MfA - Prostate Cancer

Medicine for Africa - Medical Information Service

ROSTATE ANCER

Definition:

The prostate gland is part of the male reproductive system. The name ‘prostate’ comes from Greek, meaning ‘the one who stands before’ or better worded, the ‘protector’. The prostate gland is about the size of a kiwi fruit (not as small as a walnut as often described) and weighs on average about 11 grams.

The most common form of prostate cancer is the adenocarcinoma (95%), consisting of the abnormal growth of glandular cells within the glands of the prostate. Other, rare forms of prostate cancer include, among others, the small cell carcinoma (very aggressive) and squamous cell carcinoma. Carcinomas other than the adenocarcinoma, do not influence the prostate specific antigen (PSA) test and thus, cannot be detected via the PSA blood test (see below).

The prostate’s function is to store and secrete an alkaline milky fluid, which consists of approximately 20-30% of the seminal fluid. This fluid, along with fluid from the seminal vesicles, which are located near the prostate and excrete 50-70% of the seminal fluid, and about 20 to 40 million sperms per ml (produced in the testes), make up the 1.5 to 2 ml of ejaculate during an orgasm. The semen is alkaline, in order to neutralize the acidity of the vaginal tract and to nurture and prolong the lifespan of the sperms and to support their ‘trip’ through the uterus (womb) and up the fallopian tube.

Cancer of the prostate is the third most common cause of death due to cancer in men of all ages, and the most common cause of cancer related death in men over the age of 75. While prostate cancer is rarely found in men under the age of 45, its overall occurrence is increasing worldwide.

The cause of prostate cancer is still not well known; however, there are a number of known risk factors that can increase the chance to develop prostate cancer, including:

High risk factors:

Black men;
Genetics – doubles the risk;
Age – risk increases with age, especially past age 60.

Increased risk factors:

Alcohol abuse;
Diet – high in meat and fat and low in fruits and vegetables;
Cadmium exposure;
Agent orange exposure (according to a 2007 US war veterans study);
Farmers;
Painters;
Tire plant workers
High blood pressure.

Japanese men who live in Japan have the lowest risk for prostate cancer, which, however, increases, if they move permanently abroad. Men from the USA are worldwide among the highest risk group for developing prostate cancer. Thus, it is the most common type of cancer in men in the United States and the second leading cause of cancer death in the U.S. and the United Kingdom in men after lung cancer.

Up to date, no one specific gene responsible for prostate cancer has been identified, although several have been linked, such as e.g. the BRAC1 and BRAC2, which are important risk factors for breast cancer and ovarian cancer in women. Furthermore, a so-called oncoprotein (promotes cancer growth), labeled BCL-2, has been found to be associated with the development of a form of androgen-independent prostate cancer.

The link between diet and prostate cancer is also still rather tentative. While both increased fruits and vegetables or decreased intake of red meat appear to only play a little role in the development of prostate cancer, there has been some evidence that the consumption of tomatoes and in particular, processed tomato products (due to its antioxidant lycopene), as well as green tea (due to its catechins) seem to have some preventive effect (see Prevention).

The overall role of infection of the prostate (prostatitis) on cancer development is still somewhat inconclusive, although infections with certain sexually transmitted infections, in particular infections with chlamydia, gonorrhea and syphilis bacteria seem to increase the risk of cancer development.

Symptoms:

Early prostate cancer usually does not cause any symptoms and is most often diagnosed during a routine checkup and/or during the work-up of an elevated PSA (‘Prostate Specific Antigen’) level in blood.

In a somewhat advanced stage of prostate cancer, uncharacteristic forms of pain can develop which are often misinterpreted by both the patient and the doctor. Frequently, pain develops along the perineum (between the testicles and the anus), or it can cause lower back pains, sciatic nerve pains (with radiating pain down the legs), or extend to the inner thigh areas, and be treated accordingly.

As the cancer grows to a certain size, it may cause symptoms similar to those due to hyperplasia (increased growth of cells) of the prostatic gland, called ‘benign prostatic hyperplasia’ or BPH, or due to invasion of the tumor into adjacent organs, especially the sigmoid colon (the last section of the colon). Now, symptoms may include:

Frequent urination;
Nocturia – frequent urination during the night;
Delayed or slow start of urine;
Slow urine stream with dribbling or leakage after urinating;
Straining when urinating and not being able to empty bladder completely;
Erectile dysfunction and/or painful ejaculation;
Blood in urine and/or semen;
Bone pain and/or tenderness especially of the lower back and/or pelvis (in advanced cancer, see below).

With the exception of the last three, these symptoms can also be present in benign hyperplasia, BPH, or even infection of the prostate (prostatitis) and are not diagnostic of cancer.

Advanced cancer with spread to other (neighbouring) parts of the body (metastases) can cause additional symptoms, such as intense bone pain, most often in the lower vertebral column (spine), but also in the ribs, pelvis and the thigh (femur). The metastases in the spine can result in collapse of some vertebral bones and compression of the spinal cord with subsequent leg weakness, urinary and fecal incontinence and erectile dysfunction.

Diagnosis:

There a number of ways how prostate cancer can be suspected and subsequently diagnosed.

The old-fashioned physical examination including rectal digital evaluation of the prostate can often signal the suspicion for cancer, because most cancers of the prostate develop in the posterior walls of the prostate, which is the part that can be examined by way of a rectal digital examination. Up to 70% of prostate cancer can be diagnosed by a simple finger examination.

In addition, a blood test for the so-called PSA (Prostate Specific Antigen) can indicate an abnormal prostate. An increased level of PSA (normal value is < 4.0 ng/ml [nannogram/milliliter]) can be caused by an infection (prostatitis), benign hyperplastic hyperplasia (BPH) or prostate cancer and is thus an indication to do further tests. If the PSA value is between 4.0 and 10.0 ng/ml, the free part of PSA should be determined to further specify the result. The diagnosis of cancer becomes suspect, if the amount of free PSA to total PSA is below 0.15 (less than 15%); however, a quotient of above 0.15 does not exclude the possibility of cancer.

A recently performed study by British researchers, published in the journal Clinical Cancer Research, has found a specific protein that is being secreted by prostate cancer, which they called ‘Engrailed-2 (EN2). EN2 can easily be detected in the urine of a patient via a dipstick test (similar to a pregnancy test) and can give results within just five minutes. The test is less invasive and supposedly more accurate with far less false positive results than the PSA test. However, it may still take a few years before this test will be commercially available.

Whether PSA or EN2 in the future, once any of these tests indicate the possibility of cancer, other test will have to be done to further evaluate the prostate. Thus, at this point in time, a cystoscopy, in which a flexible camera is inserted into the urethra, can help to evaluate the urinary tract from inside the bladder, as well as the section of urethra that lies within the prostate.

Also, a transrectal ultrasonography can be performed by inserting a probe into the rectum and using sound waves to create a picture of the prostate, which will signal areas of increased density, which may be consistent with BPH or cancer.

If cancer is suspected, a biopsy, or rather a set of needle biopsies, usually three to six samples from each side of the prostate, will be diagnosed by the pathologist, who can make a definite diagnosis of cancer, if present within the biopsy material. The pathologist will grade the cancer according to the so-called ‘Gleason grade’ and ‘Gleason score’, which will determine its aggressiveness.

The Gleason grade determines how aggressive the tumor cells are – the grading scale is from 1-5, with 5 being the most aggressive, i.e. the cells in grade '5' are the least differentiated ones, meaning that they barely look like normal cells anymore. Most of the time, there are cells of different Gleason grades present within the biopsies; therefore, the pathologist adds the two highest grades together resulting in the Gleason score, which is a scale from 2-10. The higher the number in the Gleason score, the more aggressive the tumor and the more likely that the tumor has spread beyond the prostate gland to other organs or organ structures (metastases).

Gleason score:

Score 2-4: Low grade cancer (well differentiated tumor cells);
Score 5-7: Intermediate grade cancer (moderately differentiated tumor cells), most frequent diagnosis;
Score 8-10: High grade cancer (poorly differentiated tumor cells).

And finally, once the diagnosis of cancer has been established by biopsy, the extent of cancer spread can be determined via the following tests:

CT scan (computer tomography scan);
Bone scan (because prostate cancer usually metastasizes into the bones – vertebral column, pelvis femur (thigh bone);
MRI – Magnetic Resonance Imaging, can be performed to closely evaluate the prostate capsule and whether the adjacent seminal vesicles are invaded.

As with all carcinomas, following the above work-up for diagnosing the aggressiveness of the tumor (Gleason score) and the extend of the tumor spread, the ‘stage’ of the tumor will be determined, which will help to decide on the appropriate form of treatment and help to define the prognosis. This is usually done by the TNM system, where:

T – stands for Tumor and is divided into several subcategories, from TX (tumor cannot be assessed) to T0, T1 and T2 cancers, which are still confined within the prostate tissue, whereas T3 and T4 express the extend of spread beyond the prostate;
N – stands for (lymph) Nodes, from NX (cannot be evaluated) to N1, N2 and N3, depending on the size and number of lymph nodes involved;
M – stands for Metastasis, with MX (cannot be assessed), M0 for no distant metastasis and M1 (a, b and c) describing metastases in various close or distant organs.

The TNM stage is important for deciding on the most appropriate form of therapy.

Treatment:

Therapy has to be decided upon each individual, as age, grade and stage of the cancer have to be considered. Thus, if the patient is in advanced age and the cancer a small low grade cancer, close surveillance via the PSA test (and possibly repeated biopsies over time) may be the most desirable form of treatment.

In younger patients, there are a number of treatment options available, again, depending on the Gleason grade and clinical stage of the tumor:

Surgery – ‘radical prostatectomy’, may be the treatment of choice, if the cancer is confined to the prostate gland and has not yet penetrated the boundaries of the prostate. The surgery includes the removal of the entire gland including its capsule, surrounding tissue and seminal vesicles. This operation carries a high risk of subsequent permanent impotence as well as loss of bladder control with urinary incontinence and even loss of bowel control.

Radiation therapy – may be done prior to surgery, in order to shrink the tumor mass, after surgery to assure that possibly remaining cancer cells will be destroyed, or, if the tumor has spread beyond the prostate gland itself and is not primarily treatable with surgery anymore. Side effects of radiation therapy can be quite debilitating, including impotence, urinary incontinence, blood in urine, loss of appetite and loss of bowel control, rectal burning or injuries, diarrhea and local skin reactions.

Proton therapy – is a variation of radiation treatment, in which proton beams are directed towards the tumor, as delineated by prior MRI testing. This form of treatment is well tolerated and causes minimal urinary and rectal side effects.
Brachytherapy – is another form of radiation treatment, in which radioactive seeds are placed inside the prostate gland, near the tumor area, as defined by prior MRI testing. The seeds are very small and cannot be felt by the patient; they can be placed temporarily or permanent. Brachytherapy is best indicated for small cancers that are detected early and grow slowly, but can also be done in advanced cases. Side effects are similar to the usual radiation therapy and include pain, swelling or bruising of penis and scrotum, blood in urine or semen, impotence, urinary incontinence and diarrhea.

Hormone therapy – can be tried in tumors that have spread. Since prostate cancers need testosterone, the main male hormone, for growth, drugs that interfere with the testosterone production or effects can help to relieve tumor symptoms; there are two groups of hormone drug:

LH-RH agonists – ‘luteinizing hormone-releasing hormone agonists are the primary type of hormone drugs. They block the body from making testosterone; these drugs are given by injection, usually every three to six months. Side effects may include nausea and vomiting, anemia (low red blood cells in blood), lethargy, osteoporosis, reduced sexual desire, impotence and weight gain.
Androgen-blocking drugs – suppress the production of the androgens and can be used after all other treatment options have been exhausted or in far advanced cases with metastases. These drugs can cause a standstill of tumor growth for several years. Side effects include erectile dysfunction, loss of sexual desire, liver problems, diarrhea and enlarged breasts (gynecomastia).
Orchiectomy – the removal of the testes is also a form of hormone therapy, as much of the testosterone is produced by the testes; however, this surgery is not done very often anymore.

Hormone-refractory prostate cancer – HRPC; most hormone dependent cancers become refractory (independent) after one to three years and will resume growth despite hormone therapy. While there are a number of drugs available to continue treatment, at this point in time, median survival rate decreased considerably to usually less than one year.

Chemotherapy – has first been introduced in the early 1970s. It can be used in addition to surgery and/or radiation therapy, after hormone therapy has failed, or if there are metastases in bone or elsewhere, since chemotherapy is systematic and can kill cancer cells throughout the body. Side effects can be considerable.

Cryotherapy – the freezing of the tumor tissue prior to removal is done in some institutions and can be effective, if other forms of therapy failed.

Following any kind of treatment, it is important to perform close follow-up tests, in order to make sure that the cancer does not resurface and/or grow. For routine check-ups, the PSA test is ideally suited and usually performed every three months to one year. If the cancer resurfaces and starts to grow again, PSA levels often start to increase before there will be any noticeable symptoms.

Prognosis

The outcome of prostate cancer varies greatly, depending on the cancer’s aggressiveness (Gleason score), size and spread (stage).

Obviously, the earlier the cancer has been diagnosed and the smaller it is, the better its prognosis. In cases, where the cancer cannot be cured anymore, hormone treatment can still extend the patient’s life for many years. And finally, many patients, who are first diagnosed in their 70s or older (25% of cases), often die of other causes than from the tumor itself.

Currently, the rate of prostate cancer is higher and its prognosis poorer in developed countries than in the rest of the world. Many of the risk factors for prostate cancer are more prevalent in the developed world, such as longer life expectancy (higher chance of prostate cancer with advanced age) and diets high in red meat and low in fruits and vegetables. According to the American Cancer Society, prostate cancer is least common among Asian men and most common among black men, with figures for white men somewhere in-between.

Prevention:

Men past the age of 40 should have regular medical check-ups (every two years, after age 50, every year), including a rectal digital examination and PSA blood test.

A healthy diet, regular exercise and Vitamin E and selenium have some preventive and supportive effect during treatment. Green tea (due to its catechins) and the ingestion of lycopene are said to have some protective effect. Especially lycopene, a carotinoid derived from tomatoes, and best ingested regularly by way of tomato ketchup or tomato sauce, has been shown by some studies to halve the risk of developing prostate cancer.

There are a number of research studies under way, trying to identify other sensitive tumor markers that can easily and early be identified and signal the presence of cancer cells in the prostate. However, these tests are currently not yet available commercially.

Other research includes preventive medications, especially with drugs that block testosterone conversion to dihydrotestosterone.

Some studies have shown that more frequent ejaculations may decrease the risk of prostate cancer, although other studies have shown no benefit.

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