Family doctor

Overview

o Prostate cancer affects about 10 percent of men

o The incidence of prostate cancer appears to be on the rise

o Dietary fat may increase the risk of prostate cancer

o Symptoms include a slow urine flow, and incomplete bladder emptying

o There may be no symptoms in the early stages

o Diagnosis includes blood tests, prostate examination, and biopsy

o Prostate cancer may either grow slowly or rapidly

o Treatment includes radiotherapy or removal of the prostate

o There is an 80-90 percent survival rate if prostate cancer is diagnosed early

1.Definition / Description:

Prostate cancer is an endemic problem in the western world. The incidence of prostate cancer appears to be increasing. Approximately 10% of men will get symptomatic prostate cancer in their lifetime, and approximately 4% die as a result of prostate cancer. Autopsy studies have revealed that half of men over age 70 have some signs of prostate cancer, however these cancers are usually microscopic (average volume 0.02ccs), and are not usually clinically relevant or detectable by clinical examination or biopsy.

It is not known what causes prostate cancer, but environmental factors appear to be important. The incidence of cancer in Asia is significantly lower than in Europe, America and Australasia. The specific environmental factors that are important have yet to be clearly defined, but evidence suggests that dietary fat may increase the risk, and "lycopenes" (found in tomatoes, especially rich in cooked tomato products) may reduce the risk of prostate cancer.

A known risk factor is a positive family history. With one first-degree relative affected, this increases the risk 2-3 times. With 2 or more the risk is 8 times.

2.Signs & symptoms:

Generally the early stages of prostate cancer is asymptomatic. Advanced local prostate cancer can cause local symptoms from urethral compression. These include slow urine flow, hesitancy, dribbling after urination, incomplete bladder emptying and urinary urgency. Sometimes pelvic pain can also occur.

Patients may present with spread of the cancer ("metastatic disease"). Spread of cancer usually first occurs to the pelvic lymph nodes. (This normally does not cause symptoms). The most common site of metastases beyond this is bone. Typically patients can experience bony pain in the pelvis or lower back, or multiple sites, usually in the axial skeleton.

However the most common way prostate cancer presents is in association with benign enlargement of the prostate. With benign enlargement of the prostate patients can experience a range of lower urinary tract symptoms, and prostate cancer may be diagnosed incidentally, on the basis of patients presenting with lower urinary tract symptoms. The lower urinary tract symptoms are usually secondary to benign enlargement of the middle part of the prostate, and incidentally the cancer is discovered, either at the time of examination of the prostate, or on the basis of an elevated PSA blood test. Prostate cancer usually arises in the peripheral zone of the prostate, and so does not normally cause urethral compression early in its development

(picture with schematic demonstration of where the prostate is in relation to the pelvis and bladder, and also a schematic diagram of the zones of the prostate, including the peripheral zone, and the transition zone, where BPH occurs &endash; this diagram would then explain why prostate cancer early on doesn't cause any symptoms).

3.PSA

PSA is a tumour marker which has been helpful both as a screening tool in the detection of prostate cancer, for the staging of the cancer, and also for measuring the response to treatment. PSA liquefies the seminal coagulum that is formed after ejaculation.

Serum values of PSA are not generally affected by prostate examination, but can be affected by urological instrumentation and prostate biopsy. Other non-malignant conditions that can elevate PSA levels include prostatitis and benign prostatic hyperplasia. The normal range of PSA in most assays is 0-4ng/ml. There are specific age ranges for PSA, which some doctors use.

These are: Age / PSA

40-49 2.5

50-59 3.5

60-69 4.5

70-79 6.5

In large-scale screening 5-10% of a population will have an abnormal PSA, and approximately 1 in 5 patients with a PSA between 4 and 10 will have prostate cancer, whereas approximately 60% of patients with a PSA greater than 10 will have cancer.

In addition to a PSA blood test, prostate examination should be done, as digital rectal examination can detect tumours missed by PSA alone (approximately 20%). Most research therefore suggests a combination of digital rectal examination and PSA as the most accurate method of detecting prostate cancer in a population.

4.Prostate Biopsy

If the PSA is elevated or the prostate examination is abnormal, a transrectal ultrasound and prostate biopsy may be indicated. This procedure is performed with a transrectal ultrasound probe, which is placed up the rectum (back passage), and several needle samples are obtained from each side of the prostate. This procedure is uncomfortable for most patients, but a general anaesthetic is not usually required. The biopsy can cause some minor bleeding in the urine, or from the rectum, but heavy bleeding is extremely rare. Blood can also occur for several weeks in the ejaculate fluid following the biopsy. Approximately 1-2% of patients despite taking antibiotics at the time of the biopsy will get a prostate infection and possibly septicaemia from the biopsy.

5.Treatment options

The treatment for prostate cancer depends on the stage of the disease

(whether the disease is localised to the prostate or has spread), and the age and fitness of the patient.

Grading + staging the disease: Prostate cancer has a wide range of behaviour (differentiation) &endash; it may be a very slow-growing tumour, but in some men the tumours are relatively aggressive and grow rapidly. We are able to grade prostate cancers on the basis of the prostate biopsy with reasonable accuracy. A grading system called the "Gleason grade and score" is used. The grade of the cancer is judged between "1": well-differentiated and slow-growing, up to "5": poorly differentiated and rapidly growing.

A Gleason score is the sum of the grade obtained, from the most common area, and the second most common area (often different in the same patient).

This total score can range between 2 and 10. Most patients with cancer have a Gleason score of 6 or 7.

The staging classification used is the TNM system

(list and diagrams)

Simplified staging:

Stage T1 non-palpable

T2 nodule

T3 extracapsular (i.e. outside the prostate capsule)

If it has spread to the bone it is often referred to as D2.

When end-stage and not responsive to hormonal treatment: D3

T1 and T2 tumours are usually curable with radical treatment, T3 tumours rarely so.

There is some error in clinical staging i.e. differentiating between T1 and T3.

Although clinical staging is difficult and subjective, radiological staging including CT / MRI and transrectal ultrasound are not as accurate as clinical staging at this time.

6.Natural History:

There have been some studies which have actively observed men diagnosed with prostate cancer that suggest that patients with well-differentiated, slow-growing tumours, have disease that may slowly progress, but only a small percentage of patients will die from prostate cancer over the next 10-15 years. A high proportion of patients in these observational studies had well-differentiated or slow-growing tumours. The majority of tumours detected nowadays however are moderately differentiated tumours, Gleason score 5-7. The natural history of these tumours has not been well defined, but from various PSA observational studies, it seems these tumours double in size about every 3 years. On this basis it is likely that most prostate cancers diagnosed will progress and cause mortality in a relatively large number of patients in 10-15 years.

Therefore if patients have a 10-15 year life expectancy (i.e. usually under the age of 70 or at most 75, if there is no other major co-morbidity), radical treatment is generally indicated.

7.Radical treatment

Radical treatment consists of either radiotherapy or radical prostatectomy. There has not been any other curative treatment established in large trials. Various dietary modifications and supplements may modify some patients' symptoms, but to date there is no good evidence that these will cure established prostate cancer.

Radical prostatectomy involves surgical removal of the prostate and seminal vesicles. This can either be done through an abdominal or perineal (behind the scrotum) incision. If diagnosed early, for 80-90% of patients prolonged remissions or "cure" can be expected.

The disadvantages of surgery include a temporary loss of continence (usually for several weeks or months following the procedure). A small number of patients (2-20%) have impaired continence longer term, although very few patients with modern surgical techniques have severe incontinence as a long-term consequence. Erectile dysfunction occurs in at least 50% of patients. Anastomotic strictures and rectal injury can also rarely occur.

The alternative to surgery is radical radiotherapy, most commonly external beam radiotherapy. This normally involves a daily treatment for 6 weeks, and has short-term side effects which include urinary frequency, urgency, sometimes blood in the urine, and also bowel frequency, urgency and bleeding. Most of these side effects are short term, but a small percentage of patients can have ongoing radiation damage to the bowel and bladder. Erectile dysfunction occurs in 30-50% of patients.

An alternative radiotherapy treatment is "brachytherapy", where radioactive seeds are placed directly in the prostate, with the potential advantage of reducing the radiotherapy dose to the nearby bowel and bladder. Initial results with brachytherapy are encouraging, but as this is a relatively new treatment there isn't good long-term data available to assess results.

Treatment of advanced local disease, tumour stage T3 &endash; controversy exists as to the best method of treatment for locally advanced prostate cancer. Rarely is this treatment curative, but it may slow progression of disease. Hormonal treatment regardless of the stage of tumour is usually effective in causing remission of prostate cancer, usually for several years. Radiotherapy, either to the prostate alone, or as an extended field to the lymph nodes in the pelvis may be effective in delaying the progression of T3 prostate cancer, but further studies regarding the effectiveness of radiation in this group of patients are currently underway.

When prostate cancer is metastatic (spread) the most effective treatment is hormonal treatment. This either involves orchidectomy (surgical removal of the testes), or medication designed to block the effects of testosterone (which stimulates growth of prostate cancer). There are several medications available, which include:

Cyproterone acetate (Androcur)

Eulixin (Flutamide)

Casodex

Goserelin Acetate (Zoladex)

And several others

These medications are usually effective in shrinking prostate cancer, even with widespread metastatic disease. Hormonal treatment is usually well tolerated. It causes a reduction in libido and often erectile dysfunction. Other side effects may be hot flushes, fatigue, mood swings and rarely gastrointestinal upset and liver disease.

Orchidectomy does not cause the voice to change or cause breast enlargement.

Flutamide may cause slight breast enlargement. With metastatic disease, in addition to shrinking the tumour, treatment is directed at managing complications of the disease.

These can include:

o Bladder outflow obstruction (a transurethral resection of the prostate may be required)

o Bleeding

o Bony pain

In addition to hormonal treatment, painkillers such as simple analgesics, anti-inflammatories, or oral morphine solutions may be required. In addition to this, palliative radiotherapy to painful bony metastases may be effective in relieving pain.

Strontium 89 given as an injection is usually also effective in relieving bony pain.

8.Screening

Currently controversy exists as to whether prostate cancer screening is appropriate.

ARGUMENTS FOR SCREENING: 10% of men will get clinical prostate cancer in their lifetime, and 2-4% die of it. Screening for prostate cancer is relatively simple to do, with an annual prostate examination and PSA test. Most patients with prostate cancer will be identified and with a relatively high chance of cure.

ARGUMENTS AGAINST SCREENING: Screening is expensive if instituted nationwide. Potentially patients with relatively small, slow-growing tumours may be over-treated, and suffer significant morbidity from investigation and treatment.

Proponents against screening also argue that there have not been any studies done that prove prostate cancer screening is effective. (As yet the issue of screening is unresolved, and no good studies have been done!). This would require a very long study interval of 15-20 years, and although such studies are underway in the USA, there have been major difficulties with these trials, as often patients who develop prostate cancer no longer want to be observed, but naturally want treatment. In the near future it is unlikely that we will have the information that we need to come to a conclusion about screening. Most countries practice so-called "case finding", where patients who are interested in screening are selected on a case by case basis.

Some indirect evidence that screening is effective is starting to appear in the USA, in some geographical areas where screening is popular, and the mortality of prostate cancer is decreasing.

9. Commonly asked questions and concerns

Q: What can I do to see if I have prostate cancer?

A: Consult your doctor, with a view to a prostate examination and PSA blood test

10. Other sources of information:

Excellent book: "Prostate and Cancer" by Sheldon Marks. This is a patient orientated overview of prostate cancer, which provides detailed information about treatment and the disease.

Mayo clinic

Prostate Ca