This is the 5th year of publishing the Palpable Prostate!
Dec 26, 2011. We added to Bradford Hill Criteria of Causation (referring to bias in the medical literature): As another example this abstract [PMID: 22089952] discusses a high relative risk for rectal cancer after radiation treatment for prostate cancer but fails to give the fact that the absolute risk if very low (1% after 10 years of follow up based on a summary of the paper by Alan Brett published in Journal Watch General Medicine December 22, 2011). Evidently the authors belong to a department of surgery. Imagine how the same data might have led to different presentation and conclusions had the authors been radiation oncologists.
Dec 15, 2011. In USPSTF Draft Report we added: the "mammography controversy attracted congressional attention from legislators responding to constituents’ outrage and demanding greater transparency in the USPSTF decision making process. [Wall Street Journal Blog May 21, 2010]
We also added: The American Cancer Society is also moving to a system of generating guidelines that exclude specialists in the area from voting to eliminate conflict of interest (although input from them will be sought). See [WSJ Blog Dec 14, 2011] [PC Infolink blog Dec 16, 2011], JAMA article: [PMID: 22166609], Institute of Medicine [Clinical Practice Guidelines We Can Trust] and Institute of Medicine [Finding What Works in Health Care Standards].
Dec 12, 2011. In Biochemical PSA Recurrence we added: Well done, grilled or barbequed red meat may be harmful. A 2011 study of 470 cases and 512 controls found that "Higher consumption of any ground beef or processed meats were positively associated with aggressive prostate cancer, with ground beef showing the strongest association (OR?=?2.30, 95% CI:1.39-3.81; P-trend?=?0.002). This association primarily reflected intake of grilled or barbequed meat, with more well-done meat conferring a higher risk of aggressive prostate cancer. Comparing high and low consumptions of well/very well cooked ground beef to no consumption gave OR's of 2.04 (95% CI:1.41-2.96) and 1.51 (95% CI:1.06-2.14), respectively. In contrast, consumption of rare/medium cooked ground beef was not associated with aggressive prostate cancer." See [PMID: 22132129]
Dec 3, 2011. In USPSTF Draft Report we added: Further suspicion that the report is being commissioned to justify government health care rationing has been aroused by (1) the fact that the draft report was supposed to be issued for public comment but according to the same New York Times article the task force is not making the comments public indicating that "public comment" was intended to only mean "public input" and (2) according to the [boxed information on the USPSTF site] the USPSTF "lost" some of the public comments through a technical glitch.
Dec 1, 2011. In Biochemical PSA Recurrence we added: A study of "127,236 men of up to 75 years of age for whom relevant information was available in the SEER database, all of whom were treated by radical prostatectomy between 1988 and 2003" is summarized in this [PC Infolink] blog post and the abstract is available at [PMID: 22114813]. The annual hazard (roughly the probability of death in the following year given one is alive at the beginning of the year) was found to be 0.4%, 0.7% and 1% for 5, 10 and 15 years post radical prostatectomy with refined estimates based on risk groups as described in these links. Note that the hazard increases over this time span in contrast to other cancers where it typically decreases.
Saturday, December 31, 2011
Saturday, November 26, 2011
Blog Updates for November 2011
Nov 24, 2011. In USPSTF Draft Report so many additions and changes were made that rather than itemizing each one we ask interested readers to simply review the entire post again.
Nov 23, 2011. In Biochemical PSA Recurrence we added: Coffee. Based on a prospective analysis of 47,911 men in the Health Professionals Follow-up Study who reported intake of regular and decaffeinated coffee in 1986 and every 4 years thereafter researchers found that those who consumed coffee had a lower risk of prostate cancer and a much lower risk of lethal prostate cancer. This study was focused on first time cancer rather than recurrence although its commonly thought that the same factors affect both. Note that this is only an observational study and so is less persuasive than a randomized study with controls; nevertheless, there are a number of supporting aspects to the portion regarding the risk of prostate cancer: There was a dose-response effect for risk of prostate cancer, i.e. the more coffee that was consumed the lower the risk. The risk reduction for 3 cups or less, 4-5 cups and 6+ cups per day was 6%, 7% and 18% (fully adjusted for other risk factors). Also reductions in risk have been found for many other cancers strengthenng the conclusion, e.g. see this metanalysis of several cancers and coffee: [PMID: 21406107]. For lethal prostate cancer the risk reduction was 19%, 14% and 60% reduction for the same categories. Although the risk reduction in fatal prostate cancer was large for the heaviest coffee drinkers, there were only 12 subjects in that category (i.e. small number of observations) and strictly increasing response with dosage was not observed. See [PMID: 21586702] [Full Text] [table 2] [NY Times] [Environmental News Network]. The last link reviews the pros and cons of various levels of coffee consumption including not only prostate cancer but other diseases.
Nov 17, 2011. We added to Bradford Hill Criteria of Causation (referring to the criterion of Temporality): Nobel Prize winning biochemist Otto Warburg noted that cancer cells generate energy using glycolysis whereas normal cells use oxidative phosphorylation and it had been hypothesized that this was an adaptive response to the oxygen deprived conditions in the tumor; however, evidence since then has determined that glycolysis emerges prior to the tumor's exposure to hypoxic conditions so the adaptation hypothesis must be rejected and we must look elsewhere for an explanation. A new theory has since emerged that adpating to the uptake of nutrients rather than to energy production is the driving force. [PMID: 19460998 [Full Text] This theory is currently supported by complex computer models which show that glycolysis is implied by enzyme constraints whereas it fails to emerge in the absence of those constraints. [PMID: 21423717]
Nov 10, 2011. In Biochemical PSA Recurrence we added: One caution is that PSA doubling times from ultrasensitive assays can be substantially different from ordinary assays. For example, in [PMID: 22014796] the authors found that "Ultrasensitive prostate specific antigen doubling time was more or less rapid than traditional prostate specific antigen doubling time by more than 15 months in 244 (62%) and 35 (9%) patients, respectively." and they therefore conclude that: "Agreement between prostate specific antigen doubling time calculated using ultrasensitive vs traditional prostate specific antigen values is poor. Ultrasensitive prostate specific antigen doubling time is often significantly more rapid than traditional prostate specific antigen doubling time, potentially overestimating the risk of clinical recurrence. Until the significance of ultrasensitive prostate specific antigen doubling time is better characterized, the decision to proceed with salvage therapy should not be based on prostate specific antigen doubling time calculated using ultrasensitive prostate specific antigen values."
Nov 7, 2011. In Choosing a Surgeon - Part 2. Finding a Surgeon we added: Teaching Hospitals and High Caseload Hospitals. Patients at teaching hospitals had few complications after surgery, fewer transfusions and shorter hospital stays. Hospitals with heavy caseloads also had better results.[PMID: 21944081].
Nov 6, 2011. Patient information regarding the treatment of advanced prostate cancer can be found on here [Uptodate on Advanced Prostate Cancer] and in the references at its end most of which are also online.
Nov 23, 2011. In Biochemical PSA Recurrence we added: Coffee. Based on a prospective analysis of 47,911 men in the Health Professionals Follow-up Study who reported intake of regular and decaffeinated coffee in 1986 and every 4 years thereafter researchers found that those who consumed coffee had a lower risk of prostate cancer and a much lower risk of lethal prostate cancer. This study was focused on first time cancer rather than recurrence although its commonly thought that the same factors affect both. Note that this is only an observational study and so is less persuasive than a randomized study with controls; nevertheless, there are a number of supporting aspects to the portion regarding the risk of prostate cancer: There was a dose-response effect for risk of prostate cancer, i.e. the more coffee that was consumed the lower the risk. The risk reduction for 3 cups or less, 4-5 cups and 6+ cups per day was 6%, 7% and 18% (fully adjusted for other risk factors). Also reductions in risk have been found for many other cancers strengthenng the conclusion, e.g. see this metanalysis of several cancers and coffee: [PMID: 21406107]. For lethal prostate cancer the risk reduction was 19%, 14% and 60% reduction for the same categories. Although the risk reduction in fatal prostate cancer was large for the heaviest coffee drinkers, there were only 12 subjects in that category (i.e. small number of observations) and strictly increasing response with dosage was not observed. See [PMID: 21586702] [Full Text] [table 2] [NY Times] [Environmental News Network]. The last link reviews the pros and cons of various levels of coffee consumption including not only prostate cancer but other diseases.
Nov 17, 2011. We added to Bradford Hill Criteria of Causation (referring to the criterion of Temporality): Nobel Prize winning biochemist Otto Warburg noted that cancer cells generate energy using glycolysis whereas normal cells use oxidative phosphorylation and it had been hypothesized that this was an adaptive response to the oxygen deprived conditions in the tumor; however, evidence since then has determined that glycolysis emerges prior to the tumor's exposure to hypoxic conditions so the adaptation hypothesis must be rejected and we must look elsewhere for an explanation. A new theory has since emerged that adpating to the uptake of nutrients rather than to energy production is the driving force. [PMID: 19460998 [Full Text] This theory is currently supported by complex computer models which show that glycolysis is implied by enzyme constraints whereas it fails to emerge in the absence of those constraints. [PMID: 21423717]
Nov 10, 2011. In Biochemical PSA Recurrence we added: One caution is that PSA doubling times from ultrasensitive assays can be substantially different from ordinary assays. For example, in [PMID: 22014796] the authors found that "Ultrasensitive prostate specific antigen doubling time was more or less rapid than traditional prostate specific antigen doubling time by more than 15 months in 244 (62%) and 35 (9%) patients, respectively." and they therefore conclude that: "Agreement between prostate specific antigen doubling time calculated using ultrasensitive vs traditional prostate specific antigen values is poor. Ultrasensitive prostate specific antigen doubling time is often significantly more rapid than traditional prostate specific antigen doubling time, potentially overestimating the risk of clinical recurrence. Until the significance of ultrasensitive prostate specific antigen doubling time is better characterized, the decision to proceed with salvage therapy should not be based on prostate specific antigen doubling time calculated using ultrasensitive prostate specific antigen values."
Nov 7, 2011. In Choosing a Surgeon - Part 2. Finding a Surgeon we added: Teaching Hospitals and High Caseload Hospitals. Patients at teaching hospitals had few complications after surgery, fewer transfusions and shorter hospital stays. Hospitals with heavy caseloads also had better results.[PMID: 21944081].
Nov 6, 2011. Patient information regarding the treatment of advanced prostate cancer can be found on here [Uptodate on Advanced Prostate Cancer] and in the references at its end most of which are also online.
Sunday, October 30, 2011
USPSTF Draft Report
[Updated January 28, 2012]
The US Preventive Service Task Force (USPSTF) has produced a draft recommendation on PSA screening available [here] based on the evidence presented [here] and [PMID: 22171385]. The USPSTF's gave PSA testing a grade of D which means that it recommends against PSA screening and discourages the use of it in practice. Note that this only refers to using the PSA test on healthy men with no suspicion of disease and does not refer to the use of PSA testing in other scenarios.
New Jersey has since passed legislation opposing the USPSTF recommendation (see [news]) and Kathleen Sebelius, Secretary of Health and Human Services, has issued [this letter] (from PC Infolink site) indicating that the US government does "not intend to eliminate coverage of this screening test under Medicare at this time" although that leaves open what future actions they might take.
Criticisms Of the USPSTF report included:
The US Preventive Service Task Force (USPSTF) has produced a draft recommendation on PSA screening available [here] based on the evidence presented [here] and [PMID: 22171385]. The USPSTF's gave PSA testing a grade of D which means that it recommends against PSA screening and discourages the use of it in practice. Note that this only refers to using the PSA test on healthy men with no suspicion of disease and does not refer to the use of PSA testing in other scenarios.
New Jersey has since passed legislation opposing the USPSTF recommendation (see [news]) and Kathleen Sebelius, Secretary of Health and Human Services, has issued [this letter] (from PC Infolink site) indicating that the US government does "not intend to eliminate coverage of this screening test under Medicare at this time" although that leaves open what future actions they might take.
Pro USPSTF (i.e. arguments against screening)
The report and other evidence supporting it includes:- Minimal Benefit/High NNT. Although there were benefits shown from PSA screening the absolute level of these benefits was low (absolute mortality advantage of less than 1 percentage point) and the number needed to treat (NNT) to save one life was high (48 men) according to [PMID: 19297566] [Full Text]
- Significant Overdiagnosis and Overtreatment. Jemal et al [PMID: 19474385] [Full Text] present statistics that one in six men is diagnosed with prostate cancer whereas only one in 34 die of prostate cancer suggesting a large amount of overdiagnosis and treatment. Another 2009 study indicated that 1.3 million additional men had been diagnosed with prostate cancer since 1986 and 1 million of those had been treated. Even if one assumes that the significant reduction in prostate cancer deaths in the nineties was all due to screening (as opposed to other improved methods) the authors show that more than 20 men must be diagnosd with prostate cancer to save one life and this suggests a large degree of overdiagnosis and treatment. See [PMID: 19720969]. The magnitude of the problem is enormous when one considers that in 2007 there were 2.2 million Americans alive who had been diagnosed with prostate cancer according to SEER statistics referenced in [PMID: 21925305].
- Significant Harms. "Radiotherapy and surgery result in adverse effects, including urinary incontinence and erectile dysfunction in at least 200 to 300 of 1,000 men treated with these therapies. Radiotherapy is also associated with bowel dysfunction." [USPSTF draft report] and [PMID: 21984740] [Full Text] Since screening leads to significant overtreatment (as per last point) screening leads to harming men who never needed the treatment in the first place.
- Independent. Regarding criticism that there were no urologists, radiologists or medical oncologists on the USPSTF task force (see AUA Foundation Dec 1, 2011 press release and task force composition here) it has been suggested that it was necessary to have "independent scientists who are better able to objectively evaluate the literature without bias" [link] and to combat the harm that urological practice may be doing to the population by not adequately disclosing that the PSA test can lead to unnecessary treatment. Also see [PC Infolink post] for additional articulation of this viewpoint. The American Cancer Society is also moving to a system of generating guidelines that exclude specialists in the area from voting to eliminate conflict of interest (although input from them will be sought). See [WSJ Blog Dec 14, 2011] [PC Infolink blog Dec 16, 2011], JAMA article: [PMID: 22166609], Institute of Medicine [Clinical Practice Guidelines We Can Trust] and Institute of Medicine [Finding What Works in Health Care Standards].
- Excessive Cost. USPSTF did not consider cost but if they did that then it is estimated that it would cost $5 million per life saved and that amount of money could save more than a single life if redirected in other ways. Allan S. Brett and Richard J. Ablin (the developer of the PSA test) [PMID: 22029759] [Full Text]
- Other government organizations. Other government organizations have also concluded that the value of PSA screening is inconclusive such as in the [UK] or outright recommended against it such as Australia and [Ontario, Canada] where PSA screening is not reimbursed.
- Inflammatory Language. It has been argued that the screening debate is unreasonably emotionally charged due to the labeling of both lethal and non-lethal forms of prostate cancer with the word "cancer" and that it would be better to have language which clearly distinguishes the two. See [NY Times].
Con USPSTF (i.e. arguments in favor of screening)
In contrast to government organizations, doctor and patient groups widely support PSA screening and have been vocal in criticizing the report. The American Urological Association (AUA) which is the primary body representing urologists wrote: "The AUA stronly opposes this position" [press release] (referring to USPSTF's grade D) and recommending its own AUA Practice Statement instead. John Hopkins University James Buchanan Brady Urological Institute stated that (referring to the USPSTF draft report) "this decision sets the clock back to before the 1990s, when “healthy” men were diagnosed with cancer that was palpable and often, too late to cure. Is this about progress, or saving money?" See [link]. A coalition of 10 prostate cancer patient groups, the Prostate Cancer Roundtable, was also critical [formal letter] [media release] as was Michael Miliken's Prostate Cancer Foundation (PCF) [PCF's USPSTF page].Criticisms Of the USPSTF report included:
- Deaths Declining. Since the 1991-1994 time period when deaths from Prostate Cancer in the US peaked at an annual rate of 39 deaths per 100,000 men the rate has declined to approximately 24 deaths per 100,000 men [statistics cited by National Cancer Institute]. This time period correlates well with the introduction of PSA screening.
- Studies too short. Prostate cancer is a slow growing disease. The benefit is increasing over time and as the studies progress it appears that the trends show an increasing benefit. The eventual benefit to screening is expected to be much higher than that shown so far. In particular the "use of only a 10-year time frame is a significant flaw with their analysis. Urologists and oncologists know that prostate cancer is a slow-growing cancer and one that thankfully responds to hormonal manipulations. Looking at only 10 years’ worth of data completely ignores the fact that the real benefit to screening would be seen in the second 10-year span, when the cancer becomes hormone-resistant and more deadly. Goldstein comment
- Important Information Omitted. the USPSTF did not consider all the information. See Catalona Comments and Martin Goldstein Comment for a list of pertinent facts that were not considered. The latter noted, in particular, the exclusion of [PMID: 20598634] [Full Text] which was published in July 2010 and showed a 44% decrease in the death rate over 14 years.
- Morbidity Ignored. "The panel makes virtually no mention of prostate cancer morbidity (sickness from the disease, including urinary obstruction and extraordinarily debilitating bone pain from cancer spreading to pelvis, ribs, back, and legs)." (See [link]) Metastatic disease, and not just death, should have been considered but were not. Fritz H. Schröder [PMID: 22029756] [Full Text]. "Murray Feldstein, MD, from Phoenix, Arizona commented to The Annals of Internal Medicine following the USPSTF recommendations, “As an elderly urologist who spent nearly half of his career in the pre-PSA era, I can personally attest to another and perhaps even more important factor that is being overlooked—suffering from advanced prostate cancer. No longer do I see patients with bulky cancer who bleed and obstruct their urinary tracts.” He pointed out that painful prostate cancer that had spread to bones was now rare, a situation undoubtedly attributable to the widespread use of PSA screenings." (Quoted in [link])
- Flawed PLCO Analysis. The USPSTF concluded that the PLCO trial showed no benefit but a re-analysis of that trial by comorbidity strata concluded that that data actually shows that "Selective use of PSA screening for men in good health appears to reduce the risk of PCSM with minimal overtreatment." [PMID: 21041707]
- Flawed ESPRC Analysis. A re-analysis of the ESRPC trial in [PMID: 20956725] showed that that trial underestimated the benefit by "(i) including in the 20% the years before the impact of the first screen becomes manifest, and (ii) not having full information for the follow-up years where the effects of the screening are most apparent."
- Flawed Handling of Low Quality Studies. The USPSTF relied on a meta-analysis which equally weighted 5 randomized controlled studies but the studies varied in quality and they ought to have down weighted or excluded the poorer quality studies. "This would be akin to using two fresh and three spoiled bananas to create a smoothie, then concluding that bananas should no longer be used in smoothies because the resultant mixture tastes bad."
Catalona Press Release and Fritz H. Schröder [PMID: 22029756] [Full Text]. - Final Assessment Wrong. Even without debating the merits of the USPSTF's report in other ways it has been suggested that they should have at least rated PSA testing as C rather than D since they did find evidence of benefit from PSA testing and they have no right to make a decision which implies that a certain number of deaths is acceptable. A grade of C would have put more of the onus on patients to make the decision whereas D is too strong as it seemingly imposes the USPSTF's value judgement on patients. Mary F. McNaughton-Collins and Michael J. Barry [PMID: 22029758] [Full Text]
- No Adjustment for Contamination. Intention-to-treat statistics should have been supplemented with statistics adjusting for contamination as such statistics show a large benefit to PSA screening. (Contamination refers mainly to the situation where subjects in the control group are actually screened. Adjusting for contamination means comparing those who were actually screened to those who were not screened as opposed to comparing those who originally intended to be screened vs. those who originally intended not to be screened. Using Intention to Treat is well established but both set of statistics should have been shown.) Fritz H. Schröder [PMID: 22029756] [Full Text].
- No Real Experts on Panel. There were no urologists, radiologists or medical oncologists on the USPSTF task force. See composition of task force here: here. Because they had no experts in prostate cancer they have been accused of just manipulating the numbers without understanding their meaning or implication. In particular the biological process prostate cancer goes through is a symptomless phase (sometimes referred to as the curability window). If it is not caught at that time then it will not be curable. Given the significant death rate due to prostate cancer its important to catch it when its most addressable. The fact that the USPSTF conclusions seem to violate biological plausibility would appear to contravene the well known Bradford Hill Criteria which are commonly used to assess studies.
- Conclusions Not Based on Practice. The USPSTF misjudged the effectiveness of PSA testing by not considering how it is used in practice. In particular, higher Gleason scores (discovered on biopsy after a PSA test) and fast rising PSA after excluding infection are both reliable indicators that treatment is needed.
- Many Men Live to their Nineties. It has been suggested that even if one rejects the report that it should still apply to older men but men age 75 have a 50% chance of living past 90 so its not appropriate to exclude those men from screening. See Dr. Charles Myers video
- Screening Has Saved Lives. Two independently produced statistical models suggest that its plausible that 45% and 70% of the decline in prostate cancer mortality during the 1990s was due to screening. See [PMID: 18027095] [Full text] so its effect has saved many lives.
- Would Deprive Patients of Useful Info. Another criticism is that without the test, patients would be prevented from using all the knowledge that could be available to make decisions about their health. As pointed out by New Jersey physician, Adam Perzin, "The federal task force misdirects the very real medical concerns about the “risks of treatment” onto screening. But screening is not treatment. It is not even diagnosis. There are essentially no risks to screening. Denying patients the opportunity to participate in decisions regarding their own health care because of concerns regarding treatment they may never get is a stick-your-head-in-the-sand approach to medicine that in my view will cost lives." See [link] .
- Significant Death Rate. Prostate cancer is one of the largest killers of men among cancers so its prudent not to reject the only test that can catch it early.
- Government Health Care Rationing. It has been pointed out that "if accepted by the government, this recommendation would essentially become healthcare rationing, in which only people who can pay out-of-pocket, would receive this life-saving test." Catalona Press Release According to a New York Times article the USPSTF's "work is mandated by the government and is administratively supported by the government". Further suspicion that the report is being commissioned to justify government health care rationing has been aroused by (1) the fact that the draft report was supposed to be issued for public comment but according to the same New York Times article the task force is not making the comments public indicating that "public comment" was intended to only mean "public input" and (2) according to the [boxed information on the USPSTF site] the USPSTF "lost" some of the public comments through a technical glitch. In 2009 the USPSTF recommended "that mammographic breast cancer screening before age 50 should be optional, and decided by a woman and her physician." At that time the "mammography controversy attracted congressional attention from legislators responding to constituents’ outrage and demanding greater transparency in the USPSTF decision making process. [Wall Street Journal Blog May 21, 2010]. HHS secretary Kathleen Sebelius eventually issued a statement emphasizing that the USPSTF does not set health policy." [USToo Hotsheet November, 2011]. . Despite such statements, a fear has been articulated by The American Enterprise Institute, a conservative think tank, in reference to the USPSTF, that the under the "Patient Protection and Affordable Care Act (PPACA), a previously obscure government advisory body has acquired vast authority to decide which health care services Americans will have access to." [The Bleeding Edge of Rationing] and 43 members of the House of Representatives [list of signatories via PC Infolink] consisting of both Democrats and Republicans have sent a [letter via PC Infolink] to Secretary of Health and Human Services Kathleen Sebelius asking for continued funding of PSA tests. The letter states that the USPSTF conclusions are based on studies which are "disputed by experts" and they further write that failing to cover the test would have "potentially dire" consequences. In another development, it has been charged that one particularly insidious approach to rationing health care is an attempt to simply rename cancer to something else so that funding bodies can get out of paying for treatment of it: [NY Times].
Blog Updates for October 2011
Oct 27, 2011. In Prostate Cancer Calculators we add: Interpretation. Caution needs to be exercised in interpretation. For example, this article shows what can go wrong by incorrectly assuming that median life expectancy is the amount of time a particular person has left to live.
Oct 26, 2011. In Advice to the Newly Diagnosed we added: Low fat diet with fish oil supplements may be beneficial. In a 2011 study of 55 men with prostate cancer were given a low fat diet with fish oil supplements to achieve a omega6:omega3 ratio of 2:1 (vs. 15:1 for Western diet). There was no change in IGF-1 status but there was a reduction in Ki-67 proliferative index relative to controls on a Western diet. See [abstract]. Note that this is not particularly strong evidence. For example, this study found improved proliferative index from antioxidants yet its conclusions were later reversed in larger studies.
Oct 26, 2011. In Advice to the Newly Diagnosed we added: Low fat diet with fish oil supplements may be beneficial. In a 2011 study of 55 men with prostate cancer were given a low fat diet with fish oil supplements to achieve a omega6:omega3 ratio of 2:1 (vs. 15:1 for Western diet). There was no change in IGF-1 status but there was a reduction in Ki-67 proliferative index relative to controls on a Western diet. See [abstract]. Note that this is not particularly strong evidence. For example, this study found improved proliferative index from antioxidants yet its conclusions were later reversed in larger studies.
Friday, September 30, 2011
Blog Updates for September 2011
Sep 29. In Biochemical PSA Recurrence we added:
Except for large randomized trials the nutrition studies provide only provisional evidence and can be overturned once such large randomized trials are performed. If the effect that they find is large it makes the nutrition study more likely to hold as competing reasons must then also be large to overturn them; however, such alternative explanations (such as those who consume X tends to also have good or bad lifestyle habits in general) are always a possibility. In fact the SELECT trial has already overturned a number of the provisional conclusions in the prostate cancer section of the WCRF/AICR report.
Sep 26. In Advice to the Newly Diagnosed we added: Although the statistics are generally much more favorable than for other cancers, it should still be noted that according to the American Cancer Society about 30,000 men died of prostate cancer in 2010 and according to the European Cancer Observatory about 70,000 men died of prostate cancer in 2008 so in total about one man dies every 5 minutes of prostate cancer in the US or EU. Thus prostate cancer should not be neglected and appropriate medical attention should be taken to minimize any risks.
Sep 8. In Prostate Cancer Calculators we add: A 2011 paper by Corcoran et al [PMID: 21895937] analyzed 684 patients with Gleason 6 or 7 on biopsy and found that 50% were upgraded. The upgraded patients had tumors which were significantly smaller than patients not upgraded suggesting that tumor volume can help in predicting an upgrade.
- "In conclusion, consumption of eggs may increase risk of developing a lethal-form of prostate cancer among healthy men." [PMID: 21930800]. Quoting from the same abstract: "Men who consumed 2.5 or more eggs per week had an 81% increased risk of lethal prostate cancer compared to men who consumed less than 0.5 eggs per week."
- "In conclusion, cruciferous vegetable intake after diagnosis may reduce risk of prostate cancer progression." [PMID: 21823116]. The study was based on "1,560 men men diagnosed with non-metastatic prostate cancer taken from a famous US database (known as CaPSURE – 40 sites, mostly community-based clinics). ... Men that reported a regular (about once a day) intake of cruciferous vegetables had a significant 59% reduction in risk of cancer returning compared to men that occasionally consumed these veggies." (quoted from Dr. Moyad article in Sep 2011 US Too). Cruciferous vegetables include brocolli, brussel sprouts, cabbage, cauliflour, bok choy, radishes, daikon, kohlrabi, rutabaga, collard greens, turnip greens, arugula and cress. See Wikipedia for a longer list.
- "Brisk walking after diagnosis may inhibit or delay prostate cancer progression among men diagnosed with clinically localized prostate cancer." [PMID: 21610110] Quoting from the same abstract: "Men who walked briskly for 3 h/wk or more had a 57% lower rate of progression than men who walked at an easy pace for less than 3 h/wk (HR = 0.43; 95% CI: 0.21-0.91; P = 0.03). Walking pace was associated with decreased risk of progression independent of duration (HR brisk vs. easy pace = 0.52; 95% CI: 0.29-0.91; P(trend) = 0.01). Few men engaged in vigorous activity, but there was a suggestive inverse association (HR =3 h/wk vs. none = 0.63; 95% CI: 0.32-1.23; P(trend) = 0.17). Walking duration and total nonvigorous activity were not associated with risk of progression independent of pace or vigorous activity, respectively."
- "Our results suggest that the postdiagnostic consumption of processed or unprocessed red meat, fish, or skinless poultry is not associated with prostate cancer recurrence or progression, whereas consumption of eggs and poultry with skin may increase the risk." [PMID: 20042525] Quoting from the same abstract: "Intakes of processed and unprocessed red meat, fish, total poultry, and skinless poultry were not associated with prostate cancer recurrence or progression. Greater consumption of eggs and poultry with skin was associated with 2-fold increases in risk in a comparison of extreme quantiles: eggs [hazard ratio (HR): 2.02; 95% CI: 1.10, 3.72; P for trend = 0.05] and poultry with skin (HR: 2.26; 95% CI: 1.36, 3.76; P for trend = 0.003). An interaction was observed between prognostic risk at diagnosis and poultry. Men with high prognostic risk and a high poultry intake had a 4-fold increased risk of recurrence or progression compared with men with low/intermediate prognostic risk and a low poultry intake (P for interaction = 0.003)."
Except for large randomized trials the nutrition studies provide only provisional evidence and can be overturned once such large randomized trials are performed. If the effect that they find is large it makes the nutrition study more likely to hold as competing reasons must then also be large to overturn them; however, such alternative explanations (such as those who consume X tends to also have good or bad lifestyle habits in general) are always a possibility. In fact the SELECT trial has already overturned a number of the provisional conclusions in the prostate cancer section of the WCRF/AICR report.
Sep 26. In Advice to the Newly Diagnosed we added: Although the statistics are generally much more favorable than for other cancers, it should still be noted that according to the American Cancer Society about 30,000 men died of prostate cancer in 2010 and according to the European Cancer Observatory about 70,000 men died of prostate cancer in 2008 so in total about one man dies every 5 minutes of prostate cancer in the US or EU. Thus prostate cancer should not be neglected and appropriate medical attention should be taken to minimize any risks.
Sep 8. In Prostate Cancer Calculators we add: A 2011 paper by Corcoran et al [PMID: 21895937] analyzed 684 patients with Gleason 6 or 7 on biopsy and found that 50% were upgraded. The upgraded patients had tumors which were significantly smaller than patients not upgraded suggesting that tumor volume can help in predicting an upgrade.
Sunday, August 28, 2011
Blog Updates for August 2011
Aug 27. A new line of journal links has been added at the top of the page. Also the news links at the top of the page were revised.
Aug 4. New post on Vitamin D summarizing conclusions in a recent review.
Aug 2. We added to Bradford Hill Criteria of Causation: In a 2008 study of Finnish smokers Ahn et al (2008) [PMID: 18505967] [Full text] found that the 20% of patients with the lowest blood levels of vitamin D has also had the lowest risk of prostate cancer. There are several reasons to be suspicious of this. Firstly, the dose response criterion is not satisfied. That prostate cancer risk did not always increase with vitamin D level as one proceeds from one quintile to the next. (The quintiles refer to the 5 groups such that the first quintile is the 20% of patients with the lowest vitamin D in their blood, the second quintile is the 20% with the next lowest, etc.) There is also a worry here about temporality and the associated reverse causation. In particular, perhaps those who had the highest vitamin D levels were sicker and were trying actively to prevent further disease through intake of vitamin D?
Aug 4. New post on Vitamin D summarizing conclusions in a recent review.
Aug 2. We added to Bradford Hill Criteria of Causation: In a 2008 study of Finnish smokers Ahn et al (2008) [PMID: 18505967] [Full text] found that the 20% of patients with the lowest blood levels of vitamin D has also had the lowest risk of prostate cancer. There are several reasons to be suspicious of this. Firstly, the dose response criterion is not satisfied. That prostate cancer risk did not always increase with vitamin D level as one proceeds from one quintile to the next. (The quintiles refer to the 5 groups such that the first quintile is the 20% of patients with the lowest vitamin D in their blood, the second quintile is the 20% with the next lowest, etc.) There is also a worry here about temporality and the associated reverse causation. In particular, perhaps those who had the highest vitamin D levels were sicker and were trying actively to prevent further disease through intake of vitamin D?
Thursday, August 4, 2011
Vitamin D Review
[August 4, 2011]
A review paper by Barnett and Beer that appeared in Urol Clin North Am. 2011 Aug;38(3):333-42 discusses the current status of Vitamin D research. [PMID: 21798396]. According to that paper it seems clear that vitamin D is involved in prostate cancer biology and that there is an anticancer effect in animals but it is much less clear whether there is a significant beneficial effect of vitamin D supplementation in humans. Below we outline the main points:
A review paper by Barnett and Beer that appeared in Urol Clin North Am. 2011 Aug;38(3):333-42 discusses the current status of Vitamin D research. [PMID: 21798396]. According to that paper it seems clear that vitamin D is involved in prostate cancer biology and that there is an anticancer effect in animals but it is much less clear whether there is a significant beneficial effect of vitamin D supplementation in humans. Below we outline the main points:
- geographic areas of low UV exposure have increased risk of prostate cancer
- in test tube and animal studies vitamin D has shown an anti-cancer effect
- because calcium tends to depress vitamin D it would be expected that if vitamin D were anti-cancer in humans then low calcium intake would correlate with lower risk of prostate cancer but of 12 recent studies 8 showed no relationship with calcium
- out of 13 studies 9 showed no association between low vitamin D and increased risk of prostate cancer
- some caveats are that the following may (or may not) be (a) it might be that the studies just cited did not have sufficient numbers of patients to detect a difference, (b) it might be that the effect of low vitamin D is to increase the risk of aggressive prostate cancer rather than increase the risk of prostate cancer
- studies relating genetic variations in Vitamin D genes and prostate cancer progression have been inconclusive
- multiple studies with calcitriol + chemo have resulted in lower PSA levels; however, a phase III trial was halted due to deaths in the treatment arm
- it may be that vitamin D therapy only works in certain targeted subgroups
"At present, there are no consistent data to support high dose vitamin D supplementation for the average patient with prostate cancer for the treatment or halting of cancer progression. In addition, there are no data to support therapeutic use of vitamin D and its analogs in treating prostate cancer. Additional studies are needed to determine if higher doses of vitamin D supplements could benefit selected populations (ie, the elderly or patients with cancer) even if they may not be beneficial for the general population."and for the average prostate cancer patient
"a recommended minimum of 600 IU of vitamin D per day, with testing at baseline to determine if additional supplementation is needed for deficiency levels (< 20 ng/mL) is reasonable."
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