Cancer Association of South Africa (CANSA) Fact Sheet on Prostate Cancer Introduction The prostate is part of the male reproductive system. It is a round gland, about the size of a pea at birth and has the size and shape of a walnut in adult life. It lies in the pelvic cavity immediately in front of the rectum. It surrounds the commencement of the urethra (urinary tube) at the base of the urinary bladder. It produces seminal fluid that assists in transporting the sperm during ejaculation. Prostate cancer is one of the leading cancers in males worldwide. It is the most prevalent cancer among White South African males. However, recent statistics indicate that Black males are at increased risk of prostate cancer and often develop an aggressive type of prostate cancer (Men’s Health 4-men). [Picture Credit – Male Pelvis] Incidence of Prostate Cancer in South Africa The following South African statistics regarding histologically diagnosed cases of prostate cancer during 2007 are available from the National Cancer Register (2007): The following South African statistics regarding prostate cancer are available from the National Cancer Register (2007): Group All males No of Cases 4 345 Lifetime Risk 1:24 The frequency of histologically diagnosed cases of prostate cancer in South Africa for 2007 was as follows (National Cancer Register, 2007): Researched and Authored by Prof Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupational Health] Approved for Distribution by Ms Elize Joubert, Acting Chief Executive Officer May 2014 Page 1 Group All males 0 – 19 Years 0 20 – 29 Years 2 30 – 39 Years 6 40 – 49 Years 95 50 – 59 Years 748 60 – 69 Years 1 626 70 – 79 Years 1 301 80+ Years 443 Prostate cancer is caused by changes in the DNA of a normal prostate cell. DNA makes up the genes, which control how cells behave. DNA is inherited from our parents. A small percentage (about 5 to 10%) of prostate cancers are linked to these inherited changes (American Cancer Society). Research shows that men with BRCA1/2 mutations were more likely than non-carriers to be diagnosed with advanced-stage prostate cancer or cancer that had already spread. Risk Factors The following are the known risk factors for prostate cancer: o Age: it occurs more frequently in older men. Most men diagnosed with prostate cancer are over 65 years of age. The disease is rare in men under 45 (National Cancer Institute) o Family history: Prostate cancer seems to run in some families, and scientists have found several inherited genes that seem to raise prostate cancer risk Risk Group Brother(s) with prostate cancer diagnosed at any age Father with prostate cancer diagnosed at any age One affected first-degree relative diagnosed at any age Affected first-degree relatives diagnosed <65 years Affected first-degree relatives diagnosed ≥65 years Second-degree relatives diagnose at any age Two or more affected first-degree relatives diagnosed at any age Relative Risk for Prostate Cancer (95% Confidence Index) * 3.14 2.35 2.48 2.87 1.92 2.52 4.39 (2.37 – 4.15) (2.02 – 2.72) (2.25 – 2.74) (2.21 – 3.74) (1.49 – 2.47) (0.99 – 6.46) (2.61 – 7.39) (*) Adapted from Kiciński, at al (2011) If there is a family history of the BRCA1 or BRCA2 gene mutation or a very strong history of women with breast cancer, the risk for prostate cancer may be higher o Inheritance of prostate cancer risk: epidemiologic studies (case-control, cohort, twin, and family) strongly suggest that prostate cancer susceptibility genes exist and play an important role in the development of prostate cancer (National Cancer Institute; Lichtenstein, et al., 2000) o BRCA1 Gene Mutation: Men with a BRCA1 gene mutation has a 3.4-fold increased risk for prostate cancer o BRCA2 Gene Mutation: Men with a BRCA2 gene mutation has an 8.6-fold increased risk for prostate cancer o Lifestyle: high fat intake, high red meat intake, low consumption of vegetables, obesity, lack of physical activity, and smoking are associated with prostate cancer Researched and Authored by Prof Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupational Health] Approved for Distribution by Ms Elize Joubert, Acting Chief Executive Officer May 2014 Page 2 risk (Kolonel, 2001; Hickey, et al., 2001; Gong, et al., 2007; Kristal & Gong, 2007; MedlinePlus) o High alcohol intake - usually stated as more than two (2) standard alcoholic drinks per day (MedlinePlus) o A standard alcoholic drink is the equivalent of: 340ml beer (average 5% alcohol by volume) 120ml wine 25ml liqueur 50ml sherry 25ml spirits (such as brandy, whiskey, gin, vodka and cane) (Life is Beautiful). o Race: Although most prevalent in White men, prostate cancer is becoming more common among Black men (National Cancer Institute) o Men who took 400 international units (I.U.) of synthetic Vitamin E daily had more prostate cancers compared to men who took a placebo (National Institutes for Health) o Use of Anabolic Steroids:- The use of anabolic steroids may have the following side effects (University of Northern Colorado): Infertility (low sperm count) Impotence Testicular shrinkage Baldness Testicular/prostate cancer Enlarged breast tissue Having had a vasectomy does NOT increase the risk for prostate cancer (Stanford, et al, 1999) In the past few years, we’ve learned that prostate cancer really is several diseases with different causes. More aggressive and fatal cancers have different underlying causes than slow-growing tumours. For example, while smoking has not been thought to be a risk factor for low-risk prostate cancer, it may be a risk factor for aggressive prostate cancer. Likewise, lack of vegetables in the diet (especially broccoli-family vegetables) is linked to a higher risk of aggressive prostate cancer, but not to low-risk prostate cancer. Body mass index is a measure of obesity and should not be used as diagnosis of prostate cancer although obese men are more likely to have aggressive prostate cancer. PSA levels should also not be used diagnostically for prostate cancer in obese men as they may have a relatively lower PSA than non-obese men due to dilution of the PSA in a larger blood volume. Other risk factors for aggressive prostate cancer include: o Lack of exercise and a sedentary lifestyle Researched and Authored by Prof Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupational Health] Approved for Distribution by Ms Elize Joubert, Acting Chief Executive Officer May 2014 Page 3 o o o High calcium intake Family history Agent Orange exposure Early Warning Signs of Prostate Cancer Early warning signs of prostate cancer include: o Difficulty in passing urine o A slow stream, often with dribbling at the end o Inability to start or stop the flow of urine o Frequent need to pass urine, especially at night o Swelling in legs o Discomfort in pelvic area (Prostate Cancer Warning Signs; Mayo Clinic). These early symptoms may be related to other factors such as inflammation of the prostate called prostatitis or enlargement of the prostate (benign prostate hyperplasia) or benign prostatic hypertrophy which are non-cancerous. Late Warning Signs of Prostate Cancer Late warning signs of prostate cancer include: o Inability to pass urine o Lower back pain o Blood in the urine or semen o Painful ejaculation o Erectile dysfunction o Weight loss o Bone pain (Prostate Cancer Warning Signs; Mayo Clinic) Types of Prostate Cancer There are many types of prostate cancer and the condition is often present in many different parts of the prostate. The precursor to prostate cancer is known as prostatic intraepithelial neoplasia, this is also found in many different locations within the prostate. Although there are many different kinds of prostate cancer the vast majority (around 95%) are of the type known as adenocarcinoma. As this type of cancer is the most widespread form of prostate cancer it has become synonymous with the term prostate cancer. Adenocarcinoma - The most common site of origin of prostate cancer is in the peripheral zone (the main glandular zone of the prostate). The term adenocarcinoma can be split up to derive its meaning. ‘Adeno’ means ‘pertaining to a gland’, whilst ‘Carcinoma’ relates to a cancer that develops in epithelial cells. The term ‘epithelial’ simply relates to cells that surround body organs or glands and basal cell carcinoma Small cell carcinoma - This kind of cancer is made up of small round cells and typically forms at nerve cells. Small cell carcinoma is very aggressive in nature and as it does not lead to an Researched and Authored by Prof Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupational Health] Approved for Distribution by Ms Elize Joubert, Acting Chief Executive Officer May 2014 Page 4 increase in prostate specific antigen (PSA) it can be somewhat harder to detect than adenocarcinoma - this usually means that it has reached an advanced form upon detection. Squamous cell carcinoma - This is a non-glandular cancer, like small cell carcinoma there is no increase in prostate specific antigens (PSA) when this is present. Squamous cell carcinoma is very aggressive in nature. There are other, more rare, forms of prostate cancer. These include sarcomas and transitional cell carcinoma; the latter rarely develop in the prostate but derives from primary tumours present in the bladder or urethra. (Prostate Cancer Guide). Screening and Diagnosis of Prostate Cancer Screening and diagnosis of prostate cancer includes: o Digital rectal examination (DRE) by a doctor where the doctor inserts a lubricated, gloved finger into the rectum to examine the prostate o Urine test to check for the presence of blood o Measurement of Prostate Specific Antigen (PSA) which is discussed in more detail below. The prostate normally secretes small amounts of PSA, A higher level may indicate a problem with the prostate. It may be cancer or merely an enlarged prostate caused by infection. (National Cancer Institute). [Picture Credit – Digital Rectal Examination] The above tests can only detect whether there is a problem in the prostate. They cannot show whether the problem is cancer or a less serious condition. The following examinations are done to determine the presence of cancer: Transrectal ultrasound – a probe is inserted into the rectum to check the prostate for abnormal areas. The probe sends out sound waves that cannot be heard. The waves bounce off the prostate to create a picture called a sonogram. Transrectal biopsy – a biopsy is the removal of tissue to look for cancer cells. It is the only sure way to diagnose prostate cancer. The doctor inserts needles through the rectum into the prostate. A small piece of tissue is removed from various areas of the prostate. Transrectal ultrasound is usually used to guide the insertion of the needles. The tissue samples are checked by a pathologist for the presence of cancer cells (National Cancer Institute). Researched and Authored by Prof Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupational Health] Approved for Distribution by Ms Elize Joubert, Acting Chief Executive Officer May 2014 Page 5 Prostate Specific Antigen Prostate Specific Antigen (PSA) is a protein produced by both cancerous (malignant) and non-cancerous (benign) prostate tissue. PSA helps to liquefy the semen. A small amount of PSA normally enters the bloodstream. Cancer cells usually make more PSA than benign cellsdo, causing PSA levels in the blood to rise. PSA can also be elevated in men with an enlarged or inflamed prostate. Therefore, determining what a high PSA score means, can be complicated (Mayo Clinic). Prostate Specific Antigen (PSA) test is a blood test which is done to determine the presence of prostate abnormalities including prostate cancer, however, PSA is not prostate cancer specific. PSA is the most widely used test for the possible detection of prostate cancer today and is simple to do. A small sample of blood is taken, usually from a vein in the arm, and is tested for the presence of prostate specific antigen (PSA). PSA level determination can now also be done by means of a finger-prick test with the result becoming available in a few minutes. PSA levels can be elevated by a number of causes. Causes of elevated PSA levels include: o Prostate cancer – the presence of prostate cancer cells increases PSA levels. o Benign Prostatic Hyperplasia – this non-cancerous condition is simply an ‘enlarged prostate’. It is common in older men and, unlike cancer, has to risk of spreading throughout the body o Prostatitis – inflammation of the prostate due to bacterial infection. This is mostly an acute condition, but some men may have chronic prostatitis o Infection of the bladder – this is called cystitis and should be treated prior to having a PSA test done o Recent ejaculation – having ejaculated within the previous 24-48 hours prior to PSA testing. To prevent this, the patient should be advised to avoid any sexual activity for at least a couple of days before having a PSA test o Prostate biopsy – men who recently undergone a prostate biopsy will have an artificially elevated PSA. After biopsy, one should wait a few weeks before having a PSA level test o Digital Rectal Examination (DRE) – a digital rectal examination may also cause an artificial increase in PSA levels, therefore, blood should be drawn for the PSA determination prior to a DRE examination Bicycle riding – there is insufficient evidence to substantiate claims that bicycle riding has the potential to increase the PSA blood levels (Crawford, et al., 1996). (Prostate Cancer Watchful Waiting; LabTestOnLine; Mayo Clinic). o Only about 1 in 4 men who have a positive (elevated) PSA test turns out to have prostate cancer (Mayo Clinic). Researched and Authored by Prof Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupational Health] Approved for Distribution by Ms Elize Joubert, Acting Chief Executive Officer May 2014 Page 6 PSA results show the level of PSA detected in the blood. The results are usually reported as nanograms of PSA per millilitre (ng/ml) of blood. In the past a PSA level below 4.0ng/ml was taken to be normal. There is, however, no normal or abnormal PSA level. In addition, as indicated above, there are several causes of an increase in a man’s PSA level. It is also common for PSA values to vary somewhat from laboratory to laboratory and also at differing intervals. One ‘abnormal’ PSA test result does not necessarily indicate the need for a prostate biopsy. (National Cancer Institute). The Prostate Health Index (PHI) Test Prostate Health Index (phi), a more precise blood test, outperformed traditional PSA screening in predicting clinically significant prostate cancer. There is no clear indication when this test will be available in South Africa. The Prostate Health Index (phi), a blood test used to evaluate the probability of prostate cancer diagnosis, outperformed commonly used prostate-specific antigen (PSA) and free/total prostate-specific antigen (%fPSA) tests in predicting the presence of clinically significant prostate cancer and in improving prostate cancer detection, according to a new study. The phi combines measurements of %fPSA(percent of protein-attached and protein-free PSA circulating in the bloodstream) and a subcategory of free PSA called pro-PSA, and is estimated to be 2.5 times more specific in detecting prostate cancer in patients than a PSA screening. The phi was approved by the US Food and Drug Administration (FDA) in June 2012 and has been available since late 2012. The study also found using a specific phi benchmark level may help identify biopsy candidates and reduce over-detection of indolent (slow-growing) prostate cancer. “The phi can play a valuable role in determining whether an elevated PSA is likely due to prostate cancer or benign changes,” said Brant Thrasher, MD, chair of Urology, University of Kansas Medical Center, Kansas City, KS. “This option may prevent patients from potentially undergoing unnecessary biopsies.” Study Details - Researchers at several leading institutions in the United States and the Netherlands, including Harvard Medical School and Johns Hopkins University, investigated whether the use of phi, as compared to total PSA and %fPSA, can reduce unnecessary biopsy and over-detection of indolent prostate cancer, while improving the detection of aggressive prostate cancer. The study consisted of 658 participants who were 50 years of age or older with a biopsyconfirmed prostate cancer diagnosis, a final PSA between 4-10 ng/mL and a benign rectal examination. Study investigators evaluated prediction of clinically significant cancer (aggressive histopathology per Epstein criteria or Gleason 7+) based on pre-biopsy measures of pro-PSA, total PSA, fPSA, %fPSA and phi and evaluated prospects for eliminating unnecessary biopsies based on results of phi prior to biopsy. The researchers found: o At 90 percent sensitivity, the specificity of phi was 31.1 percent, compared to 19.8 percent for %fPSA (p=0.024) and 10.8 percent for PSA (p<0.001). Researched and Authored by Prof Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupational Health] Approved for Distribution by Ms Elize Joubert, Acting Chief Executive Officer May 2014 Page 7 o o At a moderate to high phi range of 27 to 55, the probability of cancer varied from 9.8 to 50.1 percent and the probability of clinically significant cancer extended from 3.9 to 28.9 percent. At a phi level of 27, which is the 90 percent sensitivity cut-point, 18.8 percent of men could have been spared from undergoing prostate biopsy or over-diagnosis of nonaggressive disease. Study investigators concluded phi outperformed PSA and %fPSA in predicting the presence of clinically significant prostate cancer and for improving prostate cancer detection. Additionally, using a phi level of 27 for selecting men for prostate cancer biopsy, when total PSA is 4 to 10 ng/mL, can decrease unnecessary biopsies and reduce over-detection of indolent prostate cancer. (American Urological Association). Staging of Prostate Cancer Like other forms of cancer, the prognosis for prostate cancer depends on how far the cancer has spread at the time it is diagnosed. A system of staging is used to describe prostate cancer spread. Accurately identifying the prostate cancer stage is extremely important. Prostate cancer staging helps to determine the optimal treatment as well as prognosis. The TNM system for describing prostate cancer uses the letters ‘T’, ‘N’, and ‘M’ to signify ‘Tumour’, ‘Nodes’, and ‘Metastasis’. The following is the breakdown of exactly what each category in this system means. Primary tumour (T) TX: The primary tumour was not or could not be assessed. T0: There is no evidence of a primary tumour. T1: The tumour could not be found by examination or with the use of imaging (like ultrasound or an MRI scan), but was incidentally found during a biopsy or surgery. T1a: The tumour is found in 5% or less of the tissue that was taken. T1b: The tumour is found in more than 5% of tissue that was taken. T1c: The tumour was found by needle biopsy after an elevated PSA level. T2: The tumour is found only within the prostate itself. T2a: The tumour is found in 50% or less of one lobe. T2b: The tumour is found in more than 50% of one lobe. T2c: The tumour is found in both lobes. T3: The tumour has extended through the capsule that surrounds the prostate. T3a: The tumour has only gone through the capsule without invading the seminal vesicles. T3b: The tumour has invaded the seminal vesicles. T4: The tumour has invaded structures or tissues near the prostate other than the seminal vesicles. These include the bladder neck, the rectum, and the pelvic wall along with other structures. Nodes (N) NX: The lymph nodes were not or could not be assessed. N0: The nodes do not show evidence of cancer. N1: The nodes show evidence of cancer. Researched and Authored by Prof Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupational Health] Approved for Distribution by Ms Elize Joubert, Acting Chief Executive Officer May 2014 Page 8 Metastasis (M) MX: The presence of metastases was not or could not be assessed. M0: There is no evidence of distant metastasis. M1: There is evidence of distant metastasis. M1a: Cancer has been found in lymph nodes far from the prostate. M1b: Cancer has been found in the bone. M1c: Cancer has been found in another area of the body. (About.Com Prostate Cancer; Cancer Research UK). The following is the Number Staging Method: Stage I The prostate cancer is found in the prostate only. Stage I prostate cancer is microscopic; it cannot be felt on a digital rectal examination (DRE) and it is not seen on imaging of the prostate Stage II The tumour has grown inside the prostate but has not extended beyond the prostate Stage III The cancer has spread outside the prostate, but only barely. Prostate cancer in stage III may involve nearby tissue like the seminal vesicles Stage IV The cancer has spread (metastasised) outside the prostate to other tissues. Stage IV prostate cancer commonly spreads to lymph nodes, the bones, liver, or lungs (WebMD). The Gleason Score The Gleason score is used to help determine how quickly a tumour may grow or spread. It may seem confusing because with the Gleason system (the most common system used), there’s both a ‘grade’ and a ‘score’. The Gleason grade uses numbers 1 to 5. A number is assigned to two of the areas of the prostate that have the most cancer (based on biopsy core samples that are taken). This is because the cancer may look different in each of those two areas. Once those two numbers are determined, they are added together to come up with the Gleason score, which ranges from 2 to 10. What the Gleason grades mean Grade 1: The cells look almost like normal cells (called well differentiated) and are uniformly spaced in a tight mass. Grade 2: The cancer cells are still well differentiated, but are arranged more loosely, are more irregular in shape, and some cells have spread to other prostatic tissue. Grade 3: The cancer is moderately differentiated; cells vary in size from small to large; and more cells have invaded other prostatic tissue. Researched and Authored by Prof Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupational Health] Approved for Distribution by Ms Elize Joubert, Acting Chief Executive Officer May 2014 Page 9 Grade 4: The cancer cells are irregular, distorted, and look less like normal cells (called poorly differentiated), and there is considerable spread (called invasion) to other prostatic tissue. Grade 5: The cancer cells do not look anything like normal cells and have spread in haphazard ‘clumps’ of all different shapes and sizes through the prostate. [Picture Credit: Gleason Score] What the Gleason scores mean: o o o If the score is less than 6, the cancer may be considered to be well-differentiated or low-grade cancer A score of 7 may be considered to be moderately differentiated or intermediate-grade cancer A score of 8 to 10 may be considered to be poorly differentiated or high-grade cancer According to the American Urological Association, the lowest Gleason score that is usually found after a biopsy is 5. The cancer is considered to be more aggressive as the score rises. Scores of 8 to 10 are considered to be the most aggressive, which means that the cancer is more likely to grow and spread more quickly. The biopsy results (called the pathology report) will contain other important information that helps to assess how aggressive the cancer may be. This includes: o How many biopsy core samples were positive for cancer o How much cancer was in each core sample (this is given as a percentage) o Whether cancer was found in just one side of the prostate gland or in both sides (which is referred to as bilateral) (Hisprostatecancer). How Prostate Cancer Spreads Prostate cancer most commonly spreads to the bones. It can spread to other organs though. With prostate cancer, it is sometimes possible to have metastases (cancer spread) present even when the prostate tumour is still very small. So even if the tumour appears to be very small, when a bone scan shows that there is cancer in the bones, the prostate cancer is M1 stage. It will be treated as advanced, metastatic cancer. Advanced cancer can often be controlled for several years with treatment. Researched and Authored by Prof Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupational Health] Approved for Distribution by Ms Elize Joubert, Acting Chief Executive Officer May 2014 Page 10 Recurrent Prostate Cancer Prostate cancer may spread as indicated below: Cancer Type: Bladder Breast Colon Colorectal Kidney Lung Melanoma Ovary Pancreas Prostate Stomach Thyroid Uterus Non-melanoma skin cancer Main Sites of Metastasis (Spread) Bone, liver, lung Bone, brain, liver, lung Liver, lung Liver, lung, peritoneum (lining of abdomen) Adrenal gland, bone, brain, liver, lung Adrenal gland, bone, brain, liver, other lung Bone, brain, liver, lung, skin, muscle Liver, lung, peritoneum (lining of abdomen) Liver lung, peritoneum (lining of abdomen) Adrenal gland, bone, liver, lung Liver, lung, peritoneum (lining of abdomen), ovaries Bone, liver, lung Bones, liver, lung, peritoneum (lining of abdomen), vagina Very rare: lymph nodes, lung, bone (if in head/neck region) (National Cancer Institute). Treatment for Prostate Cancer Treatment of prostate cancer can consist of: Active Surveillance – active surveillance may be chosen if the risks and possible side effects of treatment outweigh the possible benefits. A doctor may suggest active surveillance with early-stage prostate cancer that seems to be slow growing. During active surveillance the doctor will do check-ups every 3 to 6 months, at first. Active surveillance avoids or delays the side effects of surgery and radiation therapy, but his choice may have risks for some men as it may reduce the chance to control cancer before it spreads. It may also be more difficult to cope with surgery or radiation therapy when older. The concept of active surveillance, or watchful waiting, has increasingly emerged in recent years as a viable option for men who decide not to undergo immediate surgery or radiation therapy. During active surveillance, prostate cancer is carefully monitored for signs of progression. A PSA blood test and digital rectal exam (DRE) are usually administered periodically along with a repeat biopsy of the prostate at one year and then at specific intervals thereafter. If symptoms develop, or if tests indicate the cancer is growing, treatment might be warranted. Current estimates indicate that many more men are aggressively treated for prostate cancer than is necessary to save a life from the disease. The challenge has been to identify those men who do not need immediate therapy, which is usually decided based on age, other medical conditions, and cancer factors like the PSA, stage, amount of cancer in the biopsy, and Gleason grade. Research is ongoing to develop biomarkers and additional tests that can better stratify men at risk so that this decision is easier and more accurately informed. Today, the man who is ideal for active surveillance has a low grade (Gleason 6 or under), low-risk prostate cancer (low PSA - usually under 10 and low stage), that appears to be low in volume (small amount of cancer found on biopsy, for example), and who is not eager to undergo therapy right away due to concerns about potency preservation or urinary symptoms. Researched and Authored by Prof Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupational Health] Approved for Distribution by Ms Elize Joubert, Acting Chief Executive Officer May 2014 Page 11 Active surveillance might also be a good choice for older men with limited life expectancy. In addition, if a man is currently battling other serious disorders or diseases, such as heart disease, long-standing high blood pressure, or poorly controlled diabetes, his doctors might feel it is in his best interest to hold off on therapy and avoid its potential complications. That is because many of the treatment options for prostate cancer can be difficult to endure, and better outcomes are seen in men who are otherwise healthy. Surgery – is an option for men with early (Stage I) prostate cancer. During surgery the whole prostate, or only part of it, may be removed. There are several types of surgery for prostate cancer: Open surgery through the abdomen, called a radical retropubic prostatectomy. The surgeon removes the entire prostate through a cut in the lower abdomen. o o o o o Open surgery between the scrotum and anus, called a radical perineal prostatectomy. The surgeon removes the entire prostate through a cut between the scrotum and the anus. Laparoscopic prostatectomy – the surgeon removes the entire prostate through small cuts, rather than a single long cut in the abdomen. A thin, lighted tube (a laparoscope) helps the surgeon remove the prostate. Robotic laparoscopic surgery – the surgeon removes the entire prostate through small cuts. A laparoscope and a robot are used to help remove the prostate. The surgeon used handles below a computer display to control the robot’s arms. Cryosurgery – the surgeon inserts a tool through a small cut between the scrotum and anus. The tool freezes and kills prostate tissue. Cryosurgery is currently under study. Transurethral Resection of the Prostate (TURP) – the surgeon inserts a long, thin scope through the urethra. A cutting tool at the end of the scope removes tissue from the inside of the prostate. TURP may not remove all of the cancer, but it can remove tissue that blocks the flow of urine (National Cancer Institute). External radiation therapy (also called radiotherapy) – is usually an option for men with any stage of prostate cancer. It may also be used after surgery to destroy any cancer cells that remain in the area. In later stages of prostate4 cancer, radiation treatment may be used to help relieve pain. It uses high-energy rays to kill cancer cells. It affects cells only in the treated area. The radiation comes from a large external source and focusses on the area where the cancer has been diagnosed. Treatments are usually 5 days a week for several weeks. Internal radiation therapy (brachytherapy) – the radiation comes from radioactive material usually contained in very small implants called seeds. Dozens of seeds are placed inside needles, and the needles are inserted into the prostate. The needles are removed, leaving the seeds behind. The seeds give off radiation for months. The seeds do not need to be removed. The doctor implants the radioactive seeds in your prostate using a needle guided by ultrasound images. Men who have small, early stage prostate cancers may be considered Researched and Authored by Prof Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupational Health] Approved for Distribution by Ms Elize Joubert, Acting Chief Executive Officer May 2014 Page 12 for permanent prostate brachytherapy. The treatment may be used alone or in combination with radiation given outside the body or hormone therapies. Permanent prostate brachytherapy is minimally invasive and allows patients to resume most normal physical activities within days. Permanent prostate brachytherapy uses low-energy radioactive sources. The majority of the radiation that seeds emit is delivered within 2,5cm of the seed. Once the seeds are in place, the radiation emitted to tissues around the prostate and to other people is minimal. People who have received permanent prostate brachytherapy, however, should follow several radiation safety precautions, including: o Limit prolonged close contact (less than 2 metres) for two months after the implant with children and women who are or may be pregnant o Avoid letting children sit on the recipient's lap for prolonged periods (for two months after the implant) o Flush down the toilet any seeds that are passed during urination within the first few weeks after the implant o Avoid sexual intercourse for two weeks after the implant. A seed may be passed during ejaculation o The man should wear a condom during sex for two months after the implant (Mayo Clinic). Hormone therapy - called anti-androgen therapy that consists of steroidal anti-androgens or non-steroidal anti-androgens. Testosterone is the most abundant androgen that can cause the prostate gland to grow and the hormonal therapy blocks this action. Hormone therapy is treatment to stop your body from producing the male hormone testosterone. Prostate cancer cells rely on testosterone to help them grow. Cutting off the supply of hormones may cause cancer cells to die or to grow more slowly. Hormone therapy options include: Hormone therapy is used in men with advanced prostate cancer to shrink the cancer and slow the growth of tumours. In men with early-stage prostate cancer, hormone therapy may be used to shrink tumours before radiation therapy. This can make it more likely that radiation therapy will be successful. Hormone therapy is sometimes used after surgery or radiation therapy to slow the growth of any cancer cells left behind. Side effects of hormone therapy may include erectile dysfunction, hot flashes, loss of bone mass, reduced sex drive and weight gain. Hormone therapy also increases the risk of heart disease and heart attack. (Mayo Clinic) A man with prostate cancer may have hormone therapy before, during or after radiation therapy. Hormone therapy is also used alone for prostate cancer that has returned after treatment. Male hormones (androgens) can cause prostate cancer to grow. Hormone therapy keeps prostate cancer cells from getting the male hormones they need to grow. The testicles are Researched and Authored by Prof Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupational Health] Approved for Distribution by Ms Elize Joubert, Acting Chief Executive Officer May 2014 Page 13 the body’s main source of the male hormone testosterone. The adrenal gland makes other male hormones and a small amount of testosterone. Hormone therapy employs drugs or surgery. Drugs used in hormone therapy include: - Luteinising hormone-releasing hormone (LH-RH) agonists: these drugs canprevent the testicles from making testosterone. . Drugs typically used in this type of hormone therapy include leuprolide (Lupron, Eligard), goserelin (Zoladex), triptorelin (Trelstar) and histrelin (Vantas). - Anti-androgens: these drugs can block the action of male hormones. Examples include bicalutamide (Casodex), flutamide and nilutamide (Nilandron). These drugs typically are given along with an LH-RH agonist or given before taking an LH-RH agonist. - Other drugs: some drugs can prevent the adrenal gland from making testosterone, e.g. ketoconazole and aminoglutethimide. Surgery to remove the testicles called an orchidectomy After an orchidectomy or treatment with an LH-RH agonist, the body no longer gets testosterone from the testicles. Androgen Blockage -Because the adrenal gland makes small amounts of male hormones, the patient may receive an anti-androgen to block the action of the male hormones that remain. This combination of treatments is known as total androgen blockage. Chemotherapy - may also be given in advanced stage prostate gland cancer not responding to hormone therapy (hormone refractory or resistant prostate cancer). Chemotherapy uses drugs to kill cancer cells. The drugs for prostate cancer are usually given through a vein. The side effects depend mainly on the drug used. Chemotherapy drugs kill fast-growing cancer cells, but can also harm normal cells that divide rapidly: - Blood cells: when chemotherapy lowers the levels of healthy blood cells, infection becomes a problem. The patient may bruise easily and feel very weak and tired. Regular blood counts are usually done. - Cells in hair roots: chemotherapy may cause hair loss. If hair is lost, it will grow back, but it may change in colour and texture. - Cells that line the digestive tract: chemotherapy can cause a poor appetite, nausea and vomiting, or diarrhoea. - Other side effects may include shortness of breath and oedema. Chemotherapy may also cause a skin rash, tingling or numbness in the hands and feet, and watery eyes. These side effects usually dissipate when treatment ends. Biological therapy - This treatment works with the body's immune system to help it fight cancer or to control side effects from other cancer treatments. Side effects are how the body reacts to drugs or other treatments. Biological therapy is different from chemotherapy, which attacks cancer cells directly. Researched and Authored by Prof Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupational Health] Approved for Distribution by Ms Elize Joubert, Acting Chief Executive Officer May 2014 Page 14 High-intensity focused ultrasound - This therapy directs high-energy sound waves (ultrasound) at the cancer to kill cancer cells. (Mayo Clinic; National Cancer Institute; Centers for Disease Control and Prevention). When prostate cancer is at a very early stage or not expected to progress or not suspected to cause symptoms, the doctor may ‘watch and wait’ (expectant therapy) and monitor the cancer short term. (Fred Hutchinson Cancer Research Center). Prostate Cancer Survival Rates In the United States of America (USA) the overall 5-year survival rate for prostate cancer is 100%. The 10-year survival rate is 92% and the 15-year survival rate is 70%. These high prostate cancer survival rates are primarily based on the fact that nearly 91% of cases in the USA are detected while the cancer is still contained within the prostate or in nearby areas. For men whose cancer has already spread to distant parts of the body (metastasised), the 5year survival rate is only 32%. Follow-up Care Follow-up care is very important. The doctor will check for the return of cancer. Even when the cancer seems to have been completely removed or destroyed, the disease sometimes returns because undetected cancer cells may remain somewhere in the body after treatment. Check-ups may include a digital rectal examination and a PSA test. The doctor may also order a biopsy, a bone scan, Computerised Tomography (CT scan) and Magnetic Resonance Imaging (MRI scan) or other tests. (National Cancer Institute). Living with Prostate Cancer Some treatments for prostate cancer can affect one’s sex life. Many men continue to enjoy sex throughout their lives and well into old age and may be worried about how treatment for prostate cancer will affect them. Treatments can affect: o ability to get an erection (erectile dysfunction) o desire to have sex (libido) o ability to ejaculate and have an orgasm o fertility Researched and Authored by Prof Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupational Health] Approved for Distribution by Ms Elize Joubert, Acting Chief Executive Officer May 2014 Page 15 Living with Prostate Cancer - Frequently Asked Questions about Prostate Cancer and Sex Will the person be able to have sex or masturbate after treatment This will depend on what type of treatment the patient has had and how he feels. Some men will have problems with their erections (erectile dysfunction) and some may never get back the ability to achieve or maintain an erection without the help of treatment. Can cancer be passed on to one’s partner through ejaculation? Some men worry that cancer can be transmitted when having sex. It is not possible to pass cancer through intercourse. Having sex will not affect one’s cancer or the success of the treatment. What are the effects of cancer treatment and erectile dysfunction (ED) Erectile dysfunction (ED) is when the person has difficulty getting or keeping an erection. It is also known as impotence. It is more likely to occur as men get older. It can have many possible causes, including treatment for prostate cancer. Surgery, external beam radiotherapy, brachytherapy, high intensity focused ultrasound (HIFU) and cryotherapy can all damage the nerves and blood vessels that are needed for an erection. Hormone therapy reduces levels of the hormone testosterone, which is needed for sexual desire and erections. Medical conditions such as diabetes, hypertension, stress and anxiety can also cause ED. There are a number of treatments available for ED including lifestyle changes, tablets, injections, pellets and vacuum pumps. How can prostate cancer treatment affect one’s desire for sex (libido)? Hormone therapy - Hormone therapy for prostate can reduce, or cause one to lose one’s desire for sex. This is as a result of the decrease in testosterone, which is the hormone responsible for giving one 'sex drive'. A study suggested that about 50 per cent of men taking a type of hormone therapy called LHRH agonists or who have had surgery to remove their testicles (orchidectomy) will lose their interest in sex. 'Intermittent hormone therapy' can be discussed with one’s doctor or counsellor. For some men desire for sex may return after hormone treatment is stopped, but this varies. It can take three to nine months or sometimes longer for side effects of hormone therapy to wear off. Physical and emotional impact - Testosterone is not the only factor that can affect one’s sex drive. Both physical and psychological factors can also affect how one feels about sex. Will prostate cancer treatment affect the ability for orgasm and to ejaculate? If a person has had surgery (radical prostatectomy) he will not be able to ejaculate afterwards. This is because the prostate and seminal vesicles, which store and transport semen, are removed during the operation. Instead the person may experience what is sometimes called a 'dry orgasm' where he feels the sensations of orgasm but do not release any semen from the tip of the penis. This may feel different to the orgasms the person has been used to. Occasionally, some men will find that a small amount of liquid comes out from the tip of the penis during orgasm, which may be fluid from glands lining the urethra. If the person has had radiotherapy or brachytherapy he may notice that he produces less semen after completion of treatment. Such individuals should still be able to have an orgasm but may find that it feels different than before treatment. Some men find that they have less intense orgasms when they are having hormone therapy Researched and Authored by Prof Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupational Health] Approved for Distribution by Ms Elize Joubert, Acting Chief Executive Officer May 2014 Page 16 Will prostate cancer treatment affect the appearance of one’s penis? Some studies have shown that around 50 per cent of men will find that their penis is shorter after treatment with surgery (radical prostatectomy). This happens because of changes to the tissue inside the penis. Men may be less likely to experience these changes if the surgeon has tried to save the nerves that control erections during surgery (nerve sparing surgery). Some studies have shown that encouraging blood flow to the penis after surgery may help you get erections and prevent the penis becoming smaller. Other types of prostate cancer treatment such as radiotherapy and hormone therapy may also cause changes to the size of the penis. There is not as much research into this but it may be less common than changes to men's penis size after surgery. Changes to one’s body and one’s penis can feel difficult to cope with. Talking to someone about this might be helpful. Will prostate cancer treatment affect one’s fertility? Treatment for prostate cancer can affect one’s ability to produce sperm or ejaculate and lead to infertility. It may be possible for someone to store some sperm before treatment so that they can be used later to fertilise an egg. Other infertility treatment options may also be available. If the patient is planning to have children he should seek further information from his doctor or other health professional. The person’s partner should also be included in talks about plans for having children and what this would involve. (Prostate Cancer UK). Masturbation and Prostate Cancer Masturbation is the deliberate self-stimulation of the genitals to achieve sexual arousal usually to the point of orgasm (sexual climax). It is commonly done by touching, stroking, or massaging the penis until an orgasm is achieved. Why Men Masturbate - in addition to feeling good, masturbation is a good way of relieving the sexual tension that can build up over time, especially for people without partners or whose partners are not willing or available for sex. Masturbation also is a safe sexual alternative for people who wish to avoid pregnancy and the dangers of sexually transmitted infections. It also is necessary when a man must give a semen sample for infertility testing or for sperm donation. When sexual dysfunction is present in an adult male, masturbation may be prescribed by a sex therapist to allow that person to experience an orgasm or to delay its arrival (WebMD). The truth about masturbation - throughout history there have been many myths regarding masturbation. Practically all these myths are false. There is no medical basis for any of them. Below is the TRUTH about masturbation: o o o o o It does NOT stunt growth It does NOT cause blindness It does NOT cause deafness It does NOT cause one to grow hair on the palms of one’s hands It does NOT cause stuttering Researched and Authored by Prof Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupational Health] Approved for Distribution by Ms Elize Joubert, Acting Chief Executive Officer May 2014 Page 17 o o o o o It does NOT cause pimples It does NOT mean one will be promiscuous as an adult It will NOT drive one crazy One CANNOT die from it It is perfectly healthy as long as it does not interfere with relationships with a spouse, friends and family, or with doing other activities (University of Michigan Health System; Dr Chakravarthy; Planned Parenthood). Ejaculation frequency and subsequent risk for prostate cancer - sexual activity has been hypothesised to play a role in the development of prostate cancer, but epidemiological data are virtually limited to case-control studies, which may be prone to bias because recall among individuals with prostate cancer could be distorted as a consequence of prostate malignancy or ongoing therapy. Leitzmann, et al. (2004), conducted a study to examine the association between ejaculation frequency, which includes sexual intercourse, nocturnal emission, and masturbation and risk of prostate cancer. In their study, using follow-up data from the Health Professionals Followup Study (February 1, 1992, through January 31, 2000) of 29 342 US men aged 46 to 81 years, who provided information on history of ejaculation frequency on a self-administered questionnaire in 1992 and responded to follow-up questionnaires every 2 years to 2000. Ejaculation frequency was assessed by asking participants to report the average number of ejaculations they had per month during the ages of 20 to 29 years, 40 to 49 years, and during the past year (1991). During 222 426 person-years of follow-up, there were 1 449 new cases of total prostate cancer, 953 organ-confined cases, and 147 advanced cases of prostate cancer. Most categories of ejaculation frequency were unrelated to risk of prostate cancer. However, high ejaculation frequency was related to decreased risk of total prostate cancer. The multivariate relative risks for men reporting 21 or more ejaculations per month compared with men reporting 4 to 7 ejaculations per month at ages 20 to 29 years were 0.89 (95% confidence interval [CI], 0.73-1.10); ages 40 to 49 years, 0.68 (95% CI, 0.53-0.86); previous year, 0.49 (95% CI, 0.27-0.88); and averaged across a lifetime, 0.67 (95% CI, 0.51-0.89). Similar associations were observed for organ-confined prostate cancer. Ejaculation frequency was not statistically significantly associated with risk of advanced prostate cancer. Their results suggest that ejaculation frequency is not related to increased risk of prostate cancer (Leitzmann, et al. 2004; Bartlik, et al. 2005; Cornog, M. 2003). Masturbation and zinc depletion - frequent ejaculation prevents prostate problems in the future. Frequent sex can have the same effect as masturbation. Semen comprises of: o o o o o o o fructose ascorbic acid zinc cholesterol protein calcium chlorine o o o o o o blood group antigens citric acid DNA Magnesium vitamin B12 phosphorus o o o o o o sodium potassium uric acid lactic acid nitrogen some other nutrients (Mandal, A.; NFSTC). Researched and Authored by Prof Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupational Health] Approved for Distribution by Ms Elize Joubert, Acting Chief Executive Officer May 2014 Page 18 Sperm does NOT contain a lot of Zinc - semen has some Zinc in it but it does not take a large quantity of it out of the body. That is an old wives tale. Semen also does not have a lot of protein, calcium, nutrients etcetera in it. Ejaculating frequently cleans out the prostate preventing semen from sitting in the prostate for long periods of time which can lead to future problems (MCRH.Org). In summary, it can be said that there are many positive benefits to male masturbation such as reducing stress, helping infertile couples have a child through sperm donation and stimulating the immune system. o o Masturbation benefits the immune system Masturbation keeps one in good health – it prevents the build-up of ‘stale’ prostatic fluids remaining in the prostate o Masturbation releases tension and stress – masturbation can lower blood pressure in stressful situations o Masturbation releases sexual tension without any performance anxiety o Masturbation fights depression - masturbation releases the mood-enhancing substances serotonin and dopamine o Masturbation is essential for infertility testing o Masturbation is essential for sperm donation - sperm donation can help couples who are struggling with infertility to start a family o Masturbation is the ultimate practice of safe sex – there is no chance of a sexually transmitted infection or unwanted pregnancy (Human Reproduction; Leitzmann, et al.; Denison, et al.; dba Fertility Center of California). Living with Prostate Cancer – Possible Urinary Problems after Prostate Cancer Treatment Some treatments for prostate cancer can cause problems passing urine. These can include: o leaking urine (incontinence) which can range from leaking a few drops to leaking a lot during the day and night o leaking or dribbling urine when one sneezes, coughs or exercises (stress incontinence) o passing urine more often than usual (more than eight times a day) o getting up a lot at night to pass urine (nocturia) o needing to go to the toilet urgently (urgency) and sometimes leaking before getting there (urge incontinence) o a weaker or slower flow of urine, or o problems emptying the bladder (urine retention) Urinary problems can also be caused by an enlarged prostate, also called benign prostatic enlargement or BPE. Urinary tract infections can cause symptoms such as needing to pass urine more often and without much warning, a burning feeling and cloudy, dark or strong smelling urine. Researched and Authored by Prof Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupational Health] Approved for Distribution by Ms Elize Joubert, Acting Chief Executive Officer May 2014 Page 19 Lowering the Risk for Prostate Cancer It is recommended that men with an average risk of prostate cancer make choices that benefit their overall health if they are keen on prostate cancer risk prevention as research is very diverse and controversial in this regard. The following have been recognised as playing an important role in assisting to reduce the risk for prostate cancer: o Choose a healthy diet – there is evidence that choosing a healthy diet plays an important role in prostate cancer prevention Choose a low-fat diet – limit saturated fat intake to 2% and transfat intake to 1% of total fat intake Reduce the amount of fat added to foods during preparation Limit the intake of saturated fats (mostly found in animal fats and processed meats) Eat more fat obtained from plants rather than from animals, for instance rather cook with canola oil than butter or lard o Increase the daily intake of fresh vegetables and fruit (in season) – eat at least five portions of fresh fruit and vegetables daily o Eat fish – such as salmon, sardines, tuna and trout. It also contains a fatty acid called omega-3 that has been linked to a reduced risk for prostate cancer o Restrict or avoid alcohol intake – if you decide to drink alcohol, this means not drinking more than two (2) standard alcoholic drinks per day. A standard alcoholic drink is equal to: 340ml beer (average 5% alcohol by volume) 120ml wine 25ml liqueur 50ml sherry 25ml spirits (such as brandy, whiskey, gin, vodka and cane) o Maintain a healthy weight – men who have a body mass index (BMI) of 30 or higher are considered to be obese. Being obese increases the risk of prostate cancer Exercise most days of the week – research has shown that men who regularly exercise may have a reduced risk of prostate cancer (Mayo Clinic; National Cancer Institute; Life is Beautiful). o Clinical Trials Clinical trials are research studies that involve people. They are the final step in a long process that begins with research in a lab. Most treatments used today are the results of past clinical trials. Cancer clinical trials are designed to test new ways to: o o o o Treat cancer Find and diagnose cancer Prevent cancer Manage symptoms of cancer or side effects from its treatment Researched and Authored by Prof Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupational Health] Approved for Distribution by Ms Elize Joubert, Acting Chief Executive Officer May 2014 Page 20 Every trial has a person in charge, usually a doctor, who is called the principal investigator. The principal investigator prepares a plan for the trial, called a protocol. The protocol explains what will be done during the trial. It also contains information that helps the doctor decide if this treatment is right for a particular patient. The protocol includes information about: o o o o o o The reason for doing the trial Who can join the trial (called “eligibility requirements”) How many people are needed for the trial Any drugs that will be given, how they will be given, the dose, and how often What medical tests will be done and how often What types of information will be collected about the people taking part For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment. Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward. Patients can enter clinical trials before, during, or after starting their cancer treatment. Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment (National Cancer Institute). Medical Disclaimer This Fact Sheet is intended to provide general information only and, as such, should not be considered as a substitute for advice, medically or otherwise, covering any specific situation. Users should seek appropriate advice before taking or refraining from taking any action in reliance on any information contained in this Fact Sheet. So far as permissible by law, the Cancer Association of South Africa (CANSA) does not accept any liability to any person (or his/her dependants/estate/heirs) relating to the use of any information contained in this Fact Sheet. Whilst the Cancer Association of South Africa (CANSA) has taken every precaution in compiling this Fact Sheet, neither it, nor any contributor(s) to this Fact Sheet can be held responsible for any action (or the lack thereof) taken by any person or organisation wherever they shall be based, as a result, direct or otherwise, of information contained in, or accessed through, this Fact Sheet. Support Cancer Association of South Africa (CANSA): www.cansa.org.za Toll free line (08:00 to 16:30 on weekdays): 0800 22 66 22 Researched and Authored by Prof Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupational Health] Approved for Distribution by Ms Elize Joubert, Acting Chief Executive Officer May 2014 Page 21 Other Support The Prostate Cancer Foundation: www.prostatecancerfoundation.co.za Prostate Cancer Foundation 982 Louis Trichardt Street 0084 RIETFONTEIN GEO: -25.700520, 28.231360 Phone: +27 12 342 9432/3 Fax: +27 12 342 9434 The Urological Association of South Africa: www.uronsa.co.za PO Box 13392, Cascades, Durban, 3202 Tel: +27 (0)33 345 7872 Fax: +27 (0)33 342 7142 Website: www.urosa.co.za/default.asp Researched and Authored by Prof Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupational Health] Approved for Distribution by Ms Elize Joubert, Acting Chief Executive Officer May 2014 Page 22 References and Consulted Sources About.Com. 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