Prostate Cancer

What is Cancer?

Cancer occurs when cells multiply out of control, rather like a factory with the production line switch jammed on. The cells do not know when to stop multiplying and as a result grow into other tissues and spread to other parts of the body. In the case of prostate cancer it is usually fuelled by the male hormone, testosterone and in fact for treatment for some prostate cancers the lowering of testosterone is the corner stone.

Causes of Prostate Cancer

Prostate cancer tends to run in families and if a man’s father has or has had a prostate cancer the likelihood of getting it can be increased by one and a half to two and a half times. The absolute risk is 12-20%. For two affected male relatives absolute risk is approximately 30%, three or more affected males relatives 35-45%. As men get older the risk of prostate cancer increases but it is possible that the risk of dying from prostate cancer may decrease. It is possible that men may therefore die of other causes, such as old age, heart disease, etc. There is no absolutely definite association with any particular type of diet and studies linking vasectomy with an increased risk of prostate cancer have not been confirmed. A man with Prostate Cancer who has intercourse will not “stir up” the cancer causing it to spread and will not pass it on to a partner.

Diagnosis of Prostate Cancer

When a man visits his doctor, the doctor will ask questions about symptoms which have led the patient to present. This is called a history. In some cases there may be no symptoms at all associated with prostate cancer and screening may be carried out in some men by the performance of a blood test which estimates the level of Prostate Specific Antigen, (PSA) in the blood stream.

PSA and testing for Prostate Cancer

PSA is a blood test, which measures the level of a substance in the blood stream which is only present in men. It is made in the prostate gland and leaks into the blood stream and is specific for prostate but not specific for prostate cancer.

There are two types of PSA. The PSA which is free within the circulation and that which is bound to a protein. A number of studies have shown that the ratio of free to bound PSA may result in a greater sensitivity in the possibility of being able to estimate the likelihood of a prostate cancer in an individual patient. Generally speaking, if the ratio is less that 10-15% the likelihood of a prostate cancer is increased.

The blood test may go up with things other than prostate cancer. It may go up if the prostate is enlarged, (benign or non-cancerous) which occurs as men get older or go up because of infection. Not all prostate cancers cause the blood test to go up but many do. Some patients have unsuspected prostate cancer diagnosed when the Pathologist examines the specimen after they have undergone Transurethral Resection of the Prostate(“rebore”) as treatment for obstructive urinary symptoms.

Examination

In addition to the blood test, a digital rectal examination, (DRE) is carried out by the Doctor. For this examination the doctor inserts a gloved finger into the patient’s back passage in order to feel the prostate gland. The Doctor is feeling for the size, shape, consistency and any irregularity suggestive of cancer. If either the PSA or DRE is abnormal, the doctor may suggest a biopsy be taken.

Biopsy

A biopsy from the prostate is a small piece of tissue which is taken with a special needle. It is usually necessary for the prostate to be examined with a transrectal ultrasound, (TRUS) which is carried out without the need for anaesthetic. This examination is carried out by placing the Ultrasound probe in the back passage in a similar fashion to the DRE. The TRUS enables the prostate to be visualised looking for any abnormal areas, which may or may not be felt on the DRE. If abnormal areas are seen, the biopsy needle can be directed towards them. If no abnormalities are seen then it is usual to biopsy areas which are more likely to undergo a cancerous change. This usually means at least six to eight biopsies.

Pathology

The specimens taken are sent to the Pathologist for preparation and examination under the microscope. The only way any cancer can be diagnosed correctly is by the visualisation in the pathology specimen.

Gleason Score

A Gleason Score is a number given to the type of prostate cancer cells in an attempt by the Pathologist to say “how bad” the cancer might be. It is a method of grading the tumour. A Gleason Score is a number ranging from 2 to 10.

Gleason Scores of 2 are what is referred to as “well differentiated” tumours which are likely to respond to treatment better than a Gleason Score 10 which is usually described as “undifferentiated” in that it looks nothing like the normal non-cancerous prostate tissue at all.

Staging

After the tumour has been graded it is necessary to carry out staging. Staging means trying to find any evidence of spread outside the prostate. Often a CT Scan, Ultrasound or MRI, (Magnetic Resonance Imaging) is used to inspect the abdominal cavity in order to attempt to detect any spread to the internal lymph glands or lymph nodes.

The glands or lymph nodes are small, bean - sized areas within the body which are associated with the body’s immune system and tend to fight infection and cancer. For example if a patient has a sore throat, the glands in the neck are easily felt and often tender and swollen from the infection. If a patient has a cancer of the throat, the cancer may spread to the glands of the neck. In similar fashion a prostate cancer may spread to the glands inside the body.

Bone Scan

Prostate cancer has a tendency to spread to the bones of the body, chiefly to the back. A bone scan is a Nuclear Medicine imaging procedure which involves an injection of extremely low dose radio - nucleotide material into a vein, usually in the arm which then circulates through the body and is able to show up areas of spread of prostate cancer to bone.

Treatment

The object of treatment of prostate cancer or any any other condition for that matter is such that the treatment should enable the patient to live longer and better than otherwise the patient would do without the treatment.

  1. The treatments, which would be discussed for prostate cancer will depend on the following factors:
  2. Grade of cancer
  3. Stage of cancer
  4. Patient’s age
  5. Patient’s general state of health, other medical conditions
  6. Patient’s fears, anxieties and preferences

Localised Prostate Cancer

In cases of localised prostate cancer in which it is likely that a patient will have an improvement in his quality and length of life span, the treatment options are:

  1. Observation.
  2. Surgery (Radical Prostatectomy)
  3. .Radiotherapy
    • External Beam
    • Brachytherapy
    • Combination
  4. H.I.F.U. (High Intensity Focused Ultrasound-Heating of the prostate)
  5. Cryotherapy (Freezing of the prostate)

Observation

In some cases, prostate cancers are very low in aggression and may be discovered incidentally through a raised PSA or at the time of Transurethral Resection of Prostate for obstructive symptoms. In those cases, it may be appropriate to continue to observe the patient to see how active the cancer is and whether any treatment may be beneficial in order for the patient to live for a long time and a good time. It is not usual to carry out a TRUS and biopsy to find a prostate cancer if observation is likely to be considered as a form of management because, although the risks of complications from biopsy are small, the possibility of occurrence is well recognized.

Radical Prostatectomy

A Radical Prostatectomy is an open (cutting) surgical procedure, which may also be performed in a minimally invasive (keyhole) manner under certain circumstances. It is the total removal of the prostate gland and seminal vesicles, which are two small pouches on the back surface of the prostate through which sperm pass. The bladder opening is then joined back to the urethra (pipe down the penis) with stitches just above the muscle of control (distal urethral sphincter). This procedure is designed to lead to a possible cure. The cure rate for this procedure is in the vicinity of 80% over all age groups, grades and stages. It is most effective in Gleason < 7, PSA < 10.

Side Effects of Radical Prostatectomy

Approximately 5% of men will have some degree of urinary leakage permanently following the procedure. That leakage may be what is called urge incontinence. That is, the failure to get to the toilet on time. Stress incontinence is leakage with coughing or sneezing, for example. Total incontinence is continuous leakage. A large number of men will find they are unable to achieve an erection following the procedure. Every attempt is usually made to preserve the nerves and blood vessels which cause erections. However, there can be irritation to those such that recovery is not complete. Alternatively they may have to be removed to clear the cancer. There are a number of methods of treatment for impotence. These treatments are generally best started about six weeks after the surgery as in many cases spontaneous erections may not return for 12-18 months. All patients who have a Radical Prostatectomy will find that there is no ejaculate fluid coming out when they achieve orgasm and therefore it will not be possible for them to father a child by normal means if they wish. In fact, all treatments for localized prostate cancer will cause a reduction or complete loss of ejaculate fluid.

Radiation Treatment

External Beam (EBRT) - This type of treatment usually involves attending a Radiation Oncology clinic five days a week for a period of approximately seven weeks. Approximately 70% of men will remain cancer free following this treatment ten years later. This treatment is not available in Cairns so patients must travel 350km to Townsville or 1400km to Brisbane or alternative centre.

Side Effects: Bladder irritation may occur with urinary urgency and urge incontinence. Bleeding from the bladder may occur which is usually minor and settles spontaneously. Bleeding and irritation of the bowel may also occur in approximately 50% of patients and usually settles spontaneously also. Impotence may also occur and require treatment. It may be permanent.

Brachytherapy - Brachytherapy is the insertion of radiation-containing pellets into the prostate gland under ultrasound control (similar to transrectal for biopsy). The radioactive seeds affect tissue within 2-3mm of their placement and they need to be accurately placed to be effective. The procedure is performed under General Anaesthetic and the patients usually stay in hospital for 2-3 days. It will not affect people close to the patient such as pregnant women or babies sitting on a patient’s lap. Brachytherapy is usually only considered for a Gleason Score £ 6. The current techniques used for Brachytherapy are relatively new.

Side effects include incontinence 4.3%, TURP 5.5%, damage to the bowel less than 0.1%, temporary erectile dysfunction 94.9%. Approximately 60% of patients who have erections prior to the procedure will regain that within 2 years, however it is usual to require assistance with medication to achieve erections prior to that.

10 Year Cancer Specific Survival (Radiotherapy)

Author Low Risk Medium Risk High Risk
Beyer 97% 83% 77%

High Intensity Focused Ultrasound (HIFU)

This is a method of heating the prostate to high temperatures using ultrasound to attempt to kill the cancer cells. This is done by an Ultrasound probe placed in the back passage and focused on the area being treated. The operation takes approximately 3 hours. A catheter is usually left in place for 14 days. Approximately 28% of patients require two treatments, 9 % of patients developed prolonged retention and 4% developed urethral strictures. Approximately 65 - 80% of patients developed impotence and recto-urethral fistulas were present in 1%. Results for 5 year follow - up for Gleason scores less than or equal to 6 are shown. They are based only on lowering the PSA levels. There are no Medicare or Private Insurance Fund Rebates for this procedure. Research is continuing with this type of treatment.

Author Low Risk Medium Risk High Risk
Beyer(HIFU) 78% 53% 36%

Cryotherapy

Cryotherapy is a minimally invasive procedure designed to cure prostate cancer in the early stages. It may also be used for late recurrence of localised prostate cancer after radiotherapy. This procedure is carried out in the Day Surgery. The patient is given a general anaesthetic and using an ultrasound probe in the back passage the prostate is imaged in order to accurately place the freezing needles.This is to endeavor to obliterate the tumour completely by freezing to extremely low temperatures which leads to cell destruction. A warming catheter is placed in the urethra (pipe) to protect it from the process and temperature gauges are placed between the prostate and the rectum to reduce the risks of damage there. The needles are removed at the end of the procedure. Usually the patient has a catheter in place for 3 to 5 days post operatively draining into a bag attached to his leg. The success rate for Cryotherapy in well differentiated low stage prostate cancer has been reported as 98.6% 5 year cancer specific survival and 90% 7 year cancer specific survival. At present although Cryotherapy is TGA approved there is no Medicare rebate for it. It can be carried out in Cairns so there is no need to travel and be away from home.

Results of Treatment

CATEGORIES OF RISK

  T (Stage) PSA Gleason
Low Risk T2A PSA >=10 >= 6
Medium Risk (one of) >=T2B PSA >10 >7
High Rosk (two of) >=T2B PSA >10 <7

DISEASE-FREE SURVIVAL

Author Cases Follow-up Years Low Risk Med Risk High Rsk
Bahn 590 7 92% 89% 89%
Donnelly 76 5 60% 77% 48%

Side Effects

Damage to the bowel is possible but very unusual occurring less than 1% of cases.

Impotence is usually temporary. There are several treatments available if required.

Side Effects
%
Urethral Damage
6%
Incontinence
3%
Retention
3%
Pelvic Pain
4%
Impotence
80%

 Randomised Trials

A randomised controlled trial occurs when a Doctor is testing to see whether a treatment works because the operation or radiation or medication is effective because of the way it works or through chance or luck. It is done to show that a treatment actually makes a difference and the patient would not have had the same result by just waiting to see what happens.

It is carried out by giving a group of patients as much information as we know about the treatments that are being tested including the expected benefits, side-effects and risks of the treatment compared with not having any treatment. The patients then consent to being in this trial (experiment). The patients are then randomly selected for the treatment (either treatment A or treatment B) by placing their names in a hat (for example) and then allocating a treatment based on that. In this way the Doctor or patient is not biased toward a particular treatment and we can truly find out if something works or not. If, after a short time, it appears that a treatment is no good and causes harm, the trial may be abandoned so that the conclusion is that the experimental treatment does not work.

In a randomised controlled trial comparing External Beam Radiation Therapy as primary treatment with Cryoablation in localised prostate cancer carried out by Donnelly et al1 it was concluded that at three years the results from EBRT are marginally better (EBRT 85.8% vs. Cryo 82%) but at the end of four years the results from Cryotherapy show somewhat greater improvement (EBRT 74.6% vs. Cryo 80.1%). Overall the results for control of the primary malignancy can be regarded as equivalent (Table).

 

                  Random Control EBRT vs. Cryoablation (Primary Therapy)1           

                HormoneTherapy          3 Years         4 Years          Death**         Failure *

EBRT                  Yes                      85.8%           74.6%             4                32 (26%)

Cryo                   No                       82.0%           80.1%             5                25 (20%)                        

* ASTRO (American Society for Therapeutic Radiology and Oncology) defines failure as PSA nadir + 2ng/ml increase.

** Death from Prostate Cancer.

1.Donnelly BJ, Saliken JC, Brasher P, Ernst S, Lau H, Trypkov K.

A randomised controlled trial comparing  external beam radiation and cryoablation in localized prostate cancer. JUrol 2007; 117:376-377. AUA meeting abstract #1141.

Update

FRIDAY, March 21,2008. (HealthDay News) -- In men with localized prostate cancer, cryosurgery alone provides long-term disease control equivalent to that of surgery and radiation with much milder side effects, according to a landmark study published in the March issue of Urology.

Jeffrey K. Cohen, M.D., of Allegheny General Hospital in Pittsburgh, Pa., and colleagues analyzed data on 370 patients who underwent prostate cryosurgery as primary monotherapy between 1991 and 1996.

After a median follow-up of 12.55 years, the researchers found that biochemical disease-free survival rate at 10 years -- defined as nadir plus 2 ng/dL -- was 80.56 percent for low-risk patients, 74.16 percent for moderate-risk patients and 45.54 percent for high-risk patients. They also found that the 10-year negative biopsy rate was 76.96 percent.

"Acceptance of cryotherapy as a viable therapeutic alternative for prostate cancer has steadily grown over the past decade," Cohen said in a statement. "It is still considered controversial by many as a primary treatment modality, however, because of concerns about the procedure's long-term efficacy. Our study's findings allay that concern, particularly among low-risk patients."

 A Latest Update . 

This article compares Cryotherapy with Radiation Therapy and Radical Prostatectomy.“Five year  biochemical and local control rates appear consistent with those published for irradiation and surgery for all stages and grades of prostate  cancer.” Jones S.J. et al.  Whole Gland  Primary Prostate Cryoablation: Initial Results from the Cryo Online Data Registry. J.Urol. Vol.180, 554-558, August, 2008.

 

Treatment of Focal Areas of Prostate Cancer.

Treatment of localized Prostate Cancer may be carried out to the focal areas which were found to be positive  according to the Pathology Report of the TRUS and Biopsy.This means that only that area of the gland is targeted with the freezing needles, preserving the remaining tissue.There are a number of advantages of this type of treatment which include: shorter procedure, treatment to organ-confined tissue, reduced risk of impotence as the nerves on the other side of the prostate are completely avoided. There is a disadvantage in that there may be areas in the other side which are not targeted but these can be dealt with if (or when) they are detected. This has been reported as 4-8% in the untreated side (see table).

Reference         Number       Median Follow-up        Biopsy Proven            Biopsy Proven             Potent
                                                (Months)                Positive                      Positive

                                                                           Treated Side             Untreated Side

Lambert*             25                   28                           4%                            8%                        71.0%

Bahn**                31                   70                           0%                            4%                        88.9% 

                                                                                                                                    48.1%Spontaneous

                                                                                                                                    40.8%Treated                                                                  

 

*Lambert EH, Bolte K, Masson P et al:Focal Cryosurgery: Encouraging health outcomes for unifocal prostate cancer. Urology 69: 1117-1120, 2007.

**Bahn DK, Silverman P, Lee F Sr. et al.: Focal Prostate cryoablation: Initial results show cancer control and potency preservation. J. Endourol. 20: 688-692, 2006.

Bahn et al reported results in 31 patients with clinically organ confined uni-lateral prostate cancer confirmed by targeted biopsy. With unilateral treatment tumour control data at a mean follow-up of 70 months  was impressive with a  96 per cent negative biopsy rate.  There was  a 92.8% biochemical disease free survival based on the ASTRO definition (three consecutive PSA increases) . There was no incidence of incontinence or other complications.

Cost

The cost of the procedure is reduced because of the reduction in cost of consumables and the reduced time of surgery.

 

 

Later Stage Prostate Cancer (Non-localised Prostate Cancer)

In some patients, it will be found during staging that cancer has spread to other parts of the body. Under those circumstances, the localised treatment of the prostate is unlikely to benefit the patient unless it is for symptomatic reasons. For example, the patient may undergo a Transurethral Resection of Prostate (TURP) for slow stream, incomplete emptying of the bladder etc.

Hormone Therapy

As the majority of the prostate cancers are stimulated by the male hormone testosterone, it is therefore logical that reduction of the body’s natural testosterone level may well assist in removing or reducing the “fuel” for stimulation of the tumour.

Hormone therapy is therefore directed at reducing that stimulation. There are several methods of achieving that:

  • Bilateral Orchidectomy (removal of testicles):
    As the testicles produce approximately 90% of the total body testosterone, then obviously if the testicles are removed, the testosterone production will be reduced. It is possible to carry out a procedure called Subcapsular Orchidectomy which removes the hormone manufacturing part of the testicle but leaves a small area of testicular tissue present in oder that a man may have the feeling of testicles within the scrotum. Alternatively, testicular protheses can be inserted which again give the feeling of the presence of testicles if the man wishes.
  • LHRH Agonists:
    Eligard®(Leuporelin), Lucrin Depot®(Leuporelin) and Zoladex®(Goserelin) are three preparations which are given either intramuscularly(into a muscle of the buttock or arm) by injection (Lucrin®) or subcutaneously(under the skin of the abdomen) by injection (Zoladex® and Eligard®). They cause the production of testosterone from the testicles to cease. These injections are generally given and are effective over three, four or six monthly periods depending on the medication used.
  • Medications:
    These are tablets such as Cyproterone Acetate (Androcur®) act in a different way again to reduce the majority of testosterone production.
  • Anti-Androgens:
    These are tablets such as Bicalutamide (Cosudex®), Flutamide (Eulexin®), Nilutamide(Anandron®). Anti-Androgens, which when used in combination with LHRH Agonists achieve 100% testosterone blockage.

Side Effects of Hormone Manipulation

The main side effect that men suffer is an increase in lethargy, an increase in tiredness and occasionally some sluggishness of mental activity. Weight may increase. Abdominal girth may increase and there may be breast enlargement and tenderness. There may be an increase in growth of hair on the head and a reduction in body hair growth. A high pitched voice will not occur. A reduction in sexual interest and activity may also occur. There may be hot flushes and reduced muscle strength. Osteoporosis may also occur in the long term.

Tumour Resistance

Some prostate cancers are resistant to the effects of reduction in male hormone and will progress despite treatment. Some may be sensitive initially but may develop “resistance”.

Chemotherapy

Generally speaking, chemotherapy is not used, as at this stage there have not been any well-established long-term effective results. However, trials are continuing.

Bone Spread

External Beam Radiotherapy

Localised painful areas of spread from prostate cancer to bone can be treated with localised radiotherapy (external beam) to the affected bones which is effective in pain relief.

Metastron® and Samarium®

These are radioactive substances which are injected intravenously, similarly to the low dose of radio - nucleotide injected for the performance of a bone scan. The substances lodge on the areas of spread to bone and carry out radiotherapy at those points, resulting in considerable relief of bone pain. They may also reduce the PSA and Bone Scan appearance may improve. As the bones produce the blood cells, regular check ups of blood tests are required as both cancer and the radiation can reduce the amount of blood produced.

Finally

It should always be remembered that the treatment of cancer involves a team approach between Doctors, the patient and the patient’s family, friends and carers.

The object of all the treatments should be for the patient to enjoy a good quality and quantity of life and that full and frank discussions should always occur and the patient’s opinions be sought and respected in order to achieve an appropriate outcome.

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