PROSTATE CANCER

Treatment

Taking into account the prognostic parameters identified, patients are divided into risk groups: high, intermediate and low. The options in localized prostate cancer include:

1. Active monitoring

Watchful Waiting / Active Surveillance:

In certain patients a policy of observation and monitoring might be a preferred management option. In an incidental prostate cancer found at perurethral prostate resection (T1a) the probability of disease progression may be very low. Patients who have reduced life expectancy might be monitored with regular PSA measurements, proceeding to therapy only if there was clear evidence of disease progression. Gleason histological grading is believed to be the best indicator of the probability of significant disease progression.

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2. Hormone therapy

Malignant prostate cells start off by requiring a daily supply of testosterone without which they die. In cancer, mutant clones eventually emerge which no longer depend on testosterone, and this (on average) occurs in about 80% of men within 2 years of the diagnosis of metastases; however, among the 20% who do not develop metastases within 2 years there are many who survive for decades without any treatment. Largely as a result of these and other anecdotal experiences, there was a feeling that no harm arose from deferring the treatment until metastases began to cause symptoms. This was the subject of a recent Medical Research Council controlled prospective trial, which showed an unacceptably high incidence of serious metastatic complications in patients for whom hormone therapy had been deferred.

Hormonal manipulation – cutting off or interfering with the supply of testosterone – can be achieved in a number of ways:

  • Orchidectomy:
    The testicles may be removed, or a subcapsular orchiectomy may be performed which leaves something behind which feels like a normal testicle.
  • Diethylstilboesteol:
    This is a synthetic oestrogen which blocks the products of metabolism of testosterone.
  • Luteinizing Hormone Releasing Hormone Agonist:
    Zoladex and Leuprolide overstimulate the anterior pituitary gland until it is exhausted and can produce no more luteinizing hormone. As a result the testis and adrenal no longer secrete testosterone. LH-releasing hormone (LHRH) agonists are given in combination with drugs which block the action of testosterone in the cells — anti-androgens (see below).
  • 5 Alpha-Reductase inhibitors:
    5 Alpha-reductase inhibitors such as finasteride prevent the activation of testosterone to dihydrotestosterone but they are seldom used in the treatment of prostate cancer.
  • Anti-Androgens:
    Dihydrotestosterone acts on receptors in the cytosol of the prostate cell. These receptors are blocked by two types of anti-androgen:
    • steroids such as megestrol and cyproterone;
    • non-steroids such as flutamide, nilutamide and bicalutamide.
  • Aromatase inhibitors:
    These prevent the action of aromatase, an enzyme in the prostate cell which converts adrenal steroids into testosterone. They are still under trial.
  • Maximal Androgen Blockade (MAB)
    A combination of LHRH agonists given together with anti-androgens is claimed to give a small improvement (a matter of weeks) in survival but not everyone is convinced that this is justified by the side effects, let alone the expense of this additional therapy.

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Surgery

Transurethral Resection (TURP)

As the prostate grows as you get older, it may become large enough to constrict the urethra leading to difficulty in urinating, incomplete emptying of the bladder or dribbling of urine. This Benign Prostatic Hyperplasia (BPH) may affect your quality of life but it is not cancer. TURP is an operative option to remove some of the enlarged prostate gland to improve urine flow. Some alternative treatments are described below.

TURP is usually performed under general or epidural anaethetic. A thin tube-like telescope (a resectoscope) is then inserted into your urethra through your penis. An electric current is then used to cut away and reduce the prostate, with the removed tissue being flushed away with sterile solution. A catheter is inserted during the operation and left in your bladder for a few days and is then removed when your urine begins to run clear of any residual blood clots from the operation. It usually takes up to 6 weeks to recover fully from a TURP when normal activities can be resumed. After effects may include mild incontinence and dry orgasm (retrograde ejaculation) where little or no semen is ejaculated.

Radical Prostatectomy:

There is a heated debate between those who favour radical prostatectomy for cancers that appear to be confined to the prostate, and those who are against it.

The arguments in favour of radical surgery are:

  • More of those who survive for 10–15 years after radical surgery do so without residual cancer.
  • Radical prostatectomy avoids the misery of local recurrence in the pelvis.
  • Improved surgical techniques can achieve potency preservation and continence.

The arguments against radical prostatectomy are:

  • Almost every elderly man has a small cancer in his prostate, but less than 0.5% die of it: i.e. 99.5% do not.
  • The only prospective controlled studies to have been carried out showed no differences in survival after 20 years between men treated by radical surgery or surveillance.
  • Larger retrospective studies of Medicare patients show no difference in survival between those undergoing radical surgery and surveillance.
  • The morbidity of radical prostatectomy includes incontinence, stricture and impotence in a (debated but large) proportion of patients.

Staging lymph node dissection:

Most surgeons consider that radical prostatectomy is futile if the lymph nodes are involved and usually sample the lymph nodes around the obturator nerve and vessels before going ahead with radical surgery. This can be performed laparoscopically a few days before surgery is planned, or as the first stage of an open operation.

Radical prostatectomy:

The prostate is approached through a lower abdominal incision. The lymph nodes along the internal iliac and obturator vessels are dissected and sent for frozen section, unless this has already been done. The dorsal veins of the penis are doubly ligated and divided behind the symphysis, and the neurovascular bundles going to the penis are pushed aside out of harm’s way. The urethra is transected, and the prostate lifted up, to reveal the seminal vesicles, whose vessels are ligated. The bladder is then cut across at the level of the bladder neck, which is then narrowed, and sutured to the stump of the urethra over a catheter.

Transperineal prostatectomy is a different surgical approach offered to selected patients where no lymphadenectomy is contemplated. Laparoscopic radical prostatectomy is an approach gaining wide appeal. Both techniques rely on the expertise of the urological surgeon and meticulous patient selection.

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Radiotherapy

There are numerous ways to deliver therapeutic radiation including external beam radiotherapy with the linear accelerator and brachytherapy (inserting radioactive sources into the prostate under transrectal ultrasound control, with no clear consensus as to which radiotherapy option is best. What is clear is that certain patients may be better suited for one or another or, in fact, a combination of these modalities. Pretreatment PSA levels and Gleason histological score are very important tools for prediction of response. It is important to define the patient’s risk status (High, Intermediate or Low) to determine the optional choice offered. No randomized prospective controlled study has ever shown that any type of radiation is better or worse than surveillance or radical prostatectomy. Survival is much the same, but residual cancer is found more often after radiation in the survivors than in those treated by surgery, even though it does not necessarily cause symptoms. Neoadjuvant and adjuvant hormone suppression combined with radiotherapy improves local control, prolongs disease free survival, delays the time to the development of metastatic disease and prolongs overall survival in some subsets of patients.

Painful proctitis is a common early sequel of radiation, and impotence occurs in a proportion, probably as a result of radiation arteritis.

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Brachytherapy

Brachytherapy is a technique for treating cancers locally (‘Brachy’ means near). It involves implanting iodine-125 seeds directly into the prostate gland, where they emit low level radiation for about a year. Each seed is 5mm long and 0.5mm thick and is implanted very accurately using needles positioned by transrectal ultrasound. Treatment is so highly localised that little radiation reaches adjacent normal organs such as the rectum and the bladder but up to three times more concentrated radiation is delivered directly into the prostate, compared with external beam therapy. Recent evidence shows similar success rate for Brachytherapy compared with either radical prostatectomy or external beam therapy patients. It is a relatively quick procedure with seed impantation normally taking 1-2 hours and the patient being able to leave hospital the following day, if not sooner. The risk of incontinence is low – less than 2% of patients with no prior prostate surgery. Impotence occurs in 2 or 3 out of 10 patients under age 60 and more often for older patients but this can be treated successfully.

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Cryotherapy

Complete cell destruction occurs in response to freezing down to temperatures reaching - 400C. The direct effects of cryosurgery on cells include:

  • Crystallization of extracellular fluid leading to cellular dehydration.
  • Cellular pH changes leading to electrolyte abnormalities resulting in denaturation of cellular proteins.
  • Lipoproteins are damaged in response to the thermal shock.
  • Cellular membrane disruption occurs as a result of intracellular crystalisation.
  • Membrane disruption occurs due to fluid influx during thawing following freezing.
  • Thrombosis and vascular stasis occurs after freezing.

Cryosurgery clinical experience continues to advance. Improvements and refinement of the delivery systems are promising and may lead to increase in application or this modality.

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Green light laser

The photo-selective vaporisation of the prostate (PVP), using new Green Light Laser technology, is a significant advance for the thousands of men diagnosed with benign growth in the prostate which has been preceded by serious and disabling bladder problems resulting from a major constriction of the urethra. The condition has, until now, been treated by endoscopic resection (TURP) or in some cases by major surgery. These procedures, while very often successful, usually means a hospital stay of up to a week and sometimes, a great deal of post operative pain necessitating a large catheter together with bleeding, impotence or sexual dysfunction. It has also meant an enforced recuperation of five to six weeks.

By undergoing the Green Light Laser (PVP) process, the patient can go home the same day; there is very little discomfort and bleeding and no catheter and there is little or no risk of impotence. In some cases, a patient can even return to work within a couple of days.

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HIFU (High Intensity Focused Ultrasound)

HIFU is a non-invasive technique using acoustic ablation – intersecting, tightly focused ultrasound waves – to heat and destroy target tissue to more than 80-90oC in a few seconds. Ultrasound energy is non-ionizing "clean energy" that does not affect tissue surrounding the target zone, as opposed to radiation therapies.

HIFU treatment can be given in one to three hours on an outpatient basis with epidural anesthesia or general anaesthetic . A beam of ultrasound emission from a rectal probe targets the prostate gland. A cooling balloon surrounds the probe to protect the rectal mucosa from the high temperature. A urethral or a supra-pubic catheter is inserted after the procedure to aid urinary drainage during the time the necrotic debris is expelled. Long term clinical outcome, safety and efficacy, reduction in prostate specific antigen levels, post treatment biopsy findings, survival and impact on quality of life are being audited.

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