Prostate Cancer: Causes, Symptoms and Treatments

Prostate cancer is a disease which only affects men. Cancer begins to grow in the prostate - a gland in the male reproductive system.

The word "prostate" comes from Medieval Latin prostate and Medieval French prostate. The ancient Greek word prostates means "one standing in front", from proistanai meaning "set before". The prostate is so called because of its position - it is at the base of the bladder.

Contents of this article:

1. What is the prostate?
2. Prostate cancer
3. Classification of prostate cancer
4. Signs and symptoms of prostate cancer
5. Causes of prostate cancer
6. Prostate cancer treatments
7. Possible complications

Fast facts on prostate cancer

Here are some key points about prostate cancer. More detail and supporting information is in the main article.

• After non-melanoma skin cancer, prostate cancer is the most common cancer among men in the US.
• Prostate cancer is one of the leading causes of cancer death among men of all races and Hispanic origin populations.
• In the US around 209,292 men are diagnosed with prostate cancer per year.
• Around 27,970 men die from prostate cancer in the US each year.
• According to the American Cancer Society about 1 man in 7 will be diagnosed with prostate cancer during his lifetime.
• Prostate cancer mainly occurs in older men - about 6 cases in 10 are diagnosed in men 65 years or older.
• Almost all prostate cancers are adenocarcinomas - cancers that begin in cells that make and release mucus and other fluids.
• Prostate cancer often has no early symptoms.
• Advanced prostate cancer can cause men to urinate more often or have a weaker flow of urine.
• Most men diagnosed with prostate cancer do not die from it. More than 2.9 million men in the US diagnosed with prostate cancer at some point are still alive today.

What is the prostate?

The prostate is an exocrine gland of the male reproductive system, and exists directly under the bladder, in front of the rectum. An exocrine gland is one whose secretions end up outside the body e.g. prostate gland and sweat glands. It is approximately the size of a walnut.

Diagram of the location of the prostate gland and nearby organs

The urethra - a tube that goes from the bladder to the end of the penis and carries urine and semen out of the body - goes through the prostate.

There are thousands of tiny glands in the prostate - they all produce a fluid that forms part of the semen. This fluid also protects and nourishes the sperm. When a male has an orgasm the seminal-vesicles secrete a milky liquid in which the semen travels. The liquid is produced in the prostate gland, while the sperm is kept and produced in the testicles. When a male climaxes (has an orgasm) contractions force the prostate to secrete this fluid into the urethra and leave the body through the penis.

Urine control

As the urethra goes through the prostate: the prostate gland is also involved in urine control (continence) with the use of prostate muscle fibers. These muscle fibers in the prostate contract and release, controlling the flow of urine flowing through the urethra.

The Prostate Produces Prostate-specific antigen (PSA)

The epithelial cells in the prostate gland produce a protein called PSA (prostate-specific antigen). The PSA helps keep the semen in its liquid state. Some of the PSA escapes into the bloodstream. We can measure a man's PSA levels by checking his blood. If a man's levels of PSA are high, it might be an indication of either prostate cancer or some kind of prostate condition.

It is a myth to think that a high blood-PSA level is harmful to you - it is not. High blood PSA levels are however an indication that something may be wrong in the prostate.

Male hormones affect the growth of the prostate, and also how much PSA the prostate produces. Medications aimed at altering male hormone levels may affect PSA blood levels. If male hormones are low during a male's growth and during his adulthood, his prostate gland will not grow to full size.

In some older men the prostate may continue to grow, especially the part that is around the urethra. This can make it more difficult for the man to pass urine as the growing prostate gland may be causing the urethra to collapse. When the prostate gland becomes too big in this way, the condition is called Benign Prostatic Hyperplasia (BPH). BPH is not cancer, but must be treated.

Prostate cancer

In the vast majority of cases, the prostate cancer starts in the gland cells - this is called adenocarcinoma. In this article, prostate cancer refers just to adenocarcinoma.

Prostate cancer is mostly a very slow progressing disease. In fact, many men die of old age, without ever knowing they had prostate cancer - it is only when an autopsy is done that doctors know it was there. Several studies have indicated that perhaps about 80% of all men in their eighties had prostate cancer when they died, but nobody knew, not even the doctor.

Experts say that prostate cancer starts with tiny alterations in the shape and size of the prostate gland cells - Prostatic intraepithelial neoplasia (PIN).

Doctors say that nearly 50% of all 50-year-old men have PIN. The cells are still in place - they do not seem to have moved elsewhere - but the changes can be seen under a microscope. Cancer cells would have moved into other parts of the prostate. Doctors describe these prostate gland cell changes as low-grade or high-grade; high grade is abnormal while low-grade is more-or-less normal.

Any patient who was found to have high-grade PIN after a prostate biopsy is at a significantly greater risk of having cancer cells in his prostate. Because of this, doctors will monitor him carefully and possibly carry out another biopsy later on.

Classification of prostate cancer

It is important to know the stage of the cancer, or how far it has spread. Knowing the cancer stage helps the doctor define prognosis - it also helps when selecting which therapies to use. The most common system today for determining this is the TNM (Tumor/Nodes/Metastases). This involves defining the size of the tumor, how many lymph nodes are involved, and whether there are any other metastases.

When defining with the TNM system, it is crucial to distinguish between cancers that are still restricted just to the prostate, and those that have spread elsewhere. Clinical T1 and T2 cancers are found only in the prostate, and nowhere else, while T3 and T4 have spread outside the prostate.

There are many ways to find out whether the cancer has spread. Computer tomography will check for spread inside the pelvis, bone scans will decide whether the cancer has spread to the bones, and endorectal coil magnetic resonance imaging will evaluate the prostatic capsule and the seminal vesicles.

The Gleason Score

A pathologist will look at the biopsy samples under a microscope. If cancer tissue is detected, the pathologist then grades the tumor. The Gleason System of grading goes from 2 to 10. The higher the number, the more abnormal the tissues are compared to normal prostate tissue.

Two numbers are added up to get a Gleason score:

1. A number from 1 to 5 for the most common pattern observed under the microscope. This is the predominant grade and must be more than 51% of the sample.
2. A number from 1 to 5 for the second most common pattern. This is the secondary grade and must make up more than 5% but less than 50% of the sample.

A Gleason score of 7 can have two meanings. Look at these two examples below:

1. If the predominant grade is 3 and the secondary grade is 4, the Gleason score is 7.
2. If the predominant grade is 4 and the secondary grade is 3, the Gleason score is also 7.

However, the first example, with a predominant score of 3, has a less aggressive cancer than the second example, with a predominant score of 4.

It is crucial that the tumor is graded properly, as this decides what treatments should be recommended.

Signs and symptoms of prostate cancer

During the early stages of prostate cancer there are usually no symptoms. Most men at this stage find out they have prostate cancer after a routine check up or blood test. When symptoms do exist, they are usually one or more of the following:

• The patient urinates more often
• The patient gets up at night more often to urinate
• He may find it hard to start urinating
• He may find it hard to keep urinating once he has started
• There may be blood in the urine
• Urination might be painful
• Ejaculation may be painful (less common)
• Achieving or maintaining an erection may be difficult (less common).

If the prostate cancer is advanced the following symptoms are also possible:

• Bone pain, often in the spine (vertebrae), pelvis, or ribs
• The proximal part of the femur can be painful
• Leg weakness (if cancer has spread to the spine and compressed the spinal cord)
• Urinary incontinence (if cancer has spread to the spine and compressed the spinal cord)
• Fecal incontinence (if cancer has spread to the spine and compressed the spinal cord).

Causes of prostate cancer

Nobody is really sure of what the specific causes are. There are so many possible factors, including age, race, lifestyle, medications, and genetics, to name a few.

1) Age

Age is considered as the primary risk factor. The older a man is, the higher is his risk. Prostate cancer is rare among men under the age of 45, but much more common after the age of 50.

2) Genetics

Statistics indicate that genetics is definitely a factor in prostate cancer risk. It is more common among certain racial groups - in the USA prostate cancer is significantly more common and also more deadly among Afro-Americans than White-Americans. A man has a much higher risk of developing cancer if his identical twin has it. A man whose brother or father had/had prostate cancer runs twice the risk of developing it, compared to other men.

Studies indicate that the two faulty genes - BRCA 1 and BRCA 2 - which are important risk factors for breast cancer and ovarian cancer, have also been implicated in prostate cancer risk.

In a study scientists found seven new sites in the human genome that are linked to men's risk of developing prostate cancer.

Faulty BRCA2 gene linked to aggressive form of prostate cancer - researchers at the The Institute of Cancer Research, UK, reported in the Journal of Clinical Oncology (April 2013 issue) that men who have inherited the faulty BRCA2 gene are more likely to have the faster-spreading type of prostate cancer. The scientists say these men should receive treatment immediately after diagnosis with surgery or radiation therapy, rather than receive the "watchful waiting" approach.

Senior author Ros Eeles wrote that experts have already known that those with the faulty BRCA2 gene have a higher risk of developing prostate cancer. This is the first large study to demonstrate that the faulty gene is also linked to a faster spread of the disease and poorer survival.

This new discovery will make some health authorities around the world rethink their policies and procedures. In the United Kingdom, the National Health Service offers the same prostate cancer treatment for both carriers and non-carriers of the faulty BRCA2 gene.

Prof. Eeles said "It must make sense to start offering affected men immediate surgery or radiotherapy, even for early-stage cases that would otherwise be classified as low-risk. We won't be able to tell for certain that earlier treatment can benefit men with inherited cancer genes until we've tested it in a clinical trial, but the hope is that our study will ultimately save lives by directing treatment at those who most need it."

3) Diet

A review of diets indicated that the Mediterranean diet mayreduce a person's chances of developing prostate cancer.Another study indicates that soy, selenium and green tea, offer additional possibilities for disease prevention - however, a more recent study indicated that combination therapy of vitamin E, selenium and soy does not prevent the progression from high-grade prostatic intraepithelial neoplasia (HGPIN) to prostate cancer. A diet high in vegetable consumption was found in a study to be beneficial.

A US pilot study on men with low risk prostate cancer found that following an intensive healthy diet and lifestyle regime focusing on low meat and high vegetable and fruit intake, regular exercise, yoga stretching, meditation and support group participation, can alter the way that genes behave and change the progress of cancer, for instance by switching on tumor killers and turning down tumor promoters.

Other studies have indicated that lack of vitamin D, a diet high in red meat may raise a person's chances of developing prostate cancer.

A study published in the journal Clinical Cancer Research suggests vitamin D deficiency may predict aggressive prostate cancer.

4) Medication

Some studies say there might be a link between the daily use of anti-inflammatory medicines and prostate cancer risk. A study found that statins, which are used to lower cholesterol levels, may lower a person's risk of developing prostate cancer.

5) Obesity

A study found a clear link between obesity and raised prostate cancer risk, as well as a higher risk of metastasis and death among obese people who develop prostate cancer.

6) Sexually transmitted diseases (STDs)

Men who have had gonorrhea have a higher chance of developing prostate cancer, according to research from the University of Michigan Health System.

7) Agent Orange

Veterans exposed to Agent Orange have a 48% higher risk of prostate cancer recurrence following surgery than their unexposed peers, and when the disease comes back, it seems more aggressive, researchers say. Another study found that Vietnam War veterans who had been exposed to Agent Orange have significantly increased risks of prostate cancer and even greater risks of getting the most aggressive form of the disease as compared to those who were not exposed.

8) Enzyme PRSS3 linked to aggressive prostate cancer

Scientists from the Mayo Clinic, Florida, reported in Molecular Cancer Research that PRSS3, an enzyme, changes the environment of prostate cancer cells, making the cancer much more likely to metastasize.

Senior researcher, Evette Radisky, Ph.D., said "This molecule is a protease, which means it digests other molecules. Our data suggests PRSS3 activity changes the environment around prostate cancer cells - perhaps by freeing them from surrounding tissue - to promote malignancy and invasiveness. I don't think PRSS3 is the only factor involved in driving aggressive prostate cancer, but it may be significant for a certain subset of this cancer - the kind that is potentially lethal."

Recent developments on prostate cancer causes from MNT news

Chronic prostate inflammation tied to nearly double risk of prostate cancer - a study reported in the journal Cancer Epidemiology, Biomarkers & Prevention, finds that compared to men with no such signs, men with chronic inflammationin non-cancerous prostate tissue may have nearly double the risk of developing prostate cancer.

Vasectomy linked with aggressive prostate cancer risk - In the largest and most comprehensive study of its kind, researchers from Harvard School of Public Health in Boston, MA, find that vasectomy is associated with a small increased risk of prostate cancer, and a larger increased risk for advanced or lethal prostate cancer.

Prostate cancer: high cholesterol, triglyceride levels may raise risk of recurrence - Among men who have surgery for prostate cancer, those who have high total cholesterol and triglyceride levels - two types of fat found in blood - may be at increased risk of disease recurrence. This is according to a study published in the journal Cancer Epidemiology, Biomarkers & Prevention.

Western diet could be fatal for prostate cancer patients - A new study has suggested that following a Western diet - high in red and processed meats, refined grains and high-fat dairy products - could increase the risk of death for people with prostate cancer from both prostate cancer and all causes.

Prostate cancer treatments

The following treatments are separated into early stage and advanced stage prostate cancers.

Early stage prostate cancer

If the cancer is small and contained - localized - it is usually managed by one of the following treatments:

• Watchful waiting - not immediate treatment is carried out. PSA blood levels are regularly monitored.
• Radical prostatectomy - the prostate is surgically removed.
• Brachytherapy - radioactive seeds are implanted into the prostate.
• Conformal radiotherapy - the radiation beams are shaped so that the region where they overlap is as close to the same shape as the organ or region that requires treatment, thus minimizing healthy tissue exposure to radiation.
• Intensity modulated radiotherapy - beams with variable intensity are used. An advanced form of conformal radiotherapy usually delivered by a computer-controlled linear accelerator.
  Treatment recommendations really depend on individual cases. In general, if there is a good prognosis and the cancer is in its early stages, all options can be considered. However, they all have their advantages and disadvantages. The patient should discuss available options thoroughly with his doctor.

More advanced prostate cancer

If the cancer is more aggressive, or advanced, the patient may require a combination of radiotherapy and hormone therapy. Radiotherapy requires treatment on an everyday basis for up to about eight weeks. Radical surgery is also an option - the prostate is removed. Traditional surgery requires a hospital stay of up to ten days, with a recovery time that can last up to three months. Robotic keyhole surgery has the advantage just a couple of days in hospital, followed by a much shorter recover period. However, even robotic keyhole surgery may not be ideal for very elderly patients.

In advanced prostate cancer hormone therapy is very effective in slowing down, and even stopping the growth of cancer cells. Even if the hormone therapy stops working after a while, there are still other options the patient will be able to discuss with his doctor, such as participating in clinical trials.

Radioactive injection helps advanced prostate cancer patients live longer - scientists at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, UK, reported in NEJM (New England Journal of Medicine) that radium-233, a radiation injection, directly targets tumors in the bone delivering short range radiation, causing minimal damage to healthy tissue. Radium, like calcium, is absorbed by the bone.

Delivering estrogen through skin patches may be an easier and safer way to treat prostate cancer than the hormone therapies that are currently used, British researchers explained in Lancet Oncology (March 2013 issue).

In May 2013, the US FDA approved Xofigo (radium Ra 223 dichloride) for metastatic castration-resistant prostate cancer that has reached bones but not other organs. Enzalutamide is taken in combination with docetaxel, another cancer medication.

Richard Pazdur, M.D., from the FDA, said "Xofigo binds with minerals in the bone to deliver radiation directly to bone tumors, limiting the damage to the surrounding normal tissues. Xofigo is the second prostate cancer drug approved by the FDA in the past year that demonstrates an ability to extend the survival of men with metastatic prostate cancer."

Xtandi (enzalutamide) was approved by the FDA in August 2012 for patients with metastatic castration-resistant prostate cancer that has spread or recurred.

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Scientists reveal genetic root of prostate cancer

An international team of scientists have revealed the genetic root of prostate cancers in individual men, demonstrating that tumors share common gene faults which could potentially offer new targets for treatment.

Prostate cancer is the second most common cancer and second leading cause of cancer death in men.

The research, published in Nature, is part of the International Cancer Genome Consortium - a global project committed to revealing genetic changes driving prostate cancer, using the most up-to-date gene-sequencing technology available.

Tumor samples from 10 men with prostate cancer were analyzed, allowing the researchers to map a "family tree" of changes occurring at a genetic level as the cancer develops.

The researchers also learned more about how the disease spreads through the body and forms new tumors. They discovered that the first group of cells that spread from the prostate continues to travel throughout the body, developing new tumors as it goes.

"We gained a much broader view of prostate cancer by studying both the original cancer and the cells that had spread to other parts of the body in these men," says study author Prof. Ros Eeles from the Institute of Cancer Reseach in London, UK. "And we found that all of the cells that had broken free shared a common ancestor cell in the prostate."

Prostate cancer is the second most common cancer in American men behind skin cancer and the second most common cause of cancer death behind lung cancer. Around 1 in 7 men will be diagnosed with prostate cancer during their lifetime.

According to American Cancer Society (ACS) estimates, in 2015, around 220,800 new cases of prostate cancer will be diagnosed, and 27,540 deaths will occur attributable to the disease.

The researchers have already discovered that cancer cells taken from different sites within a man's prostate can be very diverse genetically. Despite this, the new study found that cancer cells moving away from the prostate share genetic faults that are unique to the man whose cancer it is.

"The common faults we found in each man could potentially offer new targets for treatment," states Prof. Eeles. "But we found that, once cancer cells have spread, they continue to evolve genetically, so choosing the most effective treatments will remain a key challenge."

Shared mutations represent 'a potential Achilles heel' for prostate cancer

Prof. Steven Bova from the University of Tampere in Finland believes that in order to find these shared genetic faults, multiple biopsies may be needed. "We must also study more patients to learn how to apply these findings to develop more personalized treatments for people with the disease," he adds.

Learning how cancer cells change and evolve as they metastasize (spread to other parts of the body) and thus become resistant to certain forms of treatment is crucial to developing future treatments for all forms of cancer.

Senior author Dr. Ultan McDermott says that while the shared tumor-causing genetic faults mapped by their "family tree" represent a potential Achilles heel for prostate cancer, "many of these shared mutations are in tumor suppressor genes and our approach to therapeutically targeting these needs to be prioritized."

"We have to zoom in on this crucial junction and gather more data on the impact different therapies have on prostate cancer's evolution and spread," he adds.

The study authors conclude that these findings "elucidate in detail the complex patterns of metastatic spread and further our understanding of the development of resistance to androgen-deprivation therapy in prostate cancer."

Recently, Medical News Today reported on new research suggesting that taking vitamin D supplements could slow or reverse the progression of low-grade prostate tumors, reducing the need for surgery or radiation therapy.

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Androgen Deprivation Therapy For Prostate Cancer Can Cause Osteoporosis

Androgen deprivation therapy is a common and effective treatment for advanced prostate cancer. However, among other side-effects, it can cause significant bone thinning in men on long-term treatment.

A new study¹ by Vahakn Shahinian and Yong-Fang Kuo from the Universities of Michigan and Texas respectively, finds that although bone mineral density testing is carried out on some men receiving this therapy, it is not routine. They did note, however, that men were significantly more likely to be tested when they were being cared for by both a urologist and a primary care physician. Their paper² appears in the Journal of General Internal Medicine, published by Springer.

Androgen deprivation therapy cuts off the production of testosterone by the male testes. This prolongs the life of men with advanced prostate cancer, often by years. However, the therapy can cause osteoporosis which carries an increased risk of fracture. There are treatments available which can help reduce the extent of osteoporosis suffered. Despite recommendations for bone mineral density testing being incorporated into practice guidelines in 2002, it still does not seem to be carried out frequently enough.

In order to ascertain current levels of testing, the researchers looked at the medical records of over 80,000 men with prostate cancer in a Medicare claims database between 1996 and 2008. Although they noted that the levels of bone mineral density testing had increased over those years, only just over 11 percent of men received a test for osteoporosis in the last year studied.

According to the authors, "The absolute rates of bone mineral density testing remain low, but are higher in men who have a primary care physician involved in their care." Levels of testing were lowest in men being cared for by just a urologist alone.

The authors emphasize that bone care is not within the usual remit of most urologists and, as such, may be outside their comfort zone for diagnosis and management. Urologists are not alone in this, though, as breast and colorectal cancer patients also tend to fare better with the involvement of a primary care physician in addition to their oncologist.

It would therefore appear important to derive a system whereby primary care physicians remain involved in the care of men with prostate cancer. In addition, urologists need to be made more aware of the risk to bones and men starting androgen deprivation therapy need to know to ask about the test.

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Nearly Half Of All Deaths From Prostate Cancer Can Be Predicted Before Age 50

A new design of screening could improve ratio between benefit and harms of screening

Focusing prostate cancer testing on men at highest risk of developing the disease is likely to improve the ratio between benefits and the harms of screening, suggests a paper published this week on bmj.com.

Prostate specific antigen (PSA) screening is widely used for the early detection of prostate cancer, but remains highly controversial, as it became widespread long before evidence to prove its value. There is now evidence that PSA screening can reduce prostate cancer mortality in men who would not otherwise be screened. However, this can come at considerable harm.

As there is little evidence to support many aspects of screening guidelines, researchers from Sweden and the USA carried out a case-control study taking data from the Malmo Preventative Project (MPP) cohort, in an attempt to develop an evidence-based scheme for prostate cancer testing. A previous study from the MPP, published in the BMJ in 2010, demonstrated that PSA level at age 60 is strongly predictive of the risk of death from prostate cancer by age 85.

The Malmo cohort included 21,277 men aged 27 to 52 who participated in the MPP between 1974 and 1984. All these men gave a blood sample. A smaller group of these men were then invited to provide a second blood sample about six years later: 4922 (72%) of those re-invited complied.

The researchers focused their studies on men close to age 40, mid-to-late forties (45-49) and early-to-mid fifties (51-55).

Within 25 to 30 years, 44% of deaths from prostate cancer occurred in those with the top 10% of PSA levels at age 45-49, a PSA of about 1.5 ng / ml or more. The risk of prostate cancer death was more than 10 times greater in this group compared to men with the lowest 25% of PSA levels.

The researchers questioned whether PSA screening should start at age 40, mid-to-late 40s or early 50s: they found that even for men with PSA in the top decile at age 40, the risk of metastatic prostate cancer was very low at 0.6%, after 15 years of follow-up. The researchers say that due to this, it would be difficult to justify initiating PSA testing at age 40 for men with no other significant risk factor.

In contrast, the risk of developing metastatic prostate cancer within 15 years is close to three-fold higher for men in the top level PSA at age 45-49 (1.7%) and close to ten-fold higher at age 51-55 (5.2%). This suggests that initiating PSA screening after age 50 would leave a significant proportion of men at elevated risk of later being diagnosed with an incurable cancer.

The researchers also looked at screening intervals: results showed that the absolute risk of metastatic cancer remains very low within 15 years follow-up for men with PSA in the low deciles and as such, a screening interval less than five years for these men is unnecessary.

The researchers conclude that PSA levels are informative of the current risk of cancer as well as being "predictive of the future risk of prostate cancer" and any cancer-specific death. They say that screening programmes can be designed so as to "reduce the risk of over-diagnosis whilst still enabling early cancer detection for men at highest risk of death from prostate cancer". As it turns out, the best way to determine risk is a single PSA before the age of 50.

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