Prostate Cancer

Introduction

A man may be diagnosed with prostate cancer following either a routine health screen, which has, justifiably or not, shown an abnormal PSA test. This may have been combined with an abnormal digital rectal examination (DRE). Alternatively an abnormal PSA or prostate examination may have been discovered during the routine investigation of lower urinary tract symptoms or erectile dysfunction. An abnormal PSA test or DRE does not necessarily mean a diagnosis of prostate cancer. Prostate cancer can only be diagnosed following pathological examination of a section of the prostate. The removal of cores of tissue from the prostate uses a technique known as prostatic biopsy.

Indications for Transrectal Prostatic Biopsy

There are four basic reasons why it may be recommended that prostatic biopsies carried out:-

There is an elevated standard age related PSA level

There is a significant change in the standard PSA level over time (PSA velocity).
There is a standard PSA level of between 2.5 and 10 ng/ml and a low free/total PSA ratio (an F/T ratio of over 23% is unlikely to be associated with prostate cancer but an F/T ratio under 12% is much more suspicious).
The prostate feels suspicious on digital rectal examination (DRE) irrespective of the PSA value

A prostate biopsy is indicated if at least one of the above applies even if an ultrasound evaluation is normal.

What is a transrectal ultrasound (TRUS) guided biopsy of the prostate ?

Prostatic biopsies are most often carried out under ultrasound guidance. A lubricated sheathed transrectal ultrasound probe is passed into the back passage and the prostate gland examined to identify any obvious abnormalities within the peripheral zone of the prostate. The ultrasound machine will detect differences in the sonographic echoes observed within different parts of the prostate. Prostate cancers are often described as hypoechoic (echopoor) areas with irregular borders, however this is not a rule and experience has shown that only 1/3 of hypoechoic areas turn out to contain cancer. Likewise a 1/3 of cancers may comprise hyperechoic or isoechoic areas. The prostate gland is comprised of three distinct glandular zones:

The transition zone surrounds the urethra and is the site where benign prostatic enlargement occurs. It provides the central core, which is removed during a Trans Urethral Resection of the Prostate (TURP).

The peripheral zone encompasses the posterolateral aspect of the prostate from the base to the apex. It accounts for most of the volume of the prostate and is the area where 70 – 80% of prostate cancers develop.

The central zone comprises the tissue immediately surrounding the ejaculatory ducts. It is indistinguishable from the peripheral zone of the prostate.

A TRUS biopsy should target by systematic sampling the areas most likely to contain cancer.

How is a prostate biopsy carried out?

You will be required to take antibiotics before and after the biopsy, some of these are oral (Ciprofloxacin 250 mg twice a day for 3 days, starting on the day of the biopsy) the remainder an injection (gentamicin) and a rectal suppository (metronidazole) will be administered by the radiologist or nurse. A digital rectal examination is usually carried out before the biopsy to firstly exclude any anal stenosis or rectal abnormality, which might contraindicate the procedure, and to palpate the prostate for any palpable abnormality deserving of special attention.

The lubricated probe is inserted and under ultrasound guidance local anaesthetic solution (1% lignocaine) is injected into the peri prostatic tissues using a fine spinal needle.
Biopsies are taken using a disposable gun, which extracts a core of tissue approximately 18 mm long. It sounds like a small air gun and may make you jump at first. A minimum of 6 biopsies (sextant – left and right base, midzone and apex) are taken but if the subject is tolerating the procedure we will often take up to 13 cores using a 5 region technique (left and right far lateral, lateral at the base, midzone and apex),in large glands biopsies of the transition zone will also be carried out.

The specimens are then sent for histological analysis and the result usually takes a minimum of 48 hours to allow for processing and interpretation.

What should be expected after the biopsy ?

Bleeding is common and it is not unusual to experience some bleeding either in the urine or from the tail end. This may include clots but usually settles within 48 hours. Blood in the semen may continue for longer because the seminal vesicles are dilated sacs, which lie behind the bladder and connect via the ejaculatory ducts to the prostatic urethra.

Infection of the urinary tract may occur particularly in diabetics or those patients with significant bladder outflow obstruction (prostatism with impaired bladder emptying and / or urinary infection). This will usually be prevented by the antibiotics prescribed but sometimes requires further urinary cultures and a change of antibiotics. Prostatic abscesses are fortunately very rare.

The anaesthetic abolishes most of the acute pain associated with the biopsies although you may still be aware of a dull ache within the perineum both during the procedure and sometimes for a few days after. Ibuprofen 200 – 400mg will often help persistent discomfort.

When can the result be expected ?

An arrangement will usually have been made for you to be reviewed following the biopsies for the result. These are usually carried out on a Wednesday and the result available by the Friday. If you are unaware of the date please do not hesitate to contact Nikki Lewis on 0207 357 6466 who will confirm the arrangements.

What kind of outcome can be expected from the result ?

There are four different case scenarios which need to be considered :-

All biopsies negative and no evidence of dysplasia or high grade PIN
Evidence of high grade PIN or severe dysplasia
One or two of the biopsy cores show a micro focus of adenocarcinoma (equivocal biopsy result)
A number of cores showing evidence of invasive adenocarcinoma (unequivocal biopsy result)

Prostate Biopsy Case Scenarios with Recommendations for Follow up

All biopsies negative and no evidence of dysplasia or high grade PIN

This is the result which everybody would wish for. A negative result needs to be interpreted in the light of the initial PSA value, the free/total ratio and the finding on rectal examination. If there were no sinister features at presentation, the usual recommendation would be a repeat PSA test in 6/12 to 1 year.

If there were suspicious features at presentation then an early review in 4 months may be suggested or alternatively a repeat biopsy may be recommended either under local anaesthetic or saturation biopsies under a light general anaesthetic.

Evidence of high grade PIN or severe dysplasia

The prostate needle biopsy can usually distinguish between BPH and prostate cancer. However, some men are discovered to have a lesion called PIN, which stands for Prostatic Intraepithelial Neoplasia. A biopsy report may show an area of focal high grade PIN or extensive PIN. The exact nature of PIN is unclear. Many feel it may be a precursor of overt cancer but this has yet to be proven. We do know that patients with PIN have a 40 - 50% likelihood of developing prostate cancer within five years.

This result therefore requires careful follow up with serial PSAs and repeat biopsies where indicated, either through patient preference, change in rectal exam or an increase in PSA +/- fall in free/total ratio. If there is particular suspicion of underlying malignancy then repeat biopsies or saturation biopsies are indicated.

One or two of the biopsy cores show a micro focus of cancer
(equivocal biopsy result)

This result is very suspicious of an underlying cancer, in some instances, such a result may be sufficient to confirm a suspected clinical diagnosis, with an abnormal feeling prostate, a high PSA and provide an indication for treatment with active monitoring or hormonal manipulation

However to proceed to radical treatment (with the inevitable impact on continence and erectile dysfunction) on the basis of a tiny focus would generally be considered excessive (sledgehammer to crush a nut). The recommendation in these instances, where radical treatment is being considered, is to carry out repeat biopsies or saturation biopsies to confirm the grade of tumour and also to determine whether there is significant disease. Proceeding to radical surgery on an equivocal result runs the risk of finding no cancer in the final specimen

Repeat biopsies or saturation biopsies ?

As has been mentioned previously a standard biopsy regimen would involve 8 to 10 cores from right and left base, midzone and the apex. There is some evidence that targeting the biopsies to those areas that are most likely to contain cancer, the lateral peripheral zones and the apex will more often give a positive result. Likewise the greater the number of biopsy cores taken the more likely a positive result. A saturation biopsy is based upon the 5 region technique but involves 18 – 24 cores including the transitional zone, if large.
The morbidity associated with more biopsies is however greater and there is a risk that if such protocols were applied to all patients with elevated PSA that clinically insignificant cancers would be detected.

The recommendation is therefore :

Equivocal or suspicious biopsy (standard 6 – 8 cores) proceed to 5 region targeted technique (local)

Equivocal or suspicious biopsy (5 region) proceed to saturation biopsies (18 – 24 cores under general)

A number of cores showing invasive adenocarcinoma (unequivocal biopsy result)

This is the result, which of course all patients dread. It is important to remember that when a diagnosis of prostate cancer has been made on the basis of a PSA between 4 – 10 and a relatively normal feeling prostate that this will often have predated the development of significant local disease by 8 to 10 years. It is by definition early prostate cancer and as such is potentially curable.

Dealing with the diagnosis

The diagnosis of prostate cancer can be terribly emotive and have a major impact upon relationships and family. An element of depression and stress is a common feature of the normal response to the diagnosis and it is absolutely crucial that you take time to reflect upon your treatment options as explained to you. Decisions should not be taken too quickly and a focused, reasoned, and calm attitude will be an asset in dealing with the pressures you will face.

Remember - if a particular treatment doesn't feel right for you, then it probably isn't suitable for you. If a treatment feels right, then it probably is. Keep asking questions until you are satisfied. After studying all your options, spoken to the appropriate specialists, use the knowledge gained and trust your instincts.

Be realistic - If a man is not generally in good health, surgery may not be the best option. Surgery of any kind is hard, and recovery is easiest when a person is in good shape. If a man has bowel or bladder problems already, radiation of any kind may make them worse. Fortunately, there are a number of other options, including various forms of radiation therapy and hormone therapy, or a combination of treatments, which may still result in a successful outcome.

The ideal treatment - for early prostate cancer would both provide an excellent chance of cure (over 90% of the time) and minimal side effects with regard to urinary continence (leakage) and potency (erectile function). Unfortunately the ideal treatment does not exist (if it did then there would be no question about the benefit of prostate cancer screening), they all have significant side effects and an individual’s options are very dependant upon a number of interrelated factors:

The PSA level at diagnosis

The Clinical Stage – local extent of disease based on DRE and imaging.

The Gleason score – the pathological grade of the tumour.

The age and physical well being of the patient (co morbidity).

The presence or absence of significant lower urinary tract symptoms.

The current quality of erectile function (potency).

An individual’s preference for a particular treatment.

The most appropriate treatment for an individual can often be determined by the careful assessment and appraisal of these factors in conjunction with the advice of your urologist.