May 25th 2011 Posted at Uncategorized
Athletes for a Cure is a fundraising and awareness program of the Prostate Cancer Foundation. The organization assists athletes in their quest to raise money for better treatments and a cure for prostate cancer. Athletes for a Cure was founded by Scott and Greta Rose Zagarino in Hood River, OR in 2006. Mission – Athletes for a Cure was founded to create a community of people wishing to join together to fight prostate cancer. All monies raised from the program go directly to the Prostate Cancer Foundation and the research projects funded by the PCF. The Athletes for a Cure website provides athletes and organizers with the opportunity to create personalized homepages and be a part of the prostate cancer fundraising community. Registered participants can choose to upload their own photos, add personal stories to the website and even add race information to their own page. The website also allows users to define and set donation goals, send emails to their friends and family, and provides various tools to track and monitor their donations. Events – While Athletes for a Cure prides itself on a model of events “Any Time, Any Place, Any Where,” there are many opportunities and special events that have joined forces with Athletes for a Cure in order to increase support. These special events include the New York City Triathlon and the St. Anthony’s Triathlon.
Athletes for a Cure makes extensive use of social networking to “create a sustainable event fundraising model in a completely new paradigm,” according to founder Scott Zagarino. In January 2009, Athletes for a Cure won the Shorty Award for Best Producer of Nonprofit Twitter Content. The ultimate goal of prostate cancer prevention strategies is to prevent men from developing the disease. Unfortunately, despite significant progress in research over the past 18 years, this goal has not yet been achieved. Both genetic and environmental risk factors for prostate cancer have been identified, but the evidence is not yet strong enough to be helpful to men currently at risk for developing prostate cancer. By contrast, some success has been seen with strategies that can delay the development and progression of prostate cancer. Studies with finasteride and dutasteride, which are typically used for men with the noncancerous condition BPH, have shown that they can reduce by about 25% the chances that a man will be diagnosed with prostate cancer. The Prostate Cancer Prevention Trial was one of the largest prostate cancer trials ever, and involved over 18,000 men over a decade. This study showed that finasteride was able to reduce the risk of being diagnosed by 25%, but initially found a slightly higher rate of aggressive prostate cancers in men who took finasteride. Later looks at this data have suggested that this may be an artifact or due to a greater ability to find more aggressive cancers due to a smaller gland size (ie a biopsy needle can more easily hit a cancer in a smaller gland than a larger gland). Given that this agent is well tolerated, current recommendations call for a discussion about the risks and benefits of these agents in the prevention of prostate cancer, and of the potential risks and benefits of using these agents for other conditions, such as BPH. In the meantime, diet and lifestyle modifications have been shown to reduce the risk of prostate cancer development and progression, and can help men with prostate cancer live longer and better lives. More information about how dietary and lifestyle changes can be incorporated into everyday life can be found in the Nutrition, Exercise and Prostate Cancer guide. Top 10 Considerations for Preventing Prostate Cancer – To understand how to prevent prostate cancer, one must first understand what causes it. There are four major factors that influence one’s risk for developing prostate cancer, factors which unfortunately cannot be changed. Age: The average age at diagnosis of prostate cancer in the United States is 69 years and after that age the chance of developing prostate cancer becomes more common than any other cancer in men or women. Race: African Americans have a 40% greater chance of developing prostate cancer and twice the risk of dying from it. Conversely, Asian men who live in Asia have the lowest risk; however when they migrate to the west, their risk increases. Family history: A man with a father or brother who developed prostate cancer has a twofold-increased risk for developing it. This risk is further increased if the cancer was diagnosed at a younger age (less than 55 years of age) or affected three or more family members. Where you live: The risk of developing prostate cancer for men who live in rural China is 2% and for men in the United States 17%. When Chinese men move to the western culture, their risk increases substantially; men who live north of 40 degrees latitude (north of Philadelphia, Columbus, Ohio, and Provo, Utah) have the highest risk for dying from prostate cancer of any men in the United States – this effect appears to be mediated by inadequate sunlight during three months of the year which reduces vitamin D levels. Given the facts above, which are difficult to change, there are many things that men can do, however, to reduce or delay their risk of developing prostate cancer. Why is prostate cancer so common in the Western culture and much less so in Asia, and why when Asian men migrate to western countries the risk of prostate cancer increases over time? We believe the major risk factor is diet – foods that produce oxidative damage to DNA. What can you do about it to prevent or delay the onset of the disease? – Eat fewer calories or exercise more so that you maintain a healthy weight. – Try to keep the amount of fat you get from red meat and dairy products to a minimum. – Watch your calcium intake. Do not take supplemental doses far above the recommended daily allowance. Some calcium is OK, but avoid taking more than 1,500 mg of calcium a day. – Eat more fish – evidence from several studies suggest that fish can help protect against prostate cancer because they have “good fat” particularly omega-3 fatty acids. Avoid trans fatty acids (found in margarine). – Try to incorporate cooked tomatoes that are cooked with olive oil, which has also been shown to be beneficial, and cruciferous vegetables (like broccoli and cauliflower) into many of your weekly meals. Soy and green tea are also potential dietary components that may be helpful. – Avoid smoking for many reasons. Alcohol in moderation, if at all. – Seek medical treatment for stress, high blood pressure, high cholesterol, and depression.
Treating these conditions may save your life and will improve your survivorship with prostate cancer – What about supplements? Avoid over-supplementation with megavitamins. Too many vitamins, especially folate, may “fuel the cancer”, and while a multivitamin is not likely to be harmful, if you follow a healthy diet with lots of fruits, vegetables, whole grains, fish, and healthy oils you likely do not even need a multivitamin. Relax and enjoy life. Reducing stress in the workplace and home will improve your survivorship and lead to a longer, happier life. – Finally, eating all the broccoli in the world, though it may make a difference in the long run, does not take away your risk of having prostate cancer right now. If you are age 50 or over, if you are age 40 or over and African-American or have a family history of prostate cancer, you need more than a good diet can guarantee. You should consider a yearly rectal examination and PSA test. Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize (spread) from the prostate to other parts of the body, particularly the bones and lymph nodes. Prostate cancer may cause pain, difficulty in urinating, problems during sexual intercourse, or erectile dysfunction. Other symptoms can potentially develop during later stages of the disease. Rates of detection of prostate cancers vary widely across the world, with South and East Asia detecting less frequently than in Europe, and especially the United States. Prostate cancer tends to develop in men over the age of fifty and although it is one of the most prevalent types of cancer in men, many never have symptoms, undergo no therapy, and eventually die of other causes. This is because cancer of the prostate is, in most cases, slow-growing, symptom-free, and since men with the condition are older they often die of causes unrelated to the prostate cancer, such as heart/circulatory disease, pneumonia, other unconnected cancers, or old age. About 2/3 of cases are slow growing, the other third more aggressive and fast developing. Many factors, including genetics and diet, have been implicated in the development of prostate cancer. The presence of prostate cancer may be indicated by symptoms, physical examination, prostate-specific antigen (PSA), or biopsy. The PSA test increases cancer detection but does not decrease mortality. Suspected prostate cancer is typically confirmed by taking a biopsy of the prostate and examining it under a microscope. Further tests, such as CT scans and bone scans, may be performed to determine whether prostate cancer has spread. Treatment options for prostate cancer with intent to cure are primarily surgery, radiation therapy, stereotactic radiosurgery, and proton therapy. Other treatments, such as hormonal therapy, chemotherapy, cryosurgery, and high intensity focused ultrasound (HIFU) also exist, although not FDA approved, depending on the clinical scenario and desired outcome. The age and underlying health of the man, the extent of metastasis, appearance under the microscope, and response of the cancer to initial treatment are important in determining the outcome of the disease. The decision whether or not to treat localized prostate cancer (a tumor that is contained within the prostate) with curative intent is a patient trade-off between the expected beneficial and harmful effects in terms of patient survival and quality of life.
The prostate is a part of the male reproductive system that helps make and store seminal fluid. In adult men, a typical prostate is about three centimeters long and weighs about twenty grams. It is located in the pelvis, under the urinary bladder and in front of the rectum. The prostate surrounds part of the urethra, the tube that carries urine from the bladder during urination and semen during ejaculation. Because of its location, prostate diseases often affect urination, ejaculation, and rarely defecation. The prostate contains many small glands which make about twenty percent of the fluid constituting semen. In prostate cancer, the cells of these prostate glands mutate into cancer cells. The prostate glands require male hormones, known as androgens, to work properly. Androgens include testosterone, which is made in the testes; dehydroepiandrosterone, made in the adrenal glands; and dihydrotestosterone, which is converted from testosterone within the prostate itself. Androgens are also responsible for secondary sex characteristics such as facial hair and increased muscle mass. Classification – An important part of evaluating prostate cancer is determining the stage, or how far the cancer has spread. Knowing the stage helps define prognosis and is useful when selecting therapies. The most common system is the four-stage TNM system (abbreviated from Tumor/Nodes/Metastases). Its components include the size of the tumor, the number of involved lymph nodes, and the presence of any other metastases. The most important distinction made by any staging system is whether or not the cancer is still confined to the prostate. In the TNM system, clinical T1 and T2 cancers are found only in the prostate, while T3 and T4 cancers have spread elsewhere. Several tests can be used to look for evidence of spread. These include computed tomography to evaluate spread within the pelvis, bone scans to look for spread to the bones, and endorectal coil magnetic resonance imaging to closely evaluate the prostatic capsule and the seminal vesicles. Bone scans should reveal osteoblastic appearance due to increased bone density in the areas of bone metastasis—opposite to what is found in many other cancers that metastasize. After a prostate biopsy, a pathologist looks at the samples under a microscope. If cancer is present, the pathologist reports the grade of the tumor. The grade tells how much the tumor tissue differs from normal prostate tissue and suggests how fast the tumor is likely to grow. The Gleason system is used to grade prostate tumors from 2 to 10, where a Gleason score of 10 indicates the most abnormalities. The pathologist assigns a number from 1 to 5 for the most common pattern observed under the microscope, then does the same for the second-most-common pattern. The sum of these two numbers is the Gleason score. The Whitmore-Jewett stage is another method sometimes used.
Signs and symptoms – Early prostate cancer usually causes no symptoms. Often it is diagnosed during the workup for an elevated PSA noticed during a routine checkup. Sometimes, however, prostate cancer does cause symptoms, often similar to those of diseases such as benign prostatic hyperplasia. These include frequent urination, nocturia (increased urination at night), difficulty starting and maintaining a steady stream of urine, hematuria (blood in the urine), and dysuria (painful urination). Prostate cancer is associated with urinary dysfunction as the prostate gland surrounds the prostatic urethra. Changes within the gland, therefore, directly affect urinary function. Because the vas deferens deposits seminal fluid into the prostatic urethra, and secretions from the prostate gland itself are included in semen content, prostate cancer may also cause problems with sexual function and performance, such as difficulty achieving erection or painful ejaculation. Advanced prostate cancer can spread to other parts of the body, possibly causing additional symptoms. The most common symptom is bone pain, often in the vertebrae (bones of the spine), pelvis, or ribs. Spread of cancer into other bones such as the femur is usually to the proximal part of the bone. Prostate cancer in the spine can also compress the spinal cord, causing leg weakness and urinary and fecal incontinence.
The specific causes of prostate cancer remain unknown. The primary risk factors are age and family history. Prostate cancer is very uncommon in men younger than 45, but becomes more common with advancing age. The average age at the time of diagnosis is 70. However, many men never know they have prostate cancer. Autopsy studies of Chinese, German, Israeli, Jamaican, Swedish, and Ugandan men who died of other causes have found prostate cancer in thirty percent of men in their 50s, and in eighty percent of men in their 70s. Men who have first-degree family members with prostate cancer appear to have double the risk of getting the disease compared to men without prostate cancer in the family. This risk appears to be greater for men with an affected brother than for men with an affected father. In the United States in 2005, there were an estimated 230,000 new cases of prostate cancer and 30,000 deaths due to prostate cancer. Men with high blood pressure are more likely to develop prostate cancer. A 2010 study found that prostate basal cells were the most common site of origin for prostate cancers. Genetic – Genetic background may contribute to prostate cancer risk, as suggested by associations with race, family, and specific gene variants. Men with one first-degree relative with prostate cancer have a twofold higher risk, and those with two first-degree relatives have a fivefold greater risk of developing prostate cancer compared with men with no family history. In the United States, prostate cancer more commonly affects black men than white or Hispanic men, and is also more deadly in black men. In contrast, the incidence and mortality rates for Hispanic men are one third lower than for non-Hispanic whites. Men who have a brother or father with prostate cancer have twice the risk of developing prostate cancer. Studies of twins in Scandinavia suggest that forty percent of prostate cancer risk can be explained by inherited factors. No single gene is responsible for prostate cancer; many different genes have been implicated. Mutations in BRCA1 and BRCA2, important risk factors for ovarian cancer and breast cancer in women, have also been implicated in prostate cancer. Other linked genes include the Hereditary Prostate cancer gene 1 (HPC1), the androgen receptor, and the vitamin D receptor. TMPRSS2-ETS gene family fusion, specifically TMPRSS2-ERG or TMPRSS2-ETV1/4 promotes cancer cell growth. Loss of cancer suppressor genes, early in the prostatic carcinogenesis, have been localized to chromosomes 8p, 10q, 13q,and 16q. P53 mutations in the primary prostate cancer are relatively low and are more frequently seen in metastatic settings, hence, p53 mutations are late event in pathology of prostate cancer. Other tumor suppressor genes that are thought to play a role in prostate cancer include PTEN (gene) and KAI1. “Up to 70 percent of men with prostate cancer have lost one copy of the PTEN gene at the time of diagnosis” Relative frequency of loss of E-cadherin and CD44 has also been observed. Diet – Evidence from epidemiological studies supports a possible protective role in reducing prostate cancer for dietary Vitamin B6, selenium, vitamin E, lycopene, and soy foods. A study in 2007 cast doubt on the effectiveness of lycopene (found in tomatoes) in reducing the risk of prostate cancer. Lower blood levels of vitamin D may increase the risk of developing prostate cancer. This may be linked to lower exposure to ultraviolet (UV) light, since UV light exposure can increase vitamin D in the body. Studies comparing men who live in areas with high levels of selenium to men in areas with low levels suggest that this mineral protects against prostate cancer.Selenium is believed to reduce the risk of developing prostate cancer because it keeps cells from proliferating or dying off in a rapid or unusual way. An analysis in 2002 of the Nutritional Prevention of Cancer Trial revealed that the men who took selenium supplements daily were half as likely to be diagnosed with prostate cancer. These findings have been confirmed in most observational studies. However, in 2008, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) indicated that neither selenium nor vitamin E, alone or in combination, was effective for the primary prevention of prostate cancer. Whether or not selenium helps prevent prostate cancer, researchers at the Dana-Farber Cancer Institute in Boston found that higher selenium levels in the blood may worsen prostate cancer in many men who already have the disease. Green tea may be protective (due to its catechins content), although the most comprehensive clinical study indicates that it has no protective effect. Other holistic methods are also studied. Research published in the Journal of the National Cancer Institute suggests that taking multivitamins more than seven times a week can increase the risks of contracting the disease. This research was unable to highlight the exact vitamins responsible for this increase (almost double), although they suggest that vitamin A, vitamin E and beta-carotene may lie at its heart. It is advised that those taking multivitamins never exceed the stated daily dose on the label. A 2007 study published in the Journal of the National Cancer Institute found that men eating cauliflower, broccoli, or one of the other cruciferous vegetables, more than once a week were 40% less likely to develop prostate cancer than men who rarely ate those vegetables. The phytochemicals indole-3-carbinol and diindolylmethane, found in cruciferous vegetables, has antiandrogenic and immune modulating properties. Many doctors prescribe supplements to prostate cancer patients but currently the efficacy of nutrient supplements is still unknown. Supplements may not be as beneficial to prostate health as micronutrients obtained naturally from the diet. Folic acid supplements have recently been linked to an increase in risk of developing prostate cancer. A ten-year research study led by University of Southern California researchers showed that men who took daily folic acid supplements of 1 mg were three times more likely to be diagnosed with prostate cancer than men who took a placebo. Folate plays a complex role in prostate cancer and folic acid supplements have a different effect on prostate cancer than folate naturally found in foods. The supplement form, folic acid, is more bioavailable in the body compared with dietary sources of folate. Folate hydrolase activity is associated with prostate-specific antigen. A small Swedish study of 254 subjects, with a median age of 64, and a follow up of 5 years suggested that folate status is not protective against prostate cancer, however, and like folic acid may even result in a 3 fold increase in early prostate cancer development and risk. Supplements and multivitamins, alcohol and drug consumption, GI disorders, and folate bioavailability were not analyzed in this study. High alcohol intake may increase the risk of prostate cancer and interfere with folate metabolism. Low folate intake and high alcohol intake may increase the risk of prostate cancer to a greater extent than the sole effect of either one by itself. A case control study consisting of 137 veterans addressed this hypothesis and the results were that high folate intake was related to a 79% lower risk of developing prostate cancer and there was no association between alcohol consumption by itself and prostate cancer risk. Folate’s effect however was only significant when coupled with low alcohol intake. There is a significant decrease in risk of prostate cancer with increasing dietary folate intake but this association only remains in individuals with low levels of alcohol consumption. There was no association found in this study between folic acid supplements and risk of prostate cancer. The prostate gland has a high concentration of zinc so zinc may play a role in prostate cancer. Researchers studied the relationship between zinc supplement intake of 100 mg/day and the risk of prostate cancer in 46 974 US men over a 14-year period and reported in 2003 that long term zinc supplement of over 100 mg/day intake seemed to be associated with approximately double the risk of developing prostate cancer.
Greater intake of milk, calcium, or dairy calcium has been consistently associated with an elevated risk of prostate cancer in several studies. Medication exposure – There are also some links between prostate cancer and medications, medical procedures, and medical conditions. Use of the cholesterol-lowering drugs known as the statins may also decrease prostate cancer risk. Infection or inflammation of the prostate (prostatitis) may increase the chance for prostate cancer while another study shows infection may help prevent prostate cancer by increasing blood to the area. In particular, infection with the sexually transmitted infections chlamydia, gonorrhea, or syphilis seems to increase risk.Finally, obesity and elevated blood levels of testosterone may increase the risk for prostate cancer. There is an association between vasectomy and prostate cancer however more research is needed to determine if this is a causative relationship. Research released in May 2007, found that US war veterans who had been exposed to Agent Orange had a 48% increased risk of prostate cancer recurrence following surgery. Viral – In 2006, researchers associated a previously unknown retrovirus, Xenotropic MuLV-related virus or XMRV, with human prostate tumors. Subsequent reports on the virus have been contradictory. A group of US researchers found XMRV protein expression in human prostate tumors, while German scientists failed to find XMRV-specific antibodies or XMRV-specific nucleic acid sequences in prostate cancer samples. Screening – Prostate cancer screening is an attempt to find unsuspected cancers, and may lead to more specific follow-up tests such as a biopsy, with cell samples taken for closer study. Options include the digital rectal exam (DRE) and the prostate-specific antigen (PSA) blood test. A 2010 analysis concluded that routine screening with either a DRE or PSA is not supported by the evidence as there is no mortality benefit from screening. Modern screening tests have found cancers that might never have developed into serious disease, and that “the slight reduction of risk by surgically removing the prostate or treating it with radiation may not outweigh the substantial side effects of these treatments,” an opinion also shared by the CDC. Prevention – A comprehensive worldwide report Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective compiled by the World Cancer Research Fund and the American Institute for Cancer Research reports a significant relation between lifestyle (including food consumption) and cancer prevention. Other research also supports this finding. Exercise and diet may help prevent prostate cancer to the same extent as medications such as alpha-blockers and 5-alpha-reductase inhibitors. The potential role of diet in preventing prostate cancer is discussed in greater detail in the diet section of this article. Two medications which block the conversion of testosterone to dihydrotestosterone, finasteride and dutasteride, have also shown some promise. The use of these medications for primary prevention is still in the testing phase, and they are not widely used for this purpose. A 2008 study found that finasteride reduces the incidence of prostate cancer by 30%, without any increase in the risk of High-Grade prostate cancer. In the original study it turns out that the smaller prostate caused by finasteride means that a doctor is more likely to hit upon cancer nests and more likely to find aggressive-looking cells. Compared to placebo treatment, taking 5-alpha-reductase inhibitors (5-ARIs) can reduce a man’s risk of being diagnosed with prostate cancer from around 5–9% to around 4-6% during up to 7 years of treatment, according to a Cochrane Review of studies. Ejaculation frequency – More frequent ejaculation also may decrease a man’s risk of prostate cancer. One study showed that men who ejaculated 3-5 times a week at the age of 15-19 had a decreased rate of prostate cancer when they are old, though other studies have shown no benefit. The results contradict those of previous studies, which have suggested that having had many sexual partners, or a high frequency of sexual activity, increases the risk of prostate cancer by up to 40 percent. A key difference may be that these earlier studies defined sexual activity as sexual intercourse, whereas this study focused on the number of ejaculations, whether or not intercourse was involved. Another study completed in 2004 reported that “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 report abstract concluded, “Our results suggest that ejaculation frequency is not related to increased risk of prostate cancer.” Diet – Oils and fatty acids – Polyunsaturated fatty acids (PUFAs) increased prostate tumor growth,and has sped up histopathological progression, and decreased survival, while the omega-3 fatty acids, in the same situation, had the opposite, beneficial effect. Men with high serum linoleic acid, but not palmitic, can reduce the risk of prostate cancer by taking tocopherol supplementation. Men with elevated levels of long-chain omega-3 fatty acids (EPA and DHA) had lowered incidence. A long-term study reports that “blood levels of trans fatty acids, in particular trans fats resulting from the hydrogenation of vegetable oils, are associated with an increased prostate cancer risk.” Some researchers have indicated that serum myristic acid and palmitic acid and dietary myristic and palmitic saturated fatty acids and serum palmitic combined with alpha-tocopherol supplementation are associated with increased risk of prostate cancer in a dose-dependent manner. These associations may, however, reflect differences in intake or metabolism of these fatty acids between the precancer cases and controls, rather than being an actual cause. Other – The American Dietetic Association and Dieticians of Canada report a decreased incidence of prostate cancer for those following a vegetarian diet. In lab tests on mice, prostate tumors grow slower with a no-carbohydrate diet. A preliminary study found a correlation between coffee consumption and a lower risk of aggressive prostate cancer. Management – Treatment for prostate cancer may involve active surveillance (monitoring for tumor progress or symptoms), surgery (i.e. radical prostatectomy), radiation therapy including brachytherapy (prostate brachytherapy) and external beam radiation therapy, High-intensity focused ultrasound (HIFU), chemotherapy, oral chemotherapeutic drugs (Temozolomide/TMZ), cryosurgery, hormonal therapy, or some combination. William J. Catalona, MD: regarding Active Surveillance, “Watchful Waiting or for some patients, Wishful Waiting: Can delay prompt treatment of life-threatening tumors, it would require repeated biopsies that often make subsequent nerve-sparing surgery more difficult and it causes many patients anxiety about living with untreated cancer, thus diminishing their quality of life.” These men may have already been chemically castrated and impotent. Which option is best depends on the stage of the disease, the Gleason score, and the PSA level. Other important factors are age, general health, and patient views about potential treatments and their possible side-effects. Because all treatments can have significant side-effects, such as erectile dysfunction and urinary incontinence, treatment discussions often focus on balancing the goals of therapy with the risks of lifestyle alterations. Prostate cancer patients are strongly recommended to work closely with their physicians and use a combination of the treatment options when managing their prostate cancer. Although the widespread use of prostate specific antigen (PSA) screening in the USA has resulted in diagnosis at earlier age and cancer stage, the vast majority of cases are still diagnosed in men older than 65 years, and approximately 25% of cases are diagnosed in men older than 75 years. Though US National Comprehensive Cancer Network guidelines recommend using life expectancy greater than or less than 10 years to help make treatment decisions, in practice, many elderly patients are not offered curative treatment options such as radical prostatectomy (RP) or radiation therapy and are instead treated with hormonal therapy or watchful waiting. This pattern can be attributed to factors such as medical co-morbidity and patient preferences is regard to quality of life in addition to prostate cancer specific risk factors such as pretreatment PSA, Gleason score and clinical stage. As the average life expectancy increases due to advances in treatment of cardiovascular, pulmonary and other chronic disease, it is likely that more elderly patients will be living long enough to suffer the consequences of their prostate cancer. Therefore, there is currently much interest in the role of aggressive prostate cancer treatment modalities such as with surgery or radiation in the elderly population who have localized disease. The results of one randomized controlled trial published by the Scandinavian Prostate Cancer Group 4 evaluated cancer-specific mortality in patients treated with RP compared with watchful waiting. The patients receiving radical prostatectomy had a relative risk reduction of 30.7% [95% confidence interval 2.5%-50.7%], but an absolute risk reduction of 6% [95% confidence interval 0.5%-11.5%]. The number needed to treat was calculated to be 16. This means that, over the median follow up period of approximately 10 years, 16 patients with localized prostate cancer would need to receive radical prostatectomy rather than watchful waiting in order to prevent one death due to prostate cancer. Further subset analysis revealed that this benefit did not apply to all ages equally. In men younger than 65 years, patients randomized to receive radical prostatectomy actually had a 10-18% absolute risk reduction in cancer-specific mortality compared to those randomized to watchful waiting. However, in men older than 65, there was no statistically significant risk reduction even when adjusted for PSA level, Gleason score and tumor stage. Randomized, controlled trials comparing radical prostatectomy, radiation therapy, hormonal therapy and watchful waiting would provide the best evidence for how to best treat elderly patients. Such trials are urgently needed, as the elderly population is rapidly growing and is expected to continue to do so. Study results in 2011 suggest active surveillance is the best choice for older ‘low-risk’ patients. The selection of treatment options may be a complex decision involving many factors. For example, radical prostatectomy after primary radiation failure is a very technically challenging surgery and may not be an option, while salvage radiation therapy after surgical failure may have many complications. This may enter into the treatment decision. If the cancer has spread beyond the prostate, treatment options significantly change, so most doctors that treat prostate cancer use a variety of nomograms to predict the probability of spread. Treatment by watchful waiting/active surveillance, external beam radiation therapy, brachytherapy, cryosurgery, HIFU, and surgery are, in general, offered to men whose cancer remains within the prostate. Hormonal therapy and chemotherapy are often reserved for disease that has spread beyond the prostate. However, there are exceptions: radiation therapy may be used for some advanced tumors, and hormonal therapy is used for some early stage tumors. Cryotherapy (the process of freezing the tumor), hormonal therapy, and chemotherapy may also be offered if initial treatment fails and the cancer progresses. Hormone-refractory prostate cancer – Most hormone dependent cancers become refractory (independent) after one to three years and resume growth despite hormone therapy. Docetaxel has been used for HRPC with a median survival benefit of 2 to 3 months. A combination of bevacizumab (Avastin), docetaxel (taxotere), thalidomide and prednisone appears effective in the treatment of hormone-refractory prostate cancer. Provenge is also effective (better than placebo) in the treatment of hormone-refractory prostate cancer, as is Cabazitaxel. MDV3100 is in phase III trials for HRPC (chemo-naive and post-chemo patient populations). Abiraterone completed a phase 3 trial for HRPC patients who have failed chemotherapy in 2010. Results were overwhelmingly positive. Overall survival increased to about 15 months from 11 months on adding Abiraterone acetate (Zytiga) to the conventional steroid treatment. Johnson & Johnson has filed an application with the FDA to have abiraterone approved for use in this patient population. Approval is expected in mid 2011.
Prostate cancer rates are higher and prognosis poorer in developed countries than the rest of the world. Many of the risk factors for prostate cancer are more prevalent in the developed world, including longer life expectancy and diets high in red meat (People that consume larger amounts of meat and dairy also tend to consume fewer portions of fruits and vegetables. It is not currently clear whether both of these factors, or just one of them, contribute to the occurrence of prostate cancer.) Also, where there is more access to screening programs, there is a higher detection rate. Prostate cancer is the ninth-most-common cancer in the world, but is the number-one non-skin cancer in United States men. Prostate cancer affected eighteen percent of American men and caused death in three percent in 2005. In Japan, death from prostate cancer was one-fifth to one-half the rates in the United States and Europe in the 1990s. In India in the 1990s, half of the people with prostate cancer confined to the prostate died within ten years. African-American men have 50–60 times more prostate cancer and prostate cancer deaths than men in Shanghai, China. In Nigeria, two percent of men develop prostate cancer and 64% of them are dead after two years. In patients that undergo treatment, the most important clinical prognostic indicators of disease outcome are stage, pre-therapy PSA level and Gleason score. In general, the higher the grade and the stage the poorer the prognosis. Nomograms can be used to calculate the estimated risk of the individual patient. The predictions are based on the experience of large groups of patients suffering from cancers at various stages. In 1941, Charles Huggins reported that androgen ablation therapy causes regression of primary and metastatic androgen-dependent prostate cancer. Androgen ablation therapy causes remission in 80-90% of patients undergoing therapy, resulting in a median progression-free survival of 12 to 33 months. After remission, an androgen-independent phenotype typically emerges, wherein the median overall survival is 23–37 months from the time of initiation of androgen ablation therapy. The actual mechanism contributes to the progression of prostate cancer is not clear and may vary between individual patient. A few possible mechanisms have been proposed. Classification systems – Many prostate cancers are not destined to be lethal, and most men will ultimately die from causes other than of the disease. Decisions about treatment type and timing may, therefore, be informed by an estimation of the risk that the tumor will ultimately recur after treatment and/or progress to metastases and mortality. Several tools are available to help predict outcomes such as pathologic stage and recurrence after surgery or radiation therapy. Most combine stage, grade, and PSA level, and some also add the number or percent of biopsy cores positive, age, and/or other information. The D’Amico classification stratifies men by low, intermediate, or high risk based on stage, grade, and PSA. It is used widely in clinical practice and research settings. The major downside to the 3-level system is that it does not account for multiple adverse parameters (e.g., high Gleason score and high PSA) in stratifying patients. The Partin tables predict pathologic outcomes (margin status, extraprostatic extension, and seminal vesicle invasion) based on the same 3 variables, and are published as lookup tables. The Kattan nomograms predict recurrence after surgery and/or radiation therapy, based on data available either at time of diagnosis or after surgery. The nomograms can be calculated using paper graphs, or using software available on a website or for handheld computers.
The Kattan score represents the likelihood of remaining free of disease at a given time interval following treatment. The UCSF Cancer of the Prostate Risk Assessment (CAPRA) score predicts both pathologic status and recurrence after surgery. It offers comparable accuracy as the Kattan preoperative nomogram, and can be calculated without paper tables or a calculator. Points are assigned based on PSA, Grade, stage, age, and percent of cores positive; the sum yields a 0–10 score, with every 2 points representing roughly a doubling of risk of recurrence. The CAPRA score was derived from community-based data in the CaPSURE database. It has been validated among over 10,000 prostatectomy patients, including patients from CaPSURE; the SEARCH registry, representing data from several Veterans Administration and active military medical centers; a multi-institutional cohort in Germany; and the prostatectomy cohort at Johns Hopkins University. More recently, it has been shown to predict metastasis and mortality following prostatectomy, radiation therapy, watchful waiting, or androgen deprivation therapy. Epidemiology – Rates of prostate cancer vary widely across the world. Although the rates vary widely between countries, it is least common in South and East Asia, more common in Europe, and most common in the United States. According to the American Cancer Society, prostate cancer is least common among Asian men and most common among black men, with figures for white men in between. The average annual incidence rate of prostate cancer between 1988 and 1992 among Chinese men in the United States was 15 times higher than that of their counterparts living in Shanghai and Tianjin. However, these high rates may be affected by increasing rates of detection. Many suggest that prostate cancer may be under reported, yet BPH incidence in China and Japan is similar to rates in Western countries. Prostate cancer develops primarily in men over fifty. It is the most common type of cancer in men in the United States, with 186,000 new cases in 2008 and 28,600 deaths. It is the second leading cause of cancer death in U.S. men after lung cancer. In the United Kingdom it is also the second most common cause of cancer death after lung cancer, where around 35,000 cases are diagnosed every year and of which around 10,000 die of it. Many factors, including genetics and diet, have been implicated in the development of prostate cancer. The Prostate Cancer Prevention Trial found that finasteride reduces the incidence of prostate cancer rate by 30%. There had been a controversy about this also increasing the risk of more aggressive cancers, but more recent research showed this may not be the case. More than 80% of men will develop prostate cancer by the age of 80. However, in the majority of cases, it will be slow-growing and harmless. In such men, diagnosing prostate cancer is overdiagnosis—the needless identification of a technically aberrant condition that will never harm the patient—and treatment in such men exposes them to all of the adverse effects, with no possibility of extending their lives. History – Although the prostate was first described by Venetian anatomist Niccolò Massa in 1536, and illustrated by Flemish anatomist Andreas Vesalius in 1538, prostate cancer was not identified until 1853. Prostate cancer was initially considered a rare disease, probably because of shorter life expectancies and poorer detection methods in the 19th century. The first treatments of prostate cancer were surgeries to relieve urinary obstruction. Removal of the entire gland (radical perineal prostatectomy) was first performed in 1904 by Hugh H. Young at Johns Hopkins Hospital. Surgical removal of the testes (orchiectomy) to treat prostate cancer was first performed in the 1890s, but with limited success. Transurethral resection of the prostate (TURP) replaced radical prostatectomy for symptomatic relief of obstruction in the middle of the 20th century because it could better preserve penile erectile function. Radical retropubic prostatectomy was developed in 1983 by Patrick Walsh. This surgical approach allowed for removal of the prostate and lymph nodes with maintenance of penile function. In 1941, Charles B. Huggins published studies in which he used estrogen to oppose testosterone production in men with metastatic prostate cancer. This discovery of “chemical castration” won Huggins the 1966 Nobel Prize in Physiology or Medicine. The role of the hormone GnRH in reproduction was determined by Andrzej W. Schally and Roger Guillemin, who both won the 1977 Nobel Prize in Physiology or Medicine for this work. Receptor agonists, such as leuprolide and goserelin, were subsequently developed and used to treat prostate cancer. Radiation therapy for prostate cancer was first developed in the early 20th century and initially consisted of intraprostatic radium implants. External beam radiation became more popular as stronger radiation sources became available in the middle of the 20th century. Brachytherapy with implanted seeds was first described in 1983. Systemic chemotherapy for prostate cancer was first studied in the 1970s. The initial regimen of cyclophosphamide and 5-fluorouracil was quickly joined by multiple regimens using a host of other systemic chemotherapy drugs. On 30 July 2010 Owen Witte M.D. et al. of UCLA published a series of studies in Science during which they had introduced viruses known to cause cancerous mutation in prostate cells: AKT, ERG, and AR into isolated samples of basal and luminal cells and grafted the treated tissue into mice. After 16 weeks, none of the luminal samples had undergone malignant mutation, while the basal samples had mutated into prostate-like tubules which had then developed malignancy and formed cancerous tumors, which appeared identical to human samples under magnification. This led to the conclusion that the prostate basal cell may be the most likely “site of origin” of prostate cancer.
Androgen at a concentration of 10-fold higher than the physiological concentration has also been shown to cause growth suppression and reversion of androgen-independent prostate cancer xenografts or androgen-independent prostate tumors derived in vivo model to an androgen-stimulated phenotype in athymic mice.These observation suggest the possibility to use androgen to treat the development of relapsed androgen-independent prostate tumors in patients. Oral infusion of green tea catechins, a potential alternative therapy for prostate cancer by natural compounds, has been shown to inhibit the development, progression, and metastasis as well in autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP) model, which spontaneously develops prostate cancer. The insulin-like growth factor signaling axis is thought to play a key role in the progression of prostate carcinoma. It consists of two ligands (IGF-1 and IGF-2), two receptors (IGF-IR and IGF-IIR) and six related high-affinity IGF-binding proteins (IGFBP 1-6). Altered expression of IGF axis members has been implicated in the development of many different types of cancers, including prostate. A genistein derivative KBU2046 is under investigation for prostate cancer. Prostate cancer models – Scientists have established a few prostate cancer cell lines to investigate the mechanism involved in the progression of prostate cancer. LNCaP, PC-3 (PC3), and DU-145 (DU145) are commonly used prostate cancer cell lines. The LNCaP cancer cell line was established from a human lymph node metastatic lesion of prostatic adenocarcinoma. PC-3 and DU-145 cells were established from human prostatic adenocarcinoma metastatic to bone and to brain, respectively. LNCaP cells express androgen receptor (AR); however, PC-3 and DU-145 cells express very little or no AR. AR, an androgen-activated transcription factor, belongs to the steroid nuclear receptor family. Development of the prostate is dependent on androgen signaling mediated through AR, and AR is also important during the development of prostate cancer. The proliferation of LNCaP cells is androgen-dependent but the proliferation of PC-3 and DU-145 cells is androgen-insensitive. Elevation of AR expression is often observed in advanced prostate tumors in patients. Some androgen-independent LNCaP sublines have been developed from the ATCC androgen-dependent LNCaP cells after androgen deprivation for study of prostate cancer progression. These androgen-independent LNCaP cells have elevated AR expression and express prostate specific antigen upon androgen treatment. The paradox is that androgens inhibit the proliferation of these androgen-independent prostate cancer cells.