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Monday, April 28, 2008

Blog Updates for April 2008

April 2/08. In Lycopene, Selenium and Vitamin E in Combination we added: Dr. Marc Garnick (papers) of the Harvard Medical School has written a brief summary of the pros and cons of selenium here. There has been some speculation that selenium might hide rather than prevent prostate cancer.

April 2/08. Added to Bradford Hill Criteria of Causation: Patient Confusion. Patients themselves may confuse co-occurrence with causation. Assessing causation is much more difficult than it may appear on the surface and most patients are not able to evaluate it. The result is mistaking coicidence or other reasonable explanations for miraculous cures. For example, in this March 9/08 post by a patient who claims to have been cured of prostate cancer by taking cayenne pepper [link] he more likely simply had a false negative biopsy. Another patient claims that not drinking milk will cure prostate cancer and points to (1) his reduction of PSA after eliminating milk and (2) increase after resuming it. But he was also receiving conventional medical treatment which could easily account for the reduction in PSA and subsequent recurrence as could chance and numerous other factors. Both these relate to items that do have biological plausibility to them, which is one of the Bradford Hill criteria, and it may even be that the measures which appeared to work in these isolated cases turn out to be highly effective but the point is that these isolated examples should not be confused with "proof". (For more on cayenne pepper see [PMID: 16540674] and for dairy and calcium see the page labelled 129 and following of the WCRF report.)

Apr 2. On the Case Histories page: Urotoday has slides on 4 case studies [1] [2] [3] [4].

Apr 6. In Prostate Cancer Calculators we added: At the bottom of the calculators page the University of Montreal has doubling time and Life expectancy calculations.

Apr 6. Added the
PSA Doubling Time (PSADT) - Part 4. Online Calculators: University of Montreal calculator pages described more fully in this post or directly here includes a doubling time calculator. Like the Sloan Kettering calculator it will not accept PSA values less than 0.1 so if you are using an ultrasensitive assay that can detect PSA levels that low then enter all your PSA values as 10 times or 100 times the actual value. The doubling calculated will still be correct. There are no graphics provided.

Apr 6. In PSA Screening and Early Detection - Part 2 added: Cutoff Levels Traditionally a cutoff level above 4.0 has been used to indicate biospy is required; however, Dr. Catalona and a number of other sources (see PCRI pamphlet and also PCRI article) recommend 2.5 since the 4.0 level misses a significant number of prostate cancer cases. Loeb (papers) and Catalona (papers) discuss this in the March 2008 issue of the Oncologist [PMID: 18378540] where they point out that "Among men with serum PSA levels 0.5, 0.6-1.0, 1.1-2.0, 2.1-3.0, and 3.1-4.0 ng/ml, prostate cancer was detected in 6.6%, 10.1%, 17.0%, 23.9%, and 26.9%, respectively.".

In the above cited paper, which is highly recommended to all readers, Loeb and Catalona summarize their discussion into a very helpful flow chart showing the clinical actions to take based on PSA testing.

Rather than a fixed cutoff level, age-specific and race-specific levels have been proposed. Age-specific cutoff levels are discussed in the Part 1 post of this series, the Australian brochure and the above mentioned Loeb and Catalona paper. Also race-specific cutoff levels have been proposed to take into account the higher risk faced by blacks and the lower risk faced by Asians. On the other hand they are more complicated and a 2006 analysis by Grunkemeier and Vollmer [PMID: 16753606] [Full Text] found no advantage in incorporating race or age. Also see references to that article.

Loeb and Catalona recommend that rather than modifying cutoff levels based on age that age specific levels be used for risk assessment in order to determine which men need to be followed more closely in the future. Loeb and Catalona cite results from Fang et al's 796 person Baltimore study as well as their own studies showing that men with PSA values above the age-specific median are at significantly heightened risk for prostate cancer many years later. Thus the way they suggest that age-specific levels be used is that for men in their 40's, 50's, 60's and 70's that closer future monitoring be done if their PSA is found to be 0.7, 0.9, 1.3, 1.7 or higher, respectively. Use of median age-specific PSA levels to determine who needs to be followed more closely is also mentioned in the Australian brochure even if the PSA level is below the cutoff, if it is above the median PSA then the individual is still at heightened risk for prostate cancer and should be monitored more closely.

In the same March 2008 issue of The Oncologist, Michael Berry (papers) of Harvard Medical School presents an alternative view that the increased PSA testing recommended above will lead to greater number of healthy men being unnecessarily having to undergo biopsy. See [PMID: 18378541].

In the Guidelines - US line under Links to the right side of the page we have added:
[Catalona PSA] (flowchart)

April 6. In the post on Urinary Incontinence we add: The simple steps should not be discounted just because they are simple as they may have significant beneficial effects. One patient who had suffered incontinence reported that physiotherapy for his knee, unrelated to incontinence but likely also exercising the muscles involved in incontinence exercises, also appeared to improve his incontinence showing that even long term sufferers can benefit.

April 7. In NIH Funded Research to be Open Access: the new open access policy whereby all NIH funded research is to be publicly available on the net: The new policy goes into effect today!

April 18.
Also note that there is a relationship among PSA, PSAV and PSADT given by:

PSAV = log(2) PSA / PSADT

where log(2) = 0.6931472. That is the PSAV is proportional to PSA during any stretch of time for which PSADT is constant and if we were to draw the PSA and PSAV curves they would have the same shape during such time stretches -- the only difference being that one is a scaled version of the other.

April 19. Added to Free Monthly Prostate Cancer Magazines and Journals : PAACT Newsletter, This newsletter only comes out every 3 months but has interesting patient oriented articles written by urologists.
For example, a 2006 article on Vitamin D by Dr. Donald Trump was discussed in our post on Vitamin D

Added to DIY with Google:
The formulas for PSADT and PSAV using google's notation are shown here:

PSADT = (t2 - t1) / (lg(PSA2) - lg(PSA1))

Average PSAV = (PSA2 - PSA1) / (t2 - t1)

Instantaneous PSAV = ln(2) * PSA / PSADT

If PSADT is constant then PSAV will be increasing over time and the average PSAV in the second formula is the average of those various PSAV's and is normally what is calculated in a clinical setting. The instantaneous PSAV allows one to calculate the PSAV at each point in time assuming the PSADT was constant during that stretch of time.

An approximation which involves no logarithms (so it can be calculated on a 4 function calculator) but is often very close to the value calculated by the conventional formula for PSADT is .347 * (t2 - t1) * (PSA2 + PSA1) / (PSA1 - PSA1) where .347 is the value of log(2)/2. For our example of a PSA rising from 4 to 5 over 16 months we have:

.347 * 16 * (5+4)/(5-4)

which gives 50 and is within 1% of the 49.7 value using the PSADT formula that involves logarithms.

April 22. In Can Most Studies Be Wrong - Part 3: Selection bias occurs when, for example, sicker patients are given more effective treatment. Since sicker patients do worse the result makes it appear as if the more effective treatment is worse. A similar situation is where healthier patients are given more toxic treatments making it seem as if the more toxic treatment is better. In "The limits of observational data in determining outcomes from cancer therapy." Sharon H. Giordano, Yong-Fang Kuo, Zhigang Duan, Gabriel N. Hortobagyi, Jean Freeman, and James S. Goodwin. Cancer; Published Online: April 21, 2008 (DOI: 10.1002/cncr.23452); Print Issue Date: June 1, 2008 these biases are discussed in the context of prostate cancer treatment. Also see [link].

April 28. In PSA Screening and Early Detection - Part 3. Current Environment we add this reference to an April 2008 paper on the Tyrol experiment: [PMID: 18321314] (Science Daily summary).

Also, in the same post, An April 2008 a paper from the University of Bristol [PMID: 18424233] the decline in prostate cancer deaths in the US where screening is common relative to the UK where it is not:
The striking decline in prostate-cancer mortality in the USA compared with the UK in 1994-2004 coincided with much higher uptake of PSA screening in the USA. Explanations for the different trends in mortality include the possibility of an early effect of initial screening rounds on men with more aggressive asymptomatic disease in the USA, different approaches to treatment in the two countries, and bias related to the misattribution of cause of death. Speculation over the role of screening will continue until evidence from randomised controlled trials is published.

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