Moving beyond PSA

Finding prostate cancer has traditionally been a two-step process: First a simple blood test identifies men with an increased risk for the disease. For those at risk, a prostate biopsy follows. The main goal of the biopsy is to detect cancer, if it’s there. If it is, doctors also examine the tissue to try to distinguish an aggressive cancer that needs treatment from a slow-growing one that may never spread.

Determining who is at risk

Since 1986, the prostate-specific antigen (PSA) blood test has become a routine part of a doctor’s visit. The test measures levels of a protein produced by the prostate and can predict whether a man has cancer. It has enabled doctors to diagnose more than 80% of prostate cancers before they spread to lymph nodes, bones, or other tissues. In short, PSA testing helps detect tumors years — perhaps even a decade or more — before they cause symptoms. If you’re over 50, you’d think that having the test would be a no-brainer.

But even the strongest advocates of PSA testing admit that it has significant shortcomings. For one thing, PSA isn’t specific for cancer. Although the likelihood of cancer increases with greater elevations in PSA, values considered abnormal — in the range of 4 to 10 ng/ml or even higher — occur in men with benign conditions such as an enlarged prostate. In fact, about 75% of the patients who fall into this category — roughly 1.3 million men a year in the United States who have undergone a prostate biopsy (a procedure that removes snippets of tissue for examination under the microscope) — don’t have cancer. Adding to the confusion: 15% of men with a PSA below 4 ng/ml who have a biopsy actually do have prostate cancer, according to a 2004 study. That’s right: men with a “normal” PSA test result may have cancer, and most with an “abnormal” result don’t.

The PSA test also falls short in its ability to distinguish potentially deadly cancers from insignificant ones. Some cancers spread rapidly, but many grow so slowly that they may never cause problems. For the slow-growing cancers, the side effects of treatment — which include impotence and incontinence — can be worse than the disease itself.

“No one is entirely happy with PSA, including me,” says William Catalona, M.D., a prostate cancer surgeon at Northwestern University who helped pioneer PSA testing. “Because of these deficiencies, there’s a crying need to improve PSA testing.”

Researchers have spent the last several years combing through blood, tissue, and urine samples in the hopes of finding some sort of biological change, or biomarker, to more accurately diagnose prostate cancer and predict its behavior. Their efforts have recently begun to bear fruit (see Table 1 below).

Table 1: A sampling of genes and biomarkers under study

Gene/marker Where found Comments
EPCA-2 Blood May help differentiate men with organ-confined disease from those whose cancer has spread
ERG Tissue, urine Overexpressed in some prostate cancers; can fuse with TMPRSS2
GOLPH2 Urine Generally overexpressed in prostate cancers; levels assessed along with those of PCA3, SPINK1, and TMPRSS2:ERG in experimental test
miRNA Tissue Small molecules containing genetic information; can interfere with the making and regulation of proteins
PCA3 Urine Not yet approved by FDA for diagnosis of prostate cancer, but several labs in the United States offer the test; another experimental test checks levels of PCA3 with those of GOLPH2, SPINK1, and TMPRSS2:ERG
PI3K Tissue Can drive development of tumors unless kept in check by another gene, PTEN
proPSA Blood May help distinguish prostate cancer from benign conditions; higher levels associated with high-grade disease
PTEN Tissue Genetic brake that, when sufficient, can keep the cancer-causing gene PI3K in check
SPINK1 Urine Overexpressed in a subset of prostate cancers; levels assessed along with those of PCA3, GOLPH2, and TMPRSS2:ERG in experimental test
TMPRSS2 Tissue, urine Prostate-specific gene that sometimes fuses with other genes known to be involved in cancer, including ERG; fusions thought to be a marker of poor clinical outcome
Note: This is not an exhaustive list of biomarkers; others are under study. Tests named here are not approved by FDA.

Catalona has been studying a form of PSA called “free” PSA — as opposed to “bound” PSA, which binds to proteins in the blood. Today’s PSA tests measure total PSA, the sum of free and bound PSA. Catalona’s research has shown that a subcategory of free PSA called proPSA is superior to PSA in discriminating cancer from benign conditions. Its greater diagnostic accuracy likely stems from the fact that proPSA is produced in the prostate’s outer zone, the area where most cancers arise.

Subsequent studies of proPSA in 2,000 men confirmed Catalona’s initial results, and a San Diego company has developed an automated method for detecting it. The company plans to seek FDA approval for the test, which Catalona estimates could be used in clinical practice in as little as three years. While it could one day supplant PSA, experts say it will initially be an adjunct to PSA, especially in cases where the total PSA reading might prompt a biopsy.

“It’s far from perfect,” says Catalona, “but it’s definitely better than what we have now.”

Another test that may soon be available in the United States checks for the presence of an RNA dubbed PCA3. When prostate cells become cancerous, their PCA3 genes kick into overdrive, producing massive amounts of this cancer-specific nucleic acid. If a doctor massages a cancerous prostate gland, PCA3 is shed into the urine, where it can be detected with a sophisticated molecular test. PCA3 levels don’t rise if a man has an inflamed or enlarged noncancerous prostate, so this protein more closely correlates with cancer than PSA does. As a result, men with a PSA level that might normally warrant a biopsy could have a PCA3 test first. Those with a slightly elevated PSA level but a low PCA3 level could be spared a biopsy.

In February 2008, researchers at the University of Michigan announced that they had built upon the PCA3 test by screening for it and six additional biomarkers in the urine of 234 patients (see “PCA3 and other biomarkers” below). By correlating biopsy data with urine test results, researchers found that four of the biomarkers were strong predictors of prostate cancer: GOLPH2, SPINK1, PCA3, and TMPRSS2:ERG, which is a combination of two genes. In fact, the four together proved more accurate than either PSA or PCA3 alone, correctly identifying more than 75% of patients who were later found to have prostate cancer. The researchers’ next step is to prove that these initial findings hold up in tests of more men at multiple institutions.

PCA3 and other biomarkers

Laxman B, Morris DS, Yu J, et al. A First-Generation Multiplex Biomarker Analysis of Urine for the Early Detection of Prostate Cancer. Cancer Research 2008;68:645–49. PMID: 18245462.

Perhaps the most promising biomarker is EPCA-2, discovered by Robert Getzenberg, Ph.D., and other researchers at Johns Hopkins Hospital. Examining tissue samples, the team found that EPCA-2 was present in prostate cancer cells but not in normal tissue. Since biopsies are not a practical screening tool, the team tried to detect EPCA-2 in blood from 330 people.

The results were striking: healthy men and women, those with other types of cancer, and most men with benign prostate disorders had lower levels of EPCA-2 than men with prostate cancer. Only a few samples from men with prostate enlargement had elevated EPCA-2 readings, meaning the test was highly specific for cancer. Statistically speaking, the test detected 94% of prostate cancers — much better than the 65% of cases detected with PSA in this same group of people. Even better, among those who tested positive for cancer, results also correlated well with disease stage: the test correctly detected 36 of 40 men with localized cancer and 39 of 40 men with cancer that had spread (see “EPCA-2 biomarker” below). If the test performs as well in a larger group of men, it could augment or even replace PSA testing.

EPCA-2 biomarker

Lemen ES, Cannon GW, Trock BJ, et al. EPCA-2: A Highly Specific Serum Marker for Prostate Cancer. Urology 2007;69:714–20. PMID:17445657.

Determining which prostate cancers need treatment

Many men diagnosed with prostate cancer have other illnesses that may cause serious problems, even death, before the prostate cancer ever causes problems. They die with but not from prostate cancer. For that reason, doctors have been seeking clues to help determine who needs more immediate treatment and who can pursue active surveillance.

One obvious place to look, in this “post-genomic era,” is in the genes. Research has proven that several cancers can be caused by mutations in single genes and by the fusion of two genes, a specific type of mutation. Would the same hold true in prostate cancer?

In 1985, Lewis Cantley, Ph.D., a researcher at Harvard’s Beth Israel Deaconess Medical Center, discovered PI3K, a gene that acted like a switch for tumor growth. When flipped on, it drove the development of tumors in animals. But the relevance of his discovery for human cancers remained unclear until the late 1990s, when researchers at Columbia University discovered PTEN, a gene that can help prevent cancers, including those caused by PI3K. It turns out that PTEN is a brake to keep cancer-causing PI3K in check; when PTEN is deficient, PI3K is uncontrolled and drives prostate cancer. Subsequent studies showed that prostate cancer that had spread harbored more PTEN mutations or abnormalities than localized cancer — suggesting that an assay for defects in PTEN in primary prostate cancers may reveal patients who are most likely to develop metastatic cancers.

More recently, researchers have found that a category of small molecules once considered useless are emerging as key players in the development of cancers, including prostate cancer. Some of these molecules, called microRNAs, or miRNAs, interfere with the production and regulation of various proteins, which can play a role in tumor development or suppression. Pier Paolo Pandolfi, M.D., Ph.D., a geneticist at Beth Israel Deaconess Medical Center, says that drugs could be made to attack the offending miRNAs in prostate cancer.

Scientists have also discovered that the abnormal fusion of two genes — TMPRSS2 and ERG — increases the probability that prostate cancer will return and prove fatal, echoing the experience with fusion genes in other cancers. (Gene fusions occur when pieces of genetic information on a chromosome trade places with each other, altering their sequence.) The activity and location of this fused gene in the cell is being studied in prostate biopsy samples by Massimo Loda, M.D., a researcher at Harvard’s Brigham and Women’s Hospital. Loda says that the fusions may override molecular switches that prevent excess cellular growth, potentially making some prostate cancers more aggressive.

The good news: in other cancers, the discovery of fusion genes has led to the birth of powerful new treatments. After researchers found that the BCR:ABL gene fusion drives the development of chronic myeloid leukemia, they discovered that the drug imitanib (Gleevec) could send the disease into remission. To date, however, drugs that target the TMPRSS2:ERG gene fusion are not available.

Most cancers — indeed, most diseases — result not from single genes but from multiple genes. New technologies allow laboratories to identify which of the approximately 25,000 human genes are turned on and which are turned off in a cancer. For example, in a particular type of breast cancer, a test called Oncotype-DX identifies such a “gene signature” from tumor tissue and helps doctors decide whether chemotherapy is likely to prolong survival when other predictors of tumor behavior are favorable.

Researchers haven’t yet had quite the same success in finding gene signatures for prostate cancer, but they are getting closer. In 2003, one team reported a set of 17 genes in prostate tumors that predicted whether a cancer would spread to other parts of the body. It also reliably predicted poor prognosis. Another team uncovered a set of 11 genes in 2005 that seem to forecast disease-free survival after treatment. But these studies involved only a small number of prostate cancer cases — just 100 in all.

A much larger 2008 study uncovered five genetic variations that dramatically raise prostate cancer risk (see “Five genetic variations” below). By examining DNA from 2,893 men with the disease and 1,781 healthy subjects, researchers found that men with four of the five genetic variants were more than four times as likely to develop prostate cancer as those with none of the markers. Men with at least four of the five markers and a family history of the disease were more than nine times as likely to develop the disease. Interestingly, the combination of genetic variants did not correlate with PSA levels.

Five genetic variations

Zheng SL, Sun J, Wiklund F, et al. Cumulative Association of Five Genetic Variants with Prostate Cancer. New England Journal of Medicine 2008;358:910–19. PMID: 18199855.

Molecular studies designed to improve diagnosis and help physicians judge who needs treatment may also point to effective new therapies. For example, Beth Israel Deaconess’ Cantley and Pandolfi are studying drugs that might enhance PTEN’s protective effect, as well as agents that might inhibit the cancer-promoting molecule PI3K. Drugs that target PI3K have been approved for some cancers, including renal cell carcinoma. Four drugs that might inhibit PI3K-fueled prostate cancer are currently in clinical trials. Other agents affect PTEN’s switching ability and have stopped the growth of tumors in mice. But whether they might rein in prostate cancer in humans remains to be studied.

While PSA testing currently remains the best way to predict prostate cancer risk, and the cancer’s appearance under the microscope remains the best way to guess how it will behave, researchers are convinced that ongoing biomarker research and genetic analyses will lead to significant improvements in prostate cancer detection and treatment. Each individual could have a panel of tests: one for diagnosing the cancer; a second to determine if the cancer needs to be treated; and a third to determine the best treatment. That’s what the hope of “personalized medicine” is all about.

Originally published June 2009; last reviewed March 17, 2011.

Comments
5
Antonio

Can non-small cell lung cancer be found early?Usually symtmops of lung cancer do not appear until the disease is already in an advanced, non-curable stage. Even when symtmops of lung cancer do appear, many people may mistake them for other problems, such as an infection or long-term effects from smoking. This may delay the diagnosis.Some lung cancers are diagnosed early because they are found as a result of tests for other medical conditions. For example, lung cancer may be found by imaging tests (such as a chest x-ray or chest CT scan), bronchoscopy (viewing the inside of lung airways through a flexible lighted tube), or sputum cytology (microscopic examination of cells in coughed up phlegm) done for other reasons in patients with heart disease, pneumonia, or other lung conditions. A small portion of these patients do very well and may be cured of lung cancer.

Andres

Current screening rienmmcndateoosAt this time, no major professional organizations, including the American Cancer Society, recommend routine lung cancer screening, either for all people or for those at increased risk. However, as the results from the NLST are further analyzed, some organizations may update their rienmmcndateoos in the near future. In the meantime, some people who are at higher risk (and their doctors) may consider whether screening is appropriate for them.While a full cancer screening guideline is being developed, the American Cancer Society has created interim guidance for people and their doctors regarding the use of low-dose CT scans for the early detection of lung cancer:•People between the ages of 55 and 74 who meet the entry criteria of the NLST (see above) and are concerned about their risk of lung cancer may consider screening for lung cancer. With their doctor, people interested in screening should weigh the currently known benefits of screening with the currently known limits and risks in order to make a shared decision as to whether they should be screened for lung cancer.•Doctors may choose to discuss lung cancer screening with their patients who meet NLST entry criteria.•For people who do not meet the NLST entry criteria (because of younger age, smoking history, etc.), it is not clear if the possible benefits of screening outweigh the harms, so screening in these people is not recommended at this time. This is especially the case among people with no smoking history, in whom the possible harms are much more likely than benefits at this time. Whether people whose age or smoking history would have made them ineligible for the NLST should be screened will be addressed during the guidelines development process as more data becomes available.•People who choose to be screened should follow the NLST protocol for annual screening. This should be done in an organized screening program at an institution with expertise in spiral CT screening, with access to a multidisciplinary team skilled in finding and treating abnormal lung lesions. Referring doctors should help their patients find institutions with this expertise.•There is always benefit to quitting smoking. Active smokers entering a lung screening program should be urged to enter a smoking cessation program. Screening should not be viewed as an alternative to quitting smoking.•For people considering screening (and their doctors), some statistics from the NLST may be helpful. Of the nearly 26,000 people screened by low-dose CT in the NLST, 1,060 were diagnosed with lung cancer. Screening is estimated to have prevented 88 lung cancer deaths while causing 16 deaths. Six of the 16 deaths were in patients who ultimately were found not to have cancer.

Anonymous

Men beware!
A prostate cancer patient survival guide by a patient and often a victim.
Men, avoid the over diagnosis and unnecessary treatment of prostate cancer.
Prostate cancer patient exploitation, testing and treatment dangers.
Revised February 14, 2017

In my opinion:
Read the hard facts about prostate cancer testing and treatment that no one will tell you about, even after it’s too late. This is information all men over 50 should have. Also, anyone concerned about cancer in general or privacy issues should read this text. Prostate cancer patients are often elderly, over treated, misinformed and sometimes exploited for profits. The testing, treatment and well documented excessive treatment of prostate cancer often results in devastating and unnecessary side effects and sometimes death. At times profit vs. QOL (quality of life).

Per some studies:
Studies have verified more deaths caused from prostate cancer testing and treatment then from prostate cancer itself.
Extensively documented unnecessary testing and treatment of prostate cancer because of profit or poor judgment by some doctors in the USA.
Medical mistakes are the third cause of deaths in the USA (over 251,000 deaths a year, over one million deaths in 4 years) more then suicide, firearms and motor vehicle accidents combined.
1 man in 6 will be diagnosed with prostate cancer in his life.
About 233,000 new cases per year of prostate cancer.
About 1 Million prostate blind biopsy’s performed per year in the USA.
6.9% hospitalization within 30 days from a biopsy complication.
About 1.3 to 3.5 deaths per 1,000 from prostate blind biopsies.
.2% deaths as a result of prostate cancer surgery.
60% had a prescription filled for an infection after a Biopsy.
Black men are at an increased risk of prostate cancer.
Prostate cancer patients are at an increased risk for fatigue, depression, suicide and heart attacks.

Excuse the generally accurate humor and sarcasm. Its intent is to entertain and educate while reading this possibly laborious text.

Prostate cancer patients are often elderly and exploited for profit, the treatments offered has horrible side effects, and newer treatment options are either unavailable or not offered to patients or available outside the USA. Prostate cancer is often slow growing and of low risk and can just be monitored. Often no treatment is the best treatment. Over testing and treatment has been verified by numerous experts, studies and investigations, documentation, etc.

If a surgeon is financially responsible for a building lease or a large staff or an oncologist is also responsible for a lease on 5 million dollars of radiation treatment equipment, do you think they would be more or less honest about the benefits and hazards of treatment? Do you think the profit margin would compromise some doctor’s ethics?

A 12, 18 or 24 core blind biopsies, holey prostate! Men with a high PSA tests result are often sent to an urologist for a blind biopsy. Men should be told about other options: Percent free PSA test, 4Kscore test, PCA3 urine test or a MRI test before receiving a blind biopsy. These tests can often eliminate the need for a more risky and invasive blind biopsy. Insertion of 12, 18 or 24 large holes (most of the time) through the rectum into a gland the size of a walnut, a blind Biopsy can result in (per studies) prostate infections, a risk of permanent or temporary Erectile Dysfunction, urinary problems, hospitalization and sometimes even death from sepsis (About 1.3 to 3.5 deaths per 1,000 from blind biopsies). There is also controversy that a biopsy may or may not spread cancer because of needle tracking. A blind biopsy can also increase PSA reading for several weeks or months, further frightening men into an unnecessary treatment. Blind biopsies are almost never performed on other organs. One very prestigious hospital biopsy information states: “Notice that your semen has a red or rust-colored tint caused by a small amount of blood in your semen”. Another large prestigious hospital states “Blood, either red or reddish brown, may also be in your ejaculate.” These statements are often an extreme exaggeration. Very often after a biopsy a man’s semen will turn into a jet black goo. This could be an unpleasant surprise for a man and especially for his unsuspecting partner. However if a biopsy is performed before Halloween or April Fools’ day this may be of some benefit to a few patients. If some very prestigious hospitals are not factual about the color of semen, what other information is not being disclosed or misrepresented?

Bone scan scam: Prostate cancer patients are often sent for a bone scan. A bone scan has about a 13% chance of having a false positive and only 3 men in 1,000 have bone cancer who have a bone scan. Bone scans may sometimes be unnecessary in lower risk prostate cancer patients.

Low risk cancer patients or patients with advanced age are often sent for aggressive treatment by some doctors when monitoring is usually a better option. An extreme example of overtreatment is one SBRT radiation clinical trial. Prostate cancer patients (victims) where intentionally treaded with a huge dose (50Gy total, 5 fractions) of radiation resulting in disastrous long term side effect for some of these men. A large percentage of prostate cancer patients in this clinical trial had low risk prostate cancer.

Clinical trials may or may not be hazardous to patients? The goal of a clinical trial is to gather information; the intent is not necessarily to help or cure patients. In a clinical trial, if someone is given a treatment that will harm them (as in the above example) or given a placebo in place of treatment or needed treatment is withheld, the patient may be deceived or harmed. Investigate before you participate in any clinical trial.

Privacy and confidentiality may be just an illusion: Prostate cancer patients are asked to fill out a series of EPIC questionnaires and other standard questioners. The EPIC questionnaire asks several intimate details about patient’s sex life, urinary and bowl function. By a prostate cancer patient completing an EPIC questionnaire may be able to assist his doctor, nurse or other office workers track his progress or decline. By refusing to fill out these questioners and supplying other unnecessary information one can help insure his privacy, dignity and insure he do not unknowingly become part of a study or clinical trial or other collective survey or have his information forwarded to multiple databases. He may be told these questioners and records are “strictly confidential” (as stated in most EPIC questionnaires); this statement is misleading. Most of the time a patient has no idea who has access to the records or why the records are being looked at. Who has access to medical records? Probably everyone that works in a medical office or building has access to the records. This may include/however not limited to non-medical employees, office workers, bookkeepers, janitors, insurance companies, temporary high school or college interns, etc. This may also include other medical facilities, programmers, hackers, researchers, etc. Often records are placed on a health information exchange (HIE), dozens, sometimes even hundreds or thousands of people may have access to the records. Some major databases like SEER are linked to Medicare records to determine “the final outcome” for researchers, studies, drug companies, etc. SEER is an appropriate name for this database! Your drug prescription history can also be tracked. Records may be packaged and offered for sale, this does happen. Your medical records can be downloaded to servers all over the world to countries that do not have any regulations for privacy. If a doctor, patient or insurance company is involved in a criminal or civil case, medical records may become public court or law enforcement records. If a patient has radiotherapy he may have a photo taken before treatment to verify identity. All patients should get a copy and read any confidentiality disclosures statements (HIPAA statements). Patients can also become the victims of financial or medical Identity theft. Under the HIPAA laws you are entailed to a copy of all your medical records, however if you try to obtain a copy of extensive records as in a hospital stay you may be met with resistance. I recently went to a new optometrist for glasses and I was given a form that asked details about my heritage, including my mother’s maiden name and a form for my complete medical history. My family doctors office hires summer time high school interns with full access to all records. Would you like to have a high school or college student that possibly lives in your neighborhood or attends to school with your children read over your extensive family members medical records and personal information? How much curiosity or self control does a high school or college student have? I also went to a hearing aid center in a department store to get a free hearing test and was given forms inquiring about personal information and my complete medical history. This is information I do not want filed in a department store. All patients should avoid supplying unnecessary information whenever possible. Supply relevant information only. In the USA identity theft is very common, growing problem and is often financial devastating. Medical forms can be a good source of information for thieves. Recently my friend with arthritis in her hips received a letter offering a clinical trial for a new medication; coincidently looking for patients with hip and knee arthritis. How did this company determine she and not her husband was a prime candidate for this new drug study without violating any HIPAA privacy laws? Even without HIPAA privacy law violations, office records can be accessed by multiple people and appear in multiple databases. Your privacy and confidentiality is probably not that safe!

A patient’s dignity: Prostate cancer treatment is often degrading and demoralizing. EPIC questionnaires can be counterproductive impact a patient’s dignity, privacy, confidentiality, and self image. EPIC questionnaires probably have an increased potential and greater impact on patients for privacy violations because of its format, nature and personal content (potential for HIPAA privacy law violations). Patients may mistakenly believe the EPIC questionnaire is a requirement to be filled out. Also the term “strictly confidential” can be misleading and ambiguous. One blogger patient posted he filled out and turned in his “strictly confidential” EPIC questioners only to have every female office staff member read it and ogle him. He was dismayed, resulting in him not filling out any more EPIC forms or any other forms and he stated that he became very uncomfortable and evasive with the entire office staff. The drawbacks of this form seem to outweigh any potential benefit for some patients. Medical testes and procedures can be degrading and embarrassing for both men and women. Many women prefer or will only see female doctors or gynecologists, about 50% to 70%. Over half of men prefer a male doctor. (Per some respected doctors: Men stay away from medical care in large numbers because of privacy and dignity. Many men still avoid medical care because of embarrassment. Honest answers will often not be given if asked by a female doctor or nurse.) What percent of old men will feel comfortable consulting a female doctor, nurse or office worker about his prostate problems, ED, etc or would want an invasive test or procedure performed by a female?

The most common treatment options for men with prostate cancer are radiation, Brachytherapy, surgery, cryotherapy and hormones (ADT). Sometimes chemotherapy, immunotherapy and castration (orchiectomy) are used. A combination of treatments is often used. Most or all of these treatments have long term or short term side effects. Often men are not told about all of the true risks and side effects or they are downplayed for both a blind biopsy and treatments.

LDR Brachytherapy is permanent radioactive seed implant. This treatment procedure implants about 50 to 100 radioactive seeds in the prostate, sometimes resulting in urinary problems. The patient will literally become radioactive for months and up to 2 years. The patient may set off radiation alarm and also possibly metal detectors at airports. He will also be required to use a condom, have no close contact with pregnant women, infants, children and young animals or pets for months or longer. Occasionally he may even eject radioactive seeds during sexual activity or urination. The patient will become like a walking Chernobyl, having radioactive scrap metal and emit radiation from his crotch. He will also be required to carry a card in his wallet stating he is radioactive. The videos of this procedure seem to be disturbing and bizarre. However LDR Brachytherapy seems to have less sexual side effects than some of the other treatments available.

Men are sometimes prescribed hormone therapy (ADT therapy), AKA chemical castration as an additional or only treatment. Hormone (ADT) therapy is sometimes over prescribed for profit, per some studies. Hormone therapy is often very expensive (may be profitable for doctors if provided at the doctors office and not a pharmacy) and can have horrible, strange and devastating side effects, feminization, fatigue, weight gain, etc. His penis could shrink and his testicles can completely disappear, he may grow breasts. This treatment can have so many mind and body altering side effects that doctors will often not inform patients about all of them. Men are sometimes castrated (orchiectomy) as a cancer treatment to reduce testosterone. Studies (Medicare and financial) have documented some doctors do over prescribe ADT therapy for profit (depending on Insurance payout rates/profit margin). When insurance payment reimbursement for ADT decreased so did the number of patients being prescribed ADT therapy! Overtreatment is extremely unfortunate and avoidable.

Nerve sparing Robotic-assisted DaVinci surgery is touted as being a better treatment and having fewer side effects, this is usually an exaggeration. The nerves can not always be spared. Robotic surgery can result in a faster initial recovery. Long term risk of incontinence, fatigue, etc is about the same as conventional surgery, ED rates my possibly be a little better. Patients undergoing surgery are at a small risk of developing post traumatic stress disorder (PTSD) and about a 25% chance of long term or permanent fatigue. Also .2% risk of deaths as a result of prostate cancer surgery or medical mistakes. Patients are sometimes not told about the high risk of a shorter penis after surgery due to the shortening of the urethra. Patients can have unrealistic expectations about the results and regret the surgery treatment option. The ED rates and depression are often understated to patients.

Patients should not be naive: Medical mistakes are the third cause of deaths in the USA. Medical mistakes cause more deaths then suicide, firearms and motor vehicle accidents combined. Countless other patients have been harmed by medical mistakes. If you are having surgery, brachytherapy, a biopsy or a procedure take precautions if possible. Have someone qualified or knowledgeable monitor you and your medications, etc. Doctors, nurses and technicians can be profit motivated, use obsolete procedures, be lazy, incompetent, make mistakes and be apathetic or rushed. Occasionally harm can be done or not prevented with intent. Doctor’s offices and clinics can see many patients in a relatively short amount of time. This may be a disadvantage to patients, empathy and quality of care can sometimes be compromised. Sometimes a nurse, medical assistant or an office staff member may be the person that overseeing much of a patient’s cares. What are the main reasons nurses get fired: 1. Prescription drug abuse, 2. Too Many mistakes. 3. code of conduct and privacy violations. 3. Bad attitude. 4. No proper licenses 4. Abuse of patients. Patients should be aware that sometimes QOL (quality of life) may be secondary or an absent goal in treatment. Sometimes overtreatment for profit or to prevent an unlikely death or metastization from low risk cancer may be the primary or the only goals of cancer treatment.

A blind biopsy or treatments are often worse then the disease: Resulting in Chronic/permanent fatigue, incontinence, depression and sexual dysfunction. Hormone therapy may have an extensive list of side effects that can be devastating for men. Biopsies and treatment are degrading, stressful and often unnecessary. Many men may not be prepared or have unrealistic expectations about the outcome, physical and psychological impact of testing and treatment.

The risk of long term chronic and permanent fatigue (that can result in depression) is almost always understated if mentioned at all to many patients. Per some studies and depending on your treatment; the risk of long term or permanent fatigue is about 25% to 60%. Radiation with Hormone therapy has a high risk of fatigue. Long term fatigue also increases the risk of clinical depression and suicide.

In my opinion: Castration, ADT hormone therapy (chemical castration), LDR Brachytherapy (radiation seed implant), radiotherapy, surgery and blind biopsies are often psychically and emotionally brutal, traumatic and disturbing. These types of treatments are primitive and almost beyond belief in today’s world of advanced technology. Newer treatments like, HIFU, hyperthermia, Boron Neutron capture therapy, focal Ablation (only treating the cancer and not the entire prostate) and orphan drugs should be approved and used when appropriate. Biopsies should be limited to selective MRI guided samples only; blind biopsies should seldom be performed.

Approved advances in prostate cancer treatment mostly consisting of newer more accurate radiation treatments, robotic surgery and new drugs. These advances sound like greater strides have been made. However most of these approved advances are of limited benefit to prostate cancer patients and still have about the same amount of long term side effects. Compared to other technologies, computers, communications, electronics, aviation, etc, cancer treatment approved advances have been dismal. QOL (quality of life) issues have not been adequately addressed. Profit sometimes outweighs QOL.

Prostate Radiotherapy (EBRT-external beam radiation therapy) for cancer treatment. New technology consists of: IMRT, SBRT, IGRT, VMAT, TrueBeam, Cyberknife, etc. This newer, faster, more accurate and easer to setup radiation equipment is of much benefit for doctors, staff and a good selling point to patient’s. However as far as reducing long term side effects, only small gains have been made with the newer radiotherapy equipment. A patient should be skeptical if exaggerated claims are made about reduced long term side effects, especially fatigue and ED rates. About 25% of radiotherapy patients can expect an alarming temporary “bounce” (spike) in the PSA value after treatment. Patients should inquire as to the treatment plan: Gy dose and fractions, margins, testicular dose, constraints and age of radiotherapy equipment to insure excessive radiation exposure treatment is not given that can result in additional side effects. Patients should be aware that pelvic shaving, small permanent tattoo markers, fiducial marker (small seeds) are sometimes placed in the prostate, MRI, CT scan, photographs, catheters and other procedures may or may not a be required. Radiotherapy can also occasionally result in secondary cancers and damage to “organs at risk” (organs close to the prostate). Radiation has high probability of sexual dysfunction and fatigue. ED rates estimated at 35% to 75% or higher. Sometimes radiation can also cause bowel and urinary problems. A 5 day SBRT radiation treatment is now commonly available with about the same results and side effects as a 9 week radiation treatment.

Sometimes radiotherapy can result in a 5% to 30% temporary or permanent drop in testosterone levels. Excluding hormone therapy, this drop is determined by the testicular radiation dose (treatment equipment and planning). A below normal drop in testosterone can result in increased fatigue, depression, sexual dysfunction and other symptoms.

It seems all of the best treatments for prostate cancer have not been approved and most are only available outside the USA. Treatment options outside the country or under development are HIFU, Laser, Hyperthermia, Boron Neutron capture therapy and orphan drugs, just to name some. Focal Laser Ablation is a good option with fewer side effects however it is not widely available in the USA and sometimes not practical.

Any cancer patient (man or woman) who are being offered chemotherapy should be particularly cautious. Chemotherapy can be extremely toxic and sometimes deadly. Without genomic testing or proof of the effectiveness of the specific drug being used on the exact cancer type being treated, chemotherapy can often be more toxic to the patient then to the cancer. Chemotherapy may be extremely expensive, profitable for some doctors (if dispensed by the doctor and not by a third party) and can be misused or overused, sometimes for profit.

Do you think any regulatory agency will stop the exploitation of elderly men with a high PSA or prostate cancer or approve new treatments at the risk of financially bankrupting thousands of treatment facilities and jeopardizing thousands more jobs? Do you think any regulatory agency will set guidelines for treatment and monitoring at the risk of upsetting the doctors who are over treating?

Often few good choices exist for treatment. A prostate cancer patient treatment choice often ends up being the least worst choice or the choice with the side effects a patient thinks he can tolerate. Patients can be sometimes misled about the expected side effects and results of the treatment being offered. The risk of chronic fatigue and depression is often never disclosed.

Long term care consists of regular PSA testing for years. Long term care for side effects is often lacking or exploitive or ineffective. Often complaints of side effects are disregarded by nurses, doctors and sometimes referred out to other doctors. The patient is sometimes left to figure out what to do about his side effects with the resources available to him. Long term side effects often consist of fatigue, bowel or urinary problems, sexual dysfunction, depression and other symptoms. Patients with complaints of chronic fatigue are often told to exercise, get plenty of sleep, pace yours self and eat a healthy diet; this advice is of limited help for chronic fatigue. Often treatments for long term side effects are embarrassing, degrading, unavailable, nonexistent, costly, not effective, not offered or bothersome. Prostate cancer treatment often results in fatigue, depression, isolation and sometimes suicide. Billions of dollars are profited from ED drug and other ED products, catheters, pads and diapers, drugs for depression or pain or insomnia or incontinence, additional treatments and surgeries for side effects. Also treatments for the multiple and bizarre side effects from hormone ADT therapy (chemical castration) is sometimes required.

Men and ageing: If any man lives long enough it is very likely he will have a prostate problem, low testosterones or some form of sexual dysfunction. In my opinion modern medicine often has been exploitive, abusive and has provided substandard care for older men in general due to all of the explanation given in this text. I believe much of the attitudes toward older Americans need improvement and they are sometimes viewed as being subhuman and exploitable by various individuals. If documented cases of unnecessary surgery and radiotherapy or blind biopsies on children by doctors for profit were released, the vast majority of Americans would be outraged and it would quickly end. However for older men it dose not seems to be of great concern?

Depression in prostate cancer patients is common, about 27% at 5 years (per some studies) and for advanced prostate cancer patient’s depression is even higher. Prostate cancer patients are at an increased risk of suicide.

Almost all prostate cancer treatments usually result a high percentage of erectile dysfunction. Loss of libido estimated at about 45%. Lower libido is almost never disclosed as a treatment side effect. Biopsies can sometimes also cause temporary or permanent ED. Often claims of prompt effective treatment for ED if it occurs after treatment are sometimes misleading. Statistics for ED percentages from treatment are usually quoted after treatment with Viagra, Muse or other ED treatments, therefore most statistics are very misleading. ED rated at 5 years may be as high as 50% to 80% or higher for most treatments. ED rated at 15 years may be as high as 90% or higher for most treatments. For cryotherapy, ED rates are extremely high. The cost for ED drugs like Levitra, Cialis, Viagra and Muse are kept very expensive by drug companies, about $9 to $45 per 1 pill. Many insurance companies will not pay for ED drugs or treatment. The patent for Viagra should have already expired in the USA. Less expensive generic drugs are usually unavailable in the US. Viagra should have already become available in a generic (in the USA) form for about $1 to $2 a pill. This is further exploitation by the drug companies of men in general. Men are further exploited by counterfeit mail order ED drug sales. ED drugs are not always effective and may have side effects. ED treatments can also be embarrassing, not offered, not practical, painful, expensive/not covered by insurance.

The numbers game: A doctor (and literature) may state a patients chances of ED is about 35% with EBRT radiotherapy or some other treatment. A patient may think, 35% is not too bad and if I do get ED I can always take Viagra. What a doctor may not tell a patient is that the ED rate is 35% at 2 years for a patient under 65 years old and with an ED drug treatment option. For a patient at 3 years, over 65 and no ED drugs the ED rate may be about 75% or higher. Obviously, a man is more likely to refuse treatment at a 75% ED rate verses a 35% ED rate. Some side effects may not be disclosed at all. If side effects (low libido, chronic fatigue, depression, etc) are not disclosed, no percentages will need to be quoted. Results are often worse for a surgery option, the main difference in ED results between surgery and radiotherapy is; with surgery ED will start out bad and may or may not get better with time, however with radiotherapy ED will get worse over time. With both together or with ADT hormones you’re in real trouble with ED percentages. Cure rates are often quoted at the 5 years mark for most treatments. A cure rate for a treatment at 5 years may be quoted at 85%; however the cure rate at 7 to 10 years may be only 70% and 50%. Always ask what is the “biochemical recurrence” (AKA rising PSA or treatment failure) rate for well beyond 5 years with your computer software simulation. Studies and clinical trials results, side effects percentage claims, etc can be biased. Watch out for terms like “age adjusted” or ambiguous or excluded facts as given in the above examples. I have read and have been given some extremely exaggerated claims concerning cure rated, side effects, etc.

In conclusion: Prostate cancer patients are sometimes elderly and exploited for profit (per documented studies). A blind biopsy is unsafe and newer test methods should be used. The treatments offered have horrible side effects. Some doctors are treating patients with low risk cancer or advanced age when monitoring is often a better option. Patience with low risk cancer or advanced age should often be offered “watchful waiting” or “active surveillance” instead of treatment. Aftercare for long term side effects is frequently ineffective, expensive, not offered, degrading or nonexistent. Prostate cancer patients are seldom told about chronic fatigue and the true risk of side effects are usually understated. Modern medicine often fails and victimizes prostate cancer patients.

If a patient has intermediate or high risk prostate cancer and dose not have advanced age he may need treatment. He should look into other advanced treatments if available. Also he should try and avoid hormone therapy if possible because of the multiple side effects. If advanced treatments are not available a 5 day SBRT radiation treatment may be considered (In my opinion, it could be the best of the bad choices). SBRT seems to be fast, least invasive or traumatic. ED and fatigue is still a high long term risk. Radiation with Hormone therapy has a higher risk of ED and long term fatigue.

The short version of my story: I was referred to an urologist by my family doctor after a high PSA test. I will refer to the urologist as Doctor “A”; he used old testing technology (18 core blind biopsies), his medical assistant seemed to have a mental defect exhibiting arrogant, rude and abusive behavior and was intent on inflicting psychological harm to me. Shortly after my Dr. “A” visits ended, his medical assistant was no longer employed at his office and no person in that office would refer to her employment or her existence. I was diagnosed with Prostate cancer by Dr. “A”. I refused his surgery and hormone therapy recommendation because of the eminent side effects and his unprofessional medical assistant behavior, so Dr. “A” referred me to Dr. “T”. Dr. “T” was outside of my insurance network; however his office manager stated she was willing to work with my insurance, offered me a doctor consultation and would accept any insurance payment as a full payment. When I arrived in his office the waiting room was empty. Dr. “T” used older conventional technology, offered me overtreatment, hormone therapy, unnecessary procedures and testes. One week after my consultation with Dr. “T” I received an $850 bill for the consultation, in conflict with what was agreed upon with his office manager. After a recommendation from a friend, I called Clinic “O” and met with the nurse. She offered me conventional treatments with a verbal guarantee of “no long term side effects”. However this nurse could not answer any of my basic questions, lacked any credibility and sounded like a used car salesmen. Most of these office visits caused me multiple problems with offices workers processing paperwork for tests, insurance forms and billing, etc. Two of these doctors offered me an unnecessary bone scan. Two of these doctors recommended hormone therapy (ADT Therapy). After I absolutely and utterly refused hormone therapy, both doctors admitted it probably would not help me in my final outcome because of the computer estimate run on me with my PSA, biopsy report, etc. Having no advance treatments (laser, etc) available to me at that time, I decided on treatment with Dr. “K”, he seemed honest and could answer my questions and had new equipment. Before my treatment could start I was referred to “W” lab for an MRI. “W” lab had a trainee assisting and it took over 2 hours to complete my MRI. 2 days later after receiving a copy of my MRI report, I examined the MRI report; it had my name and some other patient history information. I wasted 2 more days verifying it was the correct MRI of me and not some other prostate patient MRI before my treatment could start. Dr. “K” and his staff seemed competent and I did receive treatment from Dr. “K”. I did have a relatively fast and completely noninvasive treatment (SBRT), resulting in months of fatigue and some short term side effects. At this time I am doing well, however I’m not sure what the future will bring? I also no longer trust modern medicine, doctors, nurses, etc. Modern medicine seems to be more of a gamble then a science. I have wasted hundreds of hours and thousands of dollars. I feel modern medicine has abused and failed me due to the lack of guidelines and regulation, still approved obsolete technology, better unapproved treatments, exploitation, greed, apathy and incompetence. Hindsight is 20/20, I also believe I probably should have had no PSA testing or treatment. If I could do it over again, I would also consider no PSA testing and treatment or traveling for advanced treatments from a competent provider if practical and available. I believe if I did take the two doctors recommendations and received hormone therapy in addition to the radiotherapy my quality of life (QOL) would have been severely impacted for years or permanently and could possibly have resulting in my early death. I am not sure if my bad experiences are typical of today’s level of medical care or just bad luck in picking providers?

“Do no harm”, unless you can get away with it: I was harmed physically and verbally by Dr. “A” 18 core blind biopsy and verbally abused by his medical assistant. I was potentially exploited and financially harmed by Dr. “T” and offered unnecessary testing and overtreatment. Clinic “O” nurse attempted to misinform and deceive me about the treatment outcome of “no long term side effects”. I was harmed by “W” lab by mistakes and incompetence. I did also have numerous other billing and paperwork problems probably due to mistakes and apathy. At least 40% (probably substantially more) of the health care workers I came into contact with did or attempted to do some form of harm to me: attempted excessive testing and treatment, mistakes, billing overcharges, blind biopsy, false statements, deception, misinformation, apathy and abusive behavior¬¬¬-As explained in this text. I have also observed several medical facilities do not require workers to wear name tags; this may also be a factor in health care workers not acting in an ethical manner. It seems that this prostate cancer nightmare maze was intended for increased physical, psychological, financial harm and to be of questionable benefit.

My treatment choice: In my opinion, I feel LDR Brachytherapy and hormone therapy (AKA chemical castration) seemed to be completely degrading, disturbing and bizarre. Hormone therapy would not have been an effective treatment for me. Surgery and LDR Brachytherapy are to invasive. Surgery has an imminent danger of incontinence and ED. A 9 week EBRT radiotherapy was just to long and laborious. Because castration (orchiectomy), ADT hormone therapy (chemical castration), LDR Brachytherapy and blind biopsies are what I consider Frankenstein medicine (strange, bizarre, brutal, twisted or a perverted nightmare) I avoid all of them. Unfortunately I was deceived and misguided into having a blind biopsy. I do not believe other treatments like radiotherapy are good or greater choices either, just not as bad and acceptable at that time for me. The choice I made was a 5 day SBRT radiotherapy. A 5 day SBRT also has numerous drawbacks and side effects, about the same as a 9 week EBRT radiotherapy. I also had no advanced treatment options available to me. As I have stated above, If I could do it over again I would also consider no PSA testing and treatment or traveling for advanced treatments from a competent provider if practical and available. With prostate cancer, the testing and/or treatment is often worse then the disease. I am not implying anyone should make the same design as I did. I am only giving the motives for my decisions. I was also the victim of profit motivated and substandard providers.

Protect yourself: It should not be up to a patient to protect himself or herself from harm from doctors however the new standard in medical care now seems to be substandard. Do not let the sterile, friendly and professional environment of a doctor’s office detour you from protecting yourself from overtreatment or any unnecessary life changing tests and treatments. If you are concerned about misuse or privacy issues, refuse to fill out EPIC questioners and limit the information given to relevant information only. If you have a high PSA or prostate cancer, educate yourself. A patient should be extremely skeptical if exaggerated claims are made about minimal long term side effects from conventional treatments or blind biopsies. Bring someone educated or astute with you to your consultations and appointments. Avoid doctors that are mostly profit motivated. Do not submit to a blind biopsy if other options are available. Get a second or third opinion if you are being offered treatment with low risk cancer or have advanced age. Learn about all your treatment options, testing and side effects. Verify everything you are told. Under the HIPAA law you are entitle to a copy of all your medical records and bills. Always ask the name of the person assisting you. If they refuse the request for a name leave immediately (you may or may not be in extreme danger). Be very cautious if you are ever refused a copy of your records; demand a copy of your records and a reason for any denial and seek other advice. Get a copy and keep a file of your test results, biopsy report-Gleason score, PSA, MRI report, treatment plan, bills, insurance payouts, etc. Carefully monitor your PSA. Expect a temporary increase (for weeks or months) in PSA after some procedures. Verify the accuracy of paperwork. If treatment is necessary talk to your doctor in advance about side effect management, chronic fatigue, ED, Etc. Doctors that provide treatments often have computer software to predict the outcome using test results and different treatment options. Ask to see your computer predicted cure rate outcome with your treatment options if available. This may give you some insight to your options, cure rate and also to avoid overtreatment. Always ask what is the “biochemical recurrence” (AKA rising PSA or treatment failure) rate for well beyond 5 years. Contact a good prostate cancer support without a conflict of interest.

One more time: Multiple studies have verified more deaths caused from prostate cancer testing and treatment then from prostate cancer itself. Medical mistakes are the third cause of deaths in the USA (over 251,000 deaths a year, over one million deaths in 4 years) more then suicide, firearms and motor vehicle accidents combined.

Strict guidelines for prostate cancer testing and treatment need to be created and enforced because of the extensive and documented abuses of prostate cancer patients: 1. Blind biopsies should be banned. 2. Strict standards and gridlines for testing and treatment need to be created. 3. Full mandatory industry standard disclosure forms need to be created for tests and treatment to include realistic risk factor disclosure. 4. Newer testing and treatments need to be created and approved. 5. Dignity, privacy and confidentiality need to be standardized and enforced in addition to the HIPAA laws. 6. Aftercare needs to be available, standardized and regulated. 7. The cost for drugs needs to be regulated to end financial exploitation by drug companies. 8. Medical workers should be identifiable and be required to wear name tags with first and last names. 9. A new standard “Ethical Code of Conduct” needs to be created and enforced to end patient exploitation and abuse.

It is unlikely any of the above recommendations will be implemented unless prostate cancer affected a larger percent of the population or enough prominent people are affected. Prostate cancer patients must protect themselves, as the only alternative!

Clarification: The above text may probably anger and upset some people for various reasons. The intent of this document is not to imply all doctors are dishonest or to condemn all medical providers. The intent is to educate men and prostate cancer patients of the consequences and dangers that may await them so they can take appropriate action and to inform patients of real world, typical or worst case scenarios. I have also tried to include most scenarios a prostate cancer patient should be cautious of. Would some health care providers harm a patient for profit or by accident or some other reason? Yes, absolutely! We just don’t know who or what percent would. Shockingly for me it was will over 40% (probably 50% to 60%) that intended to do me some form of harm or provided substandard care as explained in my story. Are some other doctors and nurses exceptional? Yes! Differences in opinion, variations in semantics do not invalidate this document or its intent. The information in this document is a sum of my experience, other patient’s experiences and hundreds of videos, documents, books, conversations, clinical trial, blogs, studies, articles, etc.

Disclaimer: I have no conflict of interest. I have no affiliation with any support group or other organizations. I am not a doctor. I do not prevent, treat, diagnose, cure or advise on medical matters. The information above is for educational purposes only. If you need treatment or medical advice, consult a competent and trustworthy medical doctor.

Anyone may copy or distribute this document without changing or modifying it or its content.

“The thing about the truth is, not a lot of people can handle it” Conor McGregor.
I have been extensively criticized for creating this document. In order to insure my privacy and avoid any potential reprisals, further abuse or exploitation, I will remain Anonymous.

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