Prostate Cancer

What is the prostate and what does it do?

The prostate is a small gland located at the base of the bladder. The prostate's only function is as a reproductive organ.

The prostate produces fluid that supports and assists sperm for conception. PSA is an enzyme that is produced by the prostate that assists sperm. By chance, some PSA is also released into the bloodstream. It has no known function in the bloodstream, but is measurable in all men by a blood test, and forms the basis of PSA testing for prostate cancer. PSA is by no means a perfect test for prostate cancer, but it can be an early indication of problems.

What is prostate cancer?

Cancer is an uncontrolled growth of abnormal cells that have the ability to invade across the basement membrane of cells and tissues, and spread around the body. Normal cells are controlled in their growth pattern; only the correct numbers of cells grow. Cancerous cells have lost this control mechanism; they continue to multiply, and have the potential to invade other areas of the body.

Prostate cancer occurs when cells in the prostate start to behave in this uncontrolled manner. Not all prostate cancers are aggressive; some cancers may sit in the prostate and not cause problems during a man's life. Other kinds can behave in a more aggressive way. One of the most important things a urologist does when making a diagnosis of prostate cancer is to work out if the tumour is likely to behave in an aggressive or non-aggressive manner. This is discussed in more detail below, and takes into account many factors including the PSA level, DRE findings, biopsy findings (Gleason score, and amount of cancer in the biopsies), MRI findings and family history and race.

Click here for a short video explaining what prostate cancer is:

What are the risk factors for prostate cancer?

The exact cause of prostate cancer is not known. As with other cancers, it is likely that there may be a genetic pre-disposition in some people, which makes them more susceptible to prostate cancer. In others, there may be links to things in the environment that we don't yet fully understand. Prostate cancer is a complicated disease, and it comes in different forms, some aggressive, most not aggressive. Indeed, many of us will develop low-grade prostate cancer as we age, and this rarely causes problems in a man's lifetime.

We do know that there are certain risk factors for prostate cancer:

Age

Prostate cancer is more common in older men; the older you are the more likely it is that prostate cancer will be found on a biopsy.

Family History

In some people, there seems to be a genetic link to prostate cancer. This is often hard to prove, as prostate cancer itself is quite common. But if you have male members of your family who have had prostate cancer, (particularly if they were diagnosed before the age of 60 years) then you risk of prostate cancer is higher. And the more male members of your family affected, the higher the risk.

FDR = First degree relatives (brothers, father)
2nd degree relative = uncle, nephew or grandparent

Reference: Kiciński M, Vangronsveld J, Nawrot TS: An epidemiological reappraisal of the familial aggregation of prostate cancer: a meta-analysis. PLoS One 6 (10): e27130, 2011.

There is also a link to BRCA gene mutations, although this is rare. BRCA is a gene that, if mutated, can increase the chance of breast and ovarian cancers in women and prostate cancer in men. Less than 2% of the male population have a BRCA gene mutation. To read more about BRCA mutation, click the link.

Race

There are some associations with race and prostate cancer risk. African American men have a higher incidence of prostate cancer than whites, and Asian and Pacific Islander races have a lower incidence than whites. In South Australia or Adelaide, this may have some bearing on your risk of a prostate cancer diagnosis.

How is prostate cancer diagnosed?

PSA and isoforms of PSA

The blood test for PSA is not a perfect test, but it is helpful, along with a DRE, in deciding if further investigation is needed for possible prostate cancer. The reading that comes back from the lab needs to take into account your age (PSA normally increases with age) and to some extent the size of your prostate, estimated from the DRE. There are other forms of the PSA test that are available in Adelaide, known as % free PSA, and the prostate health index (phi).

Nick Brook will talk to you about these other if they are relevant to your situation.

Prostate Biopsy

Biopsy of the prostate is the only way to make a definitive diagnosis of prostate cancer. Small samples (cores) of the prostate are taken with a thin needle, from various parts of the prostate and then examined under a microscope by a pathologist. In Adelaide, we can offer two different types of prostate biopsy, and Nick Brook will discuss these with you in detail. These are trans-rectal ultrasound biopsy (TRUS-Biopsy of the prostate) and transperineal ultrasound guided prostate biopsy.

A diagram illustrating transrectal ultrasound guided biopsy of the prostate.

What happens after you have been diagnosed with prostate cancer?

Before a decision can be made about the correct treatment, many pieces of information need to be gathered and considered. This is a complex process and can be a difficult one to grasp, but a stepwise approach with careful consideration is needed. It is important that you are involved in the whole process, and that you get as much information as you need. The information that is used comes from different sources:

1. Biopsy – Gleason score and amount of prostate cancer in the biopsies.

After your biopsies are taken, they are sent to a pathologist who examines them under a microscope, and may perform other special tests. The report that comes back to your Urologist will tell them:

• If prostate cancer is present
• If it is, how many of the biopsies ('cores') have cancer in them
• What percentage of each core has cancer in it
• What the grade of the cancer is

The grade is described as a Gleason score. This describes how abnormal the glands of the prostate look under the microscope. The more abnormal the glands, the more aggressive the prostate cancer.

Grades 1 and 2 have been abandoned, so the lowest possible grade is 3. You will have a Gleason sum score, that looks something like 3+3=6, or 4+3=7, etc. Your Urologist will explain this to you, but briefly, the first figure represents the most frequent pattern, and the second figure represents the second most frequent pattern on the biopsies. The higher the overall score, the more aggressive the prostate cancer. The lowest possible sum score is 6, and the highest possible is 10.

Why is the Gleason score so important in deciding about treatment?

From long-term studies, we know that the higher the Gleason score, the more likely it is that prostate cancer will cause trouble in the future. However, this risk depends on a patient's age at the time of diagnosis, and also your chance of dying of other medical conditions in the future. These tables come from men who had prostate cancer but were not treated, and followed up over many years. Nick Brook will talk you through these tables, and how they may apply to you. They can be very helpful in putting prostate cancer into perspective for your situation.

On the left is an Albertson Table for prostate cancer.

2. Staging of prostate cancer

Staging of prostate cancer is very important in making the decision about what treatment is best for you. Stage means how far the cancer has spread; is it just in the prostate, has is spread to the lymph nodes, and has it spread to other parts of the body. Once the cancer has spread beyond the prostate, cure is less likely. This doesn't mean cure it is impossible, but it does mean that certain treatments may not be useful, and that other kinds may need to be considered.

Prostate cancer stage considers the T Stage (the state of the tumour in the prostate) the N Stage (the state of the lymph nodes that drain the prostate) and the M Stage (any evidence that the cancer has spread to other parts of the body).

Staging information is derived from different sources:

• The DRE – digital rectal examination
• The biopsy result – how much of the prostate is involved with cancer
• The staging MRI scan – this looks at local spread beyond the prostate and the lymph nodes
• A bone scan – this is not necessary in all men, and is only done in men with very high PSA readings, and those with high-grade prostate cancer (Gleason 4+4=8 or above).

Management options for prostate cancer

There are many different options for treating prostate cancer, and it can be confusing to understand which apply to your situation, and which options are best. The very first and most important consideration is the stage of the prostate cancer; treatment options are very much dictated by whether the cancer is localised, locally advanced or metastatic. Once the sage of the prostate cancer is known, the following need to be considered:

• Gleason score (from biopsy)
• PSA level
• Other medical issues that a man has
• The patient's personal preference, including decisions about side effects of different treatments

Treatment options for localised prostate cancer

Active surveillance for localised prostate cancer

In men with very small amounts of low-grade prostate cancer (Gleason 3+3=6), or in some older men with very small amounts of Gleason 3+4=7, active surveillance may be a sensible option. We know that many men with this kind of prostate cancer will not be affected by it in any way. Active surveillance involves regular check ups, PSA tests and occasional re-biopsy to ensure there are no changes over time. Results from large studies of active surveillance over time indicate that two thirds of men remain on active surveillance at 5 years, whilst one third of men do at some point need treatment. Because these men are closely watched and treated if needed, there is no evidence that anything is lost after a period of active surveillance if you do need treatment.

In Adelaide, Nick Brook uses the PRIAS Active Surveillance Protocol for prostate cancer, which you can read more about by following the link.

Treatment options for locally advanced prostate cancer

Surgery

Surgery is still an option for locally advanced prostate cancer, but there is a lower chance that the cancer can all be removed at the time of surgery. This means that you may also need further treatment after the surgery such as radiotherapy. When treatments are combined like this, there is a higher rate of complications such as erectile dysfunction and impotence (erectile dysfunction).

Having said that, there are some situations where it may be advantageous to remove as much cancer as possible, on the understanding that you may need radiotherapy after the procedure. Your urologist will discuss this with you at length.

External Beam Radiotherapy

Radiotherapy treatment for locally advanced prostate cancer can be a very good option to control the cancer. It is usually given along with hormone treatment. It is important to know that if the cancer has moved beyond the prostate, there is a lower chance of cure, but it is still possible.

Radiotherapy with HDR brachytherapy boost.

A further way to increase the effectiveness of treatment for locally advanced prostate cancer is to combine external beam radiotherapy with HDR (high dose rate) brachytherapy. The idea is to give a shorter course of external beam radiotherapy (usually 4 weeks), followed by a boost of radiation to the prostate. This boost is given by inserting thin rods into the prostate during a short operation. High dose radiation is passed down these rods into the prostate, and the rods are then removed. You are usually able to go home the next day. The outcomes from this can be very good.

Treatments for metastatic prostate cancer

Metastatic prostate cancer cannot be cured, but it can be treated to prolong life. The basis of treatment is to hold back the prostate cancer cells, and to slow their growth. Indeed, some newer treatments seem able to reduce the number of prostate cancer cells considerably.

Testosterone manipulation (androgen deprivation therapy – ADT)

Reducing circulating testosterone is the first step in treating metastatic prostate cancer. Most patient will be started on a drug class known as LHRH-agonists or antagonists. LHRH is luteinising hormone-releasing hormone, and it ultimately controls testosterone production. By giving LHRH drugs (as injections), testosterone production is greatly reduced. Names of these drugs include Firmagon, Lupron and Zoladex. Prostate cancer cells need testosterone to grow, so there is a reduction in activity of the cells, and the PSA will usually fall quite markedly. This response does not last forever; the cancer cells eventually find a way around this and start to grow again, even in the absence of testosterone. This is often indicated by a rise in the PSA level.

When this occurs, the clinical situation is known as castrate-resistant prostate cancer (CRPC).

A common next step is to add in an anti-androgen. This is a drug that blocks the androgen receptor, and these may produce a response for a while longer.

Click here for a short video on testosterone:

Side effects of ADT

Because ADT is a powerful form of treatment it has many potential side effects (due mainly to the reduction in testosterone levels in your body) and these need to be considered carefully against the advantages of ADT.

The side effects can include:

• Reduced sex-drive
• Impotence (erectile dysfunction)
• Tiredness and lethargy
• Hot flushes
• Reduced muscle mass, bone strength and body hair
• Increased body fat
• Mood changes and depression
• Memory problems
• Possible increased risk of cardiovascular problems

Click here for a short video on side effects of hormone treatment:

Delaying the start of ADT by using watchful waiting

In some men older with prostate cancer (but without bone metastases), the best treatment option may be 'watchful waiting'. Because of the many side effects of ADT, which increase over time, it may be wise to delay starting ADT until it is really necessary. There seems to be little survival benefit from starting ADT early. Watchful waiting means that no immediate treatment is started, but that you are seen regularly for reviews and treatment is started if and when you need it. Watchful waiting needs careful discussion with your urologist to see if it is appropriate for your situation.

Next steps – Medical Oncology and consideration of other drugs for metastatic prostate cancer.

As mentioned, over time the prostate cancer cells find a way to bypass the LHRH drug effect. It is usually at this stage (and perhaps earlier) that you will be referred to a medical oncologist. These are doctors who use chemotherapy and other treatments for cancer. The last few years have seen a great expansion of the drugs available for metastatic prostate cancer. Some of these drugs include:

• Abiraterone (Zytiga)
• Enzalutamide (Xtandi)
• Docetaxel
• Cabazitaxel
• Radium-223

Other drugs such as steroids and bisphosphonates are available to help support treatment.

Clinical trials in metastatic prostate cancer

In Adelaide, South Australia these drugs are available but some may only be available in the setting of clinical trials for metastatic prostate cancer. Clinical trials do offer the possibility of access to drugs that might not otherwise be available. There are other benefits of being part of a clinical trial, and there are some potential risks. You can read more about these pros and cons by following this link http://www.australianclinicaltrials.gov.au/node/22.

The Royal Adelaide Hospital is currently running a range of randomised clinical trials in advanced prostate cancer. These include

Studies of radium 223 for patients with prostate cancer and bone metastases

• Radium 223 alone or with abiraterone for castrate resistant prostate cancer
• Radium 223 at standard dose or high dose or long duration for castrate resistant prostate cancer

Studies for patients with castrate resistant prostate cancer

• Aragon 509 – a study in castrate resistant prostate cancer that is non-metastatic
• Prostvac vaccine trial - for patients with castrate resistant prostate cancer that is progressing slowly

Study for newly diagnosed metastatic prostate cancer

• Lattitude – abiraterone study

Radiotherapy for bone metastases

If prostate cancer has spread to bone, this can be painful. Radiotherapy to these bone metastases can often be helpful in controlling pain.

Click here for a short video on radiotherapy for bone metastases: