Out of 100 men, 12 will get prostate cancer in their lifetime [PMID: 9332756]; however, it appears that there are factors involved that can reduce your risk over which you have control -- i.e. they are modifiable factors. As discussed in [PMID: 18559852] [Full Text], epidemiological evidence [PMID: 16278466], [PMID: 16425098] and migratory patterns [PMID: 2066247] [Full Text] suggest that lifestyle modifications can impact the progression of prostate cancer. Further confirmation has come from a June 2008 molecular study [PMID: 18559852] [Full Text] that found that after such interventions that gene expression of "protein metabolism and modification, intracellular protein traffic, and protein phosphorylation" had altered.
We point out some patient-oriented brochures that summarize steps that seem likely to affect the progression of prostate cancer.
Some prevention brochures are (from shortest to longest):
PCRI. 2 pages. March, 2005. This 2 page pamphlet from PCRI is a nice summary of those things that a healthy individual can do to reduce their risk for prostate cancer. Of the brochures listed here it packs quite a bit of key information into only two pages: http://www.prostate-cancer.org/resource/pdf/pamphlet.pdf. Less complete but even shorter is the one pager from the Cancer Research and Education Foundation
CCJM paper. This 2009 paper by Eric Klein in the Cleveland Clinic Journal of Medicine reviews the latest developments in prostate cancer screening and prevention.
CPHC. This link seems to have disappeared. Note to self: Remove this point if link does not come back. 20 pages. Nov, 2005. Canadian Prostate Health Council has a 20 page (but each page is quite short) patient-oriented pamphlet available online that focuses mostly on nutrition (low-fat diet, Vitamins E, D, C, A, selenium, zinc, soy and isoflavanoids, tomatos and cartotenids, green tea and polyphenols, cruciferous vegetables, allium vegetables) but also discusses lifestyle (stress reduction, exercise) and drugs (NSAIDs, 5AR inhibitors). It points out which ones have less evidence from research (zinc, lycopene). At 20 pages there is greater discussion than the prior brochure although PSA testing is not discussed.
PMH. 102 pages. Undated but appears to be 2007 or 2008. Challenging Prostate Cancer is written by a group from Princess Margaret Hospital covering urology, oncology, nutrition, physiology and psychology and their respective approaches to prostate cancer prevention. It is primarily intended for those who already have prostate cancer and so does not discuss PSA screening but is otherwise an excellent resource that can be used for healthy men as well. It is expanded from an earlier 22 page version called Prostate Cancer Nutrition and You that only covered nutrition.
WCRF/AICR. 500+ pages. 2007. Perhaps the most authoritative recent work on nutrition and cancer can be found in this freely downloadable WCRF/AICR report written by some of the world's top experts in cancer and nutrition. A summary with pointers to the report itself is available in our WCRF/AICR post.
More. Even more pamphlets can be found at The National Prostate Cancer Foundation .
PSA Cutoff Point. In the March 2008 Urology Times [article] Dr. Catalona (papers) discusses the advisability of having a biopsy if PSA > 2.5 ng/mL (rather than the older cutoff of 4.0 ng/mL) and at these lower levels a change in PSA (called PSA velocity) of > 0.3 ng/mL per year should also trigger a biospy. In this paper: [Full Text] [PMID: 19652036] Eric Klein (papers) of the Cleveland Clinic recommends biopsy to his patients if this risk calculator (or if that link does not work try [this]) assesses the risk of high grade prostate cancer to exceed 10%. (Note that the calculator gives both risk of prostate cancer and risk of high grade prostate cancer and the 10% threshold he uses applies to the high grade risk.) Note that according to a 2010 paper analyzing results from the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial [PMID 20950305] "prostate biopsy is not associated with excess mortality and fatal complications appear to be very rare".
Repeat Screening. At the 2008 American Urological Association (AUA) meeting, presenters pointed out that for PSA screening to be effective it must be done regularly. In a study of over 34,000 men the majority of prostate cancers and the majority of more serious cancers were only detected after multiple screening visits. See [link] or [link] for details.
PSA Many Years in Advance. PSA testing can be used not only for detection of prostate cancer but mounting evidence suggests that screening of men in their 40's can also potentially be used to predict the risk of developing prostate cancer many years later (see [PMID: 1892624] and [PMID: 18279502]). An increased level of PSA many years earlier is also associated with an increased risk of advanced prostate cancer. In a related result, a study by investigators from Sloan Kettering and Sweden found that patients who subsequently developed advanced prostate cancer had higher levels of PSA many years earlier relative to those who did not develop prostate cancer. [MedNews summary] [Full Text]. These results suggest that one should get more intensive subsequent screening the higher any PSA test is even if it is below thresholds used to diagnose prostate cancer. In addition to the foregoing reasons for having an initial PSA test in one's forties it also serves to establish a baseline so that later PSA test values can be calculated relative to it in the form of PSA velocity and doubling time. This is even more important if you have a risk factor for prostate cancer, namely a family member with prostate cancer or breast cancer.
Preparation. Based on recommendations by Stephen Strum (papers) published in: PCRI Insights AUGUST 2008 VOL 11: NO 3, when having your PSA tested you should try to use the same assay at the same lab and always get tested at the same time of day (morning or afternoon, say) and in the 48 hours prior to the test refrain from ejaculation and also avoid any examination of the prostate or athletic activity (such as bicycle riding) which exerts pressure on the prostate area. (There is some debate on the recommendation of avoiding prostatic examination and athletic activity.) These steps will reduce but not eliminate the random variation that occurs from one PSA test to the next. (A more comprehensive list of factors affecting PSA can be found in the Factors Affecting PSA section of PSA Screening and Early Detection Part 2 and the results of an experiment showing the natural vartiation of PSA is discussed here.)
AR5 Inhibitors. ASCO and AUA issued the following guidelines on AR5 inhibitors in February 2009:
The recommendation on AR5 inhibitors is based on the results of the large scale PCPT trial which has been following men taking the drug Finasteride (Proscar) has reported results. 18.4% of the men on finasteride vs. 24.4% of the controls developed prostate cancer -- a nearly 25% drop. (There was a greater number of advanced prostate cancer cases but that was thought to be due to the fact that it also makes prostate cancer easier to detect. See [Urosource]and [New York Times, June 15, 2008]. Finasteride is in a class of drug called 5AR inhibitors and it may be that all drugs in this class have this preventive effect. There is more on the mechanism by which it works in Testosterone Metabolism and Prostate Cancer. In the New York Times article Dr. Peter Scardino, chairman of the department of surgery at Memorial Sloan-Kettering Cancer Center is quoted as saying:"Finasteride has to be recognized as the first clearly demonstrated way to prevent prostate cancer with any medication or any oral agent at all." although in the same article Dr. Albertson, a prostate cancer specialist at the University of Connecticut says: "Finasteride might make a difference but only in a very small subset of men." Note that there may be adverse side effects.
More Information. There is further information on PSA screening in this 5 part post.
For cancer, in general, as opposed to just prostate cancer the WCRF/AICR have produced a 500+ page report, also cited above, which is the result of a 5 year study by a team of 21 world experts who commissioned 20 independent systematic literature reviews and provided judgements on the result. See this post or the AICR Guidelines for Cancer Prevention brochure which summarizes the WCRF/AICR guidelines into three groups (1) (plant-based) diet, (2) exercise (for 30 minutes a day) and (3) weight management. This is pictured in the diagram to right.
Also this six page brochure by Dr. Neal Barnard provides nutritional approaches to the prevention of cancer, in general: [link] .
A 2008 paper by Walz et al also found Free PSA to have prognostic value at lower PSA levels as well. [PMID: 18853417]. A calculator based on this paper http://nomogram.org intended only for situations where PSA is less than 2.5 inputs the DRE status (normal or suspicious) and Free PSA value and outputs the probability that a biopsy will find cancer.
PCA3. In addition a new genetic-based test, based on the PCA3 gene, available from these labs has greater specificity (i.e. its more likely to be negative when you don't have cancer) than the PSA test. Fig 9 of [this link] shows that the risk of cancer increases as the PCA3 score increases. [PMID: 18295257], [PMID: 18353398] and [PMID: 18801539] conclude, as well, that the higher the PCA3 score the greater the risk of (1) positive biopsy, (2) larger tumor volume and higher Gleason score and (3) extracapsular extension, respectively. General info on PCA3 can be found [here].
Ultrasound-based diagnostics. Ultrasound, color doppler ultrasound and power doppler ultrasound (in increasing order of ability to assess the risk of cancer) are other test methods that are used.
Diapat. A German company, Diapat, claims to have a urine test which is more accurate than the PSA test with a sensivitiy of 90% (i.e. of 100 patients with prostate cancer it would correctly identify 90) and a specificity of 60% (i.e. of 100 patients without prostate cancer it would correctly categorize 60). It is based on applying mass spectroscopy to the detection of various protein patterns that are present in the initial portion of a urine stream but absent in midstream. The underlying technology is claimed to be applicable not only to prostate cancer but also to cardiovascular disease, identifying 7 chronic renal diseases, early detection of diabetic renal failure, bladder cancer and is currently being further investigated for the possibility of using it as a diagnostic for Alzheimer's disease, pancreatic cancer, renal cancer and heart failure. See the Diapat web page, this company video, this [2008 paper - Abstract] [Full Text] and this [list of references].
Genetic Tests. Several companies are now offering prostate cancer genetic testing. Proactive Genomics offers the $300 Focus5 (TM) genetic test based on [PMID: 18199855] and deCODE diagnostics offers the ProCa(TM) genetic test for prostate cancer for $500 direct to the patient based on [PMID: 18264098]. [References: eyeondna, Medscape]. California and New York are demanding that direct-to-patient genetic testing companies show that tests ordered by their states' residents have been ordered by physicians; however, one genetic testing company has countered by pointing out that they process the information and do not do any testing themselves (its done in approved labs) so that their activities fall outside the scope of any state regulation. Wired article of June, 2008.
Ultimately if the risk is assessed to be sufficiently high a biopsy is performed.
We point out some patient-oriented brochures that summarize steps that seem likely to affect the progression of prostate cancer.
Brochures
The strategies intended for existing prostate cancer patients and and healthy men are basically the same (possibly because many prevention strategies act by slowing progression of subclinical disease rather than truly preventing it) so one can, in general, interchangably use brochures for either with the exception that brochures for healthy men may also have information on screening. To complement those that do not discuss screening see our page on PSA Screening and Early Detection which lists various guides and is followed by 4 additional parts with more information.Some prevention brochures are (from shortest to longest):
PCRI. 2 pages. March, 2005. This 2 page pamphlet from PCRI is a nice summary of those things that a healthy individual can do to reduce their risk for prostate cancer. Of the brochures listed here it packs quite a bit of key information into only two pages: http://www.prostate-cancer.org/resource/pdf/pamphlet.pdf. Less complete but even shorter is the one pager from the Cancer Research and Education Foundation
CCJM paper. This 2009 paper by Eric Klein in the Cleveland Clinic Journal of Medicine reviews the latest developments in prostate cancer screening and prevention.
CPHC. This link seems to have disappeared. Note to self: Remove this point if link does not come back. 20 pages. Nov, 2005. Canadian Prostate Health Council has a 20 page (but each page is quite short) patient-oriented pamphlet available online that focuses mostly on nutrition (low-fat diet, Vitamins E, D, C, A, selenium, zinc, soy and isoflavanoids, tomatos and cartotenids, green tea and polyphenols, cruciferous vegetables, allium vegetables) but also discusses lifestyle (stress reduction, exercise) and drugs (NSAIDs, 5AR inhibitors). It points out which ones have less evidence from research (zinc, lycopene). At 20 pages there is greater discussion than the prior brochure although PSA testing is not discussed.
PMH. 102 pages. Undated but appears to be 2007 or 2008. Challenging Prostate Cancer is written by a group from Princess Margaret Hospital covering urology, oncology, nutrition, physiology and psychology and their respective approaches to prostate cancer prevention. It is primarily intended for those who already have prostate cancer and so does not discuss PSA screening but is otherwise an excellent resource that can be used for healthy men as well. It is expanded from an earlier 22 page version called Prostate Cancer Nutrition and You that only covered nutrition.
WCRF/AICR. 500+ pages. 2007. Perhaps the most authoritative recent work on nutrition and cancer can be found in this freely downloadable WCRF/AICR report written by some of the world's top experts in cancer and nutrition. A summary with pointers to the report itself is available in our WCRF/AICR post.
More. Even more pamphlets can be found at The National Prostate Cancer Foundation .
PSA Screening
Why and Risks. Although the following facts are debated: (1) most studies show that mortality from prostate cancer is lower in areas with PSA testing. For example, US states with more urologists and greater PSA testing tend to have lower mortality from prostate cancer than other states and such difference is statistically significant. [PMID: 18268527]. Also, Tyrol, Austria, had intensive PSA screening while the rest of the country did not. After the introduction of such testing Tyrol experienced a drop in prostate cancer deaths relative to the rest of the country and the timing of the drop in the death rate was consistent with the PSA introduction. Tyrol also witnessed a stage migration to earlier stages of prostate cancer eliminating most cases of advanced cancer. (See [PMID: 18321314] and slide 38 of this powerpoint presentation). (2) it seems logical that if prostate cancer is found earlier that better outcomes can be expected since it is less likely to have spread beyond the capsule and at this localized stage it can be more easily treated. The study [summarized here] found precisely that -- those who had PSA testing prior to developing prostate cancer had a lower chance of it spreading. Unfortunately, it can be difficult to distinguish between indolent cases which will never be a threat to the patient and aggressive disease which will. Thus, the risk of not being tested is that the disease will not be caught at an earlier stage when more easily treatable while the risk of testing is that unnecessary treatment might occur. A 2009 review of prostate cancer screening and prevention by Eric Klein (papers) of the Cleveland Clinic is available here: [Full Text] [PMID: 19652036]. In a 2011 study of 160 men in Brazil the beliefs in [table 3] were given regarding prostate cancer testing and the reasons in [table 4] were given for not getting tested.PSA Cutoff Point. In the March 2008 Urology Times [article] Dr. Catalona (papers) discusses the advisability of having a biopsy if PSA > 2.5 ng/mL (rather than the older cutoff of 4.0 ng/mL) and at these lower levels a change in PSA (called PSA velocity) of > 0.3 ng/mL per year should also trigger a biospy. In this paper: [Full Text] [PMID: 19652036] Eric Klein (papers) of the Cleveland Clinic recommends biopsy to his patients if this risk calculator (or if that link does not work try [this]) assesses the risk of high grade prostate cancer to exceed 10%. (Note that the calculator gives both risk of prostate cancer and risk of high grade prostate cancer and the 10% threshold he uses applies to the high grade risk.) Note that according to a 2010 paper analyzing results from the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial [PMID 20950305] "prostate biopsy is not associated with excess mortality and fatal complications appear to be very rare".
Repeat Screening. At the 2008 American Urological Association (AUA) meeting, presenters pointed out that for PSA screening to be effective it must be done regularly. In a study of over 34,000 men the majority of prostate cancers and the majority of more serious cancers were only detected after multiple screening visits. See [link] or [link] for details.
PSA Many Years in Advance. PSA testing can be used not only for detection of prostate cancer but mounting evidence suggests that screening of men in their 40's can also potentially be used to predict the risk of developing prostate cancer many years later (see [PMID: 1892624] and [PMID: 18279502]). An increased level of PSA many years earlier is also associated with an increased risk of advanced prostate cancer. In a related result, a study by investigators from Sloan Kettering and Sweden found that patients who subsequently developed advanced prostate cancer had higher levels of PSA many years earlier relative to those who did not develop prostate cancer. [MedNews summary] [Full Text]. These results suggest that one should get more intensive subsequent screening the higher any PSA test is even if it is below thresholds used to diagnose prostate cancer. In addition to the foregoing reasons for having an initial PSA test in one's forties it also serves to establish a baseline so that later PSA test values can be calculated relative to it in the form of PSA velocity and doubling time. This is even more important if you have a risk factor for prostate cancer, namely a family member with prostate cancer or breast cancer.
Preparation. Based on recommendations by Stephen Strum (papers) published in: PCRI Insights AUGUST 2008 VOL 11: NO 3, when having your PSA tested you should try to use the same assay at the same lab and always get tested at the same time of day (morning or afternoon, say) and in the 48 hours prior to the test refrain from ejaculation and also avoid any examination of the prostate or athletic activity (such as bicycle riding) which exerts pressure on the prostate area. (There is some debate on the recommendation of avoiding prostatic examination and athletic activity.) These steps will reduce but not eliminate the random variation that occurs from one PSA test to the next. (A more comprehensive list of factors affecting PSA can be found in the Factors Affecting PSA section of PSA Screening and Early Detection Part 2 and the results of an experiment showing the natural vartiation of PSA is discussed here.)
AR5 Inhibitors. ASCO and AUA issued the following guidelines on AR5 inhibitors in February 2009:
- Men who have a PSA with a score of 3.0 or below who already get yearly PSA tests, or expect to get a yearly PSA test, and show no signs of prostate cancer may benefit from talking with their doctor about the risks and benefits of a 5-ARI, such as finasteride, for the prevention of prostate cancer. The advantages are a lower risk of prostate cancer and improvement in urinary problems (if present), and the reduction of future urinary problems. The potential risks include the possibility of developing high-grade prostate cancer and/or a chance of short-term (one to two years) sexual problems.
- Men who are already taking a 5-ARI to treat urinary problems may also benefit from talking with their doctors about using this drug for the prevention of prostate cancer, understanding that the improvement in urinary symptoms should be weighed against the potential risks of developing high-grade prostate cancer.
The recommendation on AR5 inhibitors is based on the results of the large scale PCPT trial which has been following men taking the drug Finasteride (Proscar) has reported results. 18.4% of the men on finasteride vs. 24.4% of the controls developed prostate cancer -- a nearly 25% drop. (There was a greater number of advanced prostate cancer cases but that was thought to be due to the fact that it also makes prostate cancer easier to detect. See [Urosource]and [New York Times, June 15, 2008]. Finasteride is in a class of drug called 5AR inhibitors and it may be that all drugs in this class have this preventive effect. There is more on the mechanism by which it works in Testosterone Metabolism and Prostate Cancer. In the New York Times article Dr. Peter Scardino, chairman of the department of surgery at Memorial Sloan-Kettering Cancer Center is quoted as saying:"Finasteride has to be recognized as the first clearly demonstrated way to prevent prostate cancer with any medication or any oral agent at all." although in the same article Dr. Albertson, a prostate cancer specialist at the University of Connecticut says: "Finasteride might make a difference but only in a very small subset of men." Note that there may be adverse side effects.
More Information. There is further information on PSA screening in this 5 part post.
Recent
Exercise
In a 2005 review of the data from 50,000 men in the Health Professionals study, Harvard researchers found that those with the highest level of physical activity had only one third of the rate of advanced prostate cancer relative to those at the lowest level of physical activity (after adjusting for risk factors such as BMI, etc.). Also those at the highest physical activity level had only 26% the rate of fatal prostate cancer relative to those at the lowest level. The benefit only applied to those at the highest level of physical activity. Also the overall overall prostate cancer rates were not reduced but it did reduce advanced and fatal rates. See [PMID: 15883238] [Full Text].Statins
A Finnish study published November 2007 involving 24,723 case control pairs conducted over the 1995-2002 time frame found that statins, but not other cholesterol lowering drugs, lowered the risk of advanced prostate cancer, but did not lower the risk of prostate cancer overall. The odds ratio of developing advanced cancer for torvastatin, lovastatin, and simvastatin was 0.61, 0.61 and 0.78, respectively. [PMID: 18006910]Cancer (Not Specific to Prostate)
For cancer, in general, as opposed to just prostate cancer the WCRF/AICR have produced a 500+ page report, also cited above, which is the result of a 5 year study by a team of 21 world experts who commissioned 20 independent systematic literature reviews and provided judgements on the result. See this post or the AICR Guidelines for Cancer Prevention brochure which summarizes the WCRF/AICR guidelines into three groups (1) (plant-based) diet, (2) exercise (for 30 minutes a day) and (3) weight management. This is pictured in the diagram to right.Also this six page brochure by Dr. Neal Barnard provides nutritional approaches to the prevention of cancer, in general: [link] .
If PSA is Elevated
If PSA is elevated (the cutoff was once considered to be 4.0 but is now considered to be 2.5 by many as discussed previously on this page) or PSA velocity, i.e. increase in PSA, is high (greater than 0.75 ng/ml per year although some feel that the cutoff should be lowered to 0.3 as discussed previously on this page) or if PSA doubling time, i.e. amount of time it takes PSA to double, is less than 10 years it is important to eliminate the possibility that it was caused by nonmalignant conditions (see Factors affecting PSA section of indicated link for non-cancer factors that can raise PSA). Usually Cipro or other antibiotic is prescribed and then a retest is taken.Other Diagnostic Tests
Free PSA. A Free PSA Test (described in the Free PSA section of this page) is less sensitive to inflammation and is often also given on the retest of an ordinary PSA test if the PSA is in the 4-10 range.A 2008 paper by Walz et al also found Free PSA to have prognostic value at lower PSA levels as well. [PMID: 18853417]. A calculator based on this paper http://nomogram.org intended only for situations where PSA is less than 2.5 inputs the DRE status (normal or suspicious) and Free PSA value and outputs the probability that a biopsy will find cancer.
PCA3. In addition a new genetic-based test, based on the PCA3 gene, available from these labs has greater specificity (i.e. its more likely to be negative when you don't have cancer) than the PSA test. Fig 9 of [this link] shows that the risk of cancer increases as the PCA3 score increases. [PMID: 18295257], [PMID: 18353398] and [PMID: 18801539] conclude, as well, that the higher the PCA3 score the greater the risk of (1) positive biopsy, (2) larger tumor volume and higher Gleason score and (3) extracapsular extension, respectively. General info on PCA3 can be found [here].
Ultrasound-based diagnostics. Ultrasound, color doppler ultrasound and power doppler ultrasound (in increasing order of ability to assess the risk of cancer) are other test methods that are used.
Diapat. A German company, Diapat, claims to have a urine test which is more accurate than the PSA test with a sensivitiy of 90% (i.e. of 100 patients with prostate cancer it would correctly identify 90) and a specificity of 60% (i.e. of 100 patients without prostate cancer it would correctly categorize 60). It is based on applying mass spectroscopy to the detection of various protein patterns that are present in the initial portion of a urine stream but absent in midstream. The underlying technology is claimed to be applicable not only to prostate cancer but also to cardiovascular disease, identifying 7 chronic renal diseases, early detection of diabetic renal failure, bladder cancer and is currently being further investigated for the possibility of using it as a diagnostic for Alzheimer's disease, pancreatic cancer, renal cancer and heart failure. See the Diapat web page, this company video, this [2008 paper - Abstract] [Full Text] and this [list of references].
Genetic Tests. Several companies are now offering prostate cancer genetic testing. Proactive Genomics offers the $300 Focus5 (TM) genetic test based on [PMID: 18199855] and deCODE diagnostics offers the ProCa(TM) genetic test for prostate cancer for $500 direct to the patient based on [PMID: 18264098]. [References: eyeondna, Medscape]. California and New York are demanding that direct-to-patient genetic testing companies show that tests ordered by their states' residents have been ordered by physicians; however, one genetic testing company has countered by pointing out that they process the information and do not do any testing themselves (its done in approved labs) so that their activities fall outside the scope of any state regulation. Wired article of June, 2008.
Ultimately if the risk is assessed to be sufficiently high a biopsy is performed.
No comments:
Post a Comment