PCC_DiagnosedCover:Layout 1 27/05/09 9:45 AM Page 1 JUST DIAGNOSED A GUIDE FOR MEN AND LOVED ONES June/09 For additional copies and information please visit: prostatecancer.ca or call 1-888-255-0333 prostatecancer.ca Prostate Cancer JUST DIAGNOSED: A GUIDE FOR MEN AND LOVED ONES Table of Contents What’s the prostate?................................................2 Is it cancer?.............................................................3 What is the prognosis or “How bad is it, doc”?........5 Digital rectal exam..............................................5 Prostate-specific antigen (PSA) test......................5 Biopsy & transrectal ultasound (TRUS).................7 Grading prostate cancer.......................................7 The Gleason Grading System......................8 Staging prostate cancer.....................................10 TNM staging............................................11 Whitmore-Jewett staging..........................13 Other test................................................14 Putting it all together: prediction tools & risk.....15 What are the treatment options?...........................18 Active surveillance............................................18 Surgery............................................................19 Radiotherapy.....................................................22 Brachytherapy...........................................24 Hormonal therapy..............................................27 Antiandrogen therapy..............................29 Chemotherapy..................................................31 Complementary therapies.................................33 What next?...........................................................34 Questions to ask about follow up.......................34 Living well after treatment.................................35 Where can I turn for more information or help?.......39 Prediction tools and nomograms..............................40 What’s the prostate? The prostate is a gland located deep inside a man’s pelvis below his bladder and in front of his rectum. The prostate surrounds the upper part of the urethra, the channel that lets urine and semen pass through the penis. The prostate’s function is to produce a part of the semen that nourishes and protects sperm. It also helps regulate the flow of urine, and, during a man’s orgasm, its muscle cells contract to help propel the semen out the penis. A healthy prostate is the size of a golf ball, but it is actually more like a small, ripe plum. Its outer covering is soft, and it is spongy to the touch. If, while doing a digital rectal exam (DRE), your doctor discovers an enlarged, irregularly shaped, or hard, lumpy, or tender prostate, you may have a prostate problem. The prostate also produces an enzyme that helps the semen remain in liquid form after ejaculation. This enzyme, prostate-specific antigen (PSA), is usually produced only in the prostate gland itself and can be found in semen or blood. Prostate Cancer Is it cancer? Prostate cancer is only one of a number of problems that can occur within the prostate. Prostatitis, an infection or inflammation of the prostate, is not cancer. And there is no evidence that prostatitis leads to prostate cancer. Prostatitis is usually categorized as acute or chronic and as either bacterial (being caused by bacteria) or nonbacterial. The most severe and least common form is acute bacterial prostatitis. The most common form is chronic nonbacterial prostatitis. Prostatitis treatment can include antibiotics, anti-inflammatory drugs, alpha blockers (tamsulosin), 5-alpha- reductase inhibitors (Proscar® or Avodart®), bed rest, and drinking plenty of fluids. Benign prostatic hyperplasia (BPH) is also not prostate cancer. BPH is a non-cancerous (benign) overgrowth of cells (hyperplasia) in the prostate gland (prostatic). Basically, BPH is an enlarged prostate, and the condition is common in older men. Luckily, many men with enlarged prostates experience no symptoms. But, for some men, the growing prostate can progressively squeeze the urethra, which lets urine travel from the bladder, through the prostate, and out the penis. This narrowing of the urethra can reduce or obstruct the flow of urine and lead to a gradual loss of bladder function. BPH is treated through changes in diet and lifestyle; through medications such as alpha blockers and 5-alpha-reductase inhibitors; and through surgery. Prostatic intraepithelial neoplasia (PIN) is not cancer either, but it is an abnormal and uncontrolled growth of prostate cells, specifically, of the cells that line the external and internal surfaces of the prostate gland. PIN cells do not have the ability to invade surrounding tissue, so they are not malignant (not cancerous), but they are atypical. The most abnormal cells are 2 3 classified as high grade PIN, and cells that appear almost normal are classified as low grade PIN. Low grade PIN (sometimes called mild dysplasia) does not appear to increase a man’s risk of prostate cancer. But high grade PIN, in which cells can be very irregular and share some of the genetic abnormalities of prostate cancer cells, is sometimes called a pre-cancerous condition (defined as a condition that leads to cancer). Still, having high grade PIN does not mean that you will develop prostate cancer inevitably. But, because evidence tells us that most prostate cancers start out as high grade PIN, men with this condition are monitored carefully for prostate cancer, usually through biopsies. Other than the vigilant monitoring of men with high grade PIN, no other follow-up or therapy is usually required. Prostate cancer is a disease in which some of the cells of the prostate, the cancerous ones, have lost normal control of cell growth and division. The natural processes of cell growth and death no longer apply to them. They lose their normal structure, so they cannot function properly. Also they can escape the prostate and invade other parts of the body, growing there and crowding out the normal cells necessary for the body’s health. To be cancerous, a prostate cell has to have all of these characteristics: uncontrolled growth, abnormal structure, and invasiveness (ability to invade and escape the prostate, where it originally grew). Tumours (clusters of cells growing into a mass in an uncontrolled way) are not necessarily cancer. They can be benign. A benign tumour does not spread to other parts of the body; it is not invasive. A prostate cell can be abnormal in structure and not cancerous. PIN or prostatic intraepithelial neoplasia is a condition in which prostate cells are abnormal but not malignant or invasive. 4 Prostate Cancer What’s the prognosis or “How bad is it, doc”? A prognosis is an educated assessment of the severity and nature of your cancer, as well as a medical forecast about the probable course of your illness and the best way to treat it. Your medical team will use many tools to evaluate your condition: Digital rectal exam (DRE) A digital rectal exam (DRE) is most frequently used in diagnosing prostate cancer, but it can help indicate how serious prostate cancer is or how it might be treated. During a DRE, the physician inserts a gloved and lubricated finger into the rectum to feel the rear of the prostate for hard, lumpy areas. If an abnormality is felt, the examiner can note whether it seems contained within the prostate, is distorting the gland, or appears to be pushing through and growing outside the prostate. The larger a tumour is and the closer it is to escaping the prostate the more potentially dangerous it is if a biopsy shows that it is cancerous. As biopsies can cause swelling and discomfort, which can make subsequent DREs difficult to conduct or inconclusive, the physical exam you had before the biopsy may be very important in assessing your cancer. Prostate-specific antigen (PSA) test This test detects the amount of prostate-specific antigen (PSA) in the blood. Each man’s normal level depends on individual factors such as his age or the size of his prostate. Although, in the past, most doctors considered PSA levels below 4 nanograms per millilitre of blood (4.0 ng/mL) to be normal, recent research has found prostate cancer in men with PSA levels below this. Currently, in men 49 and younger, PSA levels above 2.5 ng/mL might be considered elevated, and for men aged 50 to 59, the cut-off level might be 3.5 ng/mL. If you have an elevated PSA level, it does not mean that you have prostate 5 Prostate Cancer cancer, but your doctor may counsel you to have further tests done to investigate the possibility. In general, the higher the cancer-related PSA level, the poorer the prognosis. PSA density (PSAD) compares a man’s PSA level to the size of his prostate, which is measured when he undergoes a transrectal ultrasound (TRUS). Higher PSA densities (i.e., above 0.15) indicate increased risk. The percentage of free to total PSA may be measured too, because, as a general rule, cancer cells make less free PSA than healthy prostate cells. What is free PSA? It is prostate-specific antigen that is not bound to other proteins in the blood. So the lower the percentage of free PSA the worse the prognosis. (Readings between 10 per cent and 25 per cent are difficult to assess, but readings under 10 per cent are worrisome.) PSA velocity (PSAV), which is a measurement of how quickly levels of prostate-specific antigen increase over time, is another tool. A rise in PSA level of more than 0.75 ng/mL per year will often trigger a biopsy. PSA doubling time (PSA-DT) measures the time it takes for the amount of PSA detected in your blood to double. The shorter the doubling time the more aggressive the cancer and the worse the prognosis, in most cases. PSA levels, PSA velocity, and PSA doubling time can be used in assessing prostate cancer that recurs after treatment. If the cancer recurs at least 2 years after treatment, the PSA doubling time is greater than 12 months, and the PSA velocity is less than 0.75 ng/mL per year, the likelihood is that the cancer is recurring in the prostate or in the area where the prostate was before its removal and further local treatment (e.g., radiotherapy) may be helpful. A time of recurrence that is less than 2 years, a PSA doubling time of less than 6 months, and a PSA velocity of greater than 0.75 ng/mL per year suggest a more distant site for the cancer and the need for systemic therapy. 6 Biopsy & transrectal ultrasound (TRUS) In a biopsy of the prostate, the physician inserts into the rectum a device that incorporates an ultrasound probe and can also hold biopsy needles. The transrectal ultrasound allows the physician to position the biopsy needles close to suspicious areas of the prostate, and then these needles are deployed to remove samples of the prostate tissue. The microscopic analysis of these tissue samples is a powerful diagnostic and prognostic tool. It can give information on • The areas from which tissue samples were taken and the dimensions of these samples • Whether prostatic intraepithelial neoplasia (PIN) is present • Whether the tissue samples are positive or negative for cancer and, if they do show cancer (if they are positive), how much cancer was found in each sample • What type of cancer is present • How abnormal the cancer cells look under the microscope (the grade or Gleason score of the cancer) • Whether there is evidence that the cancer has spread along the nerves within the prostate (perineural invasion) Grading prostate cancer Grading prostate cancer means describing how closely its cells resemble the normal cells of the prostate. The lower the grade, the better the news. Low grade prostate cancer has highly differentiated cells, which means these cells still retain many of the qualities that make prostate cells unique. In intermediate grade prostate cancer, cells look more abnormal. These cells are moderately differentiated, which means that they can still be recognized as prostate cells but look odd and disorganized. High grade prostate cancer cells are poorly differentiated and barely resemble prostate cells. The Gleason grading system is commonly used. 7 Prostate Cancer The Gleason Grading System Grade 1 • Well-differentiated; cells resemble normal prostate cells • Tiny glands of the prostate are round, have defined edges, and are tightly packed; Tumour not expected to grow quickly. Grade 2 • Less well-differentiated; cells not as normal looking • The glands are still round but are loosely packed with less distinct edges Grade 3 • Moderately differentiated • The glands are larger with irregular shapes and spacing. Their edges are badly defined and show infiltration. Grade 4 • Poorly differentiated • Glands are of different sizes and shapes; they are fused together in masses or chains Grade 5 • Poorly differentiated; Cells are very strange looking • Glands are not really visible; Tissue appears composed of solid cellular sheets, single cells, or nests of tumour 8 Gleason score: A man will often have a number of different grades of cancer present within his biopsy sample, so Gleason developed a scoring system to take this into account. The Gleason score is equal to the sum of the two most common grades of cancer evident in a patient’s biopsied tissue. For example, if cells with a Gleason grade of 4 are the most common, but about 10 percent of the cells have a Gleason grade of 3, the Gleason score would be 7. (If the secondary grade makes up less than 5 per cent of the cancer cells, it is considered insignificant, so the grade of the dominant and only significant pattern would be added to itself.) • a Gleason score of 2 to 6 is usually considered low • a Gleason score of 7 is considered intermediate • a Gleason score of 8 to 10 is considered high Note, however, that even scores considered low may be composed of poorly differentiated cells with a Gleason grade of 4 or 5. The presence of these cells is worrisome, and a Gleason score of 6 that has grade 4 cells as its dominant pattern (Grade 4 + Grade 2 = Gleason 6) is riskier than the same score based on grades that indicate the presence of only moderately differentiated cells (Grade 3 + Grade 3 = Gleason 6). 9 Prostate Cancer Staging prostate cancer The stage of prostate cancer is determined by the tumour size, whether the cancer has spread to the pelvic lymph nodes that drain the prostate, or whether cancer has spread to an area of the body remote from the prostate. In other words, important factors are how big the tumour is and how much the cancer has spread: whether there are any distant metastases. Two main methods of staging are TNM and the Whitmore-Jewett system, which uses letter designations A through D. TNM staging: In this method, the T represents the primary tumour, the N represents the nodes of the lymphatic system (lymph nodes), and the M represents metastasis (or whether there is evidence of the cancer’s spread to distant areas). T STAGE TX & T0 T1 Tumour is not palpable nor visible by imaging TX Tumour cannot be assessed. T1a T1a Tumour found incidentally in less than 5% of prostate tissue sample T1b Tumour found TO incidentally in more No than 5% of prostate evidence tissue sample of tumour T1c Tumour found during needle biopsy (e.g., because of elevated PSA) 10 T2 Tumour is confined to the prostate T3 Tumour extends beyond the prostate T4 Tumour has invaded neighbouring tissues T2a Tumour involves 50% or less of one lobe T3a Tumour extends beyond the prostate capsule on one side (unilateral extracapsular extension) or on both sides (bilateral extension) The tumour is fixed or invades areas adjacent to the prostate other than the seminal vesicles, e.g., the bladder neck, the external sphincter, the rectum, and the pelvic wall T2b Tumour involves more than 50% of one lobe but not both lobes T2c Tumour involves both lobes T3b Tumour has invaded the seminal vesicles 11 Prostate Cancer Whitmore-Jewett staging: In the WhitmoreJewett staging system, prostate cancer is specified first by letter (A through D) and then by number. N STAGE NX & N0 NX Lymph nodes near the prostate were not or cannot be assessed. N1/N+ Metastasis in regional lymph nodes WHITMORE-JEWETT STAGING NO No regional lymph node metastasis A Early stage cancer confined to the prostate, not detectable by DRE and producing no symptoms A1 Cancer cells look very much like normal cells (well differentiated) and are focused in one area of the prostate A2 Cancer cells are more abnormal (moderately or poorly differentiated), and cancer is in several locations in the prostate B Cancer is confined to prostate but is detectable by either DRE or because of elevated PSA B0 Cancer cells are confined to the prostate, are not detected by DRE, but cause elevated PSA B1 There is one area (nodule) of cancer in one lobe B2 There is extensive cancer in one lobe or some cancer in both lobes C Cancer has extended out of the prostate capsule but has not spread to regional lymph nodes or more distant areas. C1 The cancer extends beyond the prostate C2 The cancer extends beyond the prostate and obstructs the bladder or urethra D Metastatic prostate cancer; the cancers has spread to regional lymph nodes or to more distant areas D1 The cancer has spread only to regional lymph nodes D2 The cancer has spread to distant lymph nodes, bones, organs, or tissues D3 Designation for D2 patients who have relapsed after treatment M STAGE MX & M0 MX Distant metastasis of cancer cannot be determined or assessed. MO No metastasis of the cancer beyond the regional lymph nodes M1 There are distant metastases; the cancer has spread beyond the regional lymph nodes M1a The cancer has spread to non-regional lymph nodes M1b The cancer has spread to the bone M1c The cancer has spread to other distant sites, with or without metastasis to the bone 12 Testis Penis 13 Prostate Cancer Other tests Your medical team may use other tools to assess your cancer and determine the best treatments. Many of these diagnostic or staging procedures investigate whether prostate cancer has spread beyond the prostate: Bone scans provide images of the skeleton to investigate whether prostate cancer has spread to the bone. During a bone scan, injected low-level radioactive material is taken up in the bone more rapidly by fast growing cells, producing “hot spots” on the scan and indicating the possibility of cancer in the bone. Chest x-rays are often ordered to see whether cancer has spread to the lungs or the ribs. Computerized axial tomography (CT or CAT) scans use computers to combine pictures gathered by rotating x-ray beams, creating cross-sectional and three-dimensional images of organs. These scans are useful for finding enlarged lymph nodes or other abnormalities. Magnetic resonance imaging (MRI) uses a large, powerful magnet, radio waves, and a computer to create images of the prostate and pelvic area or other body regions; these images are sometimes used to provide information about cancer spread outside the limits of the prostate gland or into the lymph nodes, bone, or elsewhere. Pelvic lymph node dissection, or the surgical removal of the lymph nodes in the pelvis and their microscopic analysis, is the most accurate way of determining whether prostate cancer has spread to the lymph nodes. This procedure is typically performed during surgery to remove the prostate. ProstaScint scans use radioactive monoclonal antibodies to investigate prostate cancer spread. These antibodies attach to suspect cells and expose “hot spots”– where cancer may be present. The test is not always reliable, and results can be difficult to analyse. It is not widely used nor available in Canada. 14 Putting it all together: Prediction tools and risk Most important in gauging the risk posed by prostate cancer is whether it has spread beyond the prostate. If all indications are that it has not, you have clinically localised prostate cancer, and statistics indicate that between 75 % and 93 % of men in this situation survive their disease for 10 to 15 years. This stage of prostate cancer development is called “clinically localised” because there is still a risk that microscopic cancer cells have escaped the prostate—and escaped detection by clinical tests. Because the clinical stage of a man’s prostate cancer is often difficult to gauge, especially before surgery, physicians have developed mathematical models that put together all known information about a man’s cancer and make predictions about his risk based on statistical data gathered from other men’s experiences with the disease. These are called nomograms. Partin tables use your PSA level, Gleason score, and estimated clinical stage (e.g., T1c) to calculate probability percentages that your cancer has spread. Han tables use similar information to estimate the probability that your cancer will recur after a radical prostatectomy. Modern computer technology has made possible the development of new tables and nomograms (representations of numerical relations). See the section “Where do I go for more information?” to find online versions of some of the prediction tools useful for men with prostate cancer. Remember, however, that these tools base predictions on only a few factors. They do not know, for example, much about your general health, your life, or your medical history. Your own medical team is your best resource in assessing your prognosis and in recommending appropriate treatment. Still, most predictions of prostate cancer risk are based on three clinical factors. The larger the tumour, the higher the Gleason score, and the more detectable prostate-specific antigen (PSA) in the blood, the greater this risk. 15 Prostate Cancer What are the treatment options? As is evident from the chart connecting risk category and standard treatments, the usually recommended treatments for prostate cancer that seems to be confined to the prostate are either surgery to remove the prostate (radical prostatectomy) or radiation to kill prostate cells. The greater the chance that your cancer has spread outside of the prostate, the more significant becomes a systemic (system-wide) treatment such as hormone therapy. Active surveillance This strategy, which is sometimes called watchful waiting, involves monitoring a man’s prostate cancer carefully and only treating the cancer if it becomes aggressive. This monitoring is done through regular digital rectal exams, PSA tests, and biopsies of the prostate. Is it for me? If your cancer is unlikely to threaten your health during your lifetime, it might be. Perhaps your life expectancy is less than ten years and your cancer is non-aggressive. Perhaps all tests indicate that the cancer is slow growing and will not escape the prostate or cause symptoms. Perhaps you have other health problems that make aggressive treatment an inferior option. Or you may decide that, given the anticipated low risk currently, you are not ready to undergo other treatments and can cope with the knowledge that cancer remains in your body. Disadvantages: Monitoring cancer is far from an exact science, as all bodies are unique. Your cancer might grow more rapidly than expected, escape the prostate, and reach an incurable stage before your medical team has a chance to react. Although this theoretical situation does not occur very often, you may be unwilling to live with the possibility that it might occur at all. 18 Surgery A radical prostatectomy is one of the most common and effective treatments of localised prostate cancer—prostate cancer that has not left the prostate gland. In this procedure, a surgeon removes the prostate gland, the seminal vesicles, and, sometimes, the lymph nodes in the pelvis. There are various methods of performing a radical prostatectomy: • In a radical retropubic prostatectomy, the surgeon makes an incision that begins just under the navel and runs to just above the public bone. • In a radical perineal prostatectomy, the surgeon makes the incision in the area between the scrotum and the anus. Although less used because it gives a poorer view of the bladder and other significant anatomical features, this approach makes sense in some cases, for example, when a man has extensive scar tissue from previous abdominal surgeries. • Nerve-sparing techniques are now commonly used with radical retropubic prostatectomy, as long as the cancer is not too close to the cavernous nerves. These nerves and accompanying veins run in two bundles from behind the bladder, along the sides of the prostate, and into the penis. Surgeons try to leave these nerves and veins intact because both are involved in achieving and maintaining erections. • In a laparoscopic radical prostatectomy, a scope inserted through a small incision in the abdomen lights and magnifies the area surrounding the prostate, sending an enlarged view of the surgical field to a monitor in the operating room. Then, microsurgical instruments are inserted through four or five other small incisions made on each side of the abdomen, and the prostate gland and seminal vesicles are removed. Pelvic lymph nodes may also be removed. • Robotic-assisted radical prostatectomy also uses a laparoscope and microsurgical instruments inserted through multiple, small incisions in the 19 Prostate Cancer abdomen. In this case, though, the instruments are connected to robotic arms that perform the operation, guided by the surgeon’s movements, which the robot converts into micro-movements. The patient and the surgeon need not be in the same room. Surgery without laparoscopes or robotic systems is often called “open surgery.” And, in the hands of an experienced surgeon, an open nerve-sparing radical prostatectomy can have excellent results in terms of cure, continence, and potency. Less blood loss, faster postoperative recovery, and shorter hospital stays are advantages of laparoscopic or robotic-assisted prostatectomy. But the verdict is out concerning which surgical approach offers the best treatment of prostate cancer and the least likelihood of long-term side effects. incision location for a radical retropubic prostatectomy location of small incisions for a laparoscopic radical prostatectomy Is it for me? Surgery may be for you if your cancer is confined to the prostate or the tissues immediately surrounding it, and there is no evidence of distant spread (metastasis). The clinical stages T1, T2, or a small T3 tumour would fit this description. For men 20 with localised prostate cancer, a radical prostatectomy offers one of the best chances for a cure. If your cancer has spread to the lymph nodes or if there are distant metastases, then hormone therapy or another system-wide treatment will usually be recommended, either on its own or with a radical prostatectomy. If, after the surgery, there is evidence that cancer cells have been left behind (e.g., positive surgical margins), post-operative radiotherapy may be useful. Disadvantages: Radical prostatectomy is a fairly serious surgical operation, no matter how it is performed. It will require two to five days of hospitalization and three to six weeks of recovery time at home. You will need a catheter and urine collection bag, which can usually be disposed of after one to three weeks. You will most likely experience some short-term lack of control over urination. But, in most cases, things return to normal in one month to a year. A more serious consideration for some men is that, after a prostatectomy, they will no longer be able to father children without the use of a sperm bank. Men can reach orgasm but no longer ejaculate after this surgery. Other long-term consequences of the operation can include erectile dysfunction (impotence), chronic incontinence, and narrowing of the urethra. A common long-term side effect is erectile dysfunction. Estimates are that, by two years after surgery, approximately half of the men who were fully functional before surgery have recovered erections. Penile rehabilitation and nervesparing surgical techniques are improving these odds. A smaller percentage of men will suffer permanent stress incontinence (the leakage of urine when sneezing or engaging in strenuous activity). An even smaller percentage will experience total and permanent incontinence and may require an implanted artificial sphincter. Another complication, the narrowing of the urethra because of scar tissue, can make urination difficult. Minor surgery can usually correct this problem. 21 Prostate Cancer Radiotherapy Radiation therapy directs radioactive energy to a particular area to kill cells by causing breaks in their DNA. Because cancer cells generally replicate quickly, they are more susceptible to radiation than healthy cells, which divide and multiply more slowly. Still, radiation usually causes some damage to healthy tissue and, in some patients, may produce radiotherapy-induced side effects. Radiation therapy is given in one of two main ways: by focussing an external beam of radioactive energy at the cancer (external beam radiation) or by implanting radioactive material near the cancer. External beam radiation: In external beam radiation, a computer-guided machine delivers high energy x-rays to the prostate gland containing cancer cells in brief sessions (called “fractions”) that are usually scheduled five days a week over about seven to eight weeks. As much as possible, the rays are focussed toward the location and depth of the prostate cancer, but some healthy cells will be affected as well. Both the benefits and the possible side effects of radiation therapy are gradual and cumulative because cell death or inflammation from radiation continues for several months after treatment stops. Many techniques are commonly practiced today in order to enable precision in external beam radiation therapy, thereby increasing treatment efficacy and reducing damage to healthy cells: 22 • 3-dimensional conformal radiation therapy (3DCRT) This form of external beam radiation therapy is now a standard treatment for prostate cancer. It uses a CT scan or MRI to measure the prostate in three dimensions and computers to calculate how the radiation should be delivered. An individualized plan emerges from this information, one that directs radioactive beams so they conform or shape to the area targeted to receive radiation. Before the plan is followed, a radiation oncologist will check its safety by using all data to estimate the radiation dose required to kill cancerous cells and the amount of radiation this would deliver to neighbouring healthy cells. • Intensity modulated radiation therapy (IMRT) Like 3D-CRT, this form of external beam radiation therapy uses a CT scan or and MRI to create a three dimensional picture of the prostate and a computer to calculate how to irradiate cancerous areas while sparing healthy ones. Unlike 3D-CRT, intensity modulated radiation therapy can deliver radiation at varying intensities or doses throughout the targeted area being irradiated. IMRT fine-tunes 3D-CRT by enabling the radiation’s intensity (dose) to be modulated (varied), so cancerous areas can receive high intensity radiation while radiation to other areas is minimized. • Image-guided radiation therapy (IGRT) Over the years, doctors have used steadily improving technology to view the prostate and to mark the location of a prostate cancer tumour. X-rays, ultrasounds, CT scans, and MRI technology all provide images that can help guide radiation therapy. Typically, during radiation therapy planning, radiation oncologists will consult these images and use drops of permanent ink on a patient’s skin or small metallic markers inserted into a patient’s prostate gland to indicate the area that should receive radiation. To compensate for movement of the prostate during treatment or 23 Prostate Cancer possible changes to the tumour’s shape or size between treatments, doctors expand the treatment area slightly—to be as sure as they can that all the cancer cells are irradiated. In some cancer centres today, a technology known as image-guided radiation therapy (IGRT) allows doctors to see the tumour’s location just before the delivery of radiotherapy or even during a treatment, enabling them to adjust the radiation beams to hit a tumour more precisely and reduce the amount of healthy tissue exposed to radiation. Brachytherapy: This form of radiation therapy involves introducing radioactive material directly into the prostate so as to deliver radiation at close range. • Seed brachytherapy, the most common method, uses surgery to implant tiny radioactive pellets or “seeds” into the prostate through the perineum (the region between the scrotum and the anus). A transrectal ultrasound (TRUS) helps surgeons view the prostate so the seeds can be placed appropriately. The procedure is usually done while a man is under a general or an epidural (waist down) anaesthetic and does not normally require hospitalization. The seeds, each one smaller than a grain of rice, stay in the prostate permanently, emitting radiation steadily for about 6 months or more until they lose their radioactivity. • High dose rate (HDR) brachytherapy involves similar surgical procedures but it delivers significantly higher doses of radiation over a much shorter period. Thin tubes or catheters (12 to 18 or more) are inserted into the patient’s prostate using a transrectal ultrasound probe for guidance. Doctors verify the position of these catheters using a CT scan and then connect them to the treatment machine, which releases radioactive material into the catheters. A computer helps doctors assess how long the prostate cells adjacent to each part of each catheter should be exposed to radioactivity to give 24 the tumour cells the desired dose of radiation and to avoid, as much as possible, damage to healthy cells. After treatment, the radioactive material and catheters are removed. Is radiation therapy for me? If you have localised prostate cancer and a life expectancy of between 7 and 10 years, external beam radiation therapy may be for you. It may also be the recommended treatment for younger men with low or intermediate risk cancers who have health problems that make them poor candidates for prostate surgery. An advantage of external beam radiation is that no hospitalization is necessary, and daily treatments are fast, causing minimal disruption in a man’s day if the radiation facility is nearby. Seed brachytherapy as a treatment on its own is usually recommended only to men diagnosed with early prostate cancer who are in the low risk category. Also, if you have a large prostate or a history of urinary problems, or if you have had a transurethral resection of the prostate to remove a urinary blockage, this treatment is not the best option for you. HDR brachytherapy is a relatively new treatment that may not be available locally. It is sometimes offered in combination with external beam radiation (as a boost). Research into its effectiveness as a therapy for men with stages T1 to T3b prostate cancer is ongoing. Convenience is a major benefit of brachytherapy; it allows men to avoid both the lengthy recovery time necessary after major surgery and the long-term treatment schedule needed for external beam radiation. Disadvantages: The major disadvantage of all forms of radiation therapy is that, because the prostate is not removed, cancer cells that are not killed by treatment can re-grow and new prostate cancer cells may grow. Short-term side effects of external beam radiation can include fatigue, skin 25 Prostate Cancer reactions, and hair loss in the area receiving radiation. Brachytherapy, which involves piercing the prostate in several places, can cause the gland to swell temporarily. Radiation treatment can also affect the bladder and rectum, and a man may have difficulty with urination, diarrhoea, or rectal bleeding. A common long-term complication of radiation therapy is erectile dysfunction. Erectile difficulties caused by radiation develop gradually in the months following treatment, unlike those caused by surgery. Also, radiation therapy “dries out” the prostate, which, in many cases, stops making the substances that constitute semen and nourish sperm. Most men become infertile, although still able to achieve an orgasm. Incontinence and bowel problems are rare long-term complications. Hormonal therapy Hormonal therapy works by depriving prostate cancer cells of the male hormones (androgens, including testosterone) that they need to grow and flourish. This androgen deprivation can be accomplished through undergoing an orchiectomy that removes the testicles or by taking medication that either prevents the production of androgens (LHRH analogue therapy) or blocks their effects on prostate cells (antiandrogen therapy). By itself, hormonal therapy cannot cure prostate cancer, but it can slow or stop cancer growth for many years. It is also a systemic rather than a local therapy, meaning that it can arrest prostate cancer cells no matter where they are in the body. Orchiectomy: This procedure, also known as surgical castration, involves removing the testicles, which produce most of a man’s testosterone, the principle male hormone. Although an orchiectomy is a relatively quick and simple operation that causes less long-term inconvenience and expense than drug-based hormonal therapy, few men choose this option today, possibly because its effects are not reversible. LHRH analogue therapy (medical castration): Paradoxically, luteinizing hormone-releasing hormone (LHRH) analogues interfere with the production of androgens by over-stimulating the pituitary gland to produce luteinizing hormone (LH). The gland exhausts itself and shuts down LH production altogether, thus depriving the testicles of what they need to manufacture testosterone. The therapy is usually administered by injection every 2 to 6 months or monthly. In Canada, the most used LHRH analogues are Eligard® (leuprolide acetate), Lupron Depot® (leuprolide acetate), Suprefact® (buserelin), and Zoladex® (goserelin). Because LHRH analogues initially stimulate the production of LH and, consequently, of testosterone, a man may experience a testosterone surge that heightens cancer symptoms in the first weeks of treatment. 26 27 Prostate Cancer After about two weeks, the level of testosterone falls dramatically and remains at extremely low levels as long as the drug is continued. Common LHRH Analogues Injection Route Buserelin Subcutaneous (Suprefact®) Usual time between injections 2 or 3 months Goserelin (Zoladex®) Subcutaneous 1, 3 months Leuprolide (Lupron®) Intramuscular 1, 3, or 4 months Leuprolide (Eligard®) Subcutaneous 1, 3, 4, or 6 months Antiandrogen therapy: Antiandrogens are drugs that block or otherwise interfere with the normal effects of male hormones on prostate cells. There are two types: steroidal and non-steroidal. Steroidal antiandrogens, which act like female sex hormones, are usually taken orally each day. They include megestrol acetate (Megace®) and cyproterone acetate (Androcur®). Non-steroidal antiandrogens include fultamide (Euflex®), bicalutamide (Casodex®), and nilutamide (Anandron®). Nonsteroidal antiandrogens are sometimes used in combination with LHRH analogue therapy or orchiectomy to block the effects of androgens produced outside of the testicles (in the adrenal glands, for example). Hormonal therapy is used at various times for a variety of purposes. It may be given before a local treatment, such as radiation or a radical prostatectomy, to reduce the size of a tumour, for example. This is called neoadjuvant hormonal therapy. More commonly, it is used directly after surgery or radiation to treat any microscopic cancerous cells that may remain in the body. Doctors often use the term minimal residual disease (MRD) to refer to these isolated or disseminated cancer cells. Hormonal therapy after prostatectomy or radiation is called adjuvant hormonal therapy, and studies confirm that it can prolong survival for men with locally advanced prostate cancer. Besides the different timing of hormonal therapy, there are various treatment regimes, and new ones, as well as new drugs, are being tested all the time. • Combined androgen blockade (CAB) combines the use of antiandrogens with either chemical or surgical castration. The idea is to block the action of even the small amount of androgens present in the body during LHRH analogue therapy or after an orchiectomy. Research suggests that men treated with CAB, which is sometimes called maximal androgen blockade (MAB) or total androgen blockade (TAB), may live longer, on average, than men treated by LHRH analogue therapy alone. 28 29 • Intermittent androgen blockade (IAB), often referred to as intermittent hormonal therapy or intermittent androgen suppression (IAS), is still being investigated as a treatment option. It involves administering hormone therapy drugs until a man’s prostate cancer seems in check, e.g., his PSA levels drop and stabilize. Then, the man stops hormonal therapy until his PSA rises to a predetermined level or at a certain speed. The hope is that stopping hormone therapy periodically and then restarting it will enable men to enjoy a better quality of life during offtreatment times and may postpone the day when hormone therapy no longer works well to control their cancer (i.e., they develop hormone resistant or hormone refractory prostate cancer). Is it for me? Hormone therapy is the treatment of choice for men whose prostate cancer has spread to the lymph nodes, bones, or elsewhere in the body (N1 or M1). It is also recommended for those whose cancer returns after radical prostatectomy or radiation therapy, or for those who are at a high risk of experiencing such a recurrence. Disadvantages: The main disadvantages are that hormone therapy does not cure prostate cancer and that treatments only work for a certain amount of time, until prostate cancer cells become hormone resistant or hormone refractory. (Hormone resistant prostate cancer may respond to a change in hormonal therapy while hormone refractory prostate cancer progresses in spite of any hormone therapy treatment regimen.) Men on hormonal therapy may experience hot flashes, swelling or tenderness of their breasts, lack of energy, anaemia, mood swings, or depression. Over the long term, hormone therapy can cause a loss of muscle strength and bone density, which can lead to osteoporosis. Many patients are placed on Vitamin D and calcium to prevent bone loss. The most common side effects are a decreased sex drive (libido) and the eventual loss of erections (erectile dysfunction). 30 Prostate Cancer Chemotherapy Before 2004, no chemotherapy agent had been proven to extend the lives of men with prostate cancer. In that year, two international studies confirmed that docetaxel (Taxotere®), a chemotherapy drug made from the needles of the European yew tree, improves the survival time and quality of life for men with advanced stage prostate cancer that is resistant to hormone therapy. Generally, chemotherapy uses drugs that circulate throughout the body to destroy cancer cells. Taxotere®, which has been used since 1995 in the treatment of breast and lung cancer, kills cancer cells by disrupting the formation of their internal structures, thereby stopping cells from dividing and multiplying. Still, in the treatment of prostate cancer, chemotherapy drugs are used mainly at the hormone refractory stage, when a man’s cancer no longer responds to hormone therapy. Some chemotherapy agents, such as mitoxantrone (Novantrone® and Onkotrone®), are used primarily to relieve the pain associated with the late stages of this disease. This palliative chemotherapy greatly improves the quality of life of men with advanced disease, but it does not prolong their lives. The discovery that docetaxel (Taxotere®) does prolong patients' lives (usually by about 25 % compared to similar patients not taking the drug) and also reduces the pain associated with advanced disease has led to research that provides better options for men with hormone refractory prostate cancer. What about clinical trials or new therapies? Promising new prostate cancer therapies are being tested right now. And some treatments once considered promising just a few years ago have faded from view. One way to discover relevant innovations in prostate cancer treatment is to research what clinical trials are being offered to patients like you. (A clinical trial is a carefully designed investigation into the effects and effectiveness of a drug, treatment, or medical 31 Prostate Cancer device on a particular group of people, e.g., men with clinically localised prostate cancer.) The Clinical Trials Group of the National Cancer Institute of Canada provides an online listing of all current cancer trials in the country. You might even consider participating in such a trial. Some of the more unusual or experimental prostate cancer treatments that you might hear about include the following: • Angiogenesis inhibitors are drugs that may be useful in stopping prostate cancer growth by keeping new blood vessels from forming; prostate cancer tumours depend on the growth of blood vessels (angiogenesis) to feed cancer cells. • Cryotherapy or cryosurgery uses liquid nitrogen or Argon gas, delivered to the prostate through probes positioned using transrectal ultrasound, to freeze and kill prostate tissue, including cancer cells. It may be used to treat early prostate cancer or when radiation therapy is not successful. Cryotherapy is offered in very few Canadian centres. • Gene therapy attempts to alter the genetic structure of cancer cells, so they can be killed more easily, either by other cancer treatments or by the body’s own defence mechanisms. • High-intensity focused ultrasound (HIFU) destroys prostate tissue and prostate cancer cells using focused, high-energy ultrasound waves to generate intense heat. Men treated with HIFU generally have low to intermediate risk prostate cancer. Treatments are not covered by provincial medical plans. • Immunotherapy or biotherapy is designed to repair, stimulate, or enhance the body’s immune system so it can fight prostate cancer. Vaccines such as the experimental Provenge are often used in immunotherapy. 32 • PRX302 uses prostate-specific antigen (PSA) to activate a series of steps leading to cell death. It may prove effective in treating either prostate cancer or benign prostatic hyperplasia. • Trans perineal microwave ablation of the prostate uses microwave energy to heat the prostate and destroy cells; the microwaves are delivered through needles positioned in the prostate with the help of an ultrasound probe. It has been used to treat men who still have localised prostate cancer after radiation therapy. Remember, you should always consult impartial medical experts when making treatment decisions. Also be aware that the efficacy and long-term consequences of many of these emerging therapies have yet to be tested against those of more standard prostate cancer treatments. What about complementary therapies? A complementary therapy is one that is used in addition to standard treatment. Complementary therapies for men with prostate cancer can include anything from unconventional approaches such as acupuncture, massage, and meditation to strategies that are recommended by physicians, such as lifestyle and dietary changes or other therapies that help relieve certain symptoms of the disease or side effects of its treatment. Men on hormonal therapy may need complementary therapies to minimize the risk of other health problems e.g., cardiovascular disease, diabetes, and osteoporosis. Men treated with chemotherapy may need to address pain or nausea. And some who have undergone surgery or radiation may require complementary therapies to improve their quality of life, for example, to treat incontinence or erectile dysfunction. (See “Living well after treatment” and “Life as a couple.”) 33 Prostate Cancer Always consult your medical team before adding a complementary therapy to your treatment plan. Some can interfere with both the effectiveness and side effects of standard treatments and increase your risk. What next? Questions to ask about follow up How will we judge whether the treatment has worked or is working? What follow-up medical appointments and tests should we arrange to monitor my health, and how often should these take place? What signs or symptoms of prostate cancer recurrence should I watch for? What are my options if the cancer comes back? When can I expect to recover from some of the short-term side effects of treatment? Can I do anything to encourage my recovery? Are there lifestyle changes, strategies, or therapies that will help me maintain or regain urinary control and erectile function or combat fatigue, anaemia, and bone and muscle mass loss? What are my options if I experience long-term complications or secondary health issues because of essential prostate cancer treatment? 34 Living well after treatment Most treatments for prostate cancer can cause both short-term and long-term side effects. Surgery and radiation can result in incontinence or, more rarely, damage to the bowels. Men on hormone therapy may experience hot flashes, fatigue, mood swings, and, over time, a decrease in muscle mass and an increased risk of osteoporosis. Although it is important for you to be aware of these risks, keep in mind that treatment saves lives and that the possible side effects of treatment can also be treated. Incontinence, or the loss of the ability to control urination, can be a side effect of prostate cancer surgery because the prostate is close to the bladder and surrounds the tube that allows urine to flow outside the body (the urethra). Urinary incontinence is rare following radiotherapy. Still, any treatment that removes the prostate or destroys its tissue carries the risk of interfering with the process of urination, although more precise techniques minimize this risk. Treatments for urinary incontinence include • Kegel exercises, which strengthen the muscles you squeeze to stop urinating • Lifestyle changes, such as drinking fewer liquids, avoiding caffeine and alcohol, not drinking before bed, and losing weight • Medication, such as decongestants to tighten the muscles of the urethra or anticholinergic drugs (e.g., oxybutynin) to block messages to the bladder nerves and prevent bladder spasms • Bulking agents, e.g., collagen, injected into the bladder neck to reduce urinary leakage • Opening up any stricture (narrowing) of the urethra caused by scar tissue, which can be done by cutting into the scar tissue or by stretching the urethra • Surgically introducing a sling that compresses the urethra below the sphincter • Surgically implanting an artificial urinary sphincter 35 Prostate Cancer Bowel side effects that last are rare with surgery but may occur following radiotherapy. You may experience some temporary decrease in rectal tone after a prostatectomy, so it is important to avoid constipation. Radiation therapy that exposes a significant area of the rectal wall can cause bowel inflammation, urgency, and faecal incontinence. However, new imaging techniques, more precise methods of delivering radiation, and using neoadjuvant hormonal therapy to shrink tumours reduce the risk of these complications even further. Hormonal therapy side effects can also be addressed. Hot flashes can be controlled with medication or by making lifestyle changes. Exercise (both aerobic and weight-bearing) and proper nutrition are good ways to reduce fatigue, weight gain, and the risk of bone or muscle mass loss. Bisphosphonates such as pamidronate (Aredia®) or zoledronic acid (Zometa®), as well as calcium and vitamin D are possible treatments to reduce the risk of osteoporosis or to treat it. Life as a couple Many men feel that the challenges posed by prostate cancer and its treatment eventually strengthen their loving relationships, even though changes in self-perception, in family role, and in patterns of sexual intimacy often result. Maintaining open and honest communication with partners and getting timely medical and counselling help are essential when it comes to weathering these changes, which can include infertility, decreased sex drive, and erectile dysfunction. Infertility: Most men will be infertile after surgery or radiation therapy. Ejaculation (but not orgasm) is impossible after radical prostatectomy, and the radiated prostate and seminal vesicles could produce semen that cannot transport sperm well. Hormonal therapy, which can reduce sexual desire, poses its own difficulties. Men who want to start a family after prostate cancer treatment should consider having their sperm frozen. 36 Decreased libido: For a man diagnosed with prostate cancer, a lowered interest in sex should not be treated with testosterone, which feeds the growth of cancerous cells. Talking things over with your partner or visiting a counsellor or sex therapist together is very useful. A couple may find that the need to discuss desire and not take it for granted enables a more honest and giving sexual intimacy. Erectile dysfunction (ED): Erectile dysfunction is defined as the inability to achieve or maintain an erection adequate for sexual intercourse. Varying degrees of ED are common following radical prostatectomy, even when the surgeon spares the nerve bundles upon which a man’s erections depend. After all, prostate surgery is quite traumatic. Most men treated with nerve-sparing surgery experience an improvement in their erections over time. Some, however, never recover the ability to get a spontaneous erection. Men who have radiation therapy also develop erectile difficulties, but these occur slowly and over time, as the benefits and negative side effects of radiation accrue. Erectile dysfunction can be treated in the following ways: • Oral medications such as sildenafil (Viagra®), vardenafil (Levitra®), and tadalafil (Cialis®) can help prevent the natural breakdown of chemical substances emitted by erectile nerves. These substances (neurotransmitters) are produced when a man is sexually stimulated, and they bring about a dilation of the blood vessels in the penis, which causes engorgement of penile tissue and an erection. • Injecting drugs such as alprostadil, papaverine, or phentolamine into the side of the penis (intracavernous injections) can cause blood vessels to relax and the penis to fill with blood, creating an erection even in the absence of sexual stimulation. • The medicated urethral system of erection (MUSE) involves inserting a small suppository of alprostadil into the urethra through the opening 37 in the tip of the penis. Once the penis is massaged lightly to speed absorption, blood vessels expand and an erection occurs. • Constricting rings are adjustable or elastic bands that a man can place around the base of his penis before it is aroused. The ring assists by retaining blood in the penis once an erection is achieved. • A vacuum erection device (VED) works by drawing blood into the penis and keeping it there by means of a constricting ring, but VEDs do not produce a physiological erection. Consequently, erections neither look nor feel normal, and they do not promote the healing circulation of fresh, oxygenated blood to the organ. • A penile implant is a prosthetic device introduced into the penis during surgery. It can be semi-rigid or inflatable. Prostate Cancer Where can I turn for more information or help? Prostate Cancer Canada Tel: 416-441-2131 Toll Free: 1-888-255-0333 Fax: 416-441-2325 E-mail: info@prostatecancer.ca http://www.prostatecancer.ca Canadian Prostate Cancer Network Tel: 705-652-9200 Toll Free: 1-866-810-CPCN (2726) Français: 1-888-322-5735 (service fourni par La fondation québécoise du cancer) Fax: 705-652-0663 E-mail: cpcn@nexicom.net http://www.cpcn.org Procure Alliance Tel; 514-985-1320 Toll Free: 1-866-899-CURE (2873) Fax: 514-985-1363 http://www.procure.ca La fondation québécoise du cancer (French only) Téléphone: 418-657-5334 Sans frais: 1-800-363-0063 Service en français pour CPCN: 1-888-322-5735 Télécopieur: 418-657-5921 Courriel: cancerquebec.que@fqc.qc.ca http://www.fqc.qc.ca 38 39 Prediction tools and nomograms Partin tables (Johns Hopkins) http://urology.jhu.edu/prostate/partintables.php Han tables (Johns Hopkins) http://urology.jhu.edu/prostate/hanTables.php Prostate cancer nomograms (Memorial Sloan-Kettering) http://www.mskcc.org/mskcc/html/10088.cfm Prostate Cancer Risk Calculator (Sunnybrook Health Sciences Centre) http://www.sunnybrook.ca/content/?page=3144 Prostate Cancer Assessment Tools (Prostate Cancer Canada) http://www.prostatecancer.ca/english/calculator/calculator Risk Assessment Quiz (Prostate Cancer Canada) http://www.prostatecancer.ca/Prostate-Cancer Prostate Cancer Canada thanks Dr. Robert G. Bristow for his contributions to the production of this booklet. This publication has been made possible through an unrestricted educational grant from sanofi aventis. 40
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