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Saturday, August 30, 2008

Blog Updates for August 2008

Aug 26. In PSA Screening and Early Detection - Part 3. Current Environment we add the following link to a comment by Catalona regarding the U.S. Preventive Services Task Force recommendations on PSA testing: A rebuttal to the task force recommendations by Dr. William Catalona appeared in the Washington Post [full text] on August 26, 2008 page A13.

Aug 25. In WCRF/AICR Diet and Cancer Report we added this link: [errata]

Aug 23. In Advice to the Newly Diagnosed we added: A 2006 paper in the journal, Cancer, investigated the influence of emotion, misconception, and anecdote in making treatment decisions. See Figure 1 and 2 for patient quotes and Table 3 for patient misconceptions. [PMID: 16802287] [Full Text].

Aug 23. In Advice to the Newly Diagnosed we added: A non-technical discussion of interpreting survival curves and medical statistics is available at [CancerGuide statistics] and other information on do-it-yourself research is also available at that site.

Aug 23. In Advice to the Newly Diagnosed we added: Common Practice Scott L. Sailer summarizes a common approach to treatment alternatives as follows:
Radiation is a curative treatment for prostate cancer that is most appropriate for the older patient or the patient with significant co-morbidities. Younger patients with a greater than ten-year survival are probably best treated with surgery unless the disease is high risk. For all patients, high-risk disease is best treated with hormones and radiation. The long-term superiority of surgery over radiation, however, has not been demonstrated in randomized or retrospective studies, and the recommendation for surgery in the younger, healthy patient with favorable local disease is largely based on theoretical considerations. If chosen for appropriate indications and delivered with appropriate techniques, radiation can be delivered using external beam or brachytherapy with equal efficacy. The choice of radiation treatment is based on tumor characteristics and patient preference. Radiation can be used after prostatectomy to cure patients who are not cured with surgery. Watchful waiting may be appropriate for patients with low-risk disease. Sailer, NC Med J March/April 2006, 67(2) p. 152

Aug 20. On the Community Resources page we added a link to the new Maine support group page: ME

Aug 19. Added to ED After Prostatectomy: Penile vascular status can be measured with Doppler ultrasonography (DUS) and such status has been correlated with subsequent erectile function [PMID: 18694409].

Aug 16. In Free Downloadable Materials we have added some additional information on estrogen patches: Further information can be found in [PMID: 18422771] [Medscape] by David Douglas and on the PCa in Arizona site: Transdermal Scrotal Estrogen Patches (TSEP) by Fernando Premoli.

Aug 14. In NIH Funded Research to be Open Access: The trends clearly favor open access with open access papers in medical journals relating to cancer rising from 7.2% to 8.8% of all cancer papers in the year ending July 2008 according to Biomed Central. See this [blog post].

Aug 14. In PSA Screening and Early Detection - Part 3. Current Environment A good description of lead-time bias by Dr. Barry Kramer of NIH (papers) appeared in Tara Parker-Hope's August 8, 2008 New York Times column
someone diagnosed with lung cancer at the age of 65 may die at 67 and be remembered as a two-year survivor. If the same man had been diagnosed at 57 through screening and died at the age of 67, he would be known as a 10-year survivor. That sounds a lot better, but the reality is that diagnosis and treatment didn’t prolong his life. He died at 67 either way.
(That column also provides other arguments relating to the downside of screening.)

Aug 12. In Testosterone Metabolism we add the following link to an abiraterone trial participant's blog: [link]. Also mentioned that its mechanism of action includes preventing prostate cancers from manufacturing their own androgens inhibiting androgen production in the testis, adrenals and prostate by blocking 17-alpha-hydroxylase and an enzyme required for androgen synthesis C17,20-lyase (also known as CYP17 or P450c17).

Aug 11. In Testosterone Metabolism we add: The idea is that the relative rate of growth and death of cancer cells is the key balance:
Cancer is a heterogeneous mix of cells. Some cells will slowly die off, where their rate of growth is only slightly less than their rate of death. Some cells will slowly increase in number, where their rate of growth is only slightly greater than their rate of death. However, those cells that thrive under the conditions of androgen deprivation are the ones that typically are the cause of death ... There are various reasons why such cells are able to thrive - high levels of the anti-apoptotic protein Bcl-2 is the reason for over 65% of the known androgen independent cells. Other mutations, such as in the pro-apoptotic protein p53 are also bad news.[Friedman]

For each of the hormones (testosterone, progesterone, and estradiol) there are two receptors acting in opposition to each other. In reality, for men with normal genetic makeup, all of the hormones initially increase the rate of cell death. If their levels are high enough, e.g. a typical teenage level, then PCa can not proliferate. As men age, and the hormone levels drop, then PCa can start up. Once it starts up, Darwinian evolution occurs, and each mutation that protects it from the hormones has a selective growth advantage. By the time a man becomes terminal, it is likely that the PCa will increase its growth rate in response to each of the three main hormones. ... in theory it is possible to have PCa cells die solely by using hormones, but in practice in will never happen unless you can start increasing hormone levels at the point that there is only a few cancer cells and no mutations yet.

... the initiating step in causing PCa is high local levels of estradiol (same for breast cancer). Continual high levels of estradiol immortalize those cells by producing oncogenes such as Myb which cause the cells to divide and producing telomerase which allows the cells to divide without shortening their telomeres. However, even though this initiates PCa, the hormone levels (especially T) must be low enough in order for PCa to proliferate. [Friedman]

Aug 6. In PSA Screening and Early Detection - Part 3. Current Environment we add referring to the USPSTF task force: Note that the task force had no urologists on it (see bottom of [this link] for the composition of the task force) and apparently just looked at randomized controlled clinical trials (RCTs) and since there are no large scale high quality RCTs they came to these conclusions not taking into account other clinical and epidemiological evidence. See the Study Selection section of [PMID: 18678846] [Full Text] where they state that they only considered RCTs for mortality but did consider non-RCTs for harms. The AHRQ government web site has a disclaimer near the bottom of [this page] that "Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services."

Aug 5. In Biochemical PSA Recurrence we added: A discussion of treatment options for recurrence, including two case studies, was presented at a session of the conference: Challenges in the Management of Urological Cancers (Amsterdam, The Netherlands) June 30, 2006 chaired by Thomas Keane and is summarized [here].

Aug 3. Added this comparison of Cryotherapy to Brachytherapy (abstract only) [Cryo vs. Seeds] to the Treatment Comparisons: line in the Links section found in the right margin.

Aug 3. In Pubmed Front Ends we added another sample PubMed query:

Comparative Study[Publication Type] prostatectomy

1 comment:

Charles (Chuck) Maack said...

Impressed by the collection of data provided in your August 26th "PSA Screening and Early Detection - Part 3. Current Environment." Here is something you might add that I have been provided the okay to pass on from Dr. Michael Dattoli of the Dattoli Cancer Center and Brachytherapy Research Institute in Sarasota, Florida:
Well known Urologic Oncologist Michael Dattoli of the Dattoli Cancer Center and Brachytherapy Research Institute in Sarasota, Florida has also come on board with
a rebuttal Letter to the editor of the Washington Post that may or may not be published.
He emphasized the same importance explained by Urologic Oncologist William Catalona
in a recent issue of the Washington Post.

Letter to the editor

Your Comments On...

To Screen or Not to Screen -- The U.S. Preventive Services Task Force last week handed down a startling recommendation: that men older than 75 should not be routinely screened for prostate cancer and that younger men should weigh their screening options with a physician...

Regarding the news article, “To Screen or Not to Screen" (Aug. 19, 2008), I am writing to challenge the guidelines issued by the U.S. Preventive Services Task Force, which suggested that men over the age of 75 should not be screened for prostate cancer. Having spent more than 25 years studying this disease and treating more than 10,000 men, I am well aware of the dilemmas of when to treat and when not to treat prostate cancer. The current controversies in the field about the efficacy of treatment are directly related to the question of setting an age limit for screening. In my opinion, given recent trends in life expectancy for American males, a screening cutoff at age 75 is too early for many men who are otherwise in good health.

In the past, it was argued that prostate cancer patients with a life expectancy less than 10 years should not be treated, because they were more likely to die from some other cause. But with life expectancy increasing for the population as a whole, there are actually fewer and fewer cases of prostate cancer these days that do not call for some form of treatment. Older men should be evaluated on a case by case basis. The most recent SEER-Medicare data demonstrate a significant survival advantage for patients (ages 65 to 80) treated with radiation or surgery compared to patients who were not treated. Relatively noninv asive treatments, such as the most advanced radiation therapies (brachytherapy and/or IMRT), are often appropriate for older men, including those over 75, who are otherwise in good health -- with less risk of surgical side effects that may reduce quality of life. In addition, a recent study has shown that in the early 1990's as a result of PSA screening, the U.S. and U.K. had the same incidence of prostate cancer per capita; but since that time the U.S. has enjoyed more than a 4-fold decline in mortality compared to the U.K. And this was attributed directly to our TREATING elderly patients with definitive therapies vs watchful waiting, as is the method of choice in the U.K (Lancet Oncol. 2008 May;9(5):407-9).

According to the most recent actuarial data (National Vital Statistics Reports, June, 2008), even an 80-year-old man now has a life expectancy of 8.3 years, while a 75-year-old man can expect to live 10.9 years, and the trend is rising for all age groups. In the case of an 80-year-old whose general health is good and who has no other serious health conditions, he stands a good chance of living beyond 10 years and would be wise to consider treatment. A man’s overall health should be considered as well as his age, since an 84 year old may actually be healthier than his 54 year old counterpart who smokes cigarettes, consumes excessive alcohol, etc. While many doctors continue to use 10 years life expectancy as a strict benchmark, when biopsy pathology and other lab tests ide ntify aggressive, potentially life-threatening tumors, a 5-year cutoff may be indicated, and that would suggest screening is appropriate for many men over the age of 75, who can be effectively treated with radiation and/or hormonal therapy.

Michael J. Dattoli, M.D.
Dattoli Cancer Center & Brachytherapy Research Institute,
Sarasota, FL
8/19/2008 11:54:13 AM