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PROSTATE CANCER BASICS

The Prostate Gland

Only males have prostates, so only men can get cancer of the prostate. The prostate is an important part of a male reproductive system and proper functioning of the prostate is important for bladder control and normal sexual function.

Where is the prostate?

The prostate gland is a solid organ found immediately below the bladder and in front of the rectum (see Figure 1) It surrounds the urethra which is the tube connecting the bladder and the penis through which a man empties the bladder. Other important parts of the male reproductive system are the seminal vesicles and the testicles.

The normal prostate in a young adult man is about the size of a walnut. However, its size can change over time, and in many men the prostate gets larger as we get older, particularly once a man gets over the age of 40 or 50 years. This can affect the ability to urinate.

You can obviously see or feel your penis and your testicles. However, it is impossible to see your prostate and extremely difficult to feel it. Your doctor can feel some parts of your prostate by inserting his gloved finger into your rectum. This procedure is called a digital rectal examination or DRE and can be important in trying to diagnose prostate cancer and other prostatic diseases.

What does the prostate do?

The prostate has two important functions: one is to help control urination and the other is to help sexual activity. The prostate helps to control the rate at which urine flows out of the bladder and into the urethra. It does this by the effect of the sphincter muscle in the prostate that surround the urethra.

The prostate also has an active role in sexual activity. The prostate gland makes a whitish glandular secretion which collects within the prostate and is fed into the urethra during ejaculation. This glandular secretion helps to protect the sperm after intercourse.

The growth of the prostate and control over how it works are fundamentally based on the levels of the male sex hormone testosterone, which is produced by the testes. The production of testosterone is itself controlled by another complex set of hormonal interactions.

The Symptoms of Prostate Cancer

There are no clear symptoms of prostate cancer which can be easily assessed by the patient himself. This makes prostate cancer very different from breast cancer or testicular cancer in which regular self examination can be important in finding early signs of the disease.

A big problem with prostate cancer is that many of the early signs of the disease can be caused by other disorders or, worse still, are just among the normal consequences of growing older. Another big problem is that usually prostate cancer does not cause signs or symptoms for many years after the disease starts to develop.

Despite the fact that prostate cancer has no definitive set of symptoms, all of the following have been identified by the National Cancer Institute as possible indicators of prostate cancer -- and many other clinical problems:

• Frequent urination (especially at night)
  
• Inability to urinate
  
• Trouble starting to urinate or trouble holding back urination
  
• Pain during ejaculation
  
• A weak or interrupted urine flow
  
• Pain or a burning feeling during urination
  
• Blood in the semen or in the urine
  
• Frequent pain or stiffness in the lower back, hips, or upper thighs.

Since all these symptoms may be caused not only by prostate cancer, but also by a number of other disorders (and not just other disorders of the prostate), it would be wise to talk to your family doctor if you or someone else in your family is having one or more of these problems on a regular basis. Only a properly trained, experienced physician will be able to tell whether these symptoms are, in fact, associated with the possibility of prostate cancer.

Detection and Diagnosis of Prostate Cancer

Introduction

The initial detection of signs that you may have prostate cancer is now most commonly the result of some regular form of check-up carried out by your primary care physician which may include a digital rectal examination (DRE) or a prostate specific antigen (PSA) test. The most common symptom which may make a man go to either his primary care physician or a urologist, is some form of problem with normal urination or sexual abnormality such as incipient impotence. The only way to diagnose prostate cancer in a man without symptoms is through a prostate biopsy. A urologist  sample the gland and a pathologist identifies the presence or absence of malignancy in the specimens. No other clinical test can provide an absolute diagnosis of prostate cancer in asymptomatic men except in the case of a  positive bone scan in the presence of bone pain and an elevated PSA

Indications for a Prostate Biopsy

These are a few basic reasons why your urologist would recommend a prostate biopsy:

	There is a significant change in your PSA level from year to year (more than 0.75 ng/ml) even after a course of antibiotics.
	You have a PSA level higher than 4.0 ng/ml
	You have a PSA level higher than 2.5 ng/ml at age 40
	You have a suspicious-feeling prostate on digital rectal examination.

Expert urologists now recommend that if any one of these indicators is present, you should have a biopsy even if your ultrasound evaluation is normal.

Prostate Biopsy Procedure

Biopsies of the prostate are normally carried out under ultrasound guidance by taking several samples of tissue from the prostate using a method called systematic sextant biopsy.

The urologist will order a prep a enema prior to carrying out the biopsy, and while there is no need for anesthesia you can ask for medication to ease the stress of the procedure. You will almost certainly be given an antibiotic in order to prevent any possible infection. You will also be asked to stop drugs such as aspirin for one or two weeks prior the scheduled biopsy date in order to minimize the risk of bleeding problems. Be sure to tell the doctor if you are on blood thinning medications.

In carrying out the actual biopsy, using transrectal ultrasound (TRUS) to guide the precise placement of the biopsy needle, the urologist will take six or more samples of tissue from the prostate and then send them to the pathologist for examination. The precise number of samples taken will depend upon what the urologist is able to see using the ultrasound machine. Normally, he or she would expect to take six evenly spaced specimens from different areas of the prostate (called a systematic sextant biopsy), and then additional specimens from any areas which look suspicious according to the ultrasound. In this way the urologist will maximize the chance of finding prostate cancer tissue if it is there in the prostate.

The urologist will send the biopsy specimens (often called "cores") to a pathologist for evaluation. The pathologist will then study these specimens carefully under a microscope, and will send a report back to the urologist which usually includes the following information:

	Which specimens contain prostate cancer and which do not
	The percentage of prostate cancer in the specimens positive for cancer
	The grade or grades of the prostate cancer in each specimen which shows signs of cancer.
	The total Gleason Score of the biopsy material.

This information is designed to help the urologist and the patient make a treatment decision. Because of the subjective nature of the biopsy grading it is sensible to obtain a second opinion from a pathologist specializing in prostate cancer.

Introduction

Medicine is full of acronyms. In fact there are even books which list medical acronyms so that you can look them up if you don't know what a particular acronym stands for! Acronyms are also common in the diagnosis and treatment of prostate cancer, so we thought it would be a good idea if we listed some of the most common ones here and gave a brief explanation. If you or one of your family or friends has or thinks he might have prostate cancer, chances are you will hear most of these acronyms in the future.

PSA

PSA stands for prostate specific antigen. The PSA test or prostate specific antigen test has revolutionized the detection of prostate cancer and monitoring of the effects of treatment since the mid 1980s. On its own, it is very probably responsible for the accurate diagnosis of prostate cancer in millions of men worldwide. Equally, it is probably the single most important factor in the unnecessary treatment of some men who might well have died of old age or many other reasons without the slightest reason to suspect that prostate cancer was anything for them to worry about -- which they did but shouldn't have!

The PSA test is a classic case of science providing us with information which we do not always know how to use to our best advantage. If you have to talk to your doctor about the results of PSA tests (your own or a family member's), be sure that you listen very carefully, ask a lot of questions, and do your very best to be patient with the doctor because it may be impossible -- or at least very hard -- for him or her to give you the answers you are looking for!

A PSA test tells your doctor the level of prostate specific antigen in your blood, just like a cholesterol test can tell your doctor the levels of cholesterol in your blood. Using the most common type of PSA test currently available in the USA, the average, normal, healthy, 50-year-old male is generally believed to have a PSA of less than 4.0 nanograms per milliliter of blood (4.0 ng/ml). There are a number of reasons why any one person's PSA could be higher than that. Prostate cancer is just one of those reasons. What the results of PSA tests do NOT do is tell you and your doctor how to act on the results of those tests!

PSA II

The PSA II or free/total PSA test is a new type of PSA test that can be used to help the physician discriminate between patients with relatively low standard PSA levels (say 2.5-10.0 ng/ml) who are at greatest risk of having prostate cancer (and therefore need a prostate biopsy), and those patients who are more likely to have beign prostatic hyperplasia (BPH).

Basically, the PSA II test measures the amount of PSA that is free in the blood stream, and compares it to the total free and bound PSA found in the blood (including the PSA that is "bound" to other products in the blood). The lower the ratio of free to total PSA, the higher the likelihood that the patient has prostate cancer as opposed to benign prostatic hyperplasia. Patients with a very low ratio (e.g., 0.05 or 5%) are at very high risk for prostate cancer.

The PSA II test allows the urologist to give a non-invasive test to patients with PSA values between 2.5 and 10.0 ng/ml who may be at risk for prostate cancer and to determine the degree of that risk before deciding whether to give the patient a biopsy.

PSAV

PSAV stands for PSA velocity, which is best described as the speed at which a series of PSA values increases (or decreases) in value. Some physicians believe that use of PSA velocity allows them to tell more about the way prostate cancer may be developing in individual patients. Let's say it is January 1995 and Harry, who is 68 years old and otherwise in excellent health, has a PSA test. The doctor tells him his PSA value is 4.2 ng/ml, and it's nothing to worry about but the doctor suggests to Harry that he comes back for another test a year later. In January 1996, Harry comes back for his next test. The value is 4.4 ng/ml. Again, the doctor says its nothing to worry about but to come again the next year. In January 1997, back comes Harry for the third time. This year the value is 4.6 ng/ml. Each year for two years, Harry's PSA value has increased by 0.2 ng/ml. We say that his PSA velocity is 0.2 nanograms per milliliter of blood per year (0.2 ng/ml/yr).

PSAD

PSAD stands for PSA density. PSA density is a measure of the concentration of PSA in a man's prostate. It depends upon the value of his PSA and the size of his prostate. Again, like PSA velocity, some specialists believe that PSA density can be useful in telling how to treat individual patients.

Let's say that Bill has a PSA value of 5.1 ng/ml. When his physician measures the volume of Bill's prostate, the doctor calculates that it is about 50 cubic centimeters (50 cc), which is about the same size as a large walnut. Then Bill's PSA density is 5.1 divided by 50 = 0.102 ng/ml/cc.

PSADT

PSADT stands for PSA doubling time. This is an important measurement of progression. It simply measures the time that it takes for PSA to double its value. The best way to calculate  PSADT is to plot at least three PSA values taken at least a month apart on semi-log paper. The slope of the line plotted with at least three value provides the doubling time. Very slow growing tumors cold have a four or more years PSA doubling time. Fast growing tumors can double in a matter of weeks.

DRE

DRE stands for digital rectal examination. In a digital rectal examination the physician inserts his finger into the rectum in order to be able to feel the size, shape, and texture of the prostate and other nearby organs. In classical medicine, before the availability of the modern wonders of science, the digital rectal examination was the only way a physician could tell if there was a possible disorder of the prostate, short of cutting you open and looking.

Over the years, highly experienced physicians became relatively good at using digital rectal examinations to tell whether patients had clinically important prostate disorders. However, DRE is a "subjective" technique. In other words, the ability to use a DRE well is all about the skill of the physician and his or her ability to interpret what he or she feels.

The problem with using DREs to make decisions about what to do with particular patients is that two different, experienced physicians may think that they feel quite different things when they carry out a DRE on the same patient. Neither of these physicians is necessarily right or wrong in what they think. They cannot see what they are feeling and they are doing their best to make wise decisions. Imagine trying to do something similar. You are blindfolded and wearing a pair of plastic gloves. Someone places two pool balls in your hands and tells you the red one has a tiny crack in it. Now, which one is the red ball and which is the other ball? Easy, huh? Well it would be if the crack was big enough, but when it's a really tiny crack?

RTPCR

RTPCR stands for reverse transcriptase polymerase chain reaction. RTPCR testing is only a few years old. It can be used to detect minute amounts of one of the nucleic acids which makes prostate specific antigen. Theoretically, RTPCR is so sensitive that it is capable of finding one piece of PSA nucleic acid in a blood sample containing a million other pieces of nucleic acid of comparable size. This would be wonderful if we could be sure that finding one such piece of nucleic acid absolutely always meant that prostate cancer had escaped from the prostate and was "metastasizing" to other sites in the body. Unfortunately, that isn't the case. A positive reaction to an RTPCR test can occur for all sorts of reasons in a patient who still has clinical prostate cancer confined to the prostate. Life just isn't as simple as we'd like it to be.

RTPCR testing is at best an investigational technique. It is not yet approved or recommended for use in normal clinical practice. However, if you or a friend or relation are involved in a clinical trial of a new form of prostate therapy, RTPCR testing may be a form of testing that is used in that trial as doctors and scientists try to learn more about prostate cancer and which patients most need to be treated with what types of therapy. There is little doubt we will all continue to hear more about RTPCR testing in the future. However, whether it will ever be possible to use RTPCR testing as a diagnostic or prognostic test is open to considerable question.

PAP

PAP stands for prostatic acid phosphatase. Just as RTPCR is a very new and experimental test for prostate cancer outside of the prostate, PAP is a much older test which was in very common use before PSA testing became possible. Today, PAP tests are relatively rare. However, there are still reasons why doctors may think a PAP test is valuable for a specific patient. If your doctor tells you you need a PAP test, you should ask ask him or her to explain what the PAP test may be able to tell that can't be learnt from PSA testing or other forms of available test. The commonest reason for use of a PAP test is that it may help to identify a patient with metastatic prostate cancer.

TRUS

TRUS stands for transrectal ultrasound. TRUS is most commonly used to do two things. The first is to guide the doctor when he or she is carrying out a technique known as a biopsy of the prostate, when small samples of tissue are taken from the prostate in order to make a proper diagnosis. The second is in order to try and establish the volume of the prostate, which is important if the doctor wants to know the PSA density.Specialists may also use TRUS for other reasons in some prostate cancer patients or patients suspected of prostate cancer. However, it has now been generally agreed that TRUS has no particular value in identifying patients with prostate cancer when used on its own or in combination with such techniques as DRE and PSA

Clinical staging relates to the findings of a digital rectal examination or DRE. It provides information as to the size of the tumor and whether the disease is contained or it has spread out of the prostate. Since the digital examination is limited to the peripheral zone of the prostate,  the information derived is the  least clinically reliable as compared to Gleason Score or PSA.  While some physicians are more skilled than others in performing the DRE., the actual tumor location and the individual's anatomy are important factors in the final clinical staging of a patient.

The T Staging System

	T1 disease clinically unapparent that is not palpable on DRE T1a Tumor is an incidental histologic finding and is seen in 5% or less of resected tissue T1b Tumor is an incidental histologic finding and is seen in more than 5% of resected tissue T1c Tumor identified by needle biopsy because of an elevated PSA
	T2 Tumor that is palpable and confined within the prostate T2a Tumor involves half a lobe or less T2b Tumor involves more than a half a lobe, but not both lobes T2c Tumor involves both lobes
	T3 Tumor extends through the prostatic capsule T3a Unilateral extracapsular extension T3b Bilateral extracapsular extension T3c Tumor invades seminal vesicle(s)
	T4 Tumor is fixed or invades adjacent structure other than seminal vesicles T4a Tumor invades bladder neck, or external sphincter, or rectum T4b Tumor invades levator muscles and/or is fixed to pelvic wall