Prostate Cancer

Prostate cancer is a significant disease. Each year over 12,000 men in Australia are diagnosed with prostate cancer. About 5,000 of these men are less than 70 years old.

Each year more than 2,700 Australian men die of prostate cancer. It is the second most common cancer in men after skin cancer and the second leading cause of cancer related deaths after lung cancer.

Anatomy Prostate

Diagnosis

What Are The Symptoms Of Prostate Cancer ?

Prostate cancer in it's early stages usually causes no symptoms. The urinary symptoms associated with prostate disease including poor flow, urinary hesitancy or intermittency and increased urinary day or night frequency are more commonly caused by benign prostatic hyperplasia rather than prostate cancer.

Prostate cancer can be detected in it's early stages by a prostate examination and the PSA (Prostate Specific Antigen) test.

What Is The PSA Test ?

PSA has been used as a screening test for prostate cancer for almost 25 years. It is a very powerful tool for clinicians in the management of men with prostate cancer with respect to diagnosis, prognosis and monitoring treatment.

It is a sensitive test but it lacks specificity being able to be raised in benign prostatic disease, prostatitis recent ejaculation as well as prostate cancer hence its controversy as a screening tool.

The Urological Society of Australasia believes that men in the 50 to 70 year age group with at least a 10 year life expectancy should be able to be screened after appropriate counselling regarding the potential risks and benefits.

At present, there are two schools of thought about PSA testing for prostate cancer. Advocates cite the large number of patients who die of the disease as sufficient justification to initiate screening programs, arguing that lives can be saved by early detection and treatment. Their case has recently been strengthened by evidence for the following:

  • The so called latent cancer or 'autopsy' cases do not appear to be detected by PSA screening.
  • Watchful waiting in younger patients with less differentiated tumours has a high mortality over time.
  • Modern treatments give long term control of most tumours detected by screening and produce fewer side effects than earlier techniques.
  • The falling death rate from prostate cancer may be attributable to screening.

Screening is most likely to benefit patients who have at least 10 years of life expectancy (and inappropriate screening in the much older age group can thus be avoided).

Critics of prostate cancer screening argue that the associated complications and costs are not sufficient to justify widespread implementation of aggressive screening programs. They point out that there has yet to be a randomised trial in any population proving that PSA screening programs prolong life. However in a recent 10 years analysis of 695 men with localised prostate cancer who were randomly assigned to watchful waiting or radical prostatectomy, radical prostatectomy was shown to reduce disease-specific mortality, overall mortality, and the risks of metastasis and local progression.

Until better data become available, such as trends in prostate cancer mortality and results from ongoing clinical trials, the debate about screening for prostate cancer cannot be resolved.

Only 25% of men who have a PSA level in the suspicious range (i.e. between 4 and 10ng/ml) will have cancers detected on biopsy.

  • If the PSA level is greater than 10ng/ml, 50% of men will already be incurable.
  • 15% of men with prostate cancer have a PSA level below 4ng/ml (that is, cancers that can be detected only by prostate examination).

PSA changes 10-15% from day to day due to many reasons including physical and sexual activity but also patient hydration. When interpreting PSA changes it is important to focus on large changes or consistent rises, PSA increase of >2.0ng/ml year or doubling times of two years or less generally reflect clinically significant malignancies. In the PLCO Screening Trial with a database of nearly 40,000 men screened for prostate cancer, a PSA increase of 2.0ng/ml in the year prior to diagnosis was associated with high-grade (Gleason score > 7) disease on biopsy in 44%. In general terms a rise of >0.75ng/ml per year is significant.

Transrectal Ultrasound And Prostate Biopsy

Prostate Biopsy

If the PSA is elevated or increasing rapidly or there is an abnormal prostate examination then a transrectal ultrasound and prostate biopsy may be indicated to obtain tissue to make the diagnosis of prostate cancer.

This is performed under intravenous sedation and under antibiotic cover. Ultrasound gives us important information regarding the size and shape of the prostate and prostate abnormalities suggestive of malignancy and an accurate method of sequentially sampling the prostate. We routinely sample 14-20 biopsies depending on the volume of the prostate which increases the diagnostic power of the procedure.


What Does The Stage And Grade Of Prostate Cancer Mean ?

Grading and staging prostate cancer is a determination of how fast the cancer is growing and the potential threat to life also how far it has grown helping to determine what is the most appropriate treatment for the patient.

Grading is performed by the pathologist who examines the prostate tissue from the biopsy under the microscope examining the appearance of the cancer. The most common grading system is the Gleason Scale which scores the cancer between 5 to 10. The Gleason score is made up of 2 numbers. The first number refers to the grade of the most prevalent cancer cells and the second number refers to the grade of the next most prevalent area.

In general it is uncommon to have gleason scores of 5 and less. These indicate very slow growing cancers that are unlikely to spread. Gleason score 6 cancers are slow growing but there is an 18-30% risk of dying from prostate cancer in 15 years. A score of 7 is an intermediate risk cancer and cancers with a Gleason score between 8-10 are highly aggressive cancers with a high likelihood of spread and 60-87% risk of death from prostate cancer over 15 years.

Staging of prostate cancer is indication of the size and extent of spread. The prostate examination, PSA, gleason scores all give an indication of the likelihood of whether the cancer is locally advanced or metastatic (spread elsewhere). Depending on these tests it may be reasonable to perform additional imaging studies such as a Bone scan; (this is used to check whether the prostate cancer has spread to bones which is the most common area of metastatic disease) CT scan (computerized tomography CT) which provides x-ray images of the internal organs of the abdomen and pelvis or endorectal MRI (magnetic resonance imaging) which may help to indicate whether the cancer is localized or spread outside the prostate capsule.

Surveillance

Active Surveillance

Active surveillance is becoming more popular as a treatment option for low-risk, low-grade (Gleason 3+3=6) and low volume possibly insignificant, prostate cancer.

The definition of 'insignificant prostate cancer' is unclear. Nevertheless, it is clear that men, particularly with an age of >65 years, with low-risk, low-grade (Gleason 6 or less) prostate cancer, may not die from their disease, even if it is left untreated for long periods of time.

Active surveillance is not a passive process and involves the close monitoring of tumours, to detect whether there is evidence of cancer progression. This involves regular PSA readings, regular digital rectal examinations and periodic biopsies.

If the tumour appears quiescent, or even undetectable, one can increase the period between biopsies to every 2 to 4 years, depending on the circumstances.

Trials that have looked at people who have adopted this policy, have shown that approximately 1/3 of patients will need treatment within five years of follow-up. Of those patients who did need treatment, the vast majority are still curable, even after a five-year delay, as long as there is close surveillance. It is believed that, based on careful selection of patients for active surveillance, <5% will become incurable if monitored carefully.

Watchful Waiting

Watchful waiting is a treatment option for men who either due to age or poor health who are not expected to live longer than 10 years. In these men the risk of treatment for prostate cancer may outweigh the potential threat of the cancer. In these men androgen deprivation treatment and palliative interventions may be deferred until such time as the prostate cancer becomes symptomatic. The aims of the treatments is to slow down the cancer rather than a cure.

Radical Prostatectomy

Radical prostatectomy can be performed using several surgical techniques but the most important factor is the experience and expertise of the urologic surgeon. A/Prof Peter Royce and Dr Dennis King both have extensive experience with the open prostatectomy and robotic assisted laparoscopic prostatectomy. They have a combined experience of over 1,000 radical prostatectomy procedures.

Radical prostatectomy involves the total removal of the prostate gland with its surrounding fascia, attached seminal vesicles and adjacent lymph nodes, for curative treatment of localised prostate cancer. The pelvic lymph nodes are removed in higher risk prostate cancer where spread is more likely since this can dictate the need for additional treatment and improve the survival of these men.

A 'nerve sparing technique' is performed in order to maximise postoperative sexual potency, this involves careful preservation of the neurovascular bundles which are located between the prostate and rectum, and provide neural stimulation to the penis for erectile function.

Once the prostate has been removed the bladder neck is then refashioned and sutured to the urethra and urinary sphincter muscles over a urethral catheter. The catheter will remain in place for 10 days during which time initial healing takes place. The urethral catheter is removed by the urology nurse in the urology suite.

Surgical Goals

There are 3 principal surgical objectives to remove the prostate cancer with a clear margin of tissue giving the best chance of cure maintenance of long term urinary continence in appropriately selected patients maintenance of erectile function.

The ideal patient for radical prostatectomy is a man who accepts the risks of surgery, is aware of all his options, and has a clinically localised cancer with at least 10 years of life expectancy. For localised cancer, the cure rates for radical prostatectomy (10-year, PSA-progression-free survival) are 90% for organ-confined disease and 82% for specimen-confined disease. These results can be improved further if adjuvant radiotherapy is used in patients who have extracapsular disease or a positive surgical margin.

If a PSA recurrence occurs some time after surgery, the time to death from prostate cancer still averages 13 years and may therefore not impact on the life expectancy of an older man. Even patients with poorly differentiated tumours can be cured surgically if the disease is detected while confined to the organ.

Side effects of treatment (including incontinence and impotence) have become less common with improved surgical techniques and patient selection.

Incontinence is common immediately following surgery and pelvic floor exercises are important. This reduces over time and most men are continent within 6-10 weeks following surgery. During this recovery period you will need to wear a pad and practice pelvic floor exercises as instructed by either our Urology nurses or a continence and pelvic floor physiotherapist.

In a very small percentage of patients, perhaps 1-2%, urinary control may not return to an acceptable level, and this is one of the main risks of the operation. The factors influencing recovery of urinary continence after radical prostatectomy include primarily the technique/expertise of the surgeon with preservation of the urinary sphincter, the use of properly instructed pelvic floor exercises, but is also related to patient age and the underlying urinary sphincter strength and bladder function, as well as the healing process in the individual.

Sexual Function

Erectile function is controlled by the presence of 2 neurovascular bundles. The two nerve bundles are attached to the capsule of the prostate gland and may be involved with the cancer, or inseparable from the prostate gland and therefore not able to be preserved in every case. In appropriate patients (with a low risk of extraprostatic spread) we perform a 'nerve sparing' operation on one or both sides, which will improve the likelihood of preservation of erections post operatively.

Although impotence remains a common problem of surgery, an erectile nerve-sparing procedure can preserve potency in up to 60% of carefully selected patients, especially those in younger age groups.

However a nerve sparing operation is not always possible or appropriate. Furthermore, the return of erections is usually a fairly slow process and may take 12 months before a final assessment can be made. The use of drugs such as Viagra, Cialis and Levitra or penile injection therapies in the months after surgery will usually enhance the return of erectile function, and will be prescribed once you are ready to resume sexual activity. There are alternative means of achieving an erection and sexual satisfaction, and I would be pleased to discuss these options further as appropriate.

Once you resume sexual activity you will notice that there is no ejaculatory fluid produced, this is because the ejaculatory glands have been removed, namely the prostate and seminal vesicles.

The sensation of orgasm will still be present although this may feel a bit 'weird' for a time, but most men claim it is only slightly altered from normal in the longer term.

Some men have reported shortening of the penis after radical prostatectomy, however this is uncommon and seems to bother some men more than others, but does not usually prevent sexual function.

Open Radical Prostatectomy

Open prostatectomy is the traditional method of surgery for prostate cancer and although robotic surgery has become more popular in the last few years, there are situations where open surgery is the preferred option; in particular for treatment of high grade prostate cancer where an extended pelvic lymph node dissection is required.

Currently the evidence indicates that open or robotic prostatectomy performed by very experienced surgeons are equivalent in outcome in terms of the 'patient trifecta' in regard to preservation of urinary control, sexual function and long term cancer cure.

Robotic Prostatectomy

There are over 400 machines world wide in current use. Over 60% of all radical prostatectomies in the USA (2007) have been performed using the Da Vinci robotic and system.

Robotic Assisted Radical Prostatectomy

Dennis King is one of a small group of fully trained robotic surgeons in Australia who performs this procedure regularly.

Most patients are discharged within 2-3 days. The blood loss is minimal with transfusions rate of <1%. Continence rates and margin rates have been equivalent to the major published series overseas. Over 95% of patients are fully continent within 3 months.

Da Vinci Robotic prostatectomy is the newest and most advanced surgical option for qualified patients. This method gives a surgeon greater visualization, enhanced dexterity, precision, control and superior ergonomics. This very precise surgery only requires 6 small incisions (1cm) in the abdomen.

Dennis King da Vinci Robotic

The da Vinci Surgical System is powered by state-of-the-art robotic technology. The System allows your surgeon's hand movements to be scaled, filtered and translated into precise movements of micro-instruments within the operative site. The magnified, three-dimensional view the surgeon experiences enables him to perform precise surgery in complex procedures through small surgical incisions.

The da Vinci System enhances surgical capabilities by enabling the performance of complex surgeries through tiny surgical openings. The System cannot be programmed nor can it make decisions on its own. The da Vinci System requires that every surgical maneuver be performed with direct input from your surgeon. The da Vinci Surgical System has been successfully used in thousands of prostate cancer procedures world-wide.

For suitable patients, there are numerous potential benefits including:

Surgical Benefits

3-D Visualization: Provides the surgeon with a true 3-dimensional view of the operating field. This direct and natural hand-eye instrument alignment is similar to open surgery with all-around vision and the ability to zoom-in and zoom-out.

Dexterity: The da Vinci Robotic System provides the surgeon with intuitive operative controls that allows the experienced surgeon to use his open surgery skills rather than having to use counter-intuitive motions typically required by a laparoscopic approach. Surgical Precision: permits the surgeon to manipulate instruments with such accuracy that the current definition of surgical precision is exceeded.

Range of Motion: The robotic instruments offer the surgeon full range of motion and ability to rotate the instruments through tiny incisions.

Ergonomics: The surgeon can sit in a comfortable position, allowing him to concentrate fully on the surgery.

Improved Access: Surgeons perform complex surgical maneuvers through 1-cm ports, eliminating the need for large traumatic incisions.

Diagram Open vs Robotic Incision

Radiotherapy

Radiotherapy is commonly given as a radioactive seed implant within the prostate (brachytherapy) or through Radiation beams given external to the body.

Radiotherapy uses high energy x-ray beams to kill cancer cells. The beams are applied from outside the body, in much the same way as standard diagnostic x-rays. The way they work is quite simple. The x-ray beams hit cells in their path causing damage to the DNA of the cells. However for the cell to die it must try to divide and multiply as the damaged DNA will not divide properly. For this reason cancer cells are more susceptible to radiotherapy as they tend to divide and multiply at a much faster rate than normal cells.

External Beam Radiotherapy

Up until the 1990's radiotherapy for prostate cancer was relatively ineffective. To begin with it was mainly used in cases where the cancer was too advanced to cure. Also the dose of radiation used was too low to control the majority of cancers. All this changed when CT scan was introduced. This enabled the prostate cancer to be accurately targeted, and the rectum and bladder to be excluded from the radiation field. As a result radiation doses were dramatically increased along with cure rates. This treatment technique is known as three-dimensional conformal radiotherapy and is the standard in most Australian centres.

IMRT intensity modulated radiotherapy is a way of delivering radiotherapy so that the radiation dose is curved around normal tissues allowing higher doses to be given safely. This enables the treatment days to be increased without excessive injury to the rectum.

The treatment is given Monday to Friday for seven to eight weeks. Each treatment takes about 15 minutes a day. It is completely painless. The frequency of bowel movements and passing water can increase during the treatment and mild tightness develops about halfway through the course these short-term side effects usually settle down within 3-6 months. Impotence is also common and about 50% of men will become impotent in the long-term.

Brachytherapy

Brachytherapy seed implantation is a potentially curative treatment for early localized prostate cancer. At present it is recommended for cancers of Gleason score 6 and some 7 cancers, PSA <10, in men with relatively small prostates, minimal urinary symptoms and a normal urine flow as measured by uroflometry.

Brachytherapy

The main advantage of brachytherapy is that it can deliver higher and more precise doses of radiation to the prostate gland in excess of what can be achieved with external beam radiation treatment.

There are two major forms of prostate brachytherapy.

  1. Permanent seed prostate brachytherapy.
  2. Temporary high dose rate prostate brachytherapy.

Permanent Seed Prostate Brachytherapy

This Involves the permanent implantation of tiny seeds containing radioactive iodine into the prostate where they give off low level radiation for approximately 6 months.

This is a multi step process involving a planning and a treatment phase.

In the planning phase a volume study is performed. This is an examination to determine the size amd shape of the prostate. Ultrasound images of the prostate are then used to determine the number and where the radioactive seeds need to be positioned within the prostate to treat the prostate cancer.

The implant procedure is performed under a general anaesthetic these seeds are loaded into thin needles which are passed onto the prostate gland through the skin between the scrotum and anus. As the needles are passed into the prostate their progress is visualized on an ultrasound machine to ensure accurate placement of the seeds. Their position has been predetermined by the planning phase. Usually 90-120 seeds are required.

Following the seed implantation a cystoscopy (examination of the bladder) is performed and a catheter is placed in the bladder overnight after which it is removed.

Many patients then resume normal activities within a few days to weeks.

Post Brachytherapy

  • Urinary Symptoms - Following the procedure urinary frequency, burning and dribbling commonly occur after the implantation. Flomaxtra is prescribed for a 3 month period to reduce these symptoms. In about 5% of men these symptoms are troublesome enough to require the temporary insertion of a catheter. Rarely a patient will be unable to urinate due to swelling of the prostate following the seed implantation and these patients may need placement of a catheter or to learn self catheterisation.

    If operative treatment for an obstructed prostate is required following seed implantation (ie TURP or transurethral resection of the prostate) the risk of urinary incontinence is much higher than normal (approximately 20-30% compared 1%). Therefore TURP is not routinely recommended following brachytherapy.

  • Sexual Function - Impotence or loss of erectile function resulting from treatments considered to be around 30-50% after 3 years. Most men will respond to Viagra or similar medication.

    Following the implant men can develop a dry ejaculate. This is due to semen being passed into your bladder rather than out through the penis during sexual climax. This fluid is later passed out through your urine when you next empty your bladder.

    Penile numbness occurs occasionally and can last 1-2 months. The numbness will resolve on its own and requires no specific treatment.

    There may be some blood in your ejaculate or some pain at climax with your first few ejaculates.

  • Diarrhoea - Loose bowel motions and faecal frequency is common following brachytherapy. It may be treated with medication and usually settles within 3 months.

  • Scrotal Swelling and Bruising - There may be some bruising and swelling of the scrotum. This lasts 3-4 weeks and resolves by itself.

  • Pain - Some men have mild to moderate pain at the implant site. This is usually relieved with Panadeine Forte.

Follow Up Schedule

A month following the seed implant a CT scan is performed which reviews the exact position of each seed in the prostate. This is necessary to determine that your prostate is receiving the proper amount of radiation throughout the entire gland.

You will see your urologist and radiation oncologist on a regular basis with PSA testing. The PSA reaches it's lowest level at 3-4 years and a reading <1 indicates the highest chance of a cure. There is a PSA "bounce" in 50% of patients in the first 1-2 years after brachytherapy. This indicates a good response to treatment.

Temporary High Dose Rate (HDR) Prostate Brachytherapy

In this procedure temporary needles are placed inside the prostate and needles are left in place for approximately 36 hours while the patient remains in hospital. These hollow needles allow a radioactive source to be placed on several different positions within the prostate this process is repeated 2-3x with a 6-8 hour gap between each treatment.

The potential side effects are similar between high dose rate brachytherapy and permanent seed brachytherapy except that blood in the urine, erectile dysfunction and scarring in the urethra is more common after high-dose brachytherapy.

HDR brahytherapy is indicated for locally advanced and higher risk prostate cancer as an alternative to radical prostatectomy and external beam radiation.

High Intensity Focused Ultrasound (HIFU)

HIFU is a new and minimal invasive technology for treatment of localised prostate cancer. The National Institute for Clinical Excellence, an independent government body in the United Kingdom has evaluated HIFU, and concluded that the scientific evidence is sufficient to support the use of HIFU for the treatment of prostate cancer, in the UK National Health System.

A/Prof Peter Royce Perfrming HIFU

HIFU has been used extensively in Japan and Europe where clinical studies have shown HIFU to be a safe and effective prostate cancer treatment.

A/Prof Peter Royce was the first Urologist in Melbourne, Australia to use HIFU for the treatment of prostate cancer. Since the first HIFU treatment in November 2005, an increasing number of men have chosen HIFU, instead of radical surgery or radiation therapy, as curative primary treatment or as salvage treatment after previous radiation therapy.

How Does HIFU Work ?

The HIFU probe is inserted into the rectum under anaesthesia. A crystal within the probe vibrates at a specific frequency when an electric current passes through it, and this produces ultrasound waves. The ultrasound waves pass through tissue and some of the waves are reflected back to the crystal eventually producing an image of the prostate and its surrounding structures on a screen, which can be viewed by the Urologist. At the same time, by increasing the intensity of the ultrasound waves and focusing the waves on a single point (like a magnifying lens), high energy is delivered to the prostate tissue. This will raise the temperature to 70-100 C and cause permanent tissue ablation (cell death) of the prostate cancer. Dead tissue then sloughs out and is passed with urine.

Patients are assessed prior to HIFU with an transrectal ultrasound to measure prostate volume, and to check for calcification within the prostate.

Who Would Be Suitable For HIFU ?

Men with localised biopsy proven prostate cancer, who understand the treatment options of surgery, brachytherapy, radiation therapy, cryotherapy and active cancer surveillance, and accept the risks of minimally invasive HIFU treatment, are considered suitable for HIFU.

The following are important selection criteria:

1) Lower complication and side effects

Advice based on our own prospective data of HIFU treated patients.

a) Short term complications

b) Long term complications

2) Proven efficacy as prostate cancer treatment

Following successful HIFU treatment patients are evaluated with PSA blood tests, and in some cases a repeat prostate biopsy. The objective is to achieve PSA <0.5 with either no further increase in PSA level and/or negative repeat prostate biopsy.

This is referred to as clinical disease free survival.

Long term data on prostate cancer specific mortality rates are currently not available.

Selected Reports of Efficacy HIFU treatment Localised Prostate Cancer.
(Ab = Ablatherm, Son = Sonablate)

Study Device N Mean
Pre HIFU
PSA (ng/ml)
Gleason
Score
Stage Median
Follow up
(months)
Negative
biopsy
after HIFU
Chaussy 2001 Ab 184 12 T1 - 2 80%
Thuroff 2003 Ab 402 10.9 2 - 4 (13.2%)
5 - 7 (77.5%)
8 - 10 (9.3%)
T1 - 2 13 87.2%
Blana 2004 Ab 146 7.6 T1 - 2 22 93.4%
Uchida 2005 Son 72 8.1 T1 - 2 14 68%
Uchida 2006 Son 63 11.2 2 - 4 (21%)
5 - 7 (73%)
8 - 10% (15%)
T1 - 2 23.3 87%

3) HIFU is repeatable

Some patients may not achieve complete prostate ablation after the first HIFU treatment, and this would be evident as PSA >0.5 and a repeat prostate biopsy indicating viable tissue.

This may be due to technical reasons such as prostate size and prostate calcification. These patients can undergo a repeat HIFU with the intention of achieving complete ablation of remaining viable prostate tissue.

4) Short hospital stay

Patients are taught self care of the urinary catheter before the procedure, and usually only stay in hospital overnight. Patients then return for removal of the catheter within 5-10 days.

Catheter care and removal is under the supervision of our Oncology Nurse in the Urology suite.

5) Fast recovery time

HIFU is not a painful treatment and the majority of men are back to usual physical activity within a week.

6) HIFU can be used before or after other forms of treatment

HIFU can be used as salvage treatment for men who have failed previous radiotherapy treatment.

If HIFU was used as a primary treatment and there is treatment failure, patients can then opt for other forms of treatment such as prostate surgery (radical prostatectomy) or external beam radiation therapy.

Androgen Ablation

Hormonal suppression or androgen deprivation therapy is used in prostate cancer to slow down the growth of cancer cells. It may be used as a sole treatment or in conjunction with radiotherapy.

Prostate cancer cells need the male hormone testosterone to grow. Reducing testosterone to very low levels will dramatically slow down most prostate cancers. This is not curative therapy for cancer. This can be achieved by two main methods, medical or surgical castration. The medicines currently available for use can be divided into two groups:

  1. LHRH agonists work to reduce testosterone production for example Zoladex, Lucrin or Eligard.
  2. Testosterone receptor blockers stop the testosterone reaching receptors on the cancer cell.
Side effects are common and can include:
  • Tiredness.
  • Loss of libido and erectile functon.
  • Depression or mood swings.
  • Effects on memory.
  • Genital shrinkage.
  • Breast tenderness.
  • Hot flushes.
  • Osteoporosis.
  • Muscle weakness.
  • Anaemia and a flare reaction.