancer: It has been shown that there is a familial predisposition to have prostate cancer, especially in men whose fathers or brothers are or were affected.
  • Diet: It is unclear whether diet and lifestyle play a role in the development of prostate cancer. Some studies suggest that a diet high in red meat or dairy products slightly increases the risk of developing prostate cancer. On the other hand, some studies suggests that a diet rich in lycopene from tomatoes, and selenium (a mineral mainly found in red meat, fish and seafood, eggs and cereals) both slightly decrease the risk of prostate cancer. However, more evidence is necessary. Obesity also increases the risk of having prostate cancer.
  • Lifestyle: Smoking may slightly increase the risk of having prostate cancer whereas being more physically active seems to slightly lower the risk.
  • Hormones: High blood levels of testosterone have an increased risk of prostate cancer. Also some hormones related to growth have been associated with cancer, but further studies have to be done.

Other factors have been suspected to be associated with an increased risk of prostate cancer, but the evidence is inconsistent. Unfortunately, the factors that have the highest influence on the risk of prostate cancer like age, ethnicity, genes and familial history of prostate cancer cannot be changed.

Diagnosis

PATIENT INFORMATION BASED ON ESMO CLINICAL PRACTICE GUIDELINES
As treatments are becoming more personalized due to the advances in cancer care, we would kindly ask you to contact info@anticancerfund [dot] org for a more appropriate guidance according to the most recent guidelines on this cancer type. This guide for patients is a service to patients and their families, to help them understand the nature of the disease and the existing treatment choices. 

 

How is prostate cancer diagnosed?

 

Prostate cancer develops slowly and symptoms mainly appear only when the illness is advanced. Some common symptoms in that case could be urinary symptoms like increase in urination frequency, difficulties in starting to urinate, getting up multiple times to urinate during the night, urgency or sensation of necessity to urinate immediately. Other less common symptoms are blood in the urine and semen, bone pain and loss of bladder control. These symptoms are in fact less specific than the previous ones.
Consequently, men with the previously mentioned symptoms, or risk factors like age or family history of prostate cancer should be screened.

Cancer suspicion relies on PSA level in the blood and digital rectal examination (DRE) for patients with symptoms, or those patients who request to be screened during a regular check-up. The PSA and DRE results need to be confirmed with a biopsy and histopathological examination.

  1. Digital Rectal Examination (DRE)

DRE is a clinical test to check the size, consistency, sensitivity and limits of the prostate. Because the prostate is situated in front of the rectum the doctor can feel it by inserting a gloved, lubricated finger into the rectum. DRE by itself could miss around half of the cases of prostate cancer. Therefore it should be done in combination with PSA test in an appropriately counselled patient in whom there is clinical suspicion of prostate cancer or in patients who wish to be screened for prostate cancer.

  1. PSA test

PSA stands for prostate-specific antigen. It is a protein produced exclusively by the prostate. The PSA test measures the level of PSA in the blood. Normally it is present in the blood, but an increase can suggest prostate cancer. In non-symptomatic patients PSA level is monitored over time to evaluate any changes. In patients with suspicion of cancer a biopsy is recommended. It must be considered that prostate cancer is not the only reason why the PSA level increases. Non-malignant conditions such as an inflammation (prostatitis), urinary tract infection and benign prostatic hyperplasia can cause PSA levels to rise. Administration of certain drugs, having a prostate biopsy performed previously or a DRE, riding a bike and having sex are some common reasons of having an elevated PSA level. These situations should be avoided before measuring PSA.

 

3. Biopsy

The diagnosis can only be confirmed with the laboratory examination of a sample of the tumour cells (biopsy). In this procedure, samples of prostatic tissue are taken from the prostate in order to analyse the cells. The samples can be obtained by inserting a needle through either the rectum, the perineum or the urethra.

 

 

 

 

 

 

  • Rectal route: When the biopsy is performed through the rectum, the application of an enema to clean the rectum is needed beforehand. Antibiotics can minimize the risk of infection. It can be done under local or general anaesthesia. Transrectal ultrasound (TRUS) is generally used to guide the needle to the correct biopsy location; although sometimes a needle guide is attached to the doctor’s finger, he or she has to insert a finger into the rectum. The needle is then slid along the guide through the wall of the rectum and into the prostate; the needle is turned to collect tissue samples and then pulled out. A transrectal biopsy takes around 30 minutes. This is the most commonly used route to perform a prostate biopsy.
  • Perineal route: When the biopsy is done through the perineum local or general anaesthesia can be used; the doctor will insert his or her finger into the patient’s rectum to hold the prostate while the samples are taken. A small cut (incision) is made in the patient’s perineum, then the needle is inserted through it and into the prostate. To collect a sample of tissue the needle is gently turned and pulled out. Pressure is applied to stop the bleeding and a small bandage is placed over the cut. This kind of biopsy usually takes about 15 to 30 minutes.
  • Urethral route: When the biopsy is performed through the urethra, general, spinal or local anaesthesia may be used. A lighted scope (cystoscope) is inserted into your urethra. It allows the doctor to look directly at the prostate gland. A cutting loop is passed through the cystoscope to remove small pieces of prostate tissue. A transurethral biopsy usually takes about 30 to 45 minutes.

Typically several biopsy samples will be taken from different parts of the prostate at the same time. This allows the doctor to determine where the cancer cells are located as well as the growth of the cancer.

Antibiotics prior to the procedure should be prescribed to prevent infection.

A second histopathological examination of the tumour and the lymph nodes removed by surgery will be performed later.

The decision on whether or not a biopsy is necessary should be made in the light of DRE findings, prostate size, ethnicity, age, other diseases, history of cancer in the family, patient values, history of a previous biopsy and PSA level. In case of an elevated PSA and negative initial biopsies, a new test called PCA3 test in urine can be carried out to determine whether new biopsies are indicated.

Treatment

PATIENT INFORMATION BASED ON ESMO CLINICAL PRACTICE GUIDELINES
As treatments are becoming more personalized due to the advances in cancer care, we would kindly ask you to contact info@anticancerfund [dot] org for a more appropriate guidance according to the most recent guidelines on this cancer type. This guide for patients is a service to patients and their families, to help them understand the nature of the disease and the existing treatment choices. 

 

What is important to get an optimal treatment?
 

 

Doctors will need to consider many aspects of both the patient and the cancer in order to decide on the best treatment.

 

 

Relevant information about the patient

  • Personal medical history
  • History of cancer in relatives, especially prostate cancer
  • Results from the clinical examination by the doctor
  • General well-being
  • Results from blood tests performed to assess the white blood cells, the red blood cells and the platelets and to identify any problem in the liver and renal function as well as any bone problems.
  • Patient’s age and expected lifespan
  • Patient’s other illnesses such as heart and pulmonary problems or diabetes.
  • Patient’s personal preferences about the treatment options with regard to the possible risks and side effects and to the chances of success (risks and benefits).

 

Relevant information about the cancer

The diagnosis of prostate cancer can only be confirmed after a biopsy. In this procedure, samples of prostatic tissue are taken from the prostate to analyse the cells.

As previously explained, the samples are obtained by inserting a needle through the rectum, the perineum or the urethra.

Once the samples have been analysed, the pathologist assigns a grade to the cancer cells, mostly according to the Gleason system. The Gleason system uses a 1 to 5 scale, depending on how much the cancer cells look like normal prostate cells.

 

1 means that the cancer cells look a lot like normal prostate cells.

5 means that the cancer cells seem to be spread in an unorganized way and subsequently the tissue does not resemble prostate tissue anymore.

2, 3 and 4 are between the two extremes.

1 and 2 grades are no longer used.

 

The Gleason score is determined by adding the grade assigned to the majority of the cancer cells to the highest grade observed.

A Gleason score =<6 is well differentiated or low-grade. On average, prognosis is better.

A Gleason score 7 is moderately-differentiated or intermediate-grade. On average, prognosis is intermediate.

A Gleason 8-10 is poorly-differentiated or high-grade. On average, prognosis is lower.

 

Sometimes the biopsy results are inconclusive and the procedure should be repeated.

Doctors use staging to assess the extent of the cancer and the prognosis of the patient. The TNM staging system is commonly used. The combination of size of the tumour and invasion of nearby tissue (T), involvement of lymph nodes (N) and metastasis, or spread of the cancer to other organs in the body (M), will classify the cancer into one of the following stages.

The stage is fundamental in order to make the right decision about the treatment. The more advanced the stage, the worse the prognosis. Staging may be performed twice: after clinical and radiological examination and again after surgery. If surgery is performed, staging may be changed by the laboratory examination of the removed tumour.

The table below presents the different stages prostate cancer.

 

Stage

Definition

Stage I

The tumour involves just one of the two lobes of the prostate. It can be found incidentally through a biopsy done after observing a high level of PSA. The cancer has not spread to the lymph nodes or elsewhere in the body.

Stage II

The tumour has spread to the other lobe and can involve the whole prostate without breaking out of the capsule surrounding it. The cancer has not spread to the lymph nodes or elsewhere in the body.

Stage III

The tumour has spread outside of the prostate to the seminal vesicles, which are a pair of glands above the prostate that secrete an important proportion of the fluid that contains the semen. The cancer has not spread to the lymph nodes or elsewhere in the body apart from the seminal vesicles.

Stage IV

The tumour has invaded adjacent structures other than the seminal vesicles, for instance the rectum, the muscles or pelvic wall; or, regardless of the invasion of adjacent structures, it has spread to other parts of the body including lymph nodes and bones.

 

  • Risk categories

To estimate their aggressiveness, localized prostate cancers are categorized as low-, intermediate- or high-risk according to the tumour size, Gleason score and PSA level. Low-risk prostate cancer has a tumour limited to one lobe of the prostate (which has two lobes) and a Gleason score <7 and a PSA level <10 ng/ml (nanograms per millilitre). The intermediate-risk prostate cancer has a tumour that has invaded the other lobe of the prostate, partially or completely and a Gleason score =7 or a PSA level between 11 and 19 ng/ml. The high-risk prostate cancer has a tumour that has invaded structures adjacent to the prostate with a Gleason score >7 or a PSA level >20 ng/ml.

When the risk is low no bone scintigraphy is routinely recommended. The goal of a bone scintigraphy is to look for a possible dissemination of the cancer to the bones. When the risk is intermediate there are two options: if it is planned that the patient is treated with radiotherapy he should have ideally pelvic magnetic resonance imaging (MRI), if, on the contrary, it is planned that he will have a surgery the risk/benefit of lymph node removal based on prognosis should be discussed. When the risk is high bone scintigraphy should be carried out and MRI of the pelvis should be considered. Under the suspicion of bone metastasis, bone scintigraphy is only performed if the Gleason score is at least 7 and the PSA higher than 10 ng/ml.


What are the treatment options?
 

The planning of the treatment involves an inter-disciplinary team of medical professionals. This usually implies a meeting of different specialists, called multidisciplinary opinion or tumour board review. In this meeting, the planning of the treatment will be discussed according to the relevant information mentioned above.

The extent of the treatment will depend on the stage of the cancer, on the characteristics of the tumour and on the risks involved.

There are a lot of treatment options, but there is no consensus as to what constitutes optimum management. The different kinds of treatment listed below have their benefits, their risks and their contraindications. It is advisable to ask oncologists about the expected benefits and risks of every treatment in order to be informed of the consequences of the treatment. For some kinds of treatment, several possibilities are available. After weighing up the benefits and risks of a particular kind of treatment, the right choice can be made.

 


Treatment plan by stage of prostate cancer

Treatment plan for localised prostate cancer (Stages I and II)

 

In stages I and II prostate cancer, the tumour involves just one lobe of the two lobes of the prostate, or both lobes, without invading other tissues outside the prostate. The cancer has not spread to the lymph nodes or elsewhere in the body. In low-risk patients watchful waiting is an option to be discussed, in patients with intermediate-risk surgery or radiotherapy plus hormone therapy are part of the treatment. Hormone therapy alone could be proposed to elderly patients and patients unsuitable for or unwilling to have other treatments.

Low- and intermediate- risk cancer patients belong to this group. In low-risk prostate cancer patients watchful waiting is an option that should be discussed with doctors, since so far no advantage in life prolongation has been shown from initiating early treatment in this group of patients. In patients with intermediate-risk treatment options include full removal of prostate by surgery or external radiotherapy plus hormone therapy (lowering the level of testosterone in blood) or brachytherapy.

 

Too elderly patients who do not have symptoms or patients who have other serious health problems or those unwilling to have treatment, close follow-up of their condition and, in the event of progression of symptoms, hormone therapy could be proposed.

Hormone therapy is aimed at lowering the level of the hormone called testosterone, which is linked to the growth of the cancer cells in the prostate. It is recommended to be administered upon the appearance of signs of disease progression when a patient is under watchful waiting strategy.

 

The treatment options meant to remove the cancer cells are:

  • Prostatectomy, which is the removal of the prostate by a surgical intervention. Laparoscopic prostatectomy is a modality of prostatectomy that apparently has similar results to open surgery, although recovery of bladder control may be slightly delayed. The nerve-sparing approach by laparoscopic technique increases the chance of recovery of sexual activity. Laparoscopic robotic-assisted radical prostatectomy apparently has advantages over open approach in terms of pain, blood loss and recovery time. But the time taken for surgeons to become fully proficient with the robotic techniques is a factor and since this is a new technique, long-term outcomes have yet to be evaluated.
  • Radiotherapy, which is the use of radiation to kill cancer cells, is also a treatment option. Cancer cells are less capable of recovery from radiation damage than normal cells, allowing radiotherapy to be used as a treatment. External radiotherapy and brachytherapy are the two modalities of radiotherapy in use.
    In external radiotherapy the radiation is produced by an external source and then directed at the tumour. Conformal techniques that allow the beam of radiation to be more accurate should be used in order to prevent side effects. Conformal techniques are Intensity-modulated radiotherapy (IMRT) and stereotactic radiotherapy, to name just a few.
    In brachytherapy the source of radiation is placed inside the prostate as small radioactive pellets.
    Before treatment with radiotherapy, initial treatment (neoadjuvant) of 4-6 months with hormone therapy should be considered in men with intermediate risk prostate cancer.
  • The effectiveness of radiotherapy and prostatectomy are equivalent. In order to make a choice between them, the side effects of both need to be considered and evaluated. This should be done with the support of an oncology surgeon and a radiation oncologist.
     

Treatment plan for locally advanced prostate cancer (Stage III):

In stage III prostate cancer, the tumour has spread outside of the prostate to the seminal vesicles. The cancer has not spread to the lymph nodes or elsewhere in the body apart from the seminal vesicles. Radiotherapy and additional hormone therapy is the standard of treatment. In selected cases surgery could also be an option.

 

High-risk patients are part of this group. The standard treatment is radiotherapy. Radiotherapy with additional hormone therapy for two to three years is recommended, as it was shown that this combination might have a benefit regarding life prolongation compared to radiotherapy alone. Hormone therapy alone is not recommended. In certain cases surgery including important removal of lymph nodes is another option.

For men with no symptoms who are not suitable or are unwilling to have above mentioned treatments, watchful waiting could be chosen. If afterwards there is evidence that the cancer has grown hormone therapy could be started.

In order to secure treatment efficacy, different therapies are combined as part of the same protocol. Neoadjuvant therapy is a therapy administered to the patient before the main therapy. Adjuvant therapy is the administration of a therapy in parallel to and/or following the main therapy.

For men with high-risk prostate cancer who are treated by radiotherapy, neoadjuvant hormone therapy with LHRH agonist for four to six months before starting radiotherapy is recommended. In addition, adjuvant hormone therapy is recommended for two to three years.

Adjuvant hormone therapy can be based on bicalutamide 150 mg daily rather than LHRH agonist in men who place a high value in retaining sexual function during the treatment, but they should understand that the data concerning outcome of bicalutamide are still limited.

After full prostate removal, immediate postoperative radiotherapy could be considered, although it is not routinely recommended. Patients likely to have residual disease after surgery, tumour positive margins or disease extended beyond the prostate to surrounding tissues, should be appropriately informed on the benefits and disadvantages of the administration of adjuvant radiotherapy.

Adjuvant hormone therapy after full prostate removal is not recommended.

 

Treatment plan for advanced prostate cancer (Stage IV)
 

The tumour has invaded adjacent structures other than the seminal vesicles, for instance the rectum, the muscles or pelvic wall; or, regardless of the invasion of adjacent structures, it has spread to other parts of the body including lymph nodes and bones. Hormone therapy is the standard of care. Surgery and radiotherapy can also help to relieve symptoms caused by tumour mass.

The treatment of first choice is hormone therapy. Other treatment options are external radiotherapy plus hormone therapy and surgery to relieve symptoms such as bleeding or urinary obstruction.

Hormone therapy

The goal of the hormone therapy is to decrease the level of androgens in the blood, in this case testosterone. Testosterone stimulates the growth of the cells. Hormone therapy can be achieved surgically (removal of both testicles also called bilateral orchiectomy) or non-surgically (administration of drugs called LHRH agonists). When done surgically, the organs that produce testosterone, the testicles, are removed, this is known as surgical castration. Non-surgically, the administration of LHRH agonists prevents the release of one hormone in the brain called LH (luteinizing hormone), which is responsible for the production of testosterone in the testicles, this is called chemical castration. Consequently, the hormone therapy will decrease the level of testosterone in the blood.

Considering its benefit and associated cost the first choice for hormone management of metastatic prostate cancer should be based on surgical or chemical castration that results ultimately in androgen levels decrease in blood.

Intermittent hormone therapy consists of an initial active hormone therapy period, usually between 6 and 9 months, followed by a corresponding length of time where no active therapy is undertaken. Patients are then followed and when criteria for reactivation of disease are met, active hormone therapy is reinitiated. Mature results of this intermittent approach are awaited, though early results suggest equivalence with continuous hormone therapy.

 

One particular effect of the hormone therapy deserves a detailed explanation:

  • Flare: one effect from treatment with the LHRH agonists is the initial “flare” phenomenon, in which the testosterone level in the blood increases due to the initial stimulation of the androgen receptors. This can cause a short-term increase in cancer growth; and if the patient has bone metastases they become painful. In case of spinal metastases, even a small increase in the volume can produce spinal cord compression and paralysis. To prevent this flare phenomenon, antiandrogens can be administered for a few weeks. LHRH antagonists were developed recently and appear to offer equivalent testosterone reduction without the need of an antiandrogen to control the transient testosterone surge.

 

Castration-resistant disease

During hormone therapy castration-refractory disease can develop. In this condition the cancer being treated with hormones starts to become resistant to this kind of treatment. Patients who develop resistance to castration treatments should continue androgen suppression as part of their hormone therapy and they are candidates for further hormone therapies including antiandrogens, corticosteroids, oestrogens and CYP17 inhibitors (blockers of pivotal enzyme in androgen synthesis), such as abiraterone.

Chemotherapy might be preferable in patients with poor initial response to hormones or who experience severe symptoms. Docetaxel with prednisone in a 3-weekly schedule is recommended for symptomatic patients with castration resistant disease. In patients whose disease continues to progress after the use of docetaxel, hormone therapy with abiraterone or enzalutamide with prednisone should be discussed if they were not used previously. Cabazitaxel and mitoxantrone with prednisone are other drugs to be considered in patients whose treatment with docetaxel seems unsuccessful. Cabazitaxel with prednisone has shown to improve survival in comparison to therapy with mitoxantrone and prednisone but its side effects profile should be considered.

 

Bone metastasis

With aging, men are prone to osteoporosis and consequently to fractures. The risk increases with androgen deprivation. The bone mineral density is an indicator of the risk of fracture. When this density is low, the risk of fracture is increased. Bone mineral density should be monitored annually. If the density decreases, zoledronic acid is a treatment option. Metastases by themselves can cause fractures. Spinal cord compression due to a spine fracture is a severe complication that can be diagnosed early by imaging and can be successfully treated.

A single administration of external radiotherapy should be offered to patients with moderate number of painful bone metastases from castration-refractory disease (resistant to androgen deprivation).

Radioisotope therapy/bone targeted therapy with strontium-89, radium-223 or samarium-153 should be considered for patients with painful bone metastases from castration-refractory disease. This technique is based on the intravenous injection of molecules that are radioactive and have an affinity for the bones. After injection, the molecules reach the bones and emit radiations locally.

Zoledronic acid or denosumab should be considered for patients with bone pain resistant to palliative radiotherapy and conventional analgesics.

Denosumab has shown to delay events associated to bones damage due to metastases better than zoledronic acid, however some of its side effects could be more frequent compared to zoledronic acid. Neither showed improvement in how long the patients will live.

Spinal cord compression is a devastating complication of prostate cancer with vertebral metastases and its early detection is critical for successful management. MRI of the spine should be considered in men with vertebral metastasis and back pain to detect cord compression.

 

Other treatment modalities

 

Vaccine

Sipuleucel-T is a therapeutic vaccine. These are intended to treat cancer and not to prevent it.

It is elaborated with white blood cells removed from the patient's own blood and exposed to a protein from prostate cancer cells called prostatic acid phosphatase (PAP). After this process, the cells are injected into the same patient. In the body, the cells induce other immune system cells to attack the cancer.

It is used in metastatic prostate cancer, in particular when chemical or surgical castration has not worked or no longer works and in case the patient is not yet considered to receive chemotherapy.

 

Salvage local therapies

Cryosurgery and high-intensity focused ultrasound (HIFU) are not yet part of the standard of care, they still need to be studied further.

 

Cryosurgery

This kind of treatment is used to treat localized prostate cancer by freezing it. It may not be a good choice for patients with large prostates.

It is done under anaesthesia and ultrasound guidance. Its long-term outcome has not been measured yet, as a result it is sometimes recommended when the cancer has come back after other kinds of treatment were given to the patient.

It is not recommended as an initial treatment and is rather considered as a therapy in current development.

 

High-intensity focused ultrasound (HIFU)

This kind of treatment uses a high energy focused ultrasound beam which is directed at the prostate with the help of a probe through the rectum, to heat and destroy a very precise volume of tissue. This kind of treatment is aimed at the tumour and not the whole gland. It is recommended for prostate cancer localized in just one lobe. It is not recommended as an initial treatment and is rather considered as a therapy in current development.

 

 

What are the possible side effects of the treatment?

 

Surgery

Prostate removal by surgery can result in some side effects like urinary incontinence, impotence and sterility, due to damage to the structures and nerves controlling the ability to have an erection.

 

Radiotherapy

It may cause side effects such as urinary incontinence, impotence, bladder and bowel problems, tiredness, narrowing of the urethra, lymphatic obstruction and consequently fluid retention and swelling of the tissues.

As it implies the placement of a radioactive source, brachytherapy makes the patient radioactive. Because some radiation may reach the body surface, there is a period of time in which the patient has to avoid contact with pregnant women and children.

 

Radioisotope therapy/Bone targeted therapy

Blood and urine will be radioactive for some time. Your doctor and nurses will give you advice concerning the safety measures to be taken.

 

Hormone therapy

Some of the side effects related to hormone therapy are loss of libido, impotence, hot flashes, mood changes, osteoporosis, muscle weakness, abnormal development of the breasts (gynaecomastia), insulin resistance* and an increase in body fat. Patients should be monitored if such side effects occur.

  • Abiraterone: Some specific side effects of this drug are high blood pressure, fluid retention and tissue swelling (oedema), fatigue, urinary infections, cardiac arrhythmias and liver damage.
  • Enzalutamide: It is associated, amongst others, with headache, hot flushes, high blood pressure, back pain, respiratory infections, anxiety, diarrhoea, fatigue, seizures, blood in urine and tissue swelling (oedema).

 

Chemotherapy

  • Docetaxel: Some side effects related to the use of docetaxel are neutropenia, fatigue, hair loss, diarrhoea, neuropathy, peripheral oedema and nail dystrophy.
  • Mitoxantrone: It is associated to fatigue, hair loss, nausea, vomiting, diarrhoea, lymphopenia and thrombocytopenia.
  • Cabazitaxel: Some side effects related to its use are fatigue, diarrhoea, haematuria (blood in the urine), anaemia, neutropenia, hair loss and peripheral oedema (tissue swelling due to fluid retention)

 

Zoledronic acid

Side effects due to the use of zoledronic acid include anaemia, fever, oedema (fluid retention), fatigue, myalgia (muscle pain) and also jaw necrosis. To reduce the risk of jaw necrosis (but unfortunately, not to eliminate it), good oral hygiene along with regular dental care is recommended. In selected cases of patients receiving intravenous zoledronic acid, the use of an antibiotic such as clindamycin can be indicated, combined with the use of an antimicrobial mouthwash with chlorhexidine 4 times daily.

 

Denosumab

The most common side effects associated with denosumab are back pain, skin rash sometimes with blisters, bloody urine and difficult urination, muscle and bone pain.

 

Sipuleucel-T

This therapeutic vaccine is associated with fever, signs of inflammation and sometimes infection around the site where the cells to elaborate the vaccine were taken and the site where the vaccine was administered. Its side effects also include nausea, headache, back pain and pain in different parts of the body.

 

Cryosurgery

Some side effects resulting from the freezing of adjacent structures and nerves can be urinary incontinence, impotence and fistula (or an abnormal passage between the rectum and bladder).

 

High intensity focused ultrasound (HIFU)

Its side effects can be urinary incontinence and impotence.

 

 

What happens after the treatment?
 

There is no treatment that does not have any side effects, although new techniques are intended to reduce them. The side effects of the treatment, like impotence, incontinence and infertility have to be openly discussed with the patient.

The main kinds of treatment have consequences afterwards. For example: sexual activity is mostly affected by surgery and the urinary and intestinal functions are affected by external radiotherapy and brachytherapy.

 

 

Follow-up with doctors

After the treatment has been completed, doctors will propose a follow-up program aiming to:

  • Detect possible recurrence as soon as possible.
  • Evaluate adverse effects of the treatment and treat them.
  • Provide psychological support and information to enhance the return to normal life.

Follow-up visits with the oncologist should include:

  • History-taking (reviewing a patient’s medical history), eliciting symptoms and physical examination.
  • The PSA level should be measured on a regular basis after complete tumour eradication.

After surgery, due to the removal of prostatic cancer cells, undetectable levels of PSA in the blood are to be expected, but sometimes some PSA is still circulating in the blood. In this case doctors may recommend waiting some weeks to perform this test again.

After radiotherapy the PSA levels are not expected to drop dramatically. This process happens gradually, reaching the lowest level of PSA after 2 years. In many cases, if not the majority, a patient receiving radiotherapy nowadays also undergoes hormone therapy which is initiated before radiotherapy. In this case his PSA is likely to be undetectable or very low even before radiation commences. Since in this case, the PSA remains low after radiotherapy, another protein produced only by the prostate, called prostatic acid phosphatase (PAP), can be measured during the follow-up.

The PSA values fluctuate slightly over time. A small increase does not mean cancer recurrence (or that the cancer has not been cured). However it may be an indication, so it has to be monitored.

Routine digital rectal examination (DRE) after local treatment is not recommended while the PSA remains at baseline levels.

Biopsy of the prostatic bed should not be performed in men with prostate cancer who have had a radical prostatectomy. Biopsy of the prostate after radiotherapy should only be performed in men with prostate cancer who are being considered for a salvage therapy (e.g. HIFU, cryotherapy, salvage surgery).

 

Additional treatment may be recommended if PSA levels show an increasing trend over a period of time (biochemical relapse), as follows:

  • For men who have been under active surveillance; if their PSA level has doubled in less than 3 years or if they have a PSA velocity (change in PSA level over time) of greater than 0.75 ng/ml per year, or if they have a prostate biopsy showing evidence of worsening cancer.
  • For men who have had a radical prostatectomy (removal of the prostate gland); if their PSA level does not fall below the limits of detection after surgery or if they have a detectable PSA level (> 0.3 ng/ml) that increases on two or more subsequent measurements after having no detectable PSA.
  • For men who have had other initial therapy, such as radiotherapy with or without hormone therapy; if their PSA level has risen by 2 ng/ml or more after having no detectable PSA or a very low PSA level.

 

These findings have to be combined with others, such as positive prostate biopsy, or abnormal CT scan.

Patients who present with symptoms after radiotherapy such as anorexia, diarrhoea, nausea, vomiting and weight loss should be evaluated to exclude potential inflammatory bowel disease, colorectal cancer, or radiation enteropathy.

 

Return to normal life

It can be hard to live with the idea that the cancer can come back. Based on what is known today, no specific way of decreasing the risk of recurrence after completion of the treatment can be recommended, apart from avoiding weight gain and doing regular physical activity. As a consequence of the cancer itself and of the treatment, return to normal life may not be easy for some people.

It is mostly elderly men who are affected by prostate cancer and they may have impotence, bowel and urinary problems before treatment. In general they make a full mental and physical recovery, but sometimes it can take up to 2 years after the treatment to get back to normal. Back to normal means back to how they were before the treatment. It will unfortunately include any impotence, bowel or urinary problem that was already present before treatment.

 

What if the cancer comes back?

If the cancer comes back it is called recurrence and the treatment depends on the extent of the recurrence.

Locally, prostate cancer can recur in tissues next to the prostate (muscles that help to control urination, the rectum, the wall of the pelvis) or in the seminal vesicles. The lymph nodes surrounding the prostate region or lymph nodes outside the area can also be affected by the cancer.

Prostate cancer can also reappear in other parts of the body. This is called metastases.

To determine the recurrence of the tumour and to start a new kind of treatment, tumour size, lymph node involvement, Gleason score and stage, have to be taken into account.

The abnormal increase of PSA levels, also known as PSA failure or sometimes biochemical failure, suggests that the cancer has come back. In this case other tests like imaging may have to be done.

Sometimes the disease progresses without a significant rise in PSA. In this case, neuroendocrine change should be investigated using biopsy or blood analyses looking for neuron-specific enolase and/or chromogranin A, since this indicates a low chance of response to hormone therapies. Patients with evidence of neuroendocrine change in their prostate cancer should be selected for chemotherapy rather than hormone therapy.

 

The treatment options for cancer recurrence depend on the treatment that the patient has had already.

Following full prostate removal PSA levels in the blood should be monitored. Early salvage radiotherapy to the area where the prostate was located is recommended in case of PSA failure.

Immediate hormone therapy is not usually recommended for men who have a PSA failure, except for patients with symptomatic local disease progression, proven metastases or if their PSA level has doubled in less than 3 months.

Intermittent hormone therapy consists of an initial active androgen suppression period, usually between 6 and 9 months, followed by a corresponding length of time where no active therapy is undertaken. Patients are then followed and when criteria for reactivation of disease are met, active hormone therapy is reinitiated. Although this intermittent approach is still under study early results have shown it is not inferior to the continuous regimen and has quality-of-life benefits.

If the patient becomes resistant to the initial hormone therapy a second hormone therapy option is antiandrogens, corticosteroids, oestrogens and CYP17 inhibitors.

In patients with poor response to hormone therapy or experiencing severe symptoms following chemotherapy drugs should be considered:

Docetaxel (used together with prednisone or prednisolone) has demonstrated a gain in life prolongation as treatment for castration refractory disease.

Cabazitaxel is an anticancer drug used with prednisone to treat hormone-resistant prostate cancer that has spread and that had been treated with docetaxel.

Mitoxantrone (together with prednisone or prednisolone) can be used if docetaxel is contraindicated or if expected side effects from cabazitaxel might not be tolerated. It is an active drug against prostate cancer but does not prolong life.

Synonyms

Prostate cancer

Prostate tumor

Prostate tumour

Cancer of the prostate

Tumor of the prostate

Tumour of the prostate

Prostate carcinoma

Therapies by type

The following list of treatments is based on what we have found in scientific studies about cancer. More information about the listed therapies can be found under the tab THERAPIES. For registered drugs, radiotherapy and surgical interventions, approval by the authorities is given.

Surgical interventions

Procedures involving instrumental means to investigate or treat a cancer, or to improve the body’s functions or appearance. Generally, a surgical intervention involves an incision. More

Radiotherapy

Medical use of high-energy radiation to kill cancer cells and reduce tumor size. More

Cell-based therapies

Administration to patients of their own or someone else’s manipulated human cells. More

Synthetic products (excluding registered drugs)

Synthetically produced substances or modified natural products that are not registered as anti-cancer drugs.

Diets

Controlled consumption of carefully selected foods and beverages with the intent to influence disease outcome.

Energy based therapies

Use of electromagnetic energy including electricity, magnetic fields, radio waves, microwaves, infrared rays and light to diagnose or treat disease.

Clinical trials

A clinical trial is a research study conducted with patients to evaluate whether a new treatment is safe (safety) and whether it works (efficacy). Clinical trials are performed to test the efficacy of drugs but also non-drug treatments such as radiotherapy or surgery and combinations of different treatments. Clinical trials take place in all kinds of hospitals and clinics, but mostly in academic hospitals. They are organized by researchers and doctors.

The Anticancer Fund provides a tool to search for phase III clinical trials by type of cancer and by country. For Belgium, the Netherlands, Switzerland, Luxembourg, France and the UK, the Anticancer Fund provides contacts to get more information about the phase III clinical trials currently ongoing. Discuss the possibilities of participating in one of these clinical trials with your doctor.

The list of the phase III clinical trials for prostate cancer is available here.