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Wednesday, February 27, 2008

Blog Updates for February 2008

Feb 1/08. In Choosing a Surgeon - Part 2. Finding a Surgeon we add: The PCRI site lists some doctors by speciality and name.

Feb 1. In Prostate Cancer Calculators we added:

There are two particularly comprehensive prostate cancer calculator sites. Their links are easy to remember since their links are nearly the same: (University of Montreal) and (Sloan Kettering). The Sloan Kettering site ends in "s" whereas the University of Montreal site does not.

A. Sloan Kettering. ... description unchanged ...

B. University of Montreal Cancer Prognostics and Health Outcomes Unit has a suite of calculators at This site has prostate cancer calculators for a wide variety of situations:
  • Before Treatment. There are 6 pre-biopsy calculators which can be used. They are used prior to biopsy to give the probability of biopsy results. The first is used if PSA is in the 0 - 2.5 ng/ml range, the second is for initial extended biopsy, the third is for extended repeat biopsy, the fourth is for saturation biopsy, the fifth is for 120 day mortability after biopsy based on a comorbidity score and the sixth is for initial sextant biopsy.
  • Before Treatment I. There are calculators to predict the probability of Gleason sum upgrade, extra capsular extension, seminal vesicle invasion and lymph node invasion.
  • Before Treatment II. There are calculators for calculating the probability of clinically insignificant prostate cancer, the probability of predominantly transition zone prostate cancer, probability of survival within 30 days of surgery and the probability of 10 year survival.
  • After Surgery. There are post op calculators for the probability of PSA recurrence, Local recurrence, Distant recurrence and prostate cancer specific survival.
  • After PSA Relapse. There are calculators for the probability of Metastatic progression, mortality for surgical patients undergoing subsequent hormone therapy and mortality after PSA relapse.
  • Hormone Refractory Prostate Cancer
  • . There is a calculator for the probability of survival for patients with androgen independent prostate cancer.

Feb 5. Under the Treatment line to the right we added information about the AHRQ (part of US government) report comparing treatments: [Comparison] (summary)

Feb 5. Added to ED After Prostatectomy: The web site of Henry Ford Health Systems has some radar graphs employing SHIM scores to compare outcomes here.

Feb 6. Under Advice to the Newly Diagnosed we add: These include a 187 page government report which performed a systematic review of the medical research literature to compare the various treatment options, a summary of that report, the journal paper for the report and descriptions of various treatments.

Feb 7. In Free Downloadable Materials post in the Single Topics section we have added: Guide to Biostatistics by Dr. R. K. Israni. An 11 page surprisingly easy-to-read non-mathematical outline of the main topics in biostatistics can be found here: Topics include Study Designs (How Research is Classified, Terminology, Important Epidemiological Concepts), Descriptive Statistics (Measures of Central Tendency, Measures of Spread, Measures of Frequency of Events, Measures of Association, Terms Used to Describe the Quality of Measurements, Measurements of Diagnostic Test Accuracy, Expressions Used When Making Inferences About Data, Multivariate Regression Methods) and References.

Feb 8. In Prostate Cancer Calculators we added: although not a calculator, a useful classification is to the d'Amico risk category. More on this is available here.

Feb 9. In Testosterone Metabolism and Prostate Cancer we add a second example of the full E-D model quoting Friedman directly:

Basically, there are two results that have been repeated at least twice each that seem to contradict each other. First, for men with a normal range of T, the higher the free T, the greater the chance of getting PCa. Next, for men with a low range of T, the lower the T, the greater the chance of getting PCa.

Let's look at the first case - that for normal range of T. The higher level of free T means that there is more E2 if Aromatase is turned on. This higher level means that more normal prostate cells will start dividing when they shouldn't and increases the chance of a mutation that will turn this growth cancerous. Although the rate of developing PCa is higher per year the greater the level of free T, the amount of bcl-2 produced also decreases, so that the PCa that results is less aggressive. As the level of T increases, eventually you reach a level (around teenage level) in which bcl-2 is so low that the PCa dies more quickly than it divides.

Next, looking at men with low levels of T, the rate of developing PCa each year will in fact be lower the lower the amount of T present. However, the amount of bcl-2 produced will be higher, so the PCa will be more aggressive the lower the level of bcl-2 present. The researchers are not checking for the rate of PCa developing each year - they typically would look at a bunch of 50 year olds and see how many of them have PCa. Because the lower the T the more aggressive the PCa and the lower the T the earlier in life the sooner PCa has a chance to develop, the result is that lower levels of T will result in a greater chance of PCa having grown to the size that it is capable of being detected for men at the same age.

What is interesting is that all of the above is just an examination of the PCa rate that occurs naturally. For men who don't have any PCa cells in them who take T supplementation, then bringing T to teenage levels with enough Arimidex to keep E2 within the normal range should make it almost impossible to ever get PCa.

Feb 10. On right hand side under Links on the Treatment line we added this link on Adjuvent Radiation after Prostatectomy for high risk patients based on SWOG 8794: [Adj RT].

Feb 11. Added to the Webcasts: line under Links this new one showing a robotic and non-robotic prostatectomies: [Surgery]

Feb 12. In PSA Screening and Early Detection - Part 3. Current Environment we mention that: Two mathematical modelling teams, one of the Fred Hutchinson Center and one at the University of Michigan concluded that it was plausible that 45% to 70% of the improved survival to the year 2000 could be attributed to PSA testing. [PMID: 18027095]

Feb 12. Under Advice to the Newly Diagnosed we add: There are some additional statistics on recovery progression in the abstract of this paper: [PMID: 17919694].

Feb 12. In Vitamin D and Prostate Cancer we added: In a February 2008 paper in Bioessays, Trevor Marshall writes that unlike getting vitamin D from the sun, vitamin D supplements may undesirably suppress immune function and supplements may actually block rather than enhance Vitamin D Receptor (VDR) activation: "the Vitamin D Nuclear Receptor (VDR) acts in the repression or transcription of hundreds of genes, including genes associated with diseases ranging from cancers to multiple sclerosis" and since we do not know the exact details of these numerous interactions they could include harmful ones. See [news] and [PMID: 18200565].

Feb 13. In Soy the following was expanded as shown: soy may have drug interactions with 5AR2 inhibitors [internet discussion] which can also be found [here]. To understand the discussion there the reader may wish to review the model of prostate cancer discussed in [this post].

Also the following reference to a February 2008 paper which reviews the benefits and research on soy was added: [PMID: 17923857] [Full text].

The above was also added to the Testosterone Metabolism and Prosteate Cancer post.

Feb 13. In ED After Prostatectomy. Part 2 - Rehabilitation we added as an aside: PDE-5 inhibitors may have benefits against hypertension and other vascular diseases and are also believed to enhance one's ability to work in a low oxygen atmosphere such as would be experienced on mountain tops or by pilots.

Also we added: A February 2008 study concluded that patients who were given a chance to try all three PDE-5 inhibitors and choose for themselves had better compliance with taking this medication [PMID: 18086159].

Feb 13. Added Contents of Site to the Key Posts on the right. Also added at the top of the page that there are now 100 posts.

Feb 13. Added a review of various guidelines to the Links section to the right on the Guidelines - US line. It is labelled Review and highlighted in red.

Feb 13. In Biochemical PSA Recurrence we added this introduction: In an excellent 2008 review article in the February 2008 Canadian Family Physician Wilkinson, Brundage and Siemens write [link]:
An increasing PSA level after curative therapy is termed a biochemical recurrence (BCR). Approximately one-third to half of patients will experience BCR during the course of their follow-up, regardless of modality of treatment. [PMID: 10886105] [PMID: 16600730] The significance of a BCR is in itself unclear, as not all men who have experienced BCRs will go on to experience metastatic disease. [PMID: 12605977] In one study, fewer than one-third of patients with BCR after RP developed systemic recurrence.[PMID: 12605977] In those patients who progress, BCR usually predates metastatic disease progression by an average of 7 years and prostate-cancer specific mortality by 15 years.[PMID: 16921049] [Full Text] Therefore it is useful in allowing enough lead time to implement effective salvage therapeutic strategies in those patients whose recurrences are deemed to be local (See [Table 1]).

Feb 15. In Choosing a Surgeon - Part 2. Finding a Surgeon we add: Expertmapper lists doctors based on searching research databases to locate ones that have done research in the medical area you are interested in. Obviously this has significant limitations, e.g. most clinicians don't publish research so they would be missed and you probably can't quantify the aspects of greatest interest such as surgical skills this way but nevertheless its an interesting free resource.

Feb 15. In How Healthy Men Can Reduce Their Risk we mention a study by investigators from Sloan Kettering and Sweden who 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. This suggests 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. [Full Text] [MedNews summary]

Feb 15. In Testosterone Metabolism and Prosteate Cancer we added: Note that there are many anti-apoptotic proteins similar to bcl-2 and bcl-2 may simply be regarded as a prototype that refers to them all. In fact, in [link] bax and bcl-xl were more closely related to Gleason score than bcl-2.

Feb 15. Added interview with Wilt, the AHRQ treatment study comparison investigsator as (audio) to the Treatment - Comparison line under Links on the right.

Feb 17. Reworked this section in ED After Prostatectomy:
  • surgical technique and experience. e.g. [PMID: 17626532], [PMID: 17196737], [PMID: 18261153], [PMID: 15538237], [PMID: 10799186] (Note that recovery rates which are not stratified by risk levels are less meaningful since one can get better results simply by operating only on healthier patients even without any improvement in technique. Also, as discussed elsewhere on the page, percentages can vary hugely simply by changing the definition of potency.)
  • preservation of neurovascular bundles (single nerve sparing, double nerve sparing or no nerve sparing). See Figure 2 of [Lepor, 2005] for an algorithm on deciding on nerve sparing.

Feb 17. Added video of a lecture by Grimm on Brachytherapy under [Seeds] in the Treatment line under Links to the right: [Seeds]

Feb 19. In RP vs. LRP vs. RLRP - Part 1. Open Surgery (RP) (and also part 3 of the same series) added mention of this 2008 study [PMID: 17919694] which compares open and robotic surgery. It found faster recovery and less pain from robotic surgery although the actual differences were not large.

Feb 21. Added a new line to the right in the Links section: Benchmarking: with the following links:

Feb 22. In Links section to the right, added to the Treatments line a synopsis of the review article 'Current Status of Intensity-Modulated Radiation Therapy (IMRT)' from Int J Clin Oncol. 12(6):408-15, December 2007 listed under: [IMRT].

Feb 23. In Diet Soft Drinks we found a more recent reference: Also there are indications that artificial sweeteners in soft drinks are unhealthy in any case: [PMID: 18212291]

Feb 25. In Holick's July 2007 NEJM Paper on Vitamin D we added new information on D2 which seems to contradict earlier work cited there: Although earlier work published in 1998 [PMID: 9771862] and 2004 [PMID: 15531486] seemed to support the lesser effectiveness of D2, since the NEJM paper came out Holick has specifically investigated this further and concluded that D2 is, in fact, equal to D3 in maintaining blood serum levels [PMID: 18089691] [Full text]

Feb 25. Added to the Links section on the right in the Medical/Uro line: [Medscape] [PubChem] [Pubmed]

Feb 25. In ED After Prostatectomy. Part 2 - Rehabilitation we added: a 2008 paper in the Journal of Urology found that patients who had better pretreatment sexual function responded better to PDE-5 inhibitors. [PMID: 18206926].

Feb 26. In Longevity we added:
In a January 2008 paper, UK researchers found that a combination of 4 behaviors increased longevity by 14 years on average:
  • not smoking
  • being physically active
  • moderate alcohol intake (my note: the WCRF/AICR Diet and Cancer Report concluded that alcohol, even small amounts, does increase one's risk for cancer)
  • 5 servings a day of fruit and vegetables
. [PMID: 18184033] [Full Text]. In particular:
Between 1993 and 1997, about 20,000 men and women aged 45–79 living in Norfolk UK, none of whom had cancer or cardiovascular disease (heart or circulation problems), completed a health and lifestyle questionnaire, had a health examination, and had their blood vitamin C level measured as part of the EPIC-Norfolk study. A health behavior score of between 0 and 4 was calculated for each participant by giving one point for each of the following healthy behaviors: current non-smoking, not physically inactive (physical inactivity was defined as having a sedentary job and doing no recreational exercise), moderate alcohol intake (1–14 units a week; a unit of alcohol is half a pint of beer, a glass of wine, or a shot of spirit), and a blood vitamin C level consistent with a fruit and vegetable intake of at least five servings a day. Deaths among the participants were then recorded until 2006. After allowing for other factors that might have affected their likelihood of dying (for example, age), people with a health behavior score of 0 were four times as likely to have died (in particular, from cardiovascular disease) than those with a score of 4. People with a score of 2 were twice as likely to have died.

The NIH has a page on healthy living here.

Feb 26. In ED After Prostatectomy. Part 2 - Rehabilitation
A new PDE-5 inhibitor is udenafil. See [PMID: 18221288].

Feb 26. Added to Newly Diagnosed this explanation of why better data does not exist comparing treatments: Inability to get patients to enroll in clinical trials and lack of success of prostate cancer advocacy have been cited as reasons for lack of better data in this NY Times article.

Also added:
With respect to side effects Dr. Tanya B. Dorff (papers) says in a February 8, 2006 interview:
the side effects discussion ... really comes down to a tradeoff between bowel toxicity - slightly more prevalent with radiation - and urinary toxicity, somewhat more likely with surgery. Impotence isn't part of the equation because that risk isn't decisively different between modalities. And of course, "I tell patients that most of them will not end up with these consequences, and their risk is minimised by going to a high-volume urologist and radiation oncologist."

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