Prostate cancer

Transrectal ultrasound guided (TRUS) biopsy of the prostate

The process of TRUS biopsy takes around 10 minutes to perform. It involves a finger-based examination of the prostate followed by the insertion of an ultrasound probe into the rectum. Local anaesthetic is injected through the front wall of the rectum using a small needle to reduce sensation. This is often not felt. Prostatic measurements are taken however imaging alone is not accurate enough to distinguish the source of PSA elevation. A guide attached to the probe allows control of the biopsy device. When the biopsy device is activated it makes a clicking noise and delivers a short-lived “thud” in the rectal area. The biopsies have been likened to being flicked with a rubber band.

12 biopsy cores are taken on a “random” basis from the prostate. In reality, these cores are directed using ultrasound imaging in a systematic fashion. These biopsies are designed to provide a representative sample however they do not remove the entire prostate.

As the biopsies are taken through the rectal wall there is a small risk of either bleeding or infection. Antibiotics are given routinely to reduce the risk, starting the day prior to biopsy and continuing for one day afterwards. The risk of side effects significant enough to require admission to the hospital is in the order of 2%. Blood thinners such as warfarin, clexane and clopidogrel should be stopped prior to the procedure however this process should be discussed first as alternative therapy may be required to avoid complications. Aspirin at a moderate dose (300mg/day) is usually OK to continue for the biopsy. Other preparation such as bowel cleansers is unnecessary.

Following the biopsy, strenuous exercise is avoided for the first week. Pathological results generally take at least a week to become available as various staining processes need to be undertaken. A follow-up urology visit is routine to discuss the results of the biopsy and what these will mean in terms of either treatment or the need for future screening.

Transperineal Prostate Biopsy (TPPB)

The alternative to prostate biopsy through the rectum is using an approach through the skin of the perineum (behind the scrotum and in front of the anus). This has the benefit of a significantly reduced risk of infection and bleeding from the bowel after the procedure.

Typically this approach is done under general anaesthetic which makes it painless but has the downsides of increasing cost and requiring a recovery day for the effects of the anaesthetic to wear off (when no driving or operating machinery is necessary).

The TPPB method is of particular importance in accessing the front of the prostate which is more difficult to reach via the transrectal route.

A gloved finger is inserted into the rectum to feel the condition of the prostate that lies close to the rectal wall. If an irregularity such as a lump is felt, further tests will be necessary to enable a more accurate diagnosis.

The PSA test is done via a routine blood sampling. Elevated PSA levels are associated with prostate cancer but can occur due to prostate inflammation as well.

There are two grading systems for prostate cancer that you may read about. The Gleason Score has been used for several decades but has recently been replaced with the ISUP grading system.

The Gleason Score indicates how aggressive the cancer is. The Gleason Score (or Sum) is given by a pathologist who inspects the appearances of the cancer cells under a microscope. The Gleason Score is actually made up of 2 numbers known as Gleason Grades. When a pathologist looks at the prostate cancer under the microscope, a number grade from 1 to 5 is assigned to the areas most representative of the cancer present (the primary Gleason Grade). A second number grade from 1 to 5 is given to the second most representative area within the cancer (The secondary Gleason Grade). These two numbers are added together to give the Gleason Score, the maximum Gleason Score is 10 and the minimum Gleason score is 2. The higher the score, the more aggressive the tumour is likely to be and this will impact on the likely success of treatment.

The ISUP grading score stands for International Society of Urological Pathology. It has been introduced to simplify the grading system and make it easier to work with. The system runs between 1 and 5. Again, the higher the number the more aggressive the cancer and therefore the more likely it is to spread.

Both systems are used to predict how the cancer will behave and therefore the need for treatment.

This scan assesses whether cancer has spread to the bones. A small amount of radioactive material is injected into your arm, which is then absorbed by the cells within the bones. Your body will then be scanned an hour later to view the activity of the bones and ascertain whether cancer has spread.

Magnetic Resonance Imaging detects anatomy on the basis of the way different tissues behave in a magnetic field. Dyes may be used to improve detail with these scans as well. This scan is useful to look for disease spread to the non-boney tissues not evaluated by the bone scan and may provide information about the extent of growth of the primary tumour as well (i.e. the T stage).

The Prostate Specific Membrane Antigen (PSMA) is a protein found on the surface of most prostate cancer cells. It is the target of this scan in which a small amount of a radioactive marker is given that travels around the body seeking out and attaching to cells with this protein. A Positron Emission Tomography (PET) scan detects the marker and highlights where the cells are. A Computed Tomography (CT) scan then provides the detail of the anatomy. The two scans are fused together to give an overall picture of the location of the disease spread.

PSMA PET CT scans are generally not necessary for low to intermediate-risk diseases but can be very helpful for high-risk diseases to look for spread before treatment. Alternatively, they may be used in the setting where the PSA test is increasing after treatment has already been given suggesting that there might be disease recurrence.

What is radiation therapy?

Radiation therapy uses high-energy rays to kill cancer cells using a machine called a ‘Linear Accelerator'. Damaging the cancer cells means that they cannot grow or multiply and so they die. Normal cells are also damaged in this procedure causing side effects but usually recover.

Radiation can be delivered in more than one way. In New Zealand the options are between External Beam Radiotherapy (EBRT) and Brachytherapy. EBRT involves energy rays generated by a machine outside the body which are focused on the target organ, in this case the prostate, using image guidance. The energy is broken down into small packets delivered every working day for a roughly 7-8 week period in an attempt to reduce side effects. Brachytherapy involves implanting radioactive seeds into the prostate under anaesthetic, which give off a set dose of radiation over a predictable period of time then stop working. The seeds remain in place permanently after this but have no ongoing effect.

Who gets radiation therapy?

Radiotherapy may be suitable for treatment with the intention of cure (for localized disease) or palliation (symptom relief for incurable advanced cancer).

The main choice for cure of localized prostate cancer (cancer that has not spread to other areas) is between operative removal of the prostate and radiotherapy in some form. As a general rule, younger men who are otherwise healthy will tend to opt for surgical treatment while for older men particularly with other medical conditions this may not be the safest option and radiation may be preferred. Comparisons suggest that cancer cure rates are fairly similar, perhaps slightly favouring surgery.

Before having radiation therapy a number of initial procedures need to be performed allowing doctors to specifically plan the best treatments for the type of cancer and the individual. This means that an accurate radiation dose to your cancer can be calculated while limiting the radiation to the surrounding areas such as the rectum.

What are the side effects?

The x-rays used during radiation therapy may damage normal body cells as well as cancer cells, although healthy cells usually recover from the damage. The incidence and severity of any side effects vary from patient to patient and may include

• Tiredness or fatigue

• Bladder irritation, cramps or painful urination/blood in the urine

• Diarrhoea and bowel cramps

• Proctitis or pain in the rectum/bleeding.

• A small increase in the risk of bowel cancer in the future (from 5.1 per 1000 to 10 per 1000 over 10 years)

A variety of measures can be taken to alleviate these symptoms.

Radical prostatectomy is an operation which involves removal of the prostate and reconstruction of the urinary tract by attaching the bladder to the top of the urethra (outflow pipe). It is considered by many urologists and oncologists to be the 'gold standard' as it allows complete removal of the tumour when organ-confined, as well as accurate staging. It also allows confidence in interpreting the PSA level after treatment. If the PSA is undetectable there is no sign of cancer recurrence, if the PSA increases (as it may do for a small percentage of men) recurrence is detected on average at least 3-5 years before it otherwise would cause symptoms. This may allow salvage radiotherapy to be given as well, whereas men who have failed radiotherapy are rarely offered surgery because it tends to be detected later and the side effects of salvage surgery are much greater. Having said this however “the first choice is the best choice” and whether second line treatment is available should not be the main reason for choosing an operation. Finally, surgery corrects obstruction to the drainage of urine from the bladder caused by enlargement of the prostate. Despite these advantages direct comparisons between the types of treatment have always been difficult. Cancer cure rates are probably fairly similar for localised prostate cancer so it is not possible to say which treatment is “better” with certainty. The main disadvantages of radical prostatectomy are that it is a moderate sized operation and following surgery men may be troubled by incontinence (poor control of urine resulting in leakage) and erectile dysfunction.

Within the operation there are subtle modifications that may be made depending on the stage and grade of the tumour to try and offset some of these issues. For more advanced and higher grade but localized cancer, wider excision of the prostate (removing more of the surrounding tissues) and lymphadenectomy (removing lymph nodes which act as one of the first landing sites for spreading prostate cancer cells) may be performed.

For smaller and lower grade tumours the operation may be modified to leave the neurovascular bundles intact in an attempt to preserve erectile function. The nerves which control the erection mechanism run just outside the capsule of the prostate (on average 2-4mm away) behind the gland (at the 5 and 7 o’clock positions when looking towards the feet). Removal of these nerves almost always results in loss of erectile function. In selected cases it may be possible to preserve one or both of these nerves and thereby increases the chances of a return of erectile function either with or without medications such as Viagra, Cialis or Levitra.

Following open radical prostatectomy, men usually stay in hospital 3-4 days, have a drain for the first 24 hours and a catheter which remains in place for 10 days (i.e. they go home with it initially). The post–operative recovery period is around 6 weeks.

Radical prostatectomy has traditionally been performed as an open operation with an incision in the lower abdomen. Over the last two decades, there has been a significant shift, particularly in North America and Europe towards minimally invasive surgery in an attempt to reduce surgical side effects and speed post-operative recovery. Robotic prostatectomy aims to reduce hospital stays and speed post-operative recovery without compromising cancer care.

What are the side effects?

Radical prostatectomy may cause a number of possible side effects.

During the operation, risks include bleeding, infection and adjacent organ (such as bowel or nerve) injury. Following an operation the long term side effects may include loss of urinary control (incontinence), loss of erections (impotence) and scarring at the point of reattachment of the bladder to the urethra.

Loss of both urinary control and erections should be expected initially. Urinary function returns over time with the great majority of men recovering to the point of no longer requiring pads without further treatments, however this may take some time (months). Regular pelvic floor exercises may help this process.

Recovery of erectile function is less predictable, depending on the number of nerves preserved and pre-existing level of sexual function. Although not firmly established as a standard of care, there has been a movement towards taking regular erectile medications such as Viagra, Cialis or Levitra following surgery to help with this process.

Many men consider the fact that removal of the prostate provides a pathological specimen and a definitive result as a key reason for deciding on surgical treatment. It provides clarity about the extent of disease and more information about prognosis (what the long term outcome will be).

In a small percentage of patients the tumour will extend up to the cut edge of the prostate, this is called a positive surgical margin. This happens because most prostate cancers arise in the outer part of the prostate gland. The more advanced the prostate cancer, the higher the chance of a positive surgical margin. Many men will be cured despite having a positive surgical margin however there is a greater risk of disease recurrence if this is present or with higher grade (Gleason 8 and above) and higher stage (T3) cancer found in the pathology specimen.

Men in this situation may be offered second line radiotherapy as either an adjuvant (given early after surgery with no evidence of recurrence) or salvage (given when PSA becomes and remains detectable during post-operative follow-up) therapy. The pros and cons of each approach should be considered carefully as currently it is not clear which is the most appropriate option. Adjuvant treatment may be a more effective cure as any remaining cells will be in their smallest numbers but risks over-treating (and perhaps causing side effects for) a significant number of men who would otherwise have remained PSA free and cured. Salvage treatment avoids over-treating those men who are cured but may be less effective in treating those men with recurrent disease.

The progression of prostate cancer is driven by hormones and especially by Testosterone, the male hormone. It has long been recognized that “starving” the cancer by blocking it’s supply of testosterone will slow down the rate of progression (but not cure the cancer).

The production of testosterone occurs within the testicles. Regulation of testosterone levels is controlled by a hormone released from the pituitary gland within the brain. This hormone (luteinizing hormone or LH) travels in the blood stream to the testicles. Blocking the supply of testosterone to cancer cells can therefore be achieved at several levels. The initial signal from the brain can be blocked, production of testosterone by the testicles can be blocked and the receptors on prostate cancer cells to which hormones attach can be blocked.

Originally hormonal therapy was achieved by surgical removal of the testicles. Bilateral orchidectomy is a quick and relatively minor procedure that may often be done as a day case operation. It involves an incision through the scrotum and is performed under general anaesthetic. The main risks are bleeding and infection. More recently there has been a shift towards medical hormonal therapy. The mainstay of this is an injection that blocks the LH signals coming from the pituitary gland within the brain. The medications used are known as “LHRH agonists”. There are a number of different versions however they have similar effects and side effects and are administered by an injection given at regular intervals (usually once every 3-6 months).

A second form of medical hormonal therapy blocks the hormone receptors on cancer cells directly. This group of drugs is called the “Anti-androgens” and is given as tablets on a daily basis. Although there are some small differences in side effects they are generally similar in this regard as well as in effectiveness.

There are a number of other medications which may have effects on prostate cancer, but are used less frequently and later in the treatment course. Chemotherapy has a fairly small role in prostate cancer management compared with other cancers, however is being actively investigated in a number of medical research trials.

What are the side effects of hormonal therapy?

The side effects of hormonal therapy are generally due to testosterone deprivation of normal tissues rather than because of a reaction to the medicine. There are a number of different issues seen in this situation which are grouped together as the “Androgen Deprivation Syndrome”.

Symptoms are often compared to the female menopause (which results as normal oestrogen levels decrease). They can include hot flushes, fatigue, mood swings and sexual dysfunction (loss of libido and erections). Lack of testosterone may lead to loss of muscle mass and bone density (osteoparosis) as well as weight gain. There can be growth and tenderness of the breast tissue (gynaecomastia and mastodynia). Treatment may also be associated with changes in blood cholesterol levels and possibly increase the risk of heart disease.

In an attempt to reduce the side effects of treatment, having regular breaks from therapy, “Intermittent Androgen Deprivation”, may be an option for some people.

Who is suitable for hormonal therapy?

Hormonal therapy in general is used in two situations. Firstly it has become an important addition to radiotherapy (although not to surgery) as it has been shown to improve it’s effectiveness. Secondly, it is used for the treatment of metastatic prostate cancer (that has spread to tissues other than the prostate). It can be a very valuable palliative (relief giving) therapy and may also prevent some of the complications of spreading disease.

Hormonal treatment works for most people for a period of time (on average several years) but may eventually lose effectiveness. The timing and risks of treatment should be personalized to the individual depending on their situation.