An IntroductionTo Prostate Cancer
(Everything you will ever need to know)
Written by Ron Schneider Reg. Ph. and Prostate Cancer Survivor
Disclaimer—These introductory articles were written by one of the participants of the Prostate Forum of Orange County, Retired Pharmacist Ron Schneider. While I am not an expert on prostate cancer, I have some medical background as well as extensive pharmaceutical knowledge. I have had this disease since 2015 and I now have advanced metastatic prostate cancer. I also have much personal knowledge and experience on the vast majority of the drugs, scans, and treatments discussed in this packet.
Welcome and you are not alone. If you have received this information at the Prostate Forum of Orange County, look around the room. There are many of us here that have fought this disease and won and some of us that are still fighting the disease. We look no different from you. The goal is to supply you with as much information as possible so you can make informed decisions as well as try to answer all your questions. You will gain experience and knowledge at each of these meetings listening to your fellow prostate cancer participants and hearing their stories. Knowledge is everything. You must become your own advocate for your disease. Your decision about who will manage (physicians) your prostate cancer is one of the most critically important decisions you will ever make (read again). Prostate cancer (PCa) is totally silent until it metastasizes, after which it is too late for a cure. A prostate cancer cell is just a prostate gland cell that is genetically altered. And a prostate cancer tumor is a mutation factory for more bad cells. We look forward to seeing you at each of the monthly meetings.
Listed below are the 9 main topics that will be presented in this packet. This is just an overview and you can learn much, much more about your disease and its treatments from various books and the internet. I highly recommend the book “A Primer on Prostate Cancer” (even though this book was written in 2004, much of it is still true today) and Dr. Mark Scholz’s new book, “The Key to Prostate Cancer”.
Testosterone—This androgen hormone plays a very important role in the treatment of your prostate cancer. After reading about this hormone you will have a much better understanding of this “male sex hormone” and why it is so important.
The 3 Different Types of Prostate Cancer Patients—which one are you?
Tests, Procedures, and Equipment used in Diagnosing Prostate Cancer—First you must determine where the cancer is and how advanced it is. Your goal is to determine if the cancer is still only in the prostate. Cancer that has escaped (metastasized) from the prostate gland is treated much more differently and aggressively than organ confined prostate cancer (OCPC).
Determining the Severity of your Cancer—this table will usually show the severity of your disease.
Treatment Options for Prostate Cancer—There is never a one size fit all treatment plan. Each treatment plan is tailored to the individual patient’s cancer. Please review your multiple options carefully.
Drug Treatments for Prostate Cancer—Every patient will be on some of these drugs. And advance cancer patients will be on most if not all of these drugs at some point during their treatment. And new drugs are always on the horizon.
A Layman’s Explanation of Prostate Cancer Progression—Do you have a fireplace in your house?
Insurance—The vast majority of us over 65 have Medicare and a supplement. After you have read this section about the two most popular supplemental insurance plans, please access the internet to give you much more information regarding these two main supplemental health plans—HMO vs. PPO.
Financial Assistance—Here I have listed many foundations and pharmaceutical companies that can supply financial assistance for some of the new very, very expensive drugs.
What is Testosterone and Why is it so Important?
Testosterone is an androgen hormone found mostly in men (very little in women). It is referred to as the “male sex hormone” and plays a vital role in sperm production. When you were young, you felt indestructible. You thought you would live forever. Your testosterone levels could have been as high as 1000ng/dl or more. As men age, most men’s testosterone production decreases each year. The average is about 100ng/dl of less testosterone production every 10 years. So, by the time you reach old age (late 60’s or 70’s), your testosterone levels are usually well below 500ng/dl. Remember when you had all that energy when you were young? And your libido used to be sky high also. So where does testosterone come from? It comes from 3 different sources:
The Testicles—This is by far where most of the testosterone production occurs.
The Adrenal Glands—These are 2 small glands located above the kidneys in the abdominal cavity that produce hormones that can be converted into testosterone (only about 5-10%).
The Cancer Cells—Smart diabolical little buggers aren’t they! They can actually produce their own testosterone which feeds their growth.
Now why is testosterone so important in treating cancer? Because as much as we men love this hormone and how it makes us feel, cancer cells love it even more. It becomes a “feeder” or “nutrient” to the cancer cells. Deprived of testosterone, prostate cancer cells are unable to replicate. They eventually die. This is why many of the therapies discussed in the following pages to treat prostate cancer rely heavily on reducing this male hormone. In some advance cases, your physician may want to get you all the way down to castrate (chemical orchiectomy) levels of 20ng/dl or less. Low levels of testosterone in the body can cause the following side effects:
Decreased sex drive (libido) and penile shrinkage
Less energy—fatigue/very tired—sometimes helped by Vitamin B12 injections
Emotional instability--moodiness and feeling of depression and low self-esteem
Weight gain & “pot belly”
Muscle atrophy (loss of muscle mass)
Thinner/weaker bones (osteoporosis)
Poor memory, foggy thinking, disorientation, & confusion
Breast tenderness & growth (gynecomastia)
Hot flashes/Night sweats –exasperated by heat, spicy foods, hot drinks, stress, & exercise. Can be helped by some drugs—Depo-Provera Inj, Estrogen patches, Neurontin, Pueraria root? etc.
Most of these side effects are tolerable but some are not so tolerable. And there are other therapies (both drug and others) that can help manage many of these side effects. As you experience some of these side effects, remember your physician(s) are trying to kill your cancer. This is not an easy job. Most of the drug therapy discussed on the following pages center on reducing testosterone production (cancer feeder). So why so many drugs? The main two reasons for so many drugs are (1) these drugs each work differently and (2) cancer cells get “smart” over time and they are able to learn how to defend themselves against these agents. So, when the old drug stops working and a new agent is added these cancer cells must learn all over again on how to defend themselves.
The 3 Types of Prostate Cancer Patients
Before you undergo any treatment plan for your prostate cancer, you must determine where your prostate cancer is located. Low grade disease is treated much differently than high grade disease. Which of the following types of prostate cancer patients best describes you?
Type I—Those patients who don’t know where their cancer is.
In order to treat your cancer correctly, the location of your prostate cancer must be determined first. Is it still only in the prostate? Is a tumor bulging out from the prostate? Or has your prostate cancer already spread. These questions must be answered first in order to develop the proper treatment plan for your disease. Work with your physician(s) to be sure all the various scans and tests have been done to determine exactly where your cancer is located.
Type ll—Patients who have determined their cancer is ONLY in the prostate.
If after all the various scans and tests have confirmed your cancer is only in your prostate, you and your physician(s) must work closely together to keep it confined. Or better yet eradicate this disease from your prostate using the various procedures and treatment plans discussed in this packet. If your prostate cancer disease is no longer in your body, it cannot progress to:
Type lll—Patients whose prostate cancer has spread (metastasized).
This is the worst kind of prostate cancer. It cannot be cured (for now). Prostate cancer usually first spreads to the bones. It can cause the following:
A decrease in red blood cell production (causing anemia—very tired)
A decrease in white blood cell production (affecting the immune system)
A decrease in platelet production (affecting clotting)
A decrease in bone strength (causing osteoporosis) and bone pain
And secondly prostate cancer can spread to the lymph nodes. The lymphatic system can carry cancer cells to various organs in the body.
Therefore, it is imperative if you are Type l (hopefully not) or Type ll patient that you and your physician(s) develop a treatment plan that does not allow you to become a Type lll patient. Not only will it affect your future health well-being, in the words of Dr. Andriole at one of the PCRI Conferences, it can also become a “financial toxicity”. What he means is it can become very expensive to treat metastatic prostate cancer disease. And the treatment goal of all Type lll prostate cancer patients is to keep your PSA as low as possible. Maintaining this aggressive treatment approach will insure the longest life expectancy.
Tests, Procedures, and Equipment used in Diagnosing Prostate Cancer
There are no quick solutions in the diagnosing of prostate cancer. And many times, it is difficult to distinguish between those cancers that can be cured and those which can be put into remission. Prostate cancer grows at a snail’s pace compared with other cancers. The reality is that over 90% of men who have prostate cancer live to a normal life expectancy. Listed below are some of the various physical, laboratory, pathology, and radiology tests and procedures you may have as you venture in and through the diagnosing of your disease. As mentioned earlier, your treatment options and quality of life are highly dependent on whether your disease is confined to the prostate (OCPC) or has already spread (metastasized).
Dr. Mark Scholz (one of the leading prostate cancer experts in the world) says the following about the testing for prostate cancer: “PSA testing saves lives and cannot be abandoned. If PSA is high, the first step is to confirm it by retesting. The second step is blood and urine testing. If these indicate a risk for high-grade disease, the next step is to scan with a multiparametric MRI and/or Color Doppler Ultrasound at a center of excellence. The last step, if the scans shows a suspicious lesion, is a targeted biopsy”. So, the old days of going to a urologist after getting an elevated PSA reading and getting a random biopsy and then having the prostate removed are gone. Medical advances and technology have come a long way in diagnosing and then treating your prostate cancer. You virtually should have all of the below tests (with the exception of the Random Biopsy) done to insure the proper diagnosing and treatment of your prostate cancer.
PSA (prostate-specific antigen) Test—This is the beginning blood test your family physician should have been giving you on a yearly exam basis. PSA is produced by tissue in the prostate (both cancerous and non-cancerous). Generally, any PSA number that has risen above 4.0ng/ml should be further evaluated. I say generally as everyone should know the “10 to One” rule. PSA averages 1/10th of the size of the prostate’s size in normal men. For Example, the average PSA for a 30cc prostate is 3, 5 for a 50cc prostate and 10 for a 100cc prostate. So, size does matter! Your PSA measurement is now your best friend.
Free PSA% (free PSA divided by the total PSA) Test—This is the next blood test that is given after the PSA blood test reaches above 4.0ng/ml. A low percentage number here indicates less free PSA antigen is in the blood and more is attached to something somewhere else. The lower the number generally indicates disease may be present and further evaluation is necessary. And a very low number may indicate the disease may not be organ confined (has metastasized).
PSA Velocity Test—If your PSA is rising indicated by multiple PSA readings, the velocity by which your PSA is rising can be calculated. Your physician will tell you what your PSA velocity is or you can calculate it yourself using the PSA Velocity Calculator on the internet. Generally, the faster the PSA numbers are rising, the more it is indicative of more advance disease.
DRE (digital rectal exam)—This is the first procedure the urologist or oncology specialist that your family physician referred you to will do. He will be feeling for size, ridges, lumps, or any other abnormalities. Unfortunately, the position of the prostate in the abdominal cavity does not allow for a complete exam of the prostate. And if your physician has short fingers and you are very tall, he may not be able to reach and examine much of the prostate.
Prostate Density Test—This is another tool your physician can use to determine the likelihood of prostate cancer. The physician calculates the volume of the prostate using an ultrasound machine (see internet for how to calculate). Then he takes your PSA reading and divides it by the calculated volume. This will give him the prostate density. Any number above 0.2 should be further evaluated.
Color Doppler Endorectal Ultrasound—Here is where a probe with a camera is inserted into the rectum to get a close up look at the prostate and determine whether any suspicious activity is occurring. Both the physician and patient see the image of the prostate on a monitor as the prostate is being scanned and evaluated.
Prostate MRI (magnetic resonance imaging) Machine—This machine provides a 3-dimensional image of the prostate. It has become the “gold standard” in the industry for imaging the prostate and determining if a tumor is present and if so if it still is confined to the prostate or has escaped. Version 3 Tesla (3T) is recommended and is the latest up-to-date machine. This machine will detect high-grade prostate cancer better than a random biopsy (see below) and is far less dangerous.
Random Prostate Biopsy—If the above procedures and tests have indicated the possibility of prostate cancer, a biopsy needs to be done to confirm. Here about 12 needles are inserted into the prostate and core samples are taken at systematic 5 region locations. The problem with this procedure is that considering the total displacement of the size of all the needles in relationship to the prostate size, only about 1-2% of the prostate is surveyed. And more problems are infection (sometimes hospitalization) and even a risk of impotence.
Targeted Prostate Biopsy—After a lesion is located within the prostate using the Prostate MRI 3T machine, usually only about 4 needles or less are inserted to take core samples from the suspicious area only. This test is usually much more accurate and much less invasive for the patient.
The Gleason Score—This has been the “gold standard” in the industry for determining if prostate cancer is present and the severity of the disease. Usually the results of these slides from the biopsies are sent to two different experts (these slide readings can be subjective) in the industry to be read and given a number. A number 6 is usually indicative of pre-cancer and a number 7 or above can continually be evaluated with active surveillance or have other treatments from mild to aggressive. See the internet for much more info on these scores.
Pi-RADS (Prostate Imaging Reporting and Data System) Score—This is a newer system that was developed in Europe to grade the 3T Prostate MRI image of the prostate. It too is based on a system of 1-5 like the Gleason Score but it has two levels. In Level I, each of the 4 parameters that shows up in an image is assigned a numerical value. In Level II, the values are added together. The nice thing about this system is you can get an idea of the severity of your cancer before a biopsy is even done. You can go on the internet to see the PI-RAD chart. While the PI-RADS system is useful in guiding decisions about biopsy, treatment planning, and follow-up steps, it is not a standalone diagnosis. If you have a prostate 3T MRI with a PI-RADS score the most important thing you can do now is have it analyzed by a qualified prostate MRI specialist.
Bone Density Scan—If ADT (androgen deprivation therapy) is a course of therapy, osteoporosis can be a result of this therapy. A bone density scan is done before ADT is started (this gives a base to evaluate future scans) and done again yearly while on this therapy. The QCT scan is preferred over the DEXA scan. If osteoporosis occurs, there are many treatment options.
Nuclear PET (positron emission tomography) Bone Scan—If your physician has suspected your prostate cancer has escaped (metastasized) from the prostate, these 2 radioactive isotopes (technetium-99 and Sodium Fluoride F-18) scans can determine if it has spread to your bones and show its locations. The sodium fluoride is the better of the 2 scans as it gives a clearer image. And both are usually not covered by insurance. But if your cancer has metastasized, this is a good way your physician can determine the progression of your bone mets and show if your current treatment plan is working.
Full Body PET scans—Again if your physician has suspected your cancer has metastasized, these scans can locate cancer throughout the body (bones, organs, lymph nodes, etc.). There are many of these scans available now with even better ones coming in the future. Some of these scans are Axumin, Carbon C-11 (acetate and choline), Gallium 68 PSMA, etc. Some of these scans may not be covered by many of the insurance plans.
Serum Biomarkers Tests—If your cancer has advanced, testing for these markers in the blood may help in evaluating future options for the treatment of your disease. Some of these are ALP (alkaline phosphatase), CGA (chromogranin A), NSE (neuron specific enolase), CEA (carcinoembryonic antigen), PAP (prostatic acid phosphatase), CTC (circulating tumor cells), and Liquid GPS.
Genetic Tests—New FDA-approved genetic testing helps determine which men need treatment and which can undergo active surveillance. And these new tests can predict the risks of cancer progression. Some of these blood tests are Prolaris Assay, Oncotype DX Assay, Decipher, SelectMDx, ConfirmMDx, Mitomics Assay, Guardant360, and OPKO 4Kscore. And urine testing can also help in the diagnosing of your prostate cancer. Some of these are Exosome DX, Select DX, and PCA-3. And all of these tests are usually covered by most insurance plans.
Determining the Severity of Your Prostate Cancer
As mentioned earlier, you must determine first if your cancer is still confined to the prostate (OCPC) or has spread (metastasized). Your treatment options can be dramatically different for each. And one can be cured and one cannot (but it can be controlled for many years). And new therapies are always on the horizon. In the previous pages I have given you most of the various tests to determine if you have prostate cancer. Now below is a table listing some of these tests and what they can tell us. The results of these tests can usually predict the severity of your disease. Let me emphasize USUALLY! In medicine there are always exceptions.
TEST Usually OCPC Usually Metastasized
PSA NUMBER LOW HIGH
FREE PSA NUMBER LOW-HIGH VERY LOW
PSA VELOCITY SLOW FAST
DRE EXAM NORMAL/SLIGHTLY ABNORMAL VERY ABNORMAL
ULTRASOUND CONFINED ESCAPED
PROSTATE DENSITY < 0.2 > 0.2
PROSTATE MRI CONFINED ESCAPED
PI-RADS SCORE LOW HIGH
GLEASON SCORE 7 OR BELOW 7 OR ABOVE
NUCLEAR BONE SCAN NEGATIVE? POSITIVE?
FULL BODY PET SCANS NEGATIVE POSITIVE
On the following pages, I will discuss your treatment options. Read these pages carefully and discuss these treatments with your physician(s). If your cancer is in the early stages (confined to the prostate) with low PI-RAD and Gleason scores, it is extremely important to keep it confined in the prostate or rid yourself of this disease. Your quality of life is highly dependent on managing, killing, or removing this disease. If your disease advances and spreads (metastasizes), your quality of life will decline (both health and financial wise). All of the various treatments and procedures will have side effects. Some of these may be temporary and some may be permanent. And all of the drug treatments will have side effects also.
Treatment Options for Prostate Cancer
Today there are a number of treatment options available for prostate cancer. The reason for so many options is that each patient is different and each patient’s disease state is different. It is not a one size fit all. Generally, a urologist will lean towards surgery, radiation therapists will favor one or more of the radiation options, cryosurgeons will favor cryosurgery (freezing the prostate), and oncology specialists will favor drug treatments. But once prostate cancer has been detected, your first goal is to find out if the cancer is still only in the prostate or has escaped (metastasized). As Russ Thomas (former CEO of the Prostate Forum of Orange County) would say— “once the horses have left the barn, why shut the door?”. So, what he is saying is if your cancer has already spread why go through any unnecessary surgery. Below are your options. Talk to your physician(s) and consider each one of them carefully. You have to become your own advocate of your body and its disease. Treat it methodically and carefully.
RP (radical prostatectomy)—This is removal of the prostate gland and often times the seminal vesicles (glands that produce fluid to carry the semen). This is the choice most men make. They just want the cancer out of their body. So, if the cancer is in the prostate, just take it out. There are 2 ways to do this:
General Surgery—Here is where the urologist (are trained first as surgeons) with his trusty scalpel removes the prostate gland and sometimes other diseased surrounding tissues.
Robotic Surgery (RALP)—Here is where the urologist uses a robotic device to help guide him through the removal of the prostate gland and possibly other diseased tissues.
So, which is better? The general surgery will require a longer healing time and the robotic surgery which is less invasive will provide a shorter healing time. But healing time is not what we are concerned with. It is the successful outcome that we want. And the number one reason for most successful surgeries is the skill of the surgeon. You want a urologist that has performed over 1000 surgeries. And you want a robotic surgeon/urologist to also have performed over 1000 surgeries. Experience is the most important thing correlating to successful surgeries. So, ask your urologist how many he has done. And the successful outcome is also highly dependent on these 4 things: Is it organ confined, has it spread into the margins, are the seminal vesicles involved, and your Gleason score.
So, what about side effects? Yes, you will have some. Some may be temporary and some may even be permanent. The urethra as it exits the bladder goes right through the prostate. If the prostate is now gone, this part of the urethra is now gone. Now the surgeon must establish a new connection or anastomosis between the bladder neck and penile urethra providing a new urinary channel. If this is done well, urinary incontinence will be mild and probably temporary. If not done well, permanent urinary incontinence symptoms can occur.
Another side effect that may occur is erectile dysfunction. Running alongside the prostate is the neurovascular bundle. This bundle contains the cavernous nerve which is essential for erectile function. Damage or removal of these nerves can cause ED (erectile dysfunction). Nerve grafting and nerve sparing surgeries can sometimes help this problem. And ED medications may help also.
The above two major side effects underly the importance to determine through various testing, scans, and blood/urine tests that the cancer is confined to the prostate if RP is selected as a treatment option. Even today many urologists are beginning to concede that modern radiation is better than surgery. RT (radiation therapy)—The technical advances in external beam radiation therapy have dramatically changed since the so-called “conventional” radiation therapy. The old EBRT (external beam radiation therapy) has been replaced by much newer and advanced machines. Years ago, the proton beam radiation (PBRT) was the “gold standard” for killing the cancer while sparing other tissues. It was first introduced at Loma Linda University Medical Center in 1990. Now even newer machines such as intensity-modulated proton therapy (IMPT), 3D conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), image guided radiation therapy (IGRT), and even neutron beam radiation therapy (NBRT) are now available. Some of the new current machines are called Trubeam (IMRT + IGRT), Tomotherapy, and Calypso. And now we have stereotactic body radiation therapy (SBRT) which many physicians believe will become the new “gold standard “much like PBRT was in the 1990s. The goal of all these machines is to deliver the radiation to only the affected areas sparing any surrounding tissue. These machines can deliver the radiation with incredible millimeter-level precision. And one advantage of RT is cancer cells are much more susceptible to radiation than noncancerous cells.
Brachytherapy—Brachytherapy refers to direct radiation to the prostate. There are two types of brachytherapy:
Brachytherapy LDR (low dose radiation) -- Low dose radiation therapy is where permanent radioactive seeds (the radioactive isotope is incased in a titanium shell) are implanted directly into the prostate using hollow needles through the perineum (area between the anus and scrotum). As the radioactive isotope decays, it releases radiation directly into the prostate. Depending on the isotope used, they can decay in as little as two weeks or as long as 2 months. This LDR therapy has been around for many, many years and still works very well in low to medium grade OCPC (organ confined prostate cancer) and would be this Author’s first choice.
Brachytherapy HDR (high dose radiation)—This is a newer form of brachytherapy using high dose radiation. This procedure is usually reserved for advanced tumors in the prostate. Here about 12 or more straw-like catheters are inserted through a template sewed into the perineum wall into various areas of the prostate. These catheters are then attached to tubes which are attached to a “HDR after loader” machine which dispenses the high dose (45Gys) radiation directly into the prostate. This is not a fun procedure (see internet) but is highly effective in destroying OCPC.
Cryotherapy—As indicated at the beginning, this is “freezing of the prostate” thus killing the cancer cells. Here hollow “cryoprobes” are inserted through the perineum into the prostate and liquid nitrogen or Argon gas is put into the probes to freeze the suspected area of the prostate. This therapy is usually used when only one suspected lesion is found. It can be destruction to one section of the prostate only. This “one section” procedure can usually spare any incontinence or erectile function problems.
HIFU (high-intensity focused ultrasound) -- HIFU destroys prostate cancer cells through the delivery of precise and focused sound waves to targeted prostate cancer cells. It basically burns and destroys the diseased tissue. HIFU was only approved by the FDA in 2015 for prostate cancer so it is very new and not all insurance plans may cover it.
Drug Therapy—As advances in drug therapy come about, these physicians (prostate oncologist specialists) using various drug therapies are becoming much, much more popular. Especially in metastatic disease. Please refer to the following drug treatments section for information on these drugs.
Drug Treatments for Prostate Cancer
The vast majority of drug treatments for prostate cancer center around reducing the amount of testosterone (androgen) that feeds prostate cancer cells in the body, chemotherapy (yes, poison) which kills the cancer cells, and now the new radioisotopes and immune therapy drugs. All of these drugs (like most drugs) have side effects. Some are very tolerable and some not so tolerable. But you have to remember your physician is trying their best to cure your disease or to extend your life span as long as possible. In the vast majority of cases, something else is going to do you in before the prostate cancer does. Listed below are many (not all) of the most common drug treatments used today. We refer to most of these drug treatments as ADT (androgen deprivation therapy) or TIP (testosterone inhibiting pharmaceuticals). Below are only the basics of these drugs. You can find out much more on the internet.
Anti-Androgen Drugs—One of these drugs is usually the first drug you will be put on after you have been diagnosed with prostate cancer. These drugs bind to the androgen receptors of the prostate blocking the activity of testosterone thus inhibiting cancer cell growth. The drug almost always used is Casodex (bicalutamide). Some other drugs in this class are Eulexin (flutamide) and Naladrone (nilutamide). These drugs are hardly ever used on their own and are usually started about 1-2 weeks before one of the LHRH agonist drugs are initiated to prevent flare (increase in testosterone). The combination of one of these drugs along with one of the LHRH drugs below is called ADT2 therapy.
LHRH (luteinizing hormone-releasing hormone) drugs—This is usually the second drug (Casodex is first) you are put on after you have been diagnosed with prostate cancer. The use of these drugs is called chemical castration (the testicles produce the most testosterone). They reduce the amount of testosterone produced by the testicles. All of these drugs can result in some of the worst side effects. Most of these side effects are usually not associated with the drug itself but the result of the drug’s actions—lowering the body’s testosterone (male sex hormone) levels. There are 2 types of these drugs:
LHRH AGONIST DRUGS—These drugs work by decreasing two hormones (FSH and LH) which results in reducing the production of testosterone from the testicles. The most common drug used is Lupron (leuprolide) injection. Other drugs used are Zoladex (goserelin) and Trelstar (triptorelin).
LHRH ANTAGONIST DRUGS—There is currently only one drug in this class which is Firmagon (degarelix). This drug works a little different than the agonist drugs but has the same result—reducing testosterone production. But it has the advantage of reducing the testosterone (and PSA levels) much more quickly. It also appears to have less side effects (but remember most of the side effects are caused by lower testosterone in the body). Also, Firmagon will not cause a PSA flare like Lupron upon initiation. And it is injected into the abdomen. The negative on this drug is it is much more expensive than Lupron and many insurance plans may not cover it. And the reimbursement rate to the physician is less also.
5-Alpha Reductase Enzyme Inhibitor—The addition of one of these drugs to an Anti-Androgen drug as well as one of the LHRH drugs is referred to ADT3 (triple blockade) therapy. This drug works by blocking the conversion of testosterone to dihydrotestosterone (which is much more potent). The most common drug used is Proscar or Propecia (finasteride). A newer and better one is Avodart (dutasteride).
nmCRPC (non-metastatic castration-resistant prostate cancer) drugs—These drugs are actually the next generation androgen receptor inhibitors. There are now 2 drugs in this class—Erleada (apalutamide) and Nubeqa (darolutamide). They are for castrate resistant prostate cancer that has not escaped the prostate (not metastasized). They are oral agents so they may be expensive.
Estrogens (female hormones)-These are not used much anymore due to a severe side effect—blood clots. But in some very advanced cases they may be of some help. The best method for delivery is the patches (Vivelle, Climara, Alora, Estradiol, etc.). Orally available products (DES) are discouraged.
CYP17 Inhibitor—There is only one drug in this class called Zytiga (abiraterone). This is one of the newest drugs and is only used in patients with advanced metastatic disease. It works by blocking an enzyme called CYP17 which helps stop the cancer cells from producing androgen (testosterone). It also helps in interrupting the androgen-making process in the testicles and adrenal glands. It virtually works everywhere androgen is being produced (see Testosterone page). This drug is really a life extending drug for these patients. Unfortunately, it is extremely expensive and may not be covered by some insurance plans. And even if it is, the co-pay will be very, very high. BREAKING NEWS: Sun Pharmaceuticals just announced the approval of their branded generic version of this drug called Yonsa. This should make this drug a little more affordable. Blood pressure, potassium levels, cortisol levels, and liver enzymes must be monitored very closely while on abiraterone.
Xtandi (enzalutamide)—While this drug probably should be in the anti-androgen class also, it works a little differently. I have listed it on its own and like Zytiga, it is one of the newer more exciting drugs. This drug blocks the signal telling the androgen cells to divide. And like Zytiga, it is reserved for advanced metastatic disease and has the same insurance and cost problems. Fatigue is the biggest side effect.
Antineoplastic Agents (chemotherapy drugs) -These drugs are different from the ADT drugs as they actually attack the tumors. Two of these agents have been around awhile but are still effective. They are Taxotere (docetaxel) and mitoxantrone. Taxotere by far is used the most. And yes, they have some of the worst side effects. Killing cancer cells is not easy. The newest agent in this class is a microtubule Inhibitor called Jevtana (cabazitaxel). It is for advanced metastatic hormone refractory prostate cancer previously treated with Taxotere (docetaxel). It shrinks the tumors by attacking rapidly dividing cells.
Antifungals (P450 Enzyme Inhibitors)—These drugs are also used in advanced cancer when the patient has severe metastatic disease. They work by blocking the production of testosterone mostly in the adrenal glands and some in the testicles. And they can attack the cancer cells themselves by blocking the testosterone syntheses inside the cancer cells. Nizoral (ketoconazole) is an old antifungal drug but it is still used today sometimes. But it requires very high doses and has many side effects.
Vaccine Therapies— This therapy is set to become the biggest anticancer revolution ever. There is currently only one approved drug in this class which is Provenge (Sipuleucel-T). This drug works by reprogramming your body’s immune cells to attack advanced prostate cancer cells. To make each dose, about 1.5 times your total blood volume is drawn from your body by a process called leukapheresis and passed through a machine that collects a small portion (abut 50cc) of your blood with your immune cells (the machine returns the rest back to your body). The 50cc of blood with the collected immune cells is sent to a Dendreon approved manufacturing facility (one right here in Seal Beach) to be made into a dose of Provenge which is then infused back into your body 3 days later. This is done 3 times over about a 1-month period. And currently Medicare pays for this treatment--$93,000.
Checkpoint (PD-1) Inhibitors—These immune therapy drugs are the next new step in fighting cancer. They work by overcoming one of the cancer cells main defense systems against an immune system response. You have probably heard of a couple of them as they are advertised on television—OPDIVO (nivolimab) and Keytruda (pembrolizumab). Others include Yervoy (ipilimumab), Tecentriq (atezolizumab), Erbitux (cetuximab), Adcetris (brentuximab), and Vectibix (panitumumab). And many more of these immune therapy type of drugs will be coming in the near future. While none of these are approved for prostate cancer yet, there is a blood test available which may tell which one of these drugs may be effective in treating your advanced prostate cancer. All of these drugs can cause diarrhea so treat accordingly and hydrate well. Also, cortisol levels need to be monitored very closely.
Radioactive Isotopes— This is another new exciting category. These drugs are for advanced metastatic disease. These radioactive isotopes can find the cancer cells and attack them. The first drug is Xofigo (Radium 223) and is indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease. The second drug is Lutetium-177 PSMA. This drug has been extensively tested in Germany with very positive results and is in some clinical trials in the USA.
PARP Inhibitors—Wow, new drugs just keep coming. These drugs are a type of targeted therapy that inhibit the PARP protein (poly ADP ribose polymerase) in cancer cells. PARP is responsible for repairing damaged DNA and without repair the tumor cell will die. These drugs work best when combined with a PD-1 inhibitor and in patients that have mutations and proteins that repair DNA. Lynparza (olaparib), Zejula (niraparib), and Rubraca (rucaparib) are 3 of the newest. While they have been effective in treating other types of cancers, they are now being tested in prostate cancer. And even newer ones are in clinical trials.
AKT Inhibitor—This is a new investigational drug called Ipatasertib. It works by overcoming one of the resistance mechanisms to hormonal therapy. It is currently in clinical trials combined with Zytiga and prednisone. No information is available yet on these trials.
Advanced Combination Drug Therapy—Since advanced metastatic disease cannot be cured yet, many physicians are trying “out-of-the-box” treatments. Recently there have been several studies to try and determine if combination therapy is better than the standard sequential therapy for treating advanced disease. Some of these trials have involved some of the below drug combinations:
Zytiga + Ipatasertib
Xtandi + Xofigo
Cabometyx + Tecentrig
Xofigo + Provenge
Xofigo + Keytruda
Provenge + Yervoy
Xtandi + Tecentriq
Keytruda + Xtandi (newest)
More studies must be performed on this combination drug therapy before an accurate assessment can be obtained. But with that said, the combination of a PARP Inhibitor + a Checkpoint Inhibitor has shown promising results.
ARV-110 in clinical trials— Currently approved drugs like Zytiga (abiraterone) and Xtandi (enzalutamide) target the androgen receptor (AR). However, over time the cancer tumors develop resistance to these drugs. Current thought is that this resistance develops when the cancer cells overproduce the androgen receptor or when the cells produce a variant of the androgen receptor, called AR-V7. It is believed that degrading this AR might be a promising approach for treating these progressed types of prostate cancers. A company called Arvinas has developed a protein degradation platform (ARV-110) which tags prostate cancer-causing proteins for degradation.
CBK4/6 Inhibitors—CBK4 and 6 are proteins that control how fast cells grow and divide. They become overactive in cancer, causing cells to grow and divide uncontrollably. This leads to the spread of cancer. Verzenio (abemaciclib) is a new drug in this class puts the brakes on CDK4 & 6 proteins, which delays cancer cells from growing and dividing. While this drug (plus some others) are not approved for prostate cancer, clinical trials may be available.
Clinical Trials—Manufacturers are always testing new drugs. This is your last line of defense. These are drugs that have cleared all the earlier FDA hurdles and are now being tested in humans. Your physician should be aware of what clinical trials you may qualify for. As a side note there was a drug tested years ago for high blood pressure (hypertension) but failed in clinical trials. But this drug had a weird side effect. It caused erections. That drug was Viagra@. And yes, the manufacturer ended up making a ton of money on the side effect of this drug. So, we never know what might come out of these trials.
Other Drug Treatments and Lifestyle Changes
Osteoporosis Treatment Drugs—If you go on ADT therapy, osteoporosis can occur. This is because ADT causes an imbalance between the osteoblast cells (builds new bone) and osteoclast cells (destroys old bone) within the bone. More bone is destroyed than is being formed causing the bones to become weaker and thinner. A bone mineral density (BMD) scan should be done before you start treatment and yearly thereafter. The QCT (quantitative computerized tomography) is superior to the DEXA (dual energy x-ray absorptiometry) scan. There are several drugs that will help combat this condition:
Bisphosphonates—Fosamax (alendronate) is the most commonly prescribed drug used to help bring the balance back to the osteoblast/osteoclast activity. Zometa (zoledronate) is another drug but it is not used very much as it has to be given by infusion.
RANKL Inhibitor—Xgeva (denosumab) is the newest drug for advanced bone metastasis. This drug has shown to actually delay the onset of bone metastasis. One of the serious side effects of this drug is osteonecrosis of the jaw (ONJ). Be sure your dentist is aware you are on this drug.
Calcium and Vitamin D3 should also be added as well as an exercise program (see below) while on any of these osteoporosis drugs.
S.A.M.—These letters stand for a regimen your Physician may put you on. There is evidence this regimen helps in fighting your cancer. The “S” stands for a statin which are cholesterol lowering drugs and Lipitor (atorvastatin) is the one usually prescribed. The “A” stands for Aspirin (low dose). And the “M” stands for Metformin (a diabetic drug).
Steroids—As much as these drugs have a bad name, they are necessary in some cases. Some of the newer drugs require their addition for them to work properly while other prostate cancer drugs remove cortisol from the body which must be replaced. Don’t be afraid if these are added to your drug therapy. Prednisone 5mg (a very low dose steroid) is the most common drug used.
OTC Herbal Supplements—There are many of these supplements sold everywhere. And there are many claims for these supplements and how they can help various disease states. And there are some to be avoided with prostate cancer (Multivitamins, Chondroitin, Folic Acid, Iron, Copper, Zinc, Flax seed, St. John’s Wort, Selenium, Vitamin E, etc.). Let me repeat a snippet from one of the annual PCRI conferences by Dr. Snuffy Myers (one of the Godfathers of Prostate Cancer). Dr. Myers wanted to do a study on the efficacy of the supplement Saw Palmetto to see if it could benefit prostate cancer patients. He had to go through over 20 different manufacturers before he could find 2 of them that had 90% or more of Saw Palmetto. Some of them had NO Saw Palmetto. You ask how is this possible? The FDA is in charge of rigorously policing the prescription drug industry. It pays no attention to the over the counter herbal supplement industry. It only gets involved when there is a catastrophe such as somebody dying from one of these supplements. So, if you want to take any of these supplements please consult your physician treating your prostate cancer first. In almost all cases they are not going to hurt you, but they may not help either. I also suggest if you buy any of these supplements it is best to buy them from a reputable source such as CVS, Walgreens, Target, Walmart, GNC, etc. These large companies do not want their reputation tarnished if something does go wrong. And by the way, the Saw Palmetto study failed to show any benefit in treating prostate cancer.
Diet-For the vast majority of us over 60, whatever damage we have done to our body nutritionally is done. But with that said eating healthy sure can’t hurt. The Mediterranean Diet or some version of a plant-based diet can be beneficial in the disease and your overall health. Much can be found out about this diet in books and on the internet. So, give it a try and stick to it! Dr. Moyad would love you!
Exercise—Walking is excellent exercise for the body. But if you are on any of the ADT therapies or some of the newer drugs, that will not be enough. The reason for this is because these therapies will cause muscle atrophy. You need to join a gym (some insurance plans will pay for this) and work out. If you can, hire a personal trainer at the beginning to help get you started on how to use the various machines. You will need to go 2-3 times a week and the 3rd set on each machine should be difficult (muscle burn).
Bits and Pieces and Some New Information
5-Alpha Reductase Enzyme Inhibitors- New information indicates that all patients on active surveillance or low-grade disease should be on one of these drugs with Avodart (blocks both enzymes) being the preferred drug.
CTCs (circulating tumor cells) --Circulating tumor cells are cells that break off from the cancer tumor and move into the blood stream or lymphatic system. Their goal is to move to another part of the body to form new metastases. Currently clinicians do not know why they leave their good ecosystem in the solid prostate tumor. But scientific reasoning suggests that heavy exercise, extreme sports, injury, and maybe even biopsies could result in these tumor cells breaking away from the tumor. There is now a new blood test (Cellsearch) which can test for these CTCs.
CVD (cardiovascular disease)—Prostate cancer in itself as well as its treatments can lead to a risk of cardiovascular disease. Recent trials and studies of Firmagon vs. Lupron indicates Firmagon is less likely to contribute to this risk.
Why the body’s own immune system does not work against Cancer—When a foreign-born organism such as a virus or bacteria enters the body, the body’s immune system (white blood cells) springs into action to fight the invasion. But cancer is an immuno-invasive disease and prostate cancer cells can evade or inhibit the body’s normal immune processes. And because cancer cells are “home-grown” within the body, the body’s immune response is not triggered as it does not recognize it as “foreign-born”. The new immunotherapy drugs work by trying to “trick” or re-program the immune system to respond to these home-grown cancer cells as if they were foreign-born.
Lutetium 177 PSMA Clinical Trial---A recent trial of 100 men (small sample size) treated with Lu-177 showed very promising results. All of the men had very advance metastatic disease with an average PSA of 175 and all had at least 3 or more prior therapies. 11% of the men showed a 90% PSA decline, 38% showed a 50% PSA decline, and 47% showed a 30% decline. Overall, this was a cohort of men with very aggressive disease that responded very well to this treatment.
Why are new anti-cancer drugs so expensive--The failure to innovate in cancer treatment may lie in the very poor success rate of clinical trials. Approximately 95 percent to 98 percent of new anti-cancer drugs actually fail phase III clinical trials, the phase in which new treatments are compared with existing therapy options. This is a staggering statistic. No other business could possibly survive with such an abysmal success rate.
BREAKING NEWS--Erleada which was approved for non-metastatic prostate cancer disease is now beginning to be tested in patients with metastatic disease.
A New Screening Test for Prostate Cancer--Scientists have announced the development of a highly accurate and reliable technique for diagnosing prostate cancer. The Dundee University-based team say they have used an ultrasound process called shear wave elastography (SWE) to detect prostate tumors. The method is non-invasive and cheaper than current detection techniques. The technique now needs to be tested in a much larger number of men to confirm just how well it can detect the aggressive cancers.
Possible New Break-Through--A radical ‘seek and destroy’ PSMA 617 treatment could extend the lives of thousands of men with advanced prostate cancer. The approach – described by experts as ‘game changing’ – uses high-tech molecules to track down tumors anywhere in the body and blast them with a radioactive payload. This innovative treatment is not available in the US but is currently being tested in the UK and Australia.
Butterfly IQ—This is a new hand held ultrasound device that plugs into the physician’s cell phone and gives him images of the inner workings of the body. This new technology may replace the stethoscope and possible scanning machines. It works everywhere including the heart and even the meniscus of the knee. Since the prostate is located deep in the abdominal cavity, I don’t know how well it will work here.
Oncotype DX ARV-7 Nucleus Detect Test—This is a new test used to determine if the second line hormone therapies like Xtandi, Zytiga and Erleada will be an effective treatment for men who have the diagnosis of prostate cancer that has left the gland (if they have metastases) and are no longer responding to the first line hormone (ADT) treatments like Lupron, Eligard, Prostap and Casodex.
Breaking News-- The U.S. Food and Drug Administration (FDA) has recently approved Nubeqa® (darolutamide), an androgen receptor inhibitor (ARi), for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC).
Lazarex Cancer Foundation—This foundation was set up to improve patient access to clinical trials. Contact them at 925-8204517 or www.lazarex.org.
A Layman’s Explanation of Prostate Cancer Progression
Got Prostate Cancer! Most men do not really understand their prostate cancer disease. So here is an analogy of your disease and its possible progression that is very easy to understand.
Let’s say you live in a house with a fireplace. Now let’s assume this fireplace is your prostate. It is there most of the time and just does its job (looks very nice). Now what if a fire (your prostate cancer) is started in your fireplace. Now this fire is a very low fire and your fireplace does its job. The walls keep it contained. The screen keeps any hot embers from getting out. And the flu directs any hot gasses and flames up through the chimney. This would be the basic definition of low-grade prostate cancer or organ confined prostate cancer (OCPC). You and your physician would manage this disease (active surveillance or treatments) to keep it confined. That is your goal. Just keep the fire low and confined in the fireplace (prostate). Or maybe you can extinguish the fire (surgery or other treatments). So, without any fire (cancer), you will have no problems and your house (your body) will not burn down.
Now what happens when something does go wrong. Heaven forbids! The fire in the fireplace begins to get larger. Your fireplace screen does not do its job and embers break through to cause a fire. Or the flu or chimney gets damaged and the fire is allowed to escape the fireplace into your house (your body). The fire has escaped (now metastatic disease) and has to be extinguished. So, you bring in a water hose to try and extinguish the fire. This hose (various drug or other treatments) works pretty well for a while but does not completely extinguish the flames.
So now a larger hose (more advance treatments) needs to be brought in to try and extinguish the fire. This works very well for a while again but unfortunately the fire starts up again. So now you must bring in an even larger hose (even more advanced treatments) to try and extinguish the fire. This cycle begins to repeat itself over and over again all the while you are spending more money on the hoses and water. It is now becoming expensive to try and save your house (your body).
This is a very simplistic way to explain the progression of prostate cancer in your body. As I said many times in this paper, keeping your fireplace working properly is your number one goal
When you are first diagnosed with prostate cancer, your first thoughts are how do I get rid of this disease or how do I treat this disease. You are devastated. Why me? But if you are going to get any cancer, prostate cancer is one of the better ones to have contracted. In many cases it can be cured and other cases it can be treated for a long, long time (something else will probably do you in).
Back in the days when you were young and healthy working at your job, illness was never thought about. Between your job, raising your family, and saving for retirement, you did not have time to even consider having any illness let alone prostate cancer. Now as you are older and have some or a multitude of ailments, you begin to think about your health. But you still don’t think about how you will pay for some devastating disease. Even after you have been diagnosed with prostate cancer, very little thought is given to how you will pay for the treatments. It is not until you progress into the disease you become aware how expensive it may become. So, this is where your insurance comes into play.
The following is about your choice in selecting your health insurance coverage. I won’t talk about those who are still working, or get insurance from their working spouse, or lucky enough to still have medical insurance from their previous employer, or a military/government type of insurance, etc. I am only going to talk about the vast majority of us that are over 65, retired, and on Medicare and a supplement for our insurance needs. Let me relay the following from personal experience. When I retired I went to see a Medicare Insurance Specialist for insurance advice. Her first question to me was “was I going to get healthier”. Of course, I said no. Her next question was “can I afford higher monthly premiums”. And fortunately, I said I could. This leads us to the two types of supplemental insurance available to you:
HMO (Health Maintenance Organization)—The vast majority of people that choose an HMO supplemental plan do so because the monthly premiums are much lower. Here in California we have some of the best HMOs. But even with these you will be restricted to the Doctors you can see, the Hospital you must go to, the various tests, scans, and diagnostic equipment available to you, and lastly what drugs you will be allowed to have. You are restricted to what is covered within their plan network.
PPO (Preferred Provider Organization)—These plans have higher monthly premiums. But you now will be able to see any Doctor (as long as they accept Medicare), go to any Hospital, have almost all scans, tests, and diagnostic equipment available to you, and virtually have all FDA approved drugs covered with some sort of co-pay. These are the best plans but can be expensive.
So, if you are retired with Medicare and choose an HMO supplemental plan and you can’t go to a specific Hospital don’t blame the Hospital. And if certain drugs your physician prescribed for you are not covered, don’t blame the Pharmacy. And if certain blood tests are not available to you, don’t blame the lab. And if certain diagnostic scans and tests are not available to you, don’t blame the insurance carrier. This is the choice you made choosing the lower premium policy. But maybe you just could not afford the higher premiums. That’s OK. The HMO’s save money (resulting in lower premiums to you) by restricting you to their approved criteria’s. Generally, the most expensive drugs, equipment, scans, tests, etc. may be excluded from their plan. So, when you are selecting one of these plans, be sure you understand what you are getting. You may have this disease for a long, long, time.
It is a well-known fact that a cancer diagnosis can not only be devastating physically and emotionally, but also financially.
Listed below are many Foundations and Pharmaceutical Companies that will provide aid in helping pay for most of the very, very expensive new drugs:
PAN (Patient Advocate Network)—They get funds donated to them from various foundations. It is hit or miss as they will sometimes (often) run out of money. But they are always soliciting for more funds. You can contact them at 866-316-7263 or at www.panfoundation.org and click on “apply”.
FundFinder (https://fundfinder.panfoundation.org/). FundFinder is a new web-based app that notifies its users when a disease fund opens at any charitable foundation. This program was developed by the PAN network.
Johnson and Johnson Patient Assistance Program—J & J is the parent company of the company that makes Zytiga. You can contact them at 800-652-6227. Or go online at www.jjpaf.org and click on the “How to Apply” tab and then click on the “Patient assistance Application Form” Fill the form out and follow the directions to get assistance.
Janssen Biotech—They are a subsidiary of J & J and the actual manufacturer of Zytiga. They may also offer some assistance and you can call them at 877-227-3728 or 855-998-442 EXT 1812.
Xtandi Support Solutions—Offers access and reimbursement support to help patients overcome the challenges accessing Xtandi. Contact them at 855-898-2634 or at www.XtandiSupportSolutions.com.
Astella Pharma Support Solutions—Offers access and reimbursement support to help patients and their health care providers overcome challenges to accessing Astella products such as Xtandi. Contact them at 855-898-2634 or at www.astellaspharmasupportsolutions.com.
PAF (Patient Advocate Foundation) is a national non-profit charity that provides direct services to patients. Contact them at www.patientadvocate.org, or at 800-532-5274 and 866-227-3728.
Co-Pay Relief is a subsidiary of PAF and you can contact them at www.copays.org, www.copays.org/prostate-cancer, at 866-512-0119, 866-512-3861, and 757-952-0118.
American Cancer Society (ACS)—They have offices spread around Orange County as well as the Inland Empire and LA. You can also go online at www.cancer.org/research and click on “Apply for a Grant”.
Dendreon—This company makes Provenge, one of the newer immunotherapy advanced prostate cancer drugs. If you do not have Medicare (which pays for this treatment), financial assistance may be obtained by calling 877-336-3736.
AstraZeneca Access 360—This company provides access and support for patients taking Lynparza. Contact them at 844-275-2360 or at www.lynparzahcp.com.
AZ ME—AstraZeneca Prescription Drug Program will also help in paying for Lynparza. Contact them at 800-292-6363 or at www.azandme.com.
Prescription Hope—This company offers access to over 1,500 brand-name medications through patient assistance programs. All you pay is a set service fee of $50.00 for each medication per month. This includes 100% of the medication cost, no matter the retail price. Contact them at 877-296-4673 or at www.prescriptionhope.com.
Zero 360 at 844-244-1309 or zerocancer.org
Cancer Care at 800-813-4673 or at cancercare.org
GoodDays (CDF) at 877-968-7233 or mygooddays.org
State Health Insurance Assistance Program at 800-434-0222.
Low Income Subsidy Program at 800-772-1213.
www.advocacyconnector.com and follow the links.