Showing posts with label Cancer. Show all posts
Showing posts with label Cancer. Show all posts

Cellular Phone Causes Cancer

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"If Mobile Phones Were a Type of Food, They Simply Would Not be Licensed"

Cellular phone increases the risk of brain cancer (brain tumor).


  • Cellular phones can do biological damage through heating effects.


  • Cellular phone causes symptoms: including headaches, earaches, blurring of vision, short-term memory loss, numbing, tingling, and burning sensations, bad sleep,fatigue, Anxiety.


  • Single and double strand DNA breaks in brain cells increased after exposure to RF. Exposure to both continuous wave and pulsed RF (mobil phone) produced DNA damage. Double strand breaks, if not repaired, are known to lead to cell death.


  • Research by other scientists indicates that prolonged use of mobile phones may cause hot-spots to develop inside the brain, causing damage which could lead to Alzheimer’s disease or cancer (brain tumor).


  • Dr Henry Lai and Dr N. P. Singh from the University of Washington in Seattle believe the radiation changed brain cell membranes in the rats - and the effects are so severe that it could affect humans, too.

    info@cancer-health.org

    This statement was not uttered by some uneducated anti-technology activist, but rather was written by British physicist Dr. Gerald Hyland and was printed in the prestigious medical journal The Lancet.

    A recent issue of the journal published 2 papers on the subject of cell phone safety, as well as an accompanying editorial. The editorial, written by Philip P. Dendy of Cambridge, UK, and entitled "Mobile phones and the illusory pursuit of safety" puts the 'safety' issue into perspective:


    The deceptively simple question, much loved by television and radio interviewers, "Is it safe?" is the scientist's banana skin. A Nobel prize awaits the person who first designs an experiment to show that anything is "safe".

    In the light of experience with ionizing radiation and radioactive materials, out-of-hand dismissal of the possibility of subtle effects of low-intensity, pulsed, microwave radiation is most unwise.

    Early in the 20th century radon and radium-enriched spa waters were "recommended" for a wide range of aches and minor ailments. As knowledge of the harmful effects of ionizing radiation has increased and quantitative risk estimates have become possible (notwithstanding rather large error bands), the permitted annual dose limit has been progressively reduced from the 1930s to the present day.


    Dr. Hyland writes an excellent paper, covering the possible mechanisms by which mobile phones, or cell phones, may cause adverse effects in people. Below are some exerpts from his paper, entitled "Physics and Biology of Mobile Telephony":


    …there is evidence that the low intensity, pulsed radiation currently used can exert subtle non-thermal influences. If these influences entail adverse health consequences, current guidelines would be inadequate.This review will focus on this possibility.

    The radiation used is indeed of very low intensity, but an oscillatory similitude between this pulsed microwave radiation and certain electrochemical activities of the living human being should prompt concern. …there are consistencies between some of these effects and the neurological problems reported by some mobile-telephone users and people exposed longterm to base-station radiation.

    The Stewart Report (1), published in May, 2000, makes some sensible recommendations, but unfortunately some of its greyer areas are now being exploited by the industry to obfuscate the issue.

    As yet unresolved is the question of adverse health impacts provoked by the contentious non-thermal effects of the low intensity, pulsed microwave radiation (MWR) used. For these effects are not taken into account in current safety guidelines (2), which simply restrict the intensity of the radiation to prevent tissue heating in excess of what the body's thermoregulatory mechanism can cope with….in the case of living systems (and only living ones) there are many reports over the past 30 years that MWR can exert non-thermal influences, at intensities well below those necessary to cause any detectable heating (3).

    The purpose of this review is to introduce clinicians to the physics of mobile telephony and to explain how low-intensity, pulsed microwaves can affect living organisms, both thermally and non-thermally; and then to identify some of the reported biological impacts of exposure to this radiation, particularly those provoked by the contentious non-thermal effects.

    Physics of Mobile Telephony

    A base-station antenna typically radiates 60 W and a handset between 1 and 2 W (peak). The antenna of a handset radiates equally in all directions but a base-station produces a beam that is much more directional. In addition, the stations have subsidiary beams called side-lobes, into which a small fraction of the emitted power is channelled. Unlike the mean beam, these side-lobes are localized in the immediate vicinity of the mast, and, despite their low power, the power density can be comparable with that of the main beam much further away from the mast. At 150-200 m, for example, the power density in the main beam near ground level is typically tenths of a µW/cm (2).

    A handset that is in operation also has a low-frequency magnetic field (EMF) associated, not with the emitted microwaves, but with surges of electric current from the battery that are necessary to implement "time division multiple access" (TDMA), the system currently used to increase the number of people who can simultaneously communicate with a base-station. With handsets that have an energy-saving discontinuous transmission mode (DTX), there is an even lower frequency pulsing at 2 Hz, which occurs when the user is listening but not speaking.

    Biological Impacts: Thermal

    Heating of biological tissue is a consequence of microwave energy absorption by the tissue's water content. The amount of heating produced in a living organism depends primarily on the intensity (or power density) of the radiation once it has penetrated the system, on certain electrical properties of the biomatter, and on the efficiency of the body's thermoregulation mechanism.

    Above a certain intensity of the microwaves, temperature homoeostasis is not maintained, and effects on health ensue once the temperature rise exceeds about 1°C. Safety guidelines impose upper limits on the radiation intensity to ensure that this does not happen.

    Heating occurs whether the organism is alive or dead. The frequency of the radiation, as opposed to the intensity, is taken into account only in so far as it affects (via size resonance) the ability of the organism to absorb energy from the irradiating field.

    Amongst the most thermally vulnerable areas of the body (2), because of their low blood supply, are the eyes and the testes, and cataract formation and reduced sperm counts are well-documented acute exposure hazards.

    Animal studies indicate that a variety of behavioral and physiological disorders can be provoked by temperature rises below 1°C--ie, under much less acute exposure conditions…there are reports of adverse health effects of subthermal intensities, the possible origin of which will now be considered.

    Biological Effects: Non-Thermal

    The possibility that the pulsed, low-intensity MWR currently used in GSM mobile telephony can exert subtle, non-thermal influences on a living organism arises because microwaves are waves; they have properties other than the intensity that is regulated by safety guidelines. This microwave radiation has certain well-defined frequencies, which facilitate its discernment by a living organism (despite its ultralow intensity), and via which the organism can, in turn, be affected.

    The human body is an electrochemical instrument of exquisite sensitivity whose orderly functioning and control are underpinned (6) by oscillatory electrical processes of various kinds, each characterised by a specific frequency, some of which happen to be close to those used in GSM. Thus some endogenous biological electrical activities can be interfered with via oscillatory aspects of the incoming radiation, in much the same way as can the reception on a radio.

    The biological electrical activities that are vulnerable to interference from GSM radiation include highly organised electrical activities at a cellular level whose frequency happens to lie in the microwave region, and which are a consequence of metabolism.7 Although not universally accepted, there is experimental evidence7-9 consistent with these endogenous activities, in terms of which effects of ultralow-intensity microwave radiation of a specific frequency on processes as fundamental as cell division, for example, can be understood in a rather natural way.10

    Furthermore, the DTX pulse frequency at 2 Hz and the TDMA frequency of 8·34 Hz correspond to frequencies of electrical oscillations found in the human brain, specifically the delta and alpha brain-waves, respectively. It is thus quite possible that living organisms have a two-fold sensitivity to the pulsed GSM signal--ie, to both the microwave carrier and the lower frequency pulsings of the TDMA and DTX signals.

    To deny this possibility yet admit the importance of ensuring electromagnetic compatibility with electronic instruments by banning the use of mobile phones on aircraft (11) and hospitals (a prohibition driven by concerns about non-thermal interference) seems inconsistent.

    The intensity of radiation needed for this recognition is many orders of magnitude below even that currently associated with non-thermal effects. This influence is possible only when the organism is alive, with excited endogenous frequencies; the dead have flat electroencephalograms.

    Non-thermal effects thus depend on the state of the person when exposed to the radiation--ie, non-thermal effects are non-linear. A low-intensity field can entail a seemingly disproportionately large response (or none at all), and vice versa, quite unlike the predictable thermal responses. Thus not everyone can be expected to be affected in the same way by identical exposure to the same radiation.

    A good example of human vulnerability to a non-thermal,electromagnetic influence is the ability of a light flashing at about 15 Hz to induce seizures in people with photosensitive epilepsy (12). It is not so much the amount of energy absorbed from the light that provokes the seizure, but rather the information transmitted to the brain by the (coherent) regularity of its flashing, at a frequency that the brain "recognises" because it matches or is close to a frequency utilised by the brain itself.

    What do we know experimentally about non-thermal biological influences of MWR (both pulsed and continuous) of an intensity close to that near a mobile phone handset, but often at higher microwave carrier frequencies? A selection of in vitro studies is given in panel 1.

    Panel 1: Selected in vitro studies of non-thermal effects of microwave radiation of various frequencies and intensities


    Effect Reference
    Epileptic activity in rat brain slices in conjunction with certain drugs 13
    Resonant effects on cell division of Saccharomyces cerevisiae, and on the genome conformation of Escherichia coli 9, 14
    Synchronisation of cell division in S carlsbergenis 15
    "Switch-on" of epigenetic processes, such as -phage and colicin synthesis 16, 17
    Altered ornithine decarboxylase activity 18
    Reduced lymphocyte cytotoxicity 19
    Increased permeability of erythrocyte membrane 20
    Effects on brain electrochemistry (calcium efflux) 21
    Increase in chromosome aberrations and micronuclei in human blood lymphocytes 22
    Synergism with cancer-promoting drugs such as phorbol ester 23

    In vivo evidence of non-thermal influences, including exposure to actual GSM radiation, comes predominantly from animal studies (panel 2).

    Panel 2: Selected in vivo studies of non-thermal microwave exposure, including GSM radiation

    Effect Reference
    Epileptiform activity in rats, in conjunction with certain drugs 24
    Depression of chicken immune systems (melatonin, corticosterone and IgG levels) 25
    Increase in chick embryo mortality 25
    Increased permeability of blood-brain barrier in rats 26
    Effects on brain electrochemistry (dopamine, opiates) 27
    Increases in DNA single and double strand breaks in rat brain 28
    Promotion of lymphomas in transgenic mice 29
    Synergistic effects with certain psychoactive drugs 30

    Finally, human in vivo studies, under GSM or similar conditions, include effects on the EEG and on blood pressure. A delayed increase in spectral power density (particularly in the alpha band) has been corroborated (31) in the "awake" EEG of adults exposed to GSM radiation. Influences on the "alseep" EEG include a shortening of rapid-eye-movement (REM) sleep during which the power density in the alpha band increases (32), and effects on non-REM sleep (33). Exposure to mobile phone radiation also decreases the preparatory slow potentials in certain regions of the brain (34) and affects memory tasks (35). In 1998, Braune et al (36) recorded increases in resting blood pressure during exposure to radiofrequencies.

    Non-thermal effects have proved controversial, and independent attempts to replicate them have not always been successful. Such difficulties are not unexpected, however, because these effects depend on the state of the organism when it is exposed, particularly in vivo.


    Possible Associated Adverse Health Reactions

    …GSM radiation does seem to affect non-thermally a variety of brain functions (including the neuroendocrine system), and health problems reported anecdotally do tend to be neurological, although formal confirmation of such reports, based on epidemiological studies, is still lacking.

    For example:


    reports of headache are consistent with the effect of the radiation on the dopamine-opiate system of the brain27 and
    the permeability of the blood-brain barrier (26), both of which have been connected to headache (40,41).
    Reports of sleep disruption are consistent with effects of the radiation on melatonin levels (25) and
    on rapid-eye-movement sleep (32).

    Furthermore, since there is no reason to suppose that the seizure-inducing ability (12) of a flashing visible light does not extend to microwave radiation (which can access the brain through the skull) flashing at a similarly low frequency, together with the fact that exposure to pulsed MWR can induce epileptic activity in rats (24), reports of epileptic activity in some children exposed to base-station radiation are perhaps not surprising.

    Finally, the significant increase (by a factor of between 2 and 3) in the incidence of neuroepithelial tumours (the laterality of which correlates with cell-phone use) found in a nationwide US study (42) is consistent not only with the genotoxicity of GSM radiation, as indicated by increased DNA strand breaks (28) and formation of chromosome aberrations and micronuclei but also with its promotional effect on tumour development (43).

    …it cannot be denied that non-thermal effects of the MWR used in mobile telephony do have the potential to induce adverse health reactions of the kind reported, and this possibility should not be ignored even if only a small minority of people are at risk.

    Whether a person is affected or not could depend, for example, on the level of stress before exposure; if it is high enough, the additional contribution from MWR exposure might be sufficient to trigger an abnormality that would otherwise have remained latent.

    It is often argued that anecdotal reports of health problems should be dismissed. However, given the paucity of systematic epidemiological studies of this new technology, such reports are an indispensable source of information, a point acknowledged in the 1999 report of the UK parliamentary committee (44).

    Preadolescent children can be expected to be more vulnerable to any adverse health effects than adults because absorption of GSM microwaves is greatest (5) in an object about the size of a child's head, because of the "head resonance" effect and the greater ease with which the radiation can penetrate the thinner skull of an infant (1).

    Also the multiframe repetition frequency of 8·34 Hz and the 2 Hz pulsing in the DTX mode of cellphones lie in the range of the alpha and delta brain-waves, respectively.

    In a child, alpha waves do not replace delta waves as a stable activity until the age of about 12 years. Furthermore, the immune system, whose efficacy is degraded (19,25) by this kind of radiation, is less robust in children.

    This makes them less able to cope with any adverse health effect that might be provoked by chronic exposure, not only to the pulsed microwave radiation but also to the the more penetrating low-frequency magnetic fields associated with the current surges from the handset battery which can reach 40 µT (peak) near the back of the case (45). Indications of the biological noxiousness of these magnetic fields (in animals) can be found in ref 25.

    In the context of base-station radiation, reports relating to animals are of particular value since it cannot here be claimed that the effects are psychosomatic. Of particular interest is a publication on cattle (43), recording severely reduced milk yields, emaciation, spontaneous abortions, and stillbirths. When cattle are removed to pastures well away from the mast, their condition improves, but it deteriorates once they are brought back. The adverse effects appeared only after GSM microwave antennae were installed on a tower formerly used to transmit only non-pulsed television and radio signals.

    Finally, in support of the reality of an adverse health impact of non-thermal influences of the kind of radiation used today in mobile telephony, we should recall that during the "cold war" the Soviet irradiation of western embassies with microwave radiation (of an intensity intermediate between that in the vicinity of a handset and a base-station), done with the express intention of inducing adverse health effects, was quite successful (47).

    The references to this excellent review by Dr. Hyland are given below.

    Risks on the Road

    In a separate Lancet report, Massachusetts scientist Dr. Kenneth Rothman said his research indicated the main public health concern was motor vehicle collisions rather than any possible link to brain cancer.

    He notes that one study found that the risk of a car accident was 4 times greater when the driver was using the telephone or soon after a call and that heavy mobile users were involved in twice as many fatal road accidents than light users.

    In addition, use of 'hands-free' units was no less risky than holding the telephone to the ear with one hand while talking.

    The Lancet, November 25, 2000; 356: 1833-36, 1837-40


    --------------------------------------------------------------------------------

    More Bad News for Hands Free Mobile Phones

    Many people concerned with possible adverse health effects, including myself, have recommended the use of "Hands Free" units as a way to greatly reduce the microwave exposure. However, as we reported several weeks ago this may not necessarily be any safer.

    Now, upon further review of the safety evidence, including the results of tests conducted by the British Consumers Association and published in their magazine Which? the British government has decided to withdraw its recommendation that mobile phone users switch to handsfree units.

    In addition, they plan to start issuing leaflets warning buyers of the unknown, but potentially harmful impact of mobile phone usage by children, according to a report in Newsbytes.com.

    The warnings follow the British government's continuing funding of tests into the effects of mobile phone radio frequency (RF) radiation on the soft tissue of the brain and head.

    Liam Donaldson, the UK's chief medical officer, said that the government's decision to remove the health approval on handsfree kits followed a number of investigations that claim handsfree devices may even channel radiation to the users head. "We don't have good enough science so far to say definitely one way or the other," he said, adding that further research is being conducted urgently to provide an answer to the question.


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    For more information regarding the safety of cell phones go to EMFacts Consultancy's Mobile Phone Health Hazard's page which is likely the best compilation of data on the mobile phone issue.


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    DR. MERCOLA'S COMMENT:

    This is the most comprehensive detailed and well referenced report on cell phone dangers I have yet to see.

    Cell phones are becoming increasingly popular, yet most are absolutely blinded to the damage they are doing to their brains by exposing themselves to this radiation. Even the conservative British journal The Lancet is warning that the dangers from this radiation can NOT be dismissed.

    My recommendation? Keep the use down to as low as possible (my use is less than five minutes per YEAR). Let's keep those brain cells alive!

    MOBILE phone users don’t usually get much sympathy from the rest of us - and quite rightly so. If they’re not bawling into a handset in a train carriage, they’re veering wildly across the carriageway as they try to make a call, eat a sandwich and steer a Vauxhall Vectra at the same time.
    Should mobile phones carry a health warning?

    But in what seems like an act of divine retribution, it has been discovered that not only do mobile phones make you look like a complete prat, they could give you cancer, asthma and Alzheimer’s. And if that’s not enough to make the buggers shut up, I don’t know what is.
    Researchers at the Royal Adelaide Hospital in Australia discovered earlier this year that the electromagnetic field that surrounds electrical appliances can be positively linked to development of cancer in mice (or negatively linked, if you look at it the mouse’s point of view).
    “This is the first scientific study to show such an effect,” said Dr Michael Repacholi, whose research is being funded by The World Health Organisation as part of a £2.2 million five-year investigation into the effects of electromagnetic fields which started in June 1996.
    The National Radiological Protection Board in Didcot, Oxon, which has our best interests at heart, said the findings will provide a focus for more research, but that the implications for human health were far from clear.
    Research by other scientists indicates that prolonged use of mobile phones may cause hot-spots to develop inside the brain, causing damage which could lead to Alzheimer’s disease or cancer.
    Dr Peter French, an immunologist from New Zealand, told BBC 1’s WatchDog consumer affairs program that he now only uses his mobile phone when it’s absolutely essential, and switches sides if a call lasts for more than a couple of minutes.
    But despite the warnings, users of mobile phones remain committed to their high-tech toys. Speaking from inside a special lead-lined helmet, Paul Pettengale, associate editor of technology magazine T3, poo-poohed the research, saying “The chances of you developing a brain tumor by using a mobile phone is so incredibly slim, it’s not even a consideration. Such
    suggestions are little more than scaremongery.”
    “We're not saying GSM radiation is harmful. We're saying that if you're concerned about it then we've got a solution for you”
    — ANGUS BROWN
    Sales Director, Hagenuk However, new research has found that a far worse danger is the link between the use of mobile phones and loss of concentration and lapses in short-term memory. Boffins at a mobile phone safety conference in Brussels showed the microwave radiation like that emitted by mobile phones had the power to temporarily impair the ability of rats to learn simple tasks.
    Dr Henry Lai and Dr N P Singh from the University of Washington in Seattle believe the radiation changed brain cell membranes in the rats - and the effects are so severe that it could affect humans, too.
    The mobile phone industry has so far been slow to respond to the health worries. German mobile phone company Hagenuk is the first to produce a phone that blocks radiation. “We’re not saying GSM radiation is harmful,” said sales director Angus Brown, “We’re saying that if you’re concerned about it then we’ve got a solution for you.”
    Hagenuk’s new phone has an antenna with a special radiating shield for the users head, so the potentially harmful electromagnetic energy is emitted in a kidney-shaped pattern away from the user.
    Mitsubishi and Hitachi have also designed low-radiation phones with patents stating that the aim is to prevent damage to users’ health, but Hagenuk’s is currently the only safe phone on the market.
    So the next time you see a Vectra swerving wildly between lanes on the motorway, don’t condemn the driver as a dangerous, idiotic show-off - he’s probably just forgotten how to drive his car. Poor sod.
    --------------------------------------------------------------------------------------------------------------------------

    Study: Hands-Free Cell Phones Just as Dangerous for Drivers

    Aug. 16, 2001

    (CBS) College student Tony Dhaliwal is about to attempt a very dangerous mission: In the safety of a simulator, he'll try to drive and talk on a cell phone at the same time.


    He goes over a shopping list on the phone: "You want bread, cheerios, hamburger, and--"

    Just then, the accident happens. Tony Dhaliwal just flunked the test.

    "I could have killed this guy. This is my fault," he says. But he also helped drive home an important safety point.

    "We've found a clear pattern of impaired driving behavior while you're talking on a cell phone," says Dr. David Strayer.

    Strayer, who headed a new University of Utah study on this subject, says talking on a cell phone is far riskier for drivers than, say, listening to the radio. Those using phones miss signals and are slow to react.

    Most importantly, the new study revealed, it doesn't matter if the driver is actually holding the cell phone.

    "We found that you are just as impaired when you're talking with a hands-free device as when you were using a handheld cell phone," he says.

    That suggests that new laws, like one in New York that bans handheld cell phones, won't reduce the risk of accidents.

    The distraction, experts say, is the conversation itself. Drivers can't focus on two things at once, so many tend to forget about the road.

    "The problem with talking on the phone is that you actually have to think about what you are saying. So it is not simply just listening to somebody as you might listen to music on the radio, which you can sort of put into the background of what you do," says Dr. Jordan Grafman of the National Institutes of Health.

    Safety experts expect that the risk will grow: Seventy-five percent of drivers say they routinely use cell phones on the road, where the consequences are real and not just simulated.


    ©MMII CBS Worldwide Inc. All Rights Reserved. This material may not be published, broadcast, rewritten, or redistributed.
    ---------------------------------------------------------------------------------------------------------------------

    Reuters) Britain announced plans Friday for a $10 million research program into the potential health hazards of cellular phones.

    England's Chief Medical Officer Liam Donaldson said leaflets advising people to keep calls short and to discourage children from using them will also be included with each new phone.

    "It is essential that we provide people with the evidence on this issue to allow them to make an informed choice about using their mobile phones," said Donaldson.

    Although there is no irrefutable medical evidence about health risks the government is taking a precautionary approach.

    Nearly half of Britain's population, more than 25 million people, own a cell phone. A quarter of users are under 18 years old.

    The research program and leaflets follow a report from a government inquiry into the safety of cell phones that was published in May.

    Sir William Stewart, who led the inquiry, will head the research program that will be funded by the government and the cell phone industry.

    "On the basis of the precautionary approach outlined in the Stewart report, the leaflets provide advice that, if you use a mobile phone, you can choose to minimize your exposure to radio waves by keeping your calls short," Donaldson added.

    The leaflets will also contain information about living near cellular phone base stations and the specific absorption rate (SAR), which is how much radio wave energy the body absorbs from each phone.

    Beginning next year there will be a European Standard method for measuring SAR which will be provided with each phone.

    Scientists say the jury is still out on whether cell phones cause brain tumors or other health problems. Some researchers claim they are the cause of headaches, sleeping disorders and memory loss.

    Children could be more vulnerable to any potential ill effects because they have thinner skulls, smaller heads and their nervous system is still developing.

    A study released earlier this month showed hands-free phone kits could boost the brain's exposure to radiation. The government leaflet said more studies are needed to assess the SAR of the hands-free kit.

    Research in the United States has shown that heavy users of cell phones are involved in more fatal road accidents than people who use them less often.


    from cancer-health.org
    http://our-medical-center.blogspot.com/2008/01/cellular-phone-caused-cancer.html

    Prostate cancer

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    http://our-medical-center.blogspot.com/2007/12/prostate-cancer.html

    Prostate cancer is a disease in which cancer develops in the prostate, a gland in the male reproductive system. It occurs when cells of the prostate mutate and begin to multiply out of control. These cells may spread (metastasize) from the prostate to other parts of the body, especially the bones and lymph nodes. Prostate cancer may cause pain, difficulty in urinating, erectile dysfunction and other symptoms.

    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.[1] 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.[2][3] However, these high rates may be affected by increasing rates of detection.[4]

    Prostate cancer develops most frequently in men over fifty. This cancer can occur only in men, as the prostate is exclusively of the male reproductive tract. It is the most common type of cancer in men in the United States, where it is responsible for more male deaths than any other cancer, except lung cancer. However, many men who develop prostate cancer never have symptoms, undergo no therapy, and eventually die of other causes. Many factors, including genetics and diet, have been implicated in the development of prostate cancer.

    Prostate cancer is most often discovered by physical examination or by screening blood tests, such as the PSA (prostate specific antigen) test. There is some current concern about the accuracy of the PSA test and its usefulness. Suspected prostate cancer is typically confirmed by removing a piece of the prostate (biopsy) and examining it under a microscope. Further tests, such as X-rays and bone scans, may be performed to determine whether prostate cancer has spread.

    Prostate cancer can be treated with surgery, radiation therapy, hormonal therapy, occasionally chemotherapy, proton therapy, or some combination of these. The age and underlying health of the man as well as the extent of spread, appearance under the microscope, and response of the cancer to initial treatment are important in determining the outcome of the disease. Since prostate cancer is a disease of older men, many will die of other causes before a slowly advancing prostate cancer can spread or cause symptoms. This makes treatment selection difficult.[5] 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.


    Prostate

    Main article: Prostate

    The prostate is a male reproductive organ which helps make and store seminal fluid. In adult men a typical prostate is about three centimeters long and weighs about twenty grams.[6] 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.[7] 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.[8] 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.

    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 hypertrophy. These include frequent urination, increased urination at night, difficulty starting and maintaining a steady stream of urine, blood in the urine, and painful urination. Prostate cancer may also cause problems with sexual function, such as difficulty achieving erection or painful ejaculation.[9]

    Advanced prostate cancer may cause additional symptoms as the disease spreads to other parts of the body. The most common symptom is bone pain, often in the vertebrae (bones of the spine), pelvis or ribs, from cancer which has spread to these bones. Prostate cancer in the spine can also compress the spinal cord, causing leg weakness and urinary and fecal incontinence.[10]

    Pathophysiology

    When normal cells are damaged beyond repair, they are eliminated by apoptosis. Cancer cells avoid apoptosis and continue to multiply in an unregulated manner.
    When normal cells are damaged beyond repair, they are eliminated by apoptosis. Cancer cells avoid apoptosis and continue to multiply in an unregulated manner.

    Prostate cancer is classified as an adenocarcinoma, or glandular cancer, that begins when normal semen-secreting prostate gland cells mutate into cancer cells. The region of prostate gland where the adenocarcinoma is most common is the peripheral zone. Initially, small clumps of cancer cells remain confined to otherwise normal prostate glands, a condition known as carcinoma in situ or prostatic intraepithelial neoplasia (PIN). Although there is no proof that PIN is a cancer precursor, it is closely associated with cancer. Over time these cancer cells begin to multiply and spread to the surrounding prostate tissue (the stroma) forming a tumor. Eventually, the tumor may grow large enough to invade nearby organs such as the seminal vesicles or the rectum, or the tumor cells may develop the ability to travel in the bloodstream and lymphatic system. Prostate cancer is considered a malignant tumor because it is a mass of cells which can invade other parts of the body. This invasion of other organs is called metastasis. Prostate cancer most commonly metastasizes to the bones, lymph nodes, rectum, and bladder.

    Etiology

    The specific causes of prostate cancer remain unknown.[11] A man's risk of developing prostate cancer is related to his age, genetics, race, diet, lifestyle, medications, and other factors. The primary risk factor is age. Prostate cancer is uncommon in men less than 45, but becomes more common with advancing age. The average age at the time of diagnosis is 70.[12] 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.[13] In the year 2005 in the United States, there were an estimated 230,000 new cases of prostate cancer and 30,000 deaths due to prostate cancer.[14]

    A man's genetic background contributes to his risk of developing prostate cancer. This is suggested by an increased incidence of prostate cancer found in certain racial groups, in identical twins of men with prostate cancer, and in men with certain genes. In the United States, prostate cancer more commonly affects black men than white or Hispanic men, and is also more deadly in black men.[15] Men who have a brother or father with prostate cancer have twice the usual risk of developing prostate cancer.[16] Studies of twins in Scandinavia suggest that forty percent of prostate cancer risk can be explained by inherited factors.[17] However, no single gene is responsible for prostate cancer; many different genes have been implicated. Two genes (BRCA1 and BRCA2) that are important risk factors for ovarian cancer and breast cancer in women have also been implicated in prostate cancer.[18]

    Dietary amounts of certain foods, vitamins, and minerals can contribute to prostate cancer risk. Men with higher serum levels of the short-chain ω-6 fatty acid linoleic acid have higher rates of prostate cancer. However, the same series of studies showed that men with elevated levels of long-chain ω-3 (EPA and DHA) had lowered incidence.[19] 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."[20] Other dietary factors that may increase prostate cancer risk include low intake of vitamin E (Vitamin E is found in green, leafy vegetables), omega-3 fatty acids (found in fatty fishes like salmon), and the mineral selenium. A study in 2007 cast doubt on the effectiveness of lycopene (found in tomatoes) in reducing the risk of prostate cancer.[21] Lower blood levels of vitamin D also 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.[22]

    There are also some links between prostate cancer and medications, medical procedures, and medical conditions. Daily use of anti-inflammatory medicines such as aspirin, ibuprofen, or naproxen may decrease prostate cancer risk.[23] Use of the cholesterol-lowering drugs known as the statins may also decrease prostate cancer risk.[24] More frequent ejaculation also may decrease a man's risk of prostate cancer. One study showed that men who ejaculated five times a week in their 20s had a decreased rate of prostate cancer, though others have shown no benefit.[25][26] Infection or inflammation of the prostate (prostatitis) may increase the chance for prostate cancer. In particular, infection with the sexually transmitted infections chlamydia, gonorrhea, or syphilis seems to increase risk.[27] Finally, obesity[28] and elevated blood levels of testosterone[29] may increase the risk for prostate cancer.

    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.[30]

    Prostate cancer risk can be decreased by modifying known risk factors for prostate cancer, such as decreasing intake of animal fat.[31]

    One research study, by the Cancer Council Victoria, has shown that men who report that they regularly ("more than five times per week") masturbate have up to one third fewer occurrences of prostate cancer.[32] The researchers hypothesize that this could be because regular ejaculation reduces the buildup of carcinogenic deposits which could damage the cells lining the prostate. The researchers also speculated that frequent ejaculation may cause the prostate to mature fully, making it less susceptible to carcinogens. It is also possible that there is another factor (such as hormone levels) that is a common cause of both a reduced susceptibility to prostate cancer and a tendency toward frequent masturbation. There is also some evidence that frequent sexual intercourse is associated with reduced risk of prostate cancer, although contrarily the risks associated with STDs have been shown to increase the risk of prostate cancer.[33] Once the lining of the prostate is affected with cancer, the only known treatments are surgery and radiation therapy. Both may limit the ability to have erections afterward.

    Prevention

    Several medications and vitamins may also help prevent prostate cancer. Two dietary supplements, vitamin E and selenium, may help prevent prostate cancer when taken daily. Estrogens from fermented soybeans and other plant sources (called phytoestrogens) may also help prevent prostate cancer.[34] The selective estrogen receptor modulator drug toremifene has shown promise in early trials.[35][36] Two medications which block the conversion of testosterone to dihydrotestosterone, finasteride[37] and dutasteride,[38] 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. The problem with these medications is that they may preferentially block the development of lower-grade prostate tumors, leading to a relatively greater chance of higher grade cancers, and negating any overall survival improvement. Green tea may be protective (due to its polyphenol content), though the data is mixed.[39][40] A 2006 study of green tea derivatives demonstrated promising prostate cancer prevention in patients at high risk for the disease.[41] In 2003, an Australian research team led by Graham Giles of The Cancer Council Australia concluded that frequent masturbation by males appears to help prevent the development of prostate cancer.[42] Recent 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.[43] 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. Scientists recommend a healthy, well balanced diet rich in fiber, and to reduce intake of meat. 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.[44] Scientists believe the reason for this phenomenon has to do with a phytochemical called Diindolylmethane in these vegetables that has anti-androgenic and immune modulating properties. This compound is currently under investigation by the National Cancer Institute as a natural therapeutic for prostate cancer.

    Capsaicin

    Capsaicin, the chemical found in peppers, has been shown to cause 80% of cancerous prostate cells to undergo apoptosis in mice. For prostate cancer cells whose growth is dependent upon testosterone, Capsaicin curbed the proliferation of such cells by freezing the cells in a non-proliferate state, and cancerous prostate cells that are androgen independent "suicided" as well.[45]

    "Capsaicin had a profound anti-proliferative effect on human prostate cancer cells in culture," said Sören Lehmann, M.D., Ph.D., visiting scientist at the Cedars-Sinai Medical Center and the UCLA School of Medicine. "It also dramatically slowed the development of prostate tumors formed by those human cell lines grown in mouse models."[46]

    Peppers which rank higher on the Scoville scale and thus have a higher piquancy contain a higher amount of Capsaicin. Habaneros, for example, have a Scoville rating of over 300,000, while red chili peppers have a rating of 5,000. While the UCLA and Samuel Oschin Comprehensive Cancer Institute studies show promising implications, the same effects have not yet been duplicated in men.[47]

    Screening

    Prostate cancer screening is an attempt to find unsuspected cancers. Screening tests may lead to more specific follow-up tests such as a biopsy, where small pieces of the prostate are removed for closer study. Prostate cancer screening options include the digital rectal exam and the prostate specific antigen (PSA) blood test. Screening for prostate cancer is controversial because it is not clear if the benefits of screening outweigh the risks of follow-up diagnostic tests and cancer treatments.

    Prostate cancer is usually a slow-growing cancer, very common among older men. In fact, most prostate cancers never grow to the point where they cause symptoms, and most men with prostate cancer die of other causes before prostate cancer has an impact on their lives. The PSA screening test may detect these small cancers that would never become life threatening. Doing the PSA test in these men may lead to overdiagnosis, including additional testing and treatment. Follow-up tests, such as prostate biopsy, may cause pain, bleeding and infection. Prostate cancer treatments may cause urinary incontinence and erectile dysfunction. Therefore, it is essential that the risks and benefits of diagnostic procedures and treatment be carefully considered before PSA screening.

    No major scientific or medical organizations currently support routine screening for prostate cancer.[48]

    • In 2002, the U.S. Preventive Services Task Force (USPSTF) concluded that the evidence was insufficient to recommend for or against routine screening for prostate cancer using PSA testing or digital rectal examination (DRE).[49] The previous 1995 USPSTF recommendation was against routine screening.
    • In 1997, American Cancer Society (ACS) guidelines began recommending that beginning at age 50 (age 45 for African-American men and men with a family history of prostate cancer, and since 2001, age 40 for men with a very strong family history of prostate cancer), PSA testing and DRE be offered annually to men who have a life-expectancy of 10 or more years (average life expectancy is 10 years or more for U.S. men under age 76)[50] along with information on the risks and benefits of screening.[51] The previous ACS recommendations since 1980 had been for routine screening for prostate cancer with DRE annually beginning at age 40, and since 1992 had been for routine screening with DRE and PSA testing annually beginning at age 50.[52]
    • The 2007 National Comprehensive Cancer Network (NCCN) guideline recommends offering a baseline PSA test and DRE at ages 40 and 45 and annual PSA testing and DRE beginning at age 50 (with annual PSA testing and DRE beginning at age 40 for African-American men, men with a family history of prostate cancer, and men with a PSA ≥ 0.6 ng/mL at age 40 or PSA > 0.6 ng/mL at age 45) through age 80, along with information on the risks and benefits of screening. Biopsy is recommended if DRE is positive or PSA ≥ 4 ng/mL, and biopsy considered if PSA > 2.5 ng/mL or PSA velocity ≥ 0.35 ng/mL/year when PSA ≤ 2.5 ng/mL.[53]
    • Some U.S. radiation oncologists and medical oncologists who specialize in treating prostate cancer recommend obtaining a baseline PSA in all men at age 35[54] or beginning annual PSA testing in high risk men at age 35.[55]

    Since there is no firm evidence or general agreement that the benefits of PSA screening outweigh the harms, major scientific and medical organizations recommend that clinicians use a process of shared decision-making that includes discussing with patients the risks of prostate cancer, the potential benefits and harms of screening, and involving the patients in the decision.[56]

    However, because PSA screening is widespread in the United States, following the recommendations of major scientific and medical organizations to use shared decision-making is legally perilous in some U.S. states.[57] In 2003, a Virginia jury found a family practice residency program guilty of malpractice and liable for $1 million for following national guidelines and using shared decision-making, thereby allowing a patient (subsequently found to have a high PSA and incurable advanced prostate cancer) to decline a screening PSA test, instead of routinely ordering without discussion PSA tests in all men ≥ 50 years of age as four local physicians testified was their practice, and was accepted by the jury as the local standard of care.[58]

    An estimated 20 million PSA tests are done per year in North America and possibly 20 million more outside of North America.[59]

    • In 2000, 34.1% of all U.S. men age ≥ 50 had a screening PSA test within the past year and 56.8% reported ever having a PSA test.[56]
    • In 2000, 33.6% of all U.S. men age 50–64 and 51.3% of men age ≥ 65 had a PSA test within the past year.[60]
    • In 2005, 33.5% of all U.S. men age 50–64 had a PSA test in the past year.
    • In 2000–2001, 34.1% of all Canadian men age ≥ 50 had a screening PSA test within the past year and 47.5% reported ever having a screening PSA test.[62]
    • Canadian men in Ontario were most likely to have had a PSA test within the past year and men in Alberta were least likely to have had a PSA test with the past year or ever.[63]

    Digital rectal examination

    Digital rectal examination (DRE) is a procedure where the examiner inserts a gloved, lubricated finger into the rectum to check the size, shape, and texture of the prostate. Areas which are irregular, hard or lumpy need further evaluation, since they may contain cancer. Although the DRE only evaluates the back of the prostate, 85% of prostate cancers arise in this part of the prostate. Prostate cancer which can be felt on DRE is generally more advanced.[64] The use of DRE has never been shown to prevent prostate cancer deaths when used as the only screening test.[65]

    Prostate specific antigen

    The PSA test measures the blood level of prostate-specific antigen, an enzyme produced by the prostate. Specifically, PSA is a serine protease similar to kallikrein. Its normal function is to liquify gelatinous semen after ejaculation, allowing spermatozoa to more easily navigate through the uterine cervix.

    The risk of prostate cancer increases with increasing PSA levels.[66] 4 ng/mL was chosen arbitrarily as a decision level for biopsies in the clinical trial upon which the FDA in 1994 based adding prostate cancer detection in men age 50 and over as an approved indication for the first commercially available PSA test.[67] 4 ng/mL was used as the biopsy decision level in the PLCO trial, 3 ng/mL was used in the ERSPC and ProtecT trials, and 2.5 ng/mL is used in the 2007 NCCN guideline.

    PSA levels can change for many reasons other than cancer. Two common causes of high PSA levels are enlargement of the prostate (benign prostatic hypertrophy (BPH)) and infection in the prostate (prostatitis). It can also be raised for 24 hours after ejaculation and several days after catheterization. PSA levels are lowered in men who use medications used to treat BPH or baldness. These medications, finasteride (marketed as Proscar or Propecia) and dutasteride (marketed as Avodart), may decrease the PSA levels by 50% or more.

    Several other ways of evaluating the PSA have been developed to avoid the shortcomings of simple PSA screening. The use of age-specific reference ranges improves the sensitivity and specificity of the test. The rate of rise of the PSA over time, called the PSA velocity, has been used to evaluate men with PSA levels between 4 and 10 ng/ml, but it has not proven to be an effective screening test.[68] Comparing the PSA level with the size of the prostate, as measured by ultrasound or magnetic resonance imaging, has also been studied. This comparison, called PSA density, is both costly and has not proven to be an effective screening test.[69] PSA in the blood may either be free or bound to other proteins. Measuring the amount of PSA which is free or bound may provide additional screening information, but questions regarding the usefulness of these measurements limit their widespread use.[70][71]

    Diagnosis

    Normal prostate (A) and prostate cancer (B). In prostate cancer, the regular glands of the normal prostate are replaced by irregular glands and clumps of cells, as seen in these pictures taken through a microscope.
    Normal prostate (A) and prostate cancer (B). In prostate cancer, the regular glands of the normal prostate are replaced by irregular glands and clumps of cells, as seen in these pictures taken through a microscope.

    When a man has symptoms of prostate cancer, or a screening test indicates an increased risk for cancer, more invasive evaluation is offered.

    The only test which can fully confirm the diagnosis of prostate cancer is a biopsy, the removal of small pieces of the prostate for microscopic examination. However, prior to a biopsy, several other tools may be used to gather more information about the prostate and the urinary tract. Cystoscopy shows the urinary tract from inside the bladder, using a thin, flexible camera tube inserted down the urethra. Transrectal ultrasonography creates a picture of the prostate using sound waves from a probe in the rectum.

    Biopsy

    Main article: Prostate biopsy

    If cancer is suspected, a biopsy is offered. During a biopsy a urologist obtains tissue samples from the prostate via the rectum. A biopsy gun inserts and removes special hollow-core needles (usually three to six on each side of the prostate) in less than a second. Prostate biopsies are routinely done on an outpatient basis and rarely require hospitalization. Fifty-five percent of men report discomfort during prostate biopsy.[72]

    Gleason score

    Main article: Gleason score

    The tissue samples are then examined under a microscope to determine whether cancer cells are present, and to evaluate the microscopic features (or Gleason score) of any cancer found.

    Tumor markers

    Main article: Tumor markers

    Tissue samples can be stained for the presence of PSA and other tumor markers in order to determine the origin of maligant cells that have metastasized.[73]

    New tests being investigated

    Currently, an active area of research involves non-invasive methods of prostate tumor detection. Adenoviruses modified to transfect tumor cells with harmless yet distinct genes (such as luciferase) have proven capable of early detection. So far, though, this area of research has only been tested in animal and LNCaP models.[74]

    PCA3

    Another potential non-invasive methods of early prostate tumor detection is through a molecular test that detects the presence of cell-associated PCA3 mRNA in urine. PCA3 mRNA is expressed almost exclusively by prostate cells and has been shown to be highly over-expressed in prostate cancer cells. PCA3 is not a replacement for PSA but an additional tool to help decide if, in men suspected of having prostate cancer, a biopsy is really needed. The higher the expression of PCA3 in urine, the greater the likelihood of a positive biopsy, i.e. the presence of cancer cells in the prostate. Company Diagnocure has an exclusive worldwide license for all diagnostic and therapeutic applications related to PCA3

    Early prostate cancer

    It was reported in April 2007 that a new blood test for early prostate cancer antigen-2 (EPCA-2) is being researched that may alert men if they have prostate cancer and how aggressive it will be.[75][76]

    Staging

    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 metastisis - opposite to what is found in many other cancers that metastisize.

    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. Proper grading of the tumor is critical, since the grade of the tumor is one of the major factors used to determine the treatment recommendation.

    Risk assessment

    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 to 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.

    Treatment

    Treatment for prostate cancer may involve watchful waiting, surgery, radiation therapy, High Intensity Focused Ultrasound (HIFU), chemotherapy, cryosurgery, hormonal therapy, or some combination. Which option is best depends on the stage of the disease, the Gleason score, and the PSA level. Other important factors are the man's age, his general health, and his feelings 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.

    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.[77] This may enter into the treatment decision.

    If the cancer has spread beyond the prostate, treatment options significantly change, so most doctors who treat prostate cancer use a variety of nomograms to predict the probability of spread. Treatment by watchful waiting, HIFU, radiation therapy, cryosurgery, and surgery are generally offered to men whose cancer remains within the prostate. Hormonal therapy and chemotherapy are often reserved for disease which 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, hormonal therapy, and chemotherapy may also be offered if initial treatment fails and the cancer progresses.

    Watchful waiting and active surveillance

    Watchful waiting, also called "active surveillance," refers to observation and regular monitoring without invasive treatment. Watchful waiting is often used when an early stage, slow-growing prostate cancer is found in an older man. Watchful waiting may also be suggested when the risks of surgery, radiation therapy, or hormonal therapy outweigh the possible benefits. Other treatments can be started if symptoms develop, or if there are signs that the cancer growth is accelerating (e.g., rapidly rising PSA, increase in Gleason score on repeat biopsy, etc.). Most men who choose watchful waiting for early stage tumors eventually have signs of tumor progression, and they may need to begin treatment within three years.[78] Although men who choose watchful waiting avoid the risks of surgery and radiation, the risk of metastasis (spread of the cancer) may be increased. For younger men, a trial of active surveillance may not mean avoiding treatment altogether, but may reasonably allow a delay of a few years or more, during which time the quality of life impact of active treatment can be avoided. Published data to date suggest that carefully selected men will not miss a window for cure with this approach. Additional health problems that develop with advancing age during the observation period can also make it harder to undergo surgery and radiation therapy.

    Clinically insignificant prostate tumors are often found by accident when a doctor incorrectly orders a biopsy not following the recommended guidelines (abnormal DRE and elevated PSA). The urologist must check that the PSA is not elevated for other reasons, Prostatitis, etc. An annual biopsy is often recommended by a urologist for a patient who has selected watchful waiting when the tumor is clinically insignificant (no abnormal DRE or PSA). The tumors tiny size can be monitored this way and the patient can decide to have surgery only if the tumor enlarges which may take many years or never.

    Surgery

    Surgical removal of the prostate, or prostatectomy, is a common treatment either for early stage prostate cancer, or for cancer which has failed to respond to radiation therapy. The most common type is radical retropubic prostatectomy, when the surgeon removes the prostate through an abdominal incision. Another type is radical perineal prostatectomy, when the surgeon removes the prostate through an incision in the perineum, the skin between the scrotum and anus. Radical prostatectomy can also be performed laparoscopically, through a series of small (1cm) incisions in the abdomen, with or without the assistance of a surgical robot.

    Radical prostatectomy is effective for tumors which have not spread beyond the prostate;[79] cure rates depend on risk factors such as PSA level and Gleason grade. However, it may cause nerve damage that significantly alters the quality of life of the prostate cancer survivor. The most common serious complications are loss of urinary control and impotence. Reported rates of both complications vary widely depending on how they are assessed, by whom, and how long after surgery, as well as the setting (e.g., academic series vs. community-based or population-based data). Although penile sensation and the ability to achieve orgasm usually remain intact, erection and ejaculation are often impaired. Medications such as sildenafil (Viagra), tadalafil (Cialis), or vardenafil (Levitra) may restore some degree of potency. For most men with organ-confined disease, a more limited "nerve-sparing" technique may help avoid urinary incontinence and impotence.[80]

    Radical prostatectomy has traditionally been used alone when the cancer is small. In the event of positive margins or locally advanced disease found on pathology, adjuvant radiation therapy may offer improved survival. Surgery may also be offered when a cancer is not responding to radiation therapy. However, because radiation therapy causes tissue changes, prostatectomy after radiation has a higher risk of complications.

    Laparoscopic radical prostatectomy, LRP, is the more modern form of the historical open radical retropubic prostatectomy. Contrasted with the open surgical form of prostate cancer surgery, laparoscopic radical prostatectomy does not require a large incision. Relying on modern technology, such as miniaturization, fiber optics, and the like, laparoscopic radical prostatectomy is a minimally invasive prostate cancer treatment and a departure from what historically required the application of relatively primitive surgical techniques. Laparoscopic radical prostatectomy is not a new prostate cancer treatment. Rather, laparoscopic radical prostatectomy is a modern means of performing prostate cancer surgery, the oldest treatment for prostate cancer.

    The LRP technical manual was published in 1999 by Drs. Bertrand Guillonneau, Arnon Krongrad, and Guy Vallancien. LRP is laparoscopic prostate surgery, not laser prostate surgery.

    Transurethral resection of the prostate, commonly called a "TURP," is a surgical procedure performed when the tube from the bladder to the penis (urethra) is blocked by prostate enlargement. TURP is generally for benign disease and is not meant as definitive treatment for prostate cancer. During a TURP, a small tube (cystoscope) is placed into the penis and the blocking prostate is cut away.

    In metastatic disease, where cancer has spread beyond the prostate, removal of the testicles (called orchiectomy) may be done to decrease testosterone levels and control cancer growth. (See hormonal therapy, below).

    Radiation therapy

    Brachytherapy for prostate cancer is administered using "seeds," small radioactive rods implanted directly into the tumor.
    Brachytherapy for prostate cancer is administered using "seeds," small radioactive rods implanted directly into the tumor.

    Radiation therapy, also known as radiotherapy, uses ionizing radiation to kill prostate cancer cells. When absorbed in tissue, Ionizing radiation such as Gamma and x-rays damage the DNA in cells, which increases the probability of apoptosis (cell death). Two different kinds of radiation therapy are used in prostate cancer treatment: external beam radiation therapy and brachytherapy.

    External beam radiation therapy uses a linear accelerator to produce high-energy x-rays which are directed in a beam towards the prostate. A technique called Intensity Modulated Radiation Therapy (IMRT) may be used to adjust the radiation beam to conform with the shape of the tumor, allowing higher doses to be given to the prostate and seminal vesicles with less damage to the bladder and rectum. External beam radiation therapy is generally given over several weeks, with daily visits to a radiation therapy center. New types of radiation therapy may have fewer side effects then traditional treatment, one of these is Tomotherapy.

    External beam radiation therapy for prostate cancer is delivered by a linear accelerator, such as this one.
    External beam radiation therapy for prostate cancer is delivered by a linear accelerator, such as this one.

    Permanent implant brachytherapy is a popular treatment choice for patients with low to intermediate risk features, can be performed on an outpatient basis, and is associated with good 10-year outcomes with relatively low morbidity[81] It involves the placement of about 100 small "seeds" containing radioactive material (such as iodine-125 or palladium-103) with a needle through the skin of the perineum directly into the tumor while under spinal or general anesthetic. These seeds emit lower-energy X-rays which are only able to travel a short distance. Although the seeds eventually become inert, they remain in the prostate permanently. The risk of exposure to others from men with implanted seeds is generally accepted to be insignificant.[82]

    Radiation therapy is commonly used in prostate cancer treatment. It may be used instead of surgery for early cancers, and it may also be used in advanced stages of prostate cancer to treat painful bone metastases. Radiation treatments also can be combined with hormonal therapy for intermediate risk disease, when radiation therapy alone is less likely to cure the cancer. Some radiation oncologists combine external beam radiation and brachytherapy for intermediate to high risk situations. One study found that the combination of six months of androgen suppressive therapy combined with external beam radiation had improved survival compared to radiation alone in patients with localized prostate cancer.[83] Others use a "triple modality" combination of external beam radiation therapy, brachytherapy, and hormonal therapy.

    Less common applications for radiotherapy are when cancer is compressing the spinal cord, or sometimes after surgery, such as when cancer is found in the seminal vesicles, in the lymph nodes, outside the prostate capsule, or at the margins of the biopsy.

    Radiation therapy is often offered to men whose medical problems make surgery more risky. Radiation therapy appears to cure small tumors that are confined to the prostate just about as well as surgery. However, some issues remain unresolved, such as whether radiation should be given to the rest of the pelvis, how much the absorbed dose should be, and whether hormonal therapy should be given at the same time.

    Side effects of radiation therapy might occur after a few weeks into treatment. Both types of radiation therapy may cause diarrhea and rectal bleeding due to radiation proctitis, as well as urinary incontinence and impotence. Symptoms tend to improve over time.[84] Men who have undergone external beam radiation therapy will have a higher risk of later developing colon cancer and bladder cancer.[85]

    Cryosurgery

    Cryosurgery is another method of treating prostate cancer. It is less invasive than radical prostatectomy, and general anesthesia is less commonly used. Under ultrasound guidance, a method invented by Dr. Gary Onik,[86] metal rods are inserted through the skin of the perineum into the prostate. Highly purified Argon gas is used to cool the rods, freezing the surrounding tissue at −196 °C (−320 °F). As the water within the prostate cells freeze, the cells die. The urethra is protected from freezing by a catheter filled with warm liquid. Cryosurgery generally causes fewer problems with urinary control than other treatments, but impotence occurs up to ninety percent of the time. When used as the initial treatment for prostate cancer and in the hands of an experienced cryosurgeon, cryosurgery has a 10 year biochemical disease free rate superior to all other treatments including radical prostatectomy and any form of radiation[87] Cryosurgery has also been demonstrated to be superior to radical prostatectomy for recurrent cancer following radiation therapy.

    Hormonal therapy

    Hormonal therapy in prostate cancer. Diagram shows the different organs (purple text), hormones (black text and arrows), and treatments (red text and arrows) important in hormonal therapy.
    Hormonal therapy in prostate cancer. Diagram shows the different organs (purple text), hormones (black text and arrows), and treatments (red text and arrows) important in hormonal therapy.

    Hormonal therapy uses medications or surgery to block prostate cancer cells from getting dihydrotestosterone (DHT), a hormone produced in the prostate and required for the growth and spread of most prostate cancer cells. Blocking DHT often causes prostate cancer to stop growing and even shrink. However, hormonal therapy rarely cures prostate cancer because cancers which initially respond to hormonal therapy typically become resistant after one to two years. Hormonal therapy is therefore usually used when cancer has spread from the prostate. It may also be given to certain men undergoing radiation therapy or surgery to help prevent return of their cancer.[88]

    Hormonal therapy for prostate cancer targets the pathways the body uses to produce DHT. A feedback loop involving the testicles, the hypothalamus, and the pituitary, adrenal, and prostate glands controls the blood levels of DHT. First, low blood levels of DHT stimulate the hypothalamus to produce gonadotropin releasing hormone (GnRH). GnRH then stimulates the pituitary gland to produce luteinizing hormone (LH), and LH stimulates the testicles to produce testosterone. Finally, testosterone from the testicles and dehydroepiandrosterone from the adrenal glands stimulate the prostate to produce more DHT. Hormonal therapy can decrease levels of DHT by interrupting this pathway at any point.

    There are several forms of hormonal therapy:

    • Orchiectomy is surgery to remove the testicles. Because the testicles make most of the body's testosterone, after orchiectomy testosterone levels drop. Now the prostate not only lacks the testosterone stimulus to produce DHT, but also it does not have enough testosterone to transform into DHT.
    • Antiandrogens are medications such as flutamide, bicalutamide, nilutamide, and cyproterone acetate which directly block the actions of testosterone and DHT within prostate cancer cells.
    • Medications which block the production of adrenal androgens such as DHEA include ketoconazole and aminoglutethimide. Because the adrenal glands only make about 5% of the body's androgens, these medications are generally used only in combination with other methods that can block the 95% of androgens made by the testicles. These combined methods are called total androgen blockade (TAB). TAB can also be achieved using antiandrogens.
    • GnRH action can be interrupted in one of two ways. GnRH antagonists suppress the production of LH directly, while GnRH agonists suppress LH through the process of downregulation after an initial stimulation effect. Abarelix is an example of a GnRH antagonist, while the GnRH agonists include leuprolide, goserelin, triptorelin, and buserelin. Initially, GnRH agonists increase the production of LH. However, because the constant supply of the medication does not match the body's natural production rhythm, production of both LH and GnRH decreases after a few weeks.[89]

    The most successful hormonal treatments are orchiectomy and GnRH agonists. Despite their higher cost, GnRH agonists are often chosen over orchiectomy for cosmetic and emotional reasons. Eventually, total androgen blockade may prove to be better than orchiectomy or GnRH agonists used alone.

    Each treatment has disadvantages which limit its use in certain circumstances. Although orchiectomy is a low-risk surgery, the psychological impact of removing the testicles can be significant. The loss of testosterone also causes hot flashes, weight gain, loss of libido, enlargement of the breasts (gynecomastia), impotence and osteoporosis. GnRH agonists eventually cause the same side effects as orchiectomy but may cause worse symptoms at the beginning of treatment. When GnRH agonists are first used, testosterone surges can lead to increased bone pain from metastatic cancer, so antiandrogens or abarelix are often added to blunt these side effects. Estrogens are not commonly used because they increase the risk for cardiovascular disease and blood clots. The antiandrogens do not generally cause impotence and usually cause less loss of bone and muscle mass. Ketoconazole can cause liver damage with prolonged use, and aminoglutethimide can cause skin rashes.

    Palliative care

    Palliative care for advanced stage prostate cancer focuses on extending life and relieving the symptoms of metastatic disease. Chemotherapy may be offered to slow disease progression and postpone symptoms. The most commonly used regimen combines the chemotherapeutic drug docetaxel with a corticosteroid such as prednisone.[90] Bisphosphonates such as zoledronic acid have been shown to delay skeletal complications such as fractures or the need for radiation therapy in patients with hormone-refractory metastatic prostate cancer.[91]

    Bone pain due to metastatic disease is treated with opioid pain relievers such as morphine and oxycodone. External beam radiation therapy directed at bone metastases may provide pain relief. Injections of certain radioisotopes, such as strontium-89, phosphorus-32, or samarium-153, also target bone metastases and may help relieve pain.

    High Intensity Focused Ultrasound (HIFU)

    HIFU for prostate cancer utilizes high intensity focused ultrasound (HIFU) to ablate/destroy the tissue of the prostate. During the HIFU procedure, sound waves are used to heat the prostate tissue thus destroying the cancerous cells. Essentially, ultrasonic waves are precisely focused on specific areas of the prostate to eliminate the prostate cancer with minimal risks of effecting other tissue or organs. Temperatures at the focal point of the sound waves can exceed 100oC.[92] In lay terms, the HIFU technology is similar to using a magnifying glass to burn a piece of paper by focusing sunlight at a small precise point on the sheet. The ability to focus the ultrasonic waves leads to a relatively low occurrence of both incontinence and impotence. (0.6% and 0-20%, respectively)[93] According to international studies, when compared to other procedures, HIFU has a high success rate with a reduced risk of side effects. Studies using the Sonablate 500 HIFU machine have shown that 94% of patients with a pretreatment PSA (Prostate Specific Antigen) of less than 10 g/ml were cancer-free after three years.[94] However, many studies of HIFU were performed by manufacturers of HIFU devices, or members of manufacturers' advisory panels.[95]


    HIFU was first used in the 1940’s and 1950’s in efforts to destroy tumors in the central nervous system. Since then, HIFU has been shown to be effective at destroying malignant tissue in the brain, prostate, spleen, liver, kidney, breast, and bone.[96] Today, the HIFU procedure for prostate cancer is performed using a transrectal probe. This procedure has been performed for over ten years and is currently approved for use in Japan, Europe, Canada, and parts of Central and South America.

    Although not yet approved for use in the Unites States, many patients have received the HIFU procedure at facilities in Canada, and Central and South America. Currently, therapy is available using the Sonablate 500 or the Ablatherm. The Sonablate 500 is designed by Focus Surgery of Indianapolis, Indiana and is used in international HIFU centers around the world.

    Prognosis

    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 and dairy products.[97] 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.[98] In Japan, death from prostate cancer was one-fifth to one-half the rates in the United States and Europe in the 1990s.[99] In India in the 1990s, half of the people with prostate cancer confined to the prostate died within ten years.[100] African-American men have 50–60 times more prostate cancer and prostate cancer deaths than men in Shanghai, China.[101] In Nigeria, two percent of men develop prostate cancer and 64% of them are dead after two years.[102]

    In patients who 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.[103]

    Progression

    In 1941, Charles Huggins reported that androgen ablation therapy causes regression of primary and metastatic androgen-dependent prostate cancer.[104] However, it is now known that 80–90% of prostate cancer patients develop androgen-independent tumors 12–33 months after androgen ablation therapy, leading to a median overall survival of 23–37 months from the time of initiation of androgen ablation therapy.[105] The actual mechanism contributes to the progression of prostate cancer is not clear and may vary between individual patient. A few possible mechanisms have be proposed.[106] Scientists have established a few prostate cancer cell lines to investigate the mechanism involved in the progression of prostate cancer. LNCaP, PC-3, and DU-145 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.[107][108] 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. Androgens paradoxically inhibit the proliferation of these androgen-independent prostate cancer cells.[109][110][111] 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.[112][113] 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 polyphenols, 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.


    from wikipedia

    http://our-medical-center.blogspot.com/2007/12/prostate-cancer.html