About Prostate Cancer
What do I need to know about prostate cancer?
Question 39:
What is PSA?
Answer:
PSA (Prostate Specific Antigen) is an enzyme that is produced only by prostate cells, both normal and cancer cells, and is secreted into the semen to keep it liquefied. Additionally, a small amount of PSA is continually leaked into the blood stream by prostate cells. The PSA in the blood is measured by the PSA test.
Question 40:
How much PSA is produced by a normal prostate?
Answer:
The amount of PSA is generally related to prostate size and the prostate typically enlarges as men age. Overall, a PSA level of up to 4.0 ng/ml is considered normal for men greater than age 60 and 2.5 ng/ml is the upper normal range for men age 60 or less. These are rough guidelines, for some younger men will have enlarged prostates and some older men will have normal sized glands and prostate cancer can occur with PSA less than 2.5 ng/ml.
Question 41:
How much PSA is produced by prostate cancer?
Answer:
Prostate cancer cells leak a lot more PSA into the blood stream. On average, one prostate cancer cell will produce ten times more PSA than one normal prostate cell. Consequently, a man with prostate cancer will usually, but not always, have a PSA level above 4.0 ng/ml or 2.5 ng/ml for men aged 60 or less.
Question 42:
What is the average PSA level of men with prostate cancer?
Answer:
The average PSA level is 7.2 ng/ml, but there is a wide variation. We have treated men for prostate cancer with a PSA as high as 430 ng/ml and as low as 0.3 ng/ml.
Question 43:
If a man has prostate cancer, does the amount of PSA measure how much cancer he has?
Answer:
Question 44:
Does the PSA level always measure the amount of prostate cancer?
Answer:
Unfortunately, no. Some prostate cancers will not make very much PSA and are called Low PSA Producing Cancers. Often, these are men with high Gleason scores indicating more aggressive cancers. Low PSA producing cancers can be advanced and fool doctors. We discover low PSA producing cancers based on digital rectal examination through palpation of a cancer. Additionally, these cancers can be discovered by measuring PSA velocity. Even though a man’s PSA may be within normal limits, if the PSA is progressively rising, for example 0.5 ng/ml to 1.0 ng/ml to 1.8 ng/ml in less than a year, this rise should alert doctors to the possibly of prostate cancer.
Question 45:
Is PSA made only by prostate cancer cells in the prostate or normal prostate cells?
Answer:
No. A lot of men or their wives think this, but that is not correct. Prostate cancer cells any place in a man’s body produce PSA whether bone, lung, prostate, lymph nodes or where ever. A prostate cancer cell in a man’s left shoulder makes the same amount of PSA as one in his prostate. A PSA test checks for prostate cancer throughout a man’s body, but PSA gives no information about where the cancer cells are located.
Question 46:
Do all men with a PSA above normal levels have prostate cancer?
Answer:
No. Another cause for PSA elevation is a prostate disease called benign prostate hyperplasia (BPH) or enlarged prostate. BPH is the most common prostate disease in men and is present in half of men aged 60 or older. BPH, not cancer, is the reason men have difficulty with urination such as a weak, slow urine stream because the urethra tube is squeezed by the enlarged prostate. Inflammation of the prostate, called prostatitis can also cause PSA elevation above normal.
Question 47:
What is clinical cancer stage?
Answer:
Clinical stage of cancer is determined by physical examination of the prostate called a DRE (digital rectal examination). The eight different stages are listed in the table below:
Question 48:
How accurate is staging of prostate cancer?
Answer:
Often inaccurate. In fact, compared to the PSA and Gleason score, staging of prostate cancer is the most inaccurate measure of the extent of your cancer. The biggest area of inaccuracy concerns stages T1 and T2 disease, the stages that most men have. In reality, one-third to one-half or more of men with stage T1 or T2 prostate cancer actually have stage T3 prostate cancer, cancer outside the prostate, due to microscopic capsule penetration of cancer cells, which cannot be detected before treatment.
Question 49:
I have some understanding about the prostate biopsy pathology report, PSA, clinical stage and calculation of a 10-year ICR from a computerized database. But, what does the normal prostate gland do and where is it located?
Answer:
The prostate is located behind the pubic bones in a man’s pelvis and is sandwiched between the bladder on top and the rectum underneath. A normal sized prostate is about the size of a walnut. Similar to the shell around an egg, a capsule covers and contains the prostate except at the apex (bottom). The tube called the urethra which empties the bladder runs through the middle of the prostate and out the penis for urination. Very small tubes, the ejaculatory ducts, run from each testicle into the prostate and empty into the urethra in the middle of the gland. Two sex nerves for erection of the penis are adjacent to both the right and left side of the prostate. About two-thirds of the prostate are normal prostate cells and the remaining part is the urethra, muscles that act like valves to prevent leakage of urination, fibrous tissue that holds the prostate together, blood vessels and the ejaculatory ducts. The purpose of normal prostate cells is to produce seminal fluid, which when mixed with the sperm from the testicles, is called semen – the white-colored fluid seen upon ejaculation. Prostate cells also secrete various proteins into the blood stream, one of which is called Prostate Specific Antigen or PSA. 
Question 50:
What causes prostate cancer?
Answer:
We do not know. We know that the chance of developing prostate cancer increases as a man ages but is rare below the age of forty. Cause is related to our environment and diet. Men from Western industrialized countries have a higher incidence of prostate cancer than men from Asia. African-American men also have a higher incidence of more aggressive prostate cancer than Caucasian men. Additionally, the incidence of prostate cancer is greatly increased in men who have a family history of this disease such as their father, brother, uncles or grandfather having had prostate cancer.
Question 51:
How does prostate cancer work?
Answer:
Cancer cell leakage (microscopic capsule penetration) can occur in four basic ways. One way is through perineural invasion which means cancer cells using the perineural space as a "tunnel" through the capsule to escape the prostate. Another way is through development of cancer adjacent to the capsule with the cancer simply destroying the capsule (eating a hole in the capsule) and leaking out. The third method of microscopic capsule penetration occurs at the bottom (apex) of the prostate because the prostate capsule thins out and does not exist in this location which makes it very easy for cancer cells to escape the prostate in this area. The fourth method is by invasion into the seminal vesicles which are connected to the top (base) of the prostate. The chance of microscopic capsule penetration is related to many clinical factors including higher Gleason score, location of cancer at the apex, increase in percentage of Gleason grade 4 or 5, increasing number of needle cores showing cancer, increasing amounts of cancer in needles, perineural invasion and increasing levels of PSA. Depending upon the treatment method, prostate cancer can still be cured in either Step 1 or Step 2. If left alone, Step 3 will eventually occur. Step 3 means spread of prostate cancer (metastasis) beyond the area of the prostate such as into lymph nodes, bones, lungs or any place else in the body. Step 3 is incurable prostate cancer.
Question 52:
Please explain more about microscopic capsule penetration (cancer cell leakage).
Answer:
Microscopic capsule penetration is one of the most important concepts to understand about prostate cancer and has been extensively studied at Johns Hopkins University.35 Prior to surgery (radical prostatectomy) 5,730 men between year 2000 and 2005 had a prostate biopsy, PSA and were staged either T1 or T2 based on DRE. Then surgical removal of the prostate was performed on these men and the whole prostate given to the pathologist for microscopic examination to determine, among other things, if cancer cells had leaked through the capsule and were outside the prostate (microscopic capsule penetration), which means that men were really stage T3. The chance of cancer cell leakage was then correlated with Gleason score, stage and PSA in the Partin tables. The chance of microscopic capsule penetration ranged from 7% to 89%.
Microscopic capsule penetration (cancer cell leakage) is extremely important to understand because it will determine your chance of cure. However, it is impossible to know whether or not you have microscopic capsule penetration before any treatment. Cancer cell leakage through the capsule cannot be detected before treatment because the DRE, prostate biopsies, CAT scans or MRI scans cannot detect cancer that can only be found with a microscope.
Question 53:
Please give more information about microscopic capsule penetration.
Answer:
PSA is our best measurement of the amount of cancer in a man. We obtain a PSA test on men before treatment for prostate cancer and then measure PSA every six months after treatment. As noted earlier, to be cured of prostate cancer by any of the 10 different treatment methods your PSA must fall to an undetectable level (PSA 0.2 ng/ml or lower) and remain at PSA 0.2 ng/ml or lower forever.
Question 54:
What is the connection between PSA 0.2 ng/ml and microscopic capsule penetration?
Answer:
The best way to understand both is to discuss treatment with radical prostatectomy, surgical removal of the prostate, which is where we first learned about both of these issues. Let’s assume you have 100 prostate cancer cells and all 100 are contained by the capsule inside the prostate and you have no capsule penetration (Step 1 in cancer cell growth). If you had a radical prostatectomy, the entire prostate would be cut out. Consequently, all your normal prostate cells as well as all of the 100 prostate cancer cells would be removed. Because you would no longer have any prostate cells in your body to make PSA, your PSA would then fall to an undetectable level (PSA 0.2 ng/ml). PSA 0.2 ng/ml after your radical prostatectomy would mean that you had been potentially cured of prostate cancer. 
Question 55:
If my PSA were to be 0.2 ng/ml or lower after radical prostatectomy, why do you say “potentially cured” instead of cured?
Answer:
Because you must not only achieve PSA 0.2 ng/ml, but your PSA must stay undetectable forever. To illustrate, let’s assume you have 100 prostate cancer cells and were stage T1c before radical prostatectomy which means as far as we know before your surgery all your 100 prostate cancer cells were contained inside the prostate by the capsule. However, since microscopic capsule penetration CANNOT be detected before any treatment, including surgery, let’s really assume that of your 100 prostate cancer cells, actually 95 are inside the prostate and 5 cancer cells penetrated the capsule and leaked into the area surrounding the prostate – rectum, bladder, sex nerves or muscles that control urination. With a radical prostatectomy, your prostate would be removed, which means all normal prostate cells and the 95 cancer cells inside the prostate. Some of the five cancer cells that leaked out of the prostate would also be removed, but most of the time not all of these cancer cells can be cut out since they are in your normal adjacent organs. You are not going to cut out your rectum or bladder, nor do you want to cut out the muscles that control urination or the sex nerves where microscopic cancer cells can leak through the perineural space. Let’s assume that four of the five cancer cells that leaked out of the prostate are removed at surgery, but one cancer cell was left behind. This one cancer cell would not make enough PSA to be detectable. Consequently, your PSA after surgery would be PSA 0.2 ng/ml. But you would not be cured.
Question 56:
What would happen with the one cancer cell left behind?
Answer:
Over time, this one cancer cell would multiply and make more cancer cells. Eventually, the increasing number of cancer cells would produce enough PSA to make your PSA level rise above 0.2 ng/ml.1 Any rise in PSA above 0.2 ng/ml after radical prostatectomy guarantees that you were not cured and your cancer is regrowing because the only other cells that make PSA are normal prostate cells, but they were all removed at surgery. 
Question 57:
Is that what you mean when you say to be cured of prostate cancer my PSA has to stay at 0.2 ng/ml forever?
Answer:
Yes. Remember, there are two PSA steps to cure: 1) you must not only achieve PSA 0.2 ng/ml, but 2) you must stay at 0.2 ng/ml forever. From a practical standpoint, almost all prostate cancer that is going to grow back will do so within 10 years of treatment. See Question 6, in the Cure Rate section. 
Question 58:
What would it mean if I had surgery and my PSA nadir was above 0.2 ng/ml, for example 0.6 ng/ml?
Answer:
After radical prostatectomy, a PSA above 0.2 ng/ml guarantees that you have not been cured. Let’s revisit our example of 100 cancer cells. This time let’s assume 90 cancer cells are inside the prostate and 10 are microscopic capsule penetration cancer cells. With surgery, the 90 cancer cells in the prostate would be removed, plus all normal prostate cells. And let’s assume seven out of the 10 leaked cancer cells are removed, for a total of 97 of the 100 cancer cells (three cancer cells were left behind). Let’s also assume these three cancer cells produce a total PSA of 0.6 ng/ml. Therefore, when you remove the normal prostate and the 97 cancer cells, your PSA would fall, but the three leaked cancer cells left would produce 0.6 ng/ml. You did not achieve PSA 0.2 ng/ml which means you still have cancer.
Question 59:
Why is it important that I learn about PSA 0.2 ng/ml?
Answer:
Because an understanding of PSA 0.2 ng/ml is the key to understanding how prostate cancer works. In fact, the cornerstone to understanding treatment and cure of prostate cancer is this: after any treatment, your PSA must fall to PSA 0.2 ng/ml or lower and remain at 0.2 ng/ml forever. A PSA of 0.3 ng/ml or more, or a later rise above 0.2 ng/ml, means you have not been cured. It’s as simple as that.
