Curing Prostate Cancer:
A few weeks or months ago you may not have known much about prostate cancer – or only heard anecdotal stories from friends or family. Suddenly you now need a crash course in this disease and all that it entails. In this section you will learn:
- What is a normal prostate and how does prostate cancer work
- The relationship of cure, PSA, and microscopic capsule penetration
Congratulate yourself in taking charge of your own health. You are undertaking the challenge or your life—beating cancer. Let the team at Radiotherapy Clinics of Georgia work with you on your journey. Contact us through the patient contact center.
–The Normal Prostate and How Prostate Cancer Works–
Tell me about a normal prostate gland. (See Figure 3.)
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 (see Figure 3). A normal-sized prostate is about the size of a walnut. Similar to a 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 of 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 sides 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 visible upon ejaculation. Prostate cells also secrete various proteins into the blood stream, one of which is called Prostate Specific Antigen (PSA).
What causes prostate cancer?
No one really knows. We do know, however, that the chance of developing prostate cancer increases as a man ages and that it is rare in men younger than 40 years old. Probable cause is related to a man’s environment and diet. For example, men from Western industrialized countries have a higher incidence of prostate cancer than men from Asia. African-American men have a higher incidence of more aggressive prostate cancer than Caucasian men. Additionally, the incidence of prostate cancer is significantly increased in men who have a family history of this disease, meaning their father, brother, uncles or grandfather had prostate cancer.
How does prostate cancer work? (See Figure 4.)
There are three basic steps in the growth of prostate cancer. The first step is the development of prostate cancer and growth inside the prostate gland. For reasons we do not understand, one or more normal prostate cells transform into prostate cancer cells and begin to grow. The hallmark of any cancer is cancer cell growth – reproduction, or making more cancer cells. For a long period of time, prostate cancer grows only inside the prostate and is contained by the capsule that surrounds the prostate. Eventually, the second step occurs – cancer cell leakage through the capsule outside the prostate, which is officially called microscopic capsule penetration. 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. The third step is the spread of prostate cancer (metastasis) beyond the area of the prostate such as lymph nodes, bones, lungs or any other place in the body. Step 3 is incurable prostate cancer.
Please explain more about microscopic capsule penetration – step 2 of cancer growth. (See Figure 5.)
Microscopic capsule penetration is one of the most important concepts to understand about prostate cancer and has been extensively studied at Johns Hopkins University.29 Prior to surgery (radical prostatectomy), between the years 2000 and 2005, a group of 5,730 men had a prostate biopsy, PSA and were staged either T1 or T2 based on DRE (digital rectal exam). Surgical removal of the prostate was performed on these men, and the entire prostate was 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, 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.29 The chance of microscopic capsule penetration ranged from 7% to 89%. Microscopic capsule penetration is 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.
How do cancer cells leak through the capsule and outside the prostate? (See Figure 6.)
Cancer cell leakage can occur in four basic ways. The first 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. A second way is through perineural invasion, which means cancer cells travel along branches of the sex nerve and “tunnel” through the capsule to escape the prostate (see Question 22). 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 easy for cancer cells to escape the prostate in this area. Check your pathology report to see if you have cancer at the apex because this is the most common place for positive surgical margins, meaning cancer cells cut across and left behind after radical prostatectomy. (See Questions 86, 87 and 96). The fourth method is invasion into the seminal vesicles, which are attached to the top of the prostate.
–Cure: An Undetectable PSA (PSA 0.2 ng/ml) and Microscopic Capsule Penetration–
How do you determine if someone is cured of prostate cancer? (See Figure 7.)
To be cured of prostate cancer, any treatment must destroy all the prostate cancer cells, which is possible if your cancer is located only inside the prostate contained by the capsule (Step 1) or if you have microscopic capsule penetration through the capsule (Step 2). We also want to destroy all the normal prostate cells to prevent you from getting another cancer. Cure, both destruction of all your prostate cancer cells and normal prostate cells, is determined by using the PSA test. As mentioned, the PSA test is used to find prostate cancer. An equally important use of the PSA test is to find out if men are cured of prostate cancer. To be cured of prostate cancer, your PSA must fall to an undetectable level after treatment and remain there forever.
What number is an undetectable PSA? (See Figure 7.)
An undetectable PSA is PSA 0.2 ng/ml or lower, which essentially means a “zero” PSA. PSA 0.2 ng/ml means undetectable because PSA tests are unreliable below 0.2 ng/ml. Thus, to be cured of prostate cancer using any treatment, your PSA must fall to 0.2 ng/ml or lower and remain at 0.2 ng/ml or lower forever. This PSA definition is based on medical studies of the PSA found in men cured of prostate cancer after radical prostatectomy and ProstRcision.1,5,6
What is the connection between PSA 0.2 ng/ml and cancer localized in the prostate? (See Figure 8.)
The best way to understand this connection is to discuss treatment with radical prostatectomy or 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, all 100 are contained by the capsule inside the prostate and you have no microscopic capsule penetration (this is 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 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 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.
If my PSA were to be 0.2 ng/ml or lower after radical prostatectomy, why am I only considered “potentially cured” instead of cured? (See Figure 9.)
This is because you must not only achieve PSA 0.2 ng/ml, but your PSA must stay undetectable forever. To illustrate this point, let’s assume you have 100 prostate cancer cells and were stage T1c before radical prostatectomy, which means, as far as we know, all your 100 prostate cancer cells were contained inside the prostate by the capsule prior to your surgery. However, since microscopic capsule penetration CANNOT be detected before any treatment, including surgery, let’s realistically assume that of your 100 prostate cancer cells, 95 are actually inside the prostate and five cancer cells penetrated the capsule and leaked into the area surrounding the prostate, which includes the rectum, bladder, sex nerves and muscles that control urination. With a radical prostatectomy, your prostate would be removed along with 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 typically not all of these cancer cells can be cut out since they are around your normal adjacent organs. Doctors are not going to cut out your rectum or bladder, nor do they 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 single cancer cell would not make enough PSA to be detectable. Consequently, your PSA after surgery would be PSA 0.2 ng/ml; however, you still have one cancer cell and would not be cured.
What would happen with the one cancer cell left behind? (See Figure 9.)
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. Your cancer is regrowing because the only other cells that make PSA are normal prostate cells, but they were all removed during surgery.
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?
Yes. Remember, there are two PSA steps to cure: 1) you must achieve PSA 0.2 ng/ml, 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.
What would it mean if I had surgery and my PSA nadir was above 0.2 ng/ml, for example 0.6 ng/ml? (See Figure 10.)
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. Now, 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 that 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. In this instance, you did not achieve PSA 0.2 ng/ml, which means you still have cancer
Why is it important that I learn about PSA 0.2 ng/ml?
Because 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.