Diagnosis

What Are The Symptoms Of Prostate Cancer ?

Prostate cancer in its 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 its early stages by a DRE (Digital Rectal 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 for prostate cancer, being able to be raised in benign prostatic disease, prostatitis, recent ejaculation, cycling impact on prostate gland, as well as prostate cancer, hence its controversy as a screening test.

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 have access to prostate cancer screening, 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' prostate cancers, do not appear to be detected by PSA screening.
• Watchful Waiting in younger patients with more aggressive prostate cancer 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 a public health based screening program, similar to breast cancer screening. 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.

Transperineal Prostate Biopsy
(Replaces Transrectal Ultrasound Prostate Biopsy)

Transrectal Prostate Ultra Sound (TRUS) for prostate biopsy, has been replaced in our practice with Transperineal Prostate Biopsy (TPB).

TRUS biopsy has been proven to have a higher rate of serious infection, and a lower accuracy for detecting prostate cancer, compared to TPB. We now regard TPB as the standard of care for men having prostate biopsy.

TPB is done as a day procedure under GA with antibiotic cover and rectal enema prep on the day of the procedure.
TPB is either targeted to specific MRI scan detected lesions, or as a template biopsy.
Targeted TPB samples only the suspicious areas on MRI scan, while template biopsy is used to widely sample the prostate when the MRI scan does not show a specific lesion.

So, before advising a TPB, we order a Multiparametric MRI scan to detect suspicious lesions for targeted biopsy, or a template biopsy.

MRI Prostate (Magnetic Resonance Imaging)

Multiparametric MRI scan is a non invasive way to risk stratify men for prostate biopsy, based on the PI RADS score 1-5. In general terms, a PI RADS score of 3,4 or 5 would indicate the need for a Transperineal Prostate Biopsy. This means that men with PI RADS score 1 and 2, can safely avoid a TPB, and continue with PSA testing.

MRI scans also provide information about the T and N stage of prostate cancer, that means if prostate cancer is suspected, MRI can report on the stage of cancer invasion outside the prostate, including the prostate capsule, seminal vesicles and pelvic lymph nodes and pelvic bones.

Prostate MRI scans are now Medicare funded for specific indications, and also widely available at accredited Radiology clinics. We will organise a prostate MRI scan for you, and schedule a review to show you the MRI Images and explain the report, before advising you further.

What Does The Stage And Grade Of Prostate Cancer Mean ?

Grading and staging prostate cancer is a clinical assessment of how fast the cancer is growing and the potential threat to life, and how far it has spread, 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 Score 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 an indication of the size and extent of spread. The prostate examination/DRE, PSA and Gleason score 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 necessary to perform additional imaging studies such as a Whole Body Bone Scan (this is used to check if the prostate cancer has spread to bones which is the most serious area of metastatic disease) CT scan which provides x-ray images of the internal organs of the abdomen and pelvis, and MRI which as mentioned above can assess the prostate capsule, seminal vesicles and pelvic lymph nodes for localised spread of cancer.

PSMA PET/CT SCAN

Prostate Specific Membrane Antigen is linked to a radioactive 68 Gallium isotope, injected into a vein, and imaged with Positron Emission Tomography and CT imaging, to detect prostate cancer virtually anywhere in the body. PSMA PET scan has transformed the way Urologists detect and stage prostate cancer, not only at the time of diagnosis, but also after treatment.

PSMA PET scan is capable of detecting prostate cancer which cannot be seen on conventional scans ie WBBS and CT scans. It is even possible to digitally fuse the MRI and PET images to gain more accuracy of diagnosis and staging of prostate cancer.

Unfortunately PSMA PET scans are currently not covered by Medicare, and incur a patient cost of approx. $800- 1000.

PSMA PET scans are readily available at specific Radiology clinics, and we can guide you to the most suitable clinic for a prostate PET scan.

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 3,000 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.

Radiation Therapy

Radiation Therapy (RT) is either given as a radioactive seed implant within the prostate ( Low Dose Rate Brachytherapy) or as external beam therapy known as IMRT (Intensity Modulated Radiation Therapy).

RT uses high energy x-ray beams to kill cancer cells. The x-ray energy hits cells in their path causing damage to the DNA of the cells. The damaged cells try to repair their DNA, however the cancer cells are more susceptible to radiation as they tend to divide and multiply at a much faster rate than normal cells.

External Beam Radiotherapy / IMRT

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.

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 urine can increase during the treatment and some tiredness develops about halfway through the course, these short-term side effects usually settle down within 3-6 months.

IMRT is usually combined with Hormonal Therapy for 6-24 months, also known as ADT (Androgen Deprivation Therapy). This means regular injections of drugs to cause a chemical castration while you receive IMRT, and in some cases for up to 2 years. ADT has its own set of side effects, which tend to linger even after the injections have ceased.

LDR Brachytherapy

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

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 Low Dose Rate seed prostate brachytherapy.
2. Temporary High Dose Rate prostate brachytherapy.

Permanent LDR Seed Prostate Brachytherapy

This Involves the permanent implantation of tiny seeds containing radioactive iodine 125 into the prostate where they give off low dose rate 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 and shape of the prostate. Ultrasound images of the prostate are then used to determine the number and precise location of the radioactive seeds to be positioned within the prostate to treat the prostate cancer.

The implant procedure is performed under a general anaesthetic, the I -125 seeds are preloaded 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 may be inserted into the bladder overnight, after which it is removed the next day.

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

Post LDR Brachytherapy

• Urinary Symptoms

  Following the procedure urinary frequency, burning and dribbling commonly occur after the implantation. Tamsulosin 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 still be unable to urinate due to swelling of the prostate following the seed implantation and these patients may need placement of a longer term 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 recommended following LDR Brachytherapy.

  It is far better to sort out this potential problem before having LDR Brachytherapy, or avoid it completely.

• Sexual Function

  Impotence or loss of erectile function resulting from LDR Brachytherapy is approx 30-50% after 3 years. Most men will respond to Viagra or similar medication during the initial few years.

  Following the implant men can develop a dry ejaculate. Reduced ejaculation of seminal fluid is due to fibrosis of the prostate tissue in response to radiation injury.

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

  There will be some dark blood in your ejaculate or some pain at orgasm 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 over the counter pain killers.

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 (PSA nadir) and a reading <0.5 indicates the highest chance of a cure. There is a ‘PSA bounce’ in 50% of men in the first 1-2 years after brachytherapy. This indicates a good response to treatment, but can be disconcerting if you are not aware of the PSA bounce.

PSA Relapse occurs in men if the prostate cancer has recurred. The definition of PSA relapse is known as the Phoenix Criteria, not because the cancer has arisen from the dead according to Greek mythology, but because a consensus statement was derived in Phoenix Arizona.

The Phoenix Criteria states that PSA nadir + 2.0 = PSA Relapse after RT.

For example your PSA nadir is 0.5 after 3 years, but hits 2.5 after 5 years, this means the treatment has failed to cure the prostate cancer.

In practical terms, this usually means reverting to a Watchful Waiting program, since salvage surgery is not regarded as safe or very effective after failed LDR Brachy.

You should bear this in mind when deciding on the best treatment option.

Temporary High Dose Rate (HDR) Prostate Brachytherapy

In this procedure temporary needles are placed inside the prostate and the 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 in several different positions within the prostate, and this process is repeated 2-3 times 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.

Late Onset Complications of Radiation Therapy

The late onset complications of RT occur after more than 5 years and as long as 20 years following RT for prostate cancer. These complications can be devastating and life threatening problems, which fall into the lap of Urologists to manage, long after the Radiation Oncologist has treated the patient.

Urologists are therefore very aware of these problems, and the difficulty of managing late onset complications.

• Haemorrhagic Radiation Cystitis presents as blood in the urine or haematuria, and is diagnosed with Cystoscopy examination of the bladder.

  In mild cases treatment with Hyperbaric Oxygen Treatment (HBOT) requiring 40 sessions in a hyperbaric chamber, can be beneficial.

  In moderate cases a bladder irrigation with chemicals such as Aluminium Hydroxide (Alum) or Prostaglandin, can help to stop the bleeding.

  In more severe cases admission to hospital for Cystoscopy and Laser Ablation of bleeding from the bladder, blood transfusion, temporary percutaneous urinary diversion or ultimately total cystectomy and ileal conduit diversion.

• Urethral Stricture presents as reduced uroflow and symptoms of obstructed voiding. Cystoscopy examination shows a scarred urethra usually very close to the urinary sphincter, which means surgical treatment is very likely to cause urinary incontinence.
  The urethral stricture is therefore treated with self dilatation using a stiff plastic catheter passed along the urethra, to maintain a patent urethral channel.

• Rectal Fistula presents as urinary tract infection, passing urine from the rectum and passing faeces material in the urine. This is very rare late onset complication, but requires a permanent colostomy and suprapubic urinary catheter.

• Bladder Cancer presents as blood in the urine and needs to be differentiated from Haemorrhagic Cystitis with a CT scan and Cystoscopy examination.
  SEER data from a USA database of 340,00 men over 35 years, reported a 14 to 21 fold greater risk of bladder cancer compared to the general population, after 10+ years since prostate RT. The bladder cancers were noted to be higher grade and most common after Brachytherapy compared to EBRT.
  We have performed Salvage Radical Cystectomy & Prostatectomy for bladder cancer after prostate Brachy or EBRT, and this is a high risk surgery for bleeding and rectal perforation. These men have required permanent urinary conduit diversion to a urostomy, and in some cases a permanent colostomy.
  There is a place for screening men for bladder cancer after 10 years since prostate RT with Urine Cytology and Cystoscopy.

These late onset complications from prostate RT are not common, but can be devastating if it affects you.

For these reasons, we believe that RT for prostate cancer is most appropriate for men who;

1. Are not able to have surgery due to other medical issues.
2. Need adjuvant RT after surgery.
3. Older than 70 with a life expectancy of less than 15 years.

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.