Newsletter Features 2005

2005-PCNG Newsletter Features

November 2005

Food Supplements Taken by Dr. Myers

   We take our medications and we take our food supplements―the medications because our doctor tells us so, and the food supplements because, because…… There are many reasons why we take food supplements and it might be nice to have another reason to take a particular supplement: Dr. Myers takes it too!
   In the following text, from Prostate Forum, volume 9, issue 3 (September 2005), Dr. Myers explains his methodology.

   “Over the past few years, I have been asked repeatedly what supplements I take and why. In order for you to understand my approach, you need to know that I regard these supplements as drugs and use much the same methods to evaluate them as I would a drug.
   In medicine, there is a broad consensus as to what constitutes proof that a drug is a useful treatment of a disease. The most powerful evidence is a clinical trial in which patients are randomly assigned to the drug or placebo. Alternatively, the randomization could be between a new drug and an old drug. These are sometimes called Phase III clinical trials. The best randomized controlled trials include large numbers of patients followed for years. Large numbers are needed to ensure that the differences seen are not due to chance, but indeed reflect a solid reproducible difference.
   Duration of a study is important because, with prostate cancer, we want to make sure that the benefit is durable. In prostate cancer treatment, we do not have nearly enough randomized controlled trials and we often have to make due with studies that are less convincing. For example, we have many trials where a group of prostate cancer patients are carefully characterized and treated in a consistent fashion and the results compared with what might have been expected from historical experience with similar patients. These are called Phase II clinical trials. Much of the information we have today on the impact of radical prostatectomy arises from clinical studies like this.
   The obvious weakness of this design is that the patients on the new treatment might have done better for some reason unrelated to the new treatment itself. For example, since the arrival of PSA-based screening there is a trend toward diagnosing patients with smaller cancers more likely to be confined to the prostate gland. It is natural for these patients to live longer after the diagnosis of cancer than they did in the early 1980s, even if treatment had not improved at all.
   Similarly, improvement in anesthesiology and postoperative care might reduce complications of surgery, yet the improvement might accidentally be assigned to improved surgical techniques. Even further down the ladder of quality would be the “clinical experience” of well-known physicians. In medicine, there is very convincing evidence that “clinical experience” is a remarkably poor guide to selecting treatments!
   There is yet another source of medical information and this comes from analyzing the frequency with which various human populations are diagnosed with and die of prostate cancer. This is the field of epidemiology. The goal of epidemiology is to look for associations between various factors, such as diet or screening, and the risk of being diagnosed or dying of prostate cancer.
   A good example of this is the frequently quoted fact that deaths from prostate cancer are lower in Japan than in the United States. Of course, Japan and the United States differ in many ways. While diet is different, so is the racial composition of these two populations and thus their genetics. Additionally, the details of medical care and even the willingness to diagnose prostate cancer, a disease involving a male sex organ, may also differ markedly.
   The best epidemiologists use very sophisticated statistical techniques to identify and control for such variables. Despite these efforts, few medical experts regard epidemiology studies as proof of anything. I think their major value is to identify issues that can then be addressed more definitively in well-designed randomized controlled trials.
   The final source of information would be studies that emerge from the laboratory. In my experience, this is the place where patients and some physicians make their biggest mistakes. Time and again, I will see a patient take a supplement because some study of prostate cancer cells in the laboratory suggested a possible therapeutic benefit. Overall, very few laboratory findings prove to be true when subjected to clinical trials. My best guess is that it may well be only one out of ten or twenty promising laboratory findings prove to be useful in the clinic. In fact, I am probably being overly optimistic. However, the problem does not stop there.
   Time and again, I have seen patients take a supplement at doses ten or 20 times the highest known safe dose. Time and again, I have seen patients damage themselves in this way. What do I look for? First, I would prefer to see at least one randomized controlled trial that demonstrates a supplement to be safe and effective.
   There are some exceptions. If a supplement has other well accepted health benefits and known record of safety, I will accept a well done Phase II clinical trial. As you will see, there is one situation where I have based my decision on well-accepted general health benefits and one population-based study.
With all of these rules, my list of supplements is quite short and is shown in Table 1. For your interest, Table 2 lists some of the more popular supplements I do not take because I think there is not enough information to justify their use.”

Table 1.
Recommended Supplements
Lycopene 10 mg with each meal
Selenium 200 mcgs a day
Vitamin E 200 IU a day
Fish Oil 4,000 mg a day
Soy isoflavones 200 mg a day
Vitamin D3 (or cholecalciferol) 4,000 IU a day

Table 2.
Supplements I DON’T Recommend
Curcumin
Milk Thistle
Resveratrol or grape seed extract *
Zyflamed
CoenzymeQ10
Ambertose
* I do recommend resveratrol as wine or grape juice

First Clinical Trial of Dark Chocolate

   Dr. Myers emphasizes that heart disease in prostate cancer patients kills about as many men as prostate cancer. We should know something about food supplements for both diseases.
   Our favorite food for a healthy heart is dark chocolate, preferably from Holland. But as the Lancet writes (2005 Aug 20-26;366(9486):608): ” ..<dark chocolate> needs to be .. tested in trials before any clear-cut health benefit can be ascribed to them”. Indeed, trials are needed.
   Dr. Myers and the Lancet both think so, but the Lancet editorial was apparently written without the knowledge of an article written two months earlier: Am J Hypertens. 2005 Jun;18(6):785-91. Effect of dark chocolate on arterial function in healthy individuals, by Vlachopoulos C et al.
   That article presented the results of the very first clinical trial of chocolate! The trial followed a “randomized, single-blind, sham procedure-controlled, cross-over protocol”, — 27 volunteers ate daily 100 g of dark chocolate (74% cocoa, Noir Intense, Nestlé, Vevey, Switzerland).
   Those chocolate eaters showed “a significant increase in resting and hyperemic brachial artery diameter..; the FMD increased significantly at 60 min ..and the AIx was significantly decreased..” The authors conclude that “the consumption of dark chocolate acutely decreases wave reflections, that it does not affect aortic stiffness, and that it may exert a beneficial effect on endothelial function in healthy adults.”
   We have no idea what this all means but that is not important: it suffices to know that dark chocolate has been tested in a clinical trial. And it tastes good.                                                                                                               Happy Holidays!

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October 2005

Will Rogers, Garrison Keillor,and Prostate Cancer

     How do Will Rogers and Garrison Keillor relate to prostate cancer? Will died in an airplane crash in 1935, and whether Garrison has prostate cancer—we don’t know. But both their names appear in an editorial in the September 7 issue of the Journal of the National Cancer Institute entitled “Stage Migration and Grade Inflation in Prostate Cancer: Will Rogers Meets Garrison Keillor” by Ian M. Thompson et al. Dr. Thompson is a urologist in San Antonio (TX)
     Will Rogers (1879-1935) was born in Indian Territory in what would later become the state of Oklahoma. Both his parents were Cherokees, and Will used to quip that, "My ancestors didn't come over on the Mayflower, they were here to greet the boat!" He grew up as a cowboy, and had his first vaudeville booking in New York City in 1905 and his first movie picture in 1918.
     In 1922 he began a weekly syndicated column which eventually reached a large readership through some 350 newspapers. From 1925 to 1928, Rogers traveled the length and breadth of the United States in a "lecture tour". During this time he became the first civilian to fly from coast to coast with pilots flying the mail in early air mail flights. His wit was often caustic: as he explained, "There's no trick to being a humorist when you have the whole government working for you."
Will Rogers is well-known in the medical community because he once said: "When the Okies left Oklahoma and moved to California, they raised the average intelligence level in both states". This is the ‘Will Rogers Phenomenon’: moving one element from one set to another set raises the average values of both sets.
     Consider, for a numerical example, these two sets: 2,3,4 and 5,6,7. The averages are 3 and 6, respectively. Move the 5 to the other set, and the new sets will be 2,3,4,5 and 6,7, with averages of 3.5 and 6.5, respectively. The new averages are both more than the old averages.
     An example of the Will Rogers Phenomenon in prostate cancer is the improved detection of illness (PSA!) that leads to the movement of men from the set of healthy people to the set of unhealthy people. Removing these men from the set of healthy people increases the average lifespan of the healthy group but as the migrated men are healthier than those already in the unhealthy set, adding them raises the average lifespan of that group as well.
     This example of the Will Rogers Phenomenon is the effect of 'stage migration', the discovery of illness by improved diagnostic methods. Survival rates rise in each group, but this can happen without any changes in individual outcomes. An increased 5-year survival rate is not necessarily a proof of progress against prostate cancer! Patients appear to have an extension of their survival after cancer diagnosis when they have in fact experienced no prolongation of their lives.
     Grade inflation is when students receive higher grades now than a few years ago. Do students get smarter, or do teachers give higher scores? A good question and we can ask a similar question in prostate cancer. Gleason scores have become higher over the past 20 years: do patients have a more aggressive cancer, or do pathologists give higher scores?
     This question has been addressed in an article by Dr. Peter Albertsen et al., also in the September 7 issue of the Journal of the National Cancer Institute. Histology slides of the biopsy cores of 1858 men in Connecticut were reread by a pathologist blinded to the original scores; the mean score increased from 5.95 to 6.8. During the 12-year follow-up period 358 men died.
     Grade inflation of the Gleason score appears thus a reality, and as a result the clinical outcomes improved: patients with a Gleason score of 6 now do better than they would have done 12 years ago.
     Why this grade inflation? A premier pathologist, Dr. JI Epstein, wrote an editorial in 2000 with this title: “Gleason score 2-4 adenocarcinoma of the prostate on needle biopsy: a diagnosis that should not be made.” Another pathologist, Dr. C Pan, suggested that the Gleason score should represent small quantities of high-grade cancer, not the two dominant grades.
     Whatever the explanation of the grade inflation, most prostate cancer patients in the Connecticut contingent did ‘better’ with their new, contemporary Gleason score than they did with their old score. Less chance to die of prostate cancer but the total number of deaths (358) did not change!

after Fig. 2 in Albertsen PC. et al.: ‘Prostate cancer and the Will Rogers phenomenon.’ J Natl Cancer Inst. 2005 Sep 7; 97(17):1248-53.

The lines in the graphs are the survival curves for patients whose tumors were assigned Gleason scores 6, 7 or 8 in the original reading (dashed line O) or the contemporary reading (solid line C). The numbers in each panel represent numbers of patients and numbers of deaths [in square brackets].
Only deaths due to prostate cancer are listed.

The diagnosis of higher-grade prostate cancer does not necessarily improve survival, and neither does the diagnosis of additional cancers:

“If all men were screened using the current threshold of 4.0 ng/mL, 1.5 million American men aged 40 to 69 years would be labeled abnormal. Lowering the PSA threshold to 2.5 ng/mL would more than double this number, such that approximately 1.8 million additional men aged 40 to 69 years would be labeled abnormal and face negative consequences of the test result (i.e., biopsy or a cycle of repeated testing and anxiety as long as the uncertainty about whether or not they have prostate cancer persists). If all 1.8 million men had a biopsy, about 1.35 million men would undergo the procedure unnecessarily (i.e., their PSA test results would be considered false positives). The remaining men, approximately 450,000, would be diagnosed with prostate cancer. Whether the lower PSA threshold would have any benefit on morbidity or mortality is not known, but its burden is clear. If all of these men underwent radical prostatectomy, approximately 180,000 men would be expected to be made impotent, approximately 40,000 men would be expected to have at least moderate incontinence, and approximately 1000 men would be expected to die from the procedure alone. The problem is that although it is easy to diagnose more prostate cancer, it is not easy to know who has clinically important disease.”
(from HG Welch et al.: Prostate-specific antigen levels in the United States: implications of various definitions for abnormal. J Natl Cancer Inst. 2005 Aug 3;97(15):1132-7).

Being aware of these issues makes it easy to understand why Ian M. Thompson finished his editorial with a reference to Garrison Keillor who mentions Lake Wobegon as a place “where all the women are strong, the men are good looking and the children are above average”. Dr. Thompson writes: “our current assessment <of prostate cancer> might be: “ ..where all the biopsies are necessary and all cancers require treatment, as all have Gleason scores above 5”.

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September 2005

Prescription Drugs from Canada

   One of our members asked us about pharmacies in Canada. Such a question can be expected from a long-time member of PCNG. Yes, we have long-time and short-time members.
   Short-time members are typically newly diagnosed, and in the process of selecting one of he possible therapies that would ‘cure’ their prostate cancer. Watchful Waiting or Active Surveillance don’t promise a cure – they promise control, or an extension of the decision making time.
   After an apparently successful treatment prostate cancer fades into the background and the patient does not come to our meetings anymore. We are happy for him, and don’t expect anything else.
   Unfortunately, some patients are not that lucky. If you were one of Dr. Walsh’s patients (he is now retired, but was generally considered as the top prostate cancer surgeon in the USA), your chance that the prostate cancer would come back 15 years after the operation would be 31% if you were younger than 50 years when operated, and 42% if you were older than 70 years (Urology, 2003 Jul;62(1):86-91 (Khan et al.).
   Many patients with recurring prostate cancer end up on hormonal therapy, and nowadays Casodex is one of the more popular hormonal medications. Some patients take one capsule per day; others take three capsules per day. One capsule costs a little less than $14 at Costco (the least expensive pharmacy in the USA) and a little more than $7 in Canada, for a potential savings of about $600 per month!
   Many of our long-term members are taking hormonal medicines, and some of them are fortunate enough to have insurance that covers all or almost all of these expensive products. Others are not that fortunate and they may be interested in how to obtain drugs from Canada.
   Excellent information can be found in an article from the October 2005 issue of Consumer Reports, and the following is taken from this article:

Prescription Drugs:The Facts about Canada.

“Even though the practice is illegal, Americans in droves have been importing prescription drugs from Canada. Last year, an estimated 2 million U.S. citizens spent $800 million on medicines purchased from Canadian pharmacies by fax, phone, or Web site. That's 33 percent more than in 2003. ..
What's happening is controversial. The U.S. Food and Drug Administration stands foursquare against imports, arguing that it cannot ensure they are safe. Many Americans, however, believe that buying from Canada, a familiar next-door neighbor, is no more dangerous than picking up a prescription at a local drugstore. ..
Here's the reality of the government's arguments against buying from Canada:
Canadian drugs are not as safe as U.S. drugs. False. The FDA maintains that “many drugs obtained from foreign sources that purport and appear to be the same as U.S.-approved prescription drugs, are, in fact, of unknown quality.” Furthermore, FDA officials have expressed the concern that news of product recalls issued in Canada may not reach U.S. consumers.
But Canada's manufacturing and regulatory system is comparable to that of the U.S., according to an October 2003 study by the state of Illinois' Office of Special Advocate for Prescription Drugs. FDA critics counter, moreover, that the agency cannot entirely ensure the safety of drugs manufactured in the U.S.
The Illinois study also concluded that Canada's pricing and distribution system is less likely to foster the drug counterfeiting that concerns the FDA. Drugs in the U.S. typically move through multiple vendors (manufacturers, wholesalers, repackagers, retailers, second repackagers, etc.) before reaching the patient. In Canada, medications are dispensed mainly in typical dosages and shipped in sealed packages directly from manufacturer to pharmacy. In a June 2004 report, the U.S. Government Accountability Office said that all of the prescription drugs it ordered from Canadian Internet pharmacies contained the proper chemical compositions, were shipped in accordance with special handling requirements, and arrived undamaged…
Canadian drugs are not always cheaper. True. To see how much consumers can expect to save by buying from Canadian pharmacies, we asked PharmacyChecker.com, a group that evaluates online pharmacies, to compare drug prices from its highest-rated Canadian and U.S. Web sites. When we compared the lowest prices of five well-known brand-name drugs from both Canadian and U.S. sources, the Canadian pharmacies saved consumers between $72 and $226 per prescription (including shipping charges). Such medications are cheaper in Canada in large part because its federal Patented Medicine Prices Review Board has the authority to limit prices that it deems to be excessive.
But in a similar comparison, a U.S. site had the best prices for the five most prescribed generic drugs. Because generic drugs cost less, the savings are less: from $7 to $31 per prescription. “The larger, more competitive generic market in the U.S. helps keep prices down,” says Thomas McGinnis, the FDA's director of pharmacy affairs.
You could get arrested. True but unlikely. Ordering prescriptions from Canadian Web sites violates the Federal Food, Drug, and Cosmetic Act, which generally makes it a crime for anyone other than the original manufacturer to import a drug, even if it was first manufactured in the U.S.
So far, however, the FDA has focused its enforcement efforts only on those who “commercialize” drug importation. One example: RxDepot, an Oklahoma prescription drug service that was forced to shut down in 2003. But there are currently no plans to charge consumers. McGinnis says, “We are allowed to exercise enforcement discretion, and it's not our policy to go after individuals.”
Many Internet sites are not legitimate pharmacies. True but avoidable. CIPA warns that many Web sites selling medications have been created to lure U.S. consumers seeking cheaper prices. Patients who order from such sites run the risk of receiving medications that are subpotent, improperly handled, or counterfeit. Furthermore, the FDA says some Web sites may not tell you that a drug they sell you is obtained from an overseas supplier. “You may be sent a drug that originated in Australia, Great Britain, or Pakistan,” says McGinnis. “We don't know anything about the strength, quality, or purity of those medications.”
Patients, however, can avoid such problems by ordering only from pharmacies that have been thoroughly scrutinized by CIPA. To display a CIPA seal on its Web site an online pharmacy must have a valid Canadian license, submit to a quarterly on-site inspection, and keep personal information confidential in compliance with PIPEDA, the Canadian privacy act similar to The Health Insurance Portability and Accountability Act, or HIPAA, in the U.S.
The online pharmacy must also require you to submit a valid prescription and medical history and to check for possible drug interactions. And CIPA members must let you know in advance if they are supplying you with a medication from another country so you have the right to refuse. You can find a list of the 37 Canadian pharmacies with CIPA seals at www.ciparx.ca/cipa_pharmacies.html.
Another source of information about online pharmacies is PharmacyChecker.com (P4 in “LINKS” on PCNG’s web page) whose review process is similar to CIPA's. ..

WHAT TO DO

The flow of prescription drugs from Canada may not last forever. Ujjal Dosanjh, the Canadian Health Minister, proposed on June 29 that a new supply network be established to keep tabs on the nation's drugs and that bulk shipments to the U.S. be stopped if the system detects a shortage. In addition, he proposed a requirement that “an established patient-practitioner relationship” should exist before a physician may prescribe any medications. Whether or not this means that U.S. citizens will have to meet face-to-face with a Canadian doctor before they can purchase drugs will not be determined until sometime this fall, when the minister plans to introduce legislation.
But whatever happens, you should take the following steps before ordering:
• Check Consumer Reports Best Buy Drugs (www.CRBestBuyDrugs.org) to learn about drug options, including generics and over-the-counter drugs, that could save you money.
• Ask your doctor to prescribe generic drugs, which cost much less than brand-name drugs. Remember to buy them in the U.S., where they are generally cheaper than in Canada.
• If you need a high-priced, brand-name drug, check with the Partnership for Prescription Assistance (www.pparx.com; 888-477-2669), which lets you find out in one step whether you are eligible for any of the 275 programs that offer cost savings to consumers.
• If ordering from Canada is the only way you can afford the medication you need, go to PharmacyChecker.com for recommendations of approved outlets, and look for the CIPA seal to protect yourself.”

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August 2005

Your PSA is 0.8; my PSA is 1.1, and his PSA is 2.3 - what does that mean?

We have been asking friends and colleagues whether they know their PSA. 'Oh yes' many answer, 'My doctor says that it is OK, and he knows it'. 'But do you know it?' is our response. 'Uh, no'. That is typical, unfortunately.
    We have been bugging Rick about his PSA and he finally realized that in order to get rid of our questioning he had to remember the number. It was 1.1. What does it mean that Rick has a PSA of 1.1?
    Here, in the USA any value below 4.0 is generally considered normal, and 1.1 is thus a normal value. But so is 0.8, or 2.3. All normal values, but they are not the same.
    The significance of the differences in normal values can be deduced from a recent study: 4-YEAR PROSTATE SPECIFIC ANTIGEN PROGRESSION AND DIAGNOSIS OF PROSTATE CANCER IN THE EUROPEAN RANDOMIZED STUDY OF SCREENING FOR PROSTATE CANCER, SECTION ROTTERDAM, by Schroder, FH et al., and published in The Journal of Urology, Volume 174(2), August 2005, pp 489-494.
    In Rotterdam (The Netherlands) 42,376 men were randomized into two groups: 21,210 in the screening group, and 21,166 in the control group. 19,970 men were actually screened. In 9,779 of these men a biopsy was recommended if the PSA was 4.0 ng/ml or greater, and/or an abnormal rectal examination and/or a suspicious transrectal ultrasound were found. As of May 1997 the PSA cutoff for recommending a biopsy was decreased to 3.0 ng/ml, and the use of rectal examination and transrectal ultrasound was discontinued.
    A total of 10,191 men were found to have a PSA greater than 3.0, and 541 of these men (5.3%) had prostate cancer.
The group of men with a PSA less than 3.0 consisted originally of 21,210 minus10,191, or 11,019 men, but for various reasons only 5,771 men were followed into the second round of screening, four year later. There were 662 men (11.5% of 5,771) with a PSA greater than 3.0 in this second round; 578 of those men were biopsied, and 152 men had prostate cancer.
    This makes one pause when the doctor says that everything is fine because the PSA is normal, i.e., below 4.0 ng/ml. We have summarized, in the February 2005 issue of this newsletter, an article that maintains that a PSA of 0-4.0 ng/ml should not be considered as a range that excludes prostate cancer.
    So what is Rick's chance of being diagnosed with prostate cancer in the next few years? His PSA is not the lowest possible. Of the 2,622 men with a PSA less than 1.0 in the first round only 23 men (less than 1 percent) had a PSA more than 3.0 in the second round. Four had prostate cancer.
    There were 2,268 men with a PSA between 1.0 and 1.9 in the first round ─ 211 men (almost 10 percent) had a PSA greater than 3.0, and 43 men had prostate cancer in the second round of screening. There were only 881 men with a PSA between 2.0 and 2.9 in the first round, but 428 (almost 50%) had a PSA greater than 3.0 in the second round, and 105 had prostate cancer.
   Look at these numbers, and one sees that Rick is fortunate of having a PSA of only 1.1 ng/ml. He is just outside the group with the lowest PSA, and his chances of being diagnosed with prostate cancer are slim indeed. Not as slim as those in the group with the lowest PSAs, but still much better than those with a PSA between 2.0 and 3.0.
    So what is the morale of this story? Know your PSA, keep track of the changes over time, in particular when your PSA is between 2.0 and 3.0. ‘Serial PSAs’ are the name of the game, and ‘PSA progression’ is critical. It should be small.
    Good luck!

Acne as a Teenager? Good for the Heart, Bad for the Prostate.

Am J Epidemiol. 2005 Jun 15;161(12):1094-101. Acne in adolescence and cause-specific mortality: lower coronary heart disease but higher prostate cancer mortality: the Glasgow Alumni Cohort Study. Galobardes B et al. ...This study investigated the association between history of acne in young adulthood, a marker of hormone activity, and cause-specific mortality in the Glasgow Alumni Cohort Study. Male students who attended Glasgow University between 1948 and 1968 and participated in voluntary health checks reported history of acne (n = 11,232). ... The two groups did not differ in other adolescent (height, body mass index, blood pressure, and number of siblings) or in most adult risk factors. Students who reported a history of acne had a lower risk of all-cause (hazard ratio = 0.89, 95% confidence interval (CI): 0.76, 1.04) and coronary heart disease (hazard ratio = 0.67, 95% CI: 0.48, 0.94) mortality but had some evidence of a higher risk of prostate cancer mortality (hazard ratio = 1.67, 95% CI: 0.79, 3.55). This study shows that androgen activity during adolescence may protect against coronary heart disease but confer a higher risk of prostate cancer mortality.

Shocking Percentages!

J Clin Oncol. 2005 Jul 25,Riding the Crest of the Teachable Moment: Promoting Long-Term Health After the Diagnosis of Cancer. Demark-Wahnefried W et al. Cancer survivors are at increased risk for several comorbid conditions, and many seek lifestyle change to reduce dysfunction and improve long-term health. … that only 25% to 42% of survivors consume adequate amounts of fruits and vegetables, and approximately 70% of breast and prostate cancer survivors are overweight or obese. ...

Statins Reduce Prostate Cancer Risk?

Am J Epidemiol. 2005 Aug 15;162(4):318-25. Statins and prostate cancer risk: a case-control study. Shannon J et al. …Thirty-six percent of 100 prostate cancer patients and 49 percent of controls had a record of any statin use. Following adjustment for other potential risk factors, statin use was associated with a significant reduction in prostate cancer risk (odds ratio = 0.38, 95% confidence interval: 0.21, 0.69). Furthermore, in analyses stratified by Gleason score, the inverse association with statin use was maintained only among men with Gleason scores of >/=7 (odds ratio = 0.24, 95% confidence interval: 0.11, 0.53). The results of this case-control study suggest that statins may reduce the risk of total prostate cancer and, specifically, more aggressive prostate cancer.

Small Pilot Study Shows that Pilots Stabilized their PSA with Statins
(Dr. Myers prescribes statins to most of his patients)

J Urol. 2005 Jun;173(6):1923-5. The effect of statins on serum prostate specific antigen levels in a cohort of airline pilots: a preliminary report. Cyrus-David MS et al. PURPOSE: Reports of the effect of treatment with statins on prostate cancer risk are inconsistent. We performed a pilot study to assess the effect of statin treatment on a surrogate marker for prostate cancer risk, that is serum prostate specific antigen (PSA), in a cohort of airline pilots from 1992 to 2001. ... The treatment group was composed of 15 men with hypercholesterolemia [cholesterol was high] who received statins and the comparison group of 85 with normal serum lipid levels [cholesterol was normal] during the review period. ...Serum PSA was significantly higher in the treatment group at baseline relative to the comparison group (p = 0.05). Interestingly there was no significant difference between the groups on subsequent followup. There was a 41.6% decrease in mean serum PSA in the treated group by visit 4. Simultaneously mean serum PSA increased by 38% in the untreated group. CONCLUSIONS: Our results suggest that treatment with stay lower serum PSA with time. These results must be confirmed in a larger study population ...

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July 2005

What is New in Prostate Cancer Research and Treatment?
(Comments on abstracts presented at the Annual Meeting of the AUA in San Antonio, TX)

Thousands of urologists, other physicians, and scientists convened in San Antonio (TX) to look at posters, listen to talks, and watch videos at the Annual Meeting of the American Urological Association, May 2005.

We were not there, but have nevertheless an idea what was going on by reading the abstracts. Nowadays we read them “on line”. Click on http://www.aua2005.org/am05/content/abstracts/ and enter “prostate cancer” ─ there are 474 presentations on prostate cancer! Many are presented as text files only, but some can be seen as they were presented in the poster sessions, as PDF files. Click on http://www.posters2view.com/aua/search.php to find the posters. The presentations vary in significance. They are screened, but not as carefully as papers in refereed journals. There are progress reports of on-going studies that have already been published or will be published shortly, and there are presentations with brand-new information. The full text of the presentations referred to in this newsletter can be seen in http://pcngcincinnati.org/.

Patients diagnosed with prostate cancer need time to educate themselves about the disease, to schedule treatment, and to receive insurance OKs. How much time between diagnosis and treatment is permissible?

This question is answered in the # 1002 poster: “The Impact Of Time From Biopsy To Surgery On Biochemical Recurrence Following Radical Prostatectomy For Clinically Localized Prostate Cancer”. Stephen Boorjian, Fernando J. Bianco Jr., Peter T. Scardino, and James A. Eastham, NYC, NY. The data from these authors suggest that a delay from prostate biopsy to RP of up to 1 year is permissible, even for patients classified as high risk of recurrence. “These findings may be used to allay patient anxiety.”

We looked for new information on Intermittent Androgen Deprivation. There was one presentation, #813: “Phase III study Intermittent Monotherapy versus Continuous Combined Androgen Deprivation, an International Cooperative Study”. Fernando EC Calais da Silva, Lisbon, Portugal; Frederico Gonçalves, Bratislava, Slovakia; Americo Santos, Portugal; Jan Kliment, , Slovakia; Spyros Pastides, Greece; Marques Queimadelos, Spain; Cris Robertson, Spain were the authors. An international study indeed! Most other presentations and articles on Intermittent Hormonal Therapy (IHT) have also been authored outside the USA, in Canada, Belgium, and Germany. The results are all about the same: IHT is as good as or better than Continuous Hormonal Therapy and the side effects are less.

Your Insurance Determines your Treatment: #192 “Prostate Cancer Treatment and Insurance Status: Data from CaPSURE”. Natalia Sadetsky, Eric P. Elkin, David M. Latini*, San Francisco, CA; Janeen DuChane, Lake Forest, IL; Peter R. Carroll, Lake Forest, IL. Insurance status was summarized by 6 categories: Medicare only, Medicare plus supplement, HMO, PPO, fee for service (FFS), and Veteran’s Administration (VA). 4491 men met the inclusion criteria. There was a strong association of initial treatment and insurance. Compared to Medicare patients, men in the VA system were more likely to receive BT (brachytherapy) than RP (radical prostatectomy), while patients with PPO insurance were less likely to receive BT. Men with PPO and HMO insurance were less likely to receive HT (hormonal therapy) when compared to patients insured by Medicare, and VA patients received hormonal therapy more often than Medicare patients.

African Americans are at Increased Risk for Prostate Specific Mortality but Adjustment for Insurance and Income Diminishes the Effect of Race on Survival! #465 “Impact of Socio-economic Factors on Long Term Mortality in Men Diagnosed with Clinically Localized Prostate Cancer.” Ash Tewari*, Lee Richstone, Assaad El-Hakim, New York City, NY; George Divine, Mani Menon, Detroit, MI. identified 2,046 men with local or regional prostate cancer: 1243 Caucasian and 803 African-American (AA) men. Patients received radical prostatectomy (RRP, 37%) radiation therapy (RT, 34%), or watchful waiting (29%). African Americans had higher baseline PSA (12.8 vs. 10.2, respectively). There were no significant differences in tumor stage or grade. Caucasian men were more likely to receive RRP compared with AAs (43% vs. 23%), whereas AAs were more likely to be treated with RT (41 % vs. 28%). Caucasians had higher incomes; 55% earned >$40,000 compared to 12% of AAs. African Americans were more likely to have HMO coverage versus Caucasians (42% vs. 35%). African Americans had decreased cancer specific survival (CSS). Multivariable models demonstrated that adjusting for clinical factors or type of treatment had minimal impact on the association of race with CCS. However, when adjusting for HMO insurance and income, the association of race with poor outcome greatly diminished.

When should patients on watchful waiting stop waiting? #1003 “Progression of Biopsy Grade in Men with Prostate Cancer Managed by Watchful Waiting”. Jonathan R Osborn,, Gerald W Chodak, et al., Chicago, IL assessed if changes in pathologic tumor grade on repeat prostate biopsies could help identify patients that should undergo definitive therapy following watchful waiting. Men with clinically localized CaP treated by watchful waiting were advised to undergo repeat biopsies every 1-2 years after initial diagnosis.
Patients underwent up to 7 repeat biopsies: 35% percent (14/40) of the patients showed an increase in biopsy grade to Gleason 7 or greater. Three progressed to Gleason 7 within 2 years, 4 progressed between 2 and 4 years, and 7 progressed at greater than 4 years from initial diagnosis. Among patients showing progression, 4 continued with watchful waiting, 4 chose androgen ablation, 1 had a radical prostatectomy, 1 had brachytherapy, 3 opted for a combination of therapies and 1 has not yet decided. Of 12 men with more than 1 year of PSA results prior to the Gleason 7 biopsy, 7 (58%) had a PSA rise of >2.0 ng/mL within a year of progression. In contrast, 14/26 (54 %) had a rise of more than 2 ng in the year prior to a biopsy when there was no change in the biopsy grade. Seven patients (26%) underwent definitive local or systemic therapies without histological progression beyond Gleason 6. Median length of follow up (to curative treatment, or most recent PSA measurement) was 61.0 months (range 6-153). Conclusions: “In men managed without local or systemic treatment for CaP, the risk of progressing to a Gleason score of 7 or greater on repeat biopsy is approximately 35% of those followed for more than 4 years. A rise of >2 ng/ml in the year prior to the biopsy failed to identify the patients with an increase to Gleason 7. Serial biopsies in patients undergoing watchful waiting may offer a good option for identifying men with more aggressive cancers who will need definitive therapy but changes in PSA was not a useful parameter.”

Viagra is important for RP patients. #270 “Five-year Potency Status after Radical Prostatectomy…”Kalyana C Nandipati*, Rupesh Raina, Ashok Agarwal, Craig D Zippe, Cleveland, OH. ”The reported potency rates after radical prostatectomy (RP) vary from 11-86% and are often reported 12-24 months after surgery. 5-year potency status after RP has not been reported in the literature… At 5 years, sexual activity following radical prostatectomy decreases 50%, most of them due to loss of interest and associated medical co-morbidities. At 5 years 38% (43/113) were sexually inactive. The vast majority (77.8%) of radical prostatectomy patients are Viagra/erectaid dependent, with only 22.2 % having natural erections sufficient for intercourse.”

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June 2005

Your PSA is High – What Next

Your PSA (produced by the prostate and measured through a blood test) is 4.5, and your doctor says that this is not normal, it is too high. Normal is a PSA of less than 4.0, he says, and that is what you had a year ago. You worry because your great-uncle died of prostate cancer ― does this anomalous PSA reading mean that you have cancer? No!! Although it could be possible, it is more likely that you don’t have prostate cancer that needs to be treated. But it IS likely that a minor change in your PSA may lead to several visits to doctors, and you better be somewhat knowledgeable about the prostate and its high PSA. The following pages may help you to acquire the knowledge that gives self-confidence and to prepare you to make better decisions. That knowledge will also make it easier to communicate with your doctor

prelude

1. An unexpected high PSA should not lead automatically to a biopsy of the prostate. A biopsy (the taking of tissue samples, with hollow needles) can demonstrate the presence of cancer, but there is no need to undergo a transrectal ultrasound (TRUS) guided biopsy if cancer can be ruled out beforehand. Biopsies are invasive, sometimes painful, and costly. A positive rectal examination (DRE) should be followed by a biopsy, but if the DRE is negative and the PSA elevated, a blood test that determines the free PSA percentage can be useful. A free PSA percentage over 25% is associated with a low risk of prostate cancer, whereas a free PSA percentage under 15% is associated with a higher risk of prostate cancer1. (The 1 refers to a reference at the end of this document, and clicking on the 1 in pcngcincinnati.org leads to an abstract of that article).

2. A high PSA can point towards prostatitis (inflammation of the prostate), an entirely benign disease that does not increase a man’s chance to develop prostate cancer. Acute and chronic bacterial prostatitis is caused by bacterial infections, and nonbacterial prostatitis is an inflammation of unknown cause. Asymptomatic prostatitis has no urinary problems but the PSA is elevated nevertheless. To exclude bacterial prostatitis as the cause of your high PSA the doctor will proscribe 4 to 6 weeks of Cipro or a similar antibiotic. Some of the nonbacterial prostatitis responds to NSAIDs such as ibuprofen (Motrin, Advil, etc.) or naproxen (Aleve etc.). The PSA is measured again after the Cipro therapy― you probably had bacterial prostatitis if there is significant lowering of the PSA! Prostatitis is one of the reasons that cancer is not found in about 70% of men with a PSA of 4-10 ng/ml.

3. You may also have BPH: Benign Prostate Hyperplasia. BPH is common, occurring in 70% of men 60-70 years old. The prostate grows over time but that growth is not the result of cancer. It is a ‘benign’ growth, but that word appears a misnomer if your BPH made it difficult to urinate or created urinary problems such as urinary retention. Your doctor may feel the size of your prostate with his finger (DRE: Digital Rectal Examination – digit means finger) or refer you to an urologist who can measure the prostate’s volume more precisely with ultrasound. As the amount of PSA produced by the prostate is about the same per cubic centimeter or milliliter, a large prostate will produce more PSA than a small one. This is the reason that a biopsy report negative for cancer must include the volume of the prostate. BPH makes it difficult to urinate because the urethra gets squeezed by the growing prostate. Increasing the diameter of the urethra is done with the TURP procedure, but that is only after Hytrin and other so-called alpha-blockers, or Proscar or Avodart have been unsuccessful. Alpha-blocker treated patients have been reported to have a higher risk of TURP compared to patients treated with Proscar or Avodart2.

4. What if the free PSA % is high (25 or more) and your prostate is of normal size? Don’t panic. Your doctor will most probably ask you to come back in 1 or 2 months for another blood test (remember that a high free PSA % is associated with a low risk of prostate cancer). A high PSA can have resulted from prostate massaging by riding a bicycle or from sexual intercourse less than 24 hours before the blood test. PSAs that go up and down are more indicative of a benign process than a malignant process such as cancer.

5. A biopsy after a negative DRE but a high PSA >4 but < 10 ng/ml results in a cancer diagnosis in less than one third of the men. A better indicator for a biopsy is the uPM3 urine test, predicting cancer, as confirmed by biopsy, with 81% accuracy, compared to 47% accuracy for PSA elevations3. At present (early 2005) only one laboratory can do the test (Bostwick Labs: tel. 800-214.6628); Medicare and most private health insurance plans will pay the cost.

6. Your doctor will refer you to an urologist as a result of a positive DRE; a consistent increase in PSA values; a low free PSA percentage, or a positive uPM3 urine test. He (or she) ruled out prostatitis and BPH as cause of the elevated PSA. The urologist will advise you to have a biopsy of your prostate by inserting 6 or 10 or even 12 hollow needles in it. The prostate tissue in the needles (the ‘cores’) will be studied by a pathologist. Ask the urologist to determine the volume of your prostate! Ask him also for a printout of one of the transrectal ultrasound (TRUS) images he used to determine where to shoot his needles. Most men think that the biopsy was not painful, but there are exceptions.

7. The urologist will present the pathologist’s report at your next visit. It is an important document, and you should ask for a copy. There may be or may not be adenocarcinoma (the most common form of prostate cancer) or “PIN”. (Don’t worry about having PIN—"…isolated PIN was never predictive for prostate cancer. PIN should not be an indication for repeat biopsy"4). The pathologist looks also for cancer growing near nerve cells, describing this as perineural invasion, or finds that perineural invasion is absent. Prostate cancer is further defined with the ‘Gleason Score’ and the amount of cancer in the core, the ‘core percentage’. The Gleason score (GS) is nowadays written as follows: 7 (3,4), a number followed by two numbers between parentheses. The sum of the two numbers is the score. Better is the addition of a percentage: 7 (3, 4-5%). The numbers indicate the aggressiveness of the cancer: 4 is worse than 3 and 5 (the maximum) is worse than 4. A cancer with a GS of 7 (4,3) is worse than a 7 (3,4) cancer, and a 7 (3, 4-40%) is worse than a 7 (3, 4-5%) cancer. The core percentage gives the percentage of cancerous tissue in the cores – it may range between 5 and 100%. Is it 5% in one of nine cores, or 5% in 4 of six cores? The number of positive cores is also important.

8. The urologist says that you have cancer: you are in a panic. He (or she) says that you should do something about it. You very much agree. One of the options, he says, is a radical prostatectomy (RP). The prostate will be cut out, and you will be rid of your cancer. The urologist will tell you that RP is considered the ‘golden standard’ in prostate cancer therapy, but that there are other treatments and that YOU must make the decision what to do. He (or she) most likely will discourage "watchful waiting", but may give you a referral to see a radiation oncologist.

9. You come home, and are still in a panic. This is the moment that you should begin three activities: getting your papers in order, learning about prostate cancer, and getting your partner involved (we hope you have one). Those activities will help you to get through the ordeal.
1. Getting your papers in order does not imply writing your last will and testament as the chance that you will expire in the next 5 years is very small indeed. Getting your papers in order entails going to your PCP asking for copies of all PSA measurements, and combining those with a copy of the pathologist’s report and any other relevant document. This collection will become your prostate cancer digest to be shown to other doctors you are going to see. An additional PSA? Other blood tests? Add these and other measurements to your PC digest!
2. Learning implies reading books, surfing the Internet and sharing information with other patients at a support group.
3. Getting your partner involved: share with your partner your knowledge, your fears, and your hopes.

10. Learning about prostate cancer begins with learning some basic percentages. It begins with the percentage of men with prostate cancer. Not cancer detected with a biopsy but cancer detected by autopsies. Amazingly, having prostate cancer at 65 (the average age that prostate cancer is detected) is normal ― being without cancer is NOT normal. About 65% of all 65 year old men have cancer of the prostate according to autopsies! Most of those cancers are not detected because there was no biopsy, or because the hollow biopsy needles missed the cancer. Still, the American Cancer Society expects that 232,900 men will be diagnosed with prostate cancer in 2005. Only 30,350 men are expected to die of this disease, and the percentage of men with prostate cancer dying of the disease is thus not that large. Compare these percentages with those having lung cancer or pancreatic cancer – yes, you are relatively fortunate to have prostate cancer and not another more lethal cancer. Prostate cancer grows slow-most of the time.

staging

You will discover that the urologist was not kidding when he said that you must make up your own mind what to do. Doctors give advice and members of a prostate cancer support group such as PCNG share their experiences. You will have a great deal of knowledge in addition to that what you gathered from the Internet and from reading books. What to do? As always, learn before making a decision.

11. The first question you could ask yourself is: must I be in a hurry? It depends. Have additional PSAs measured ― it may help to determine your sense of urgency. A rapidly increasing PSA –e.g., in one month from 4.5 to 4.8 or from 11.0 to 11.5-- is worrisome. Another test that may help you in that respect is the PAP (prostatic acid phosphatase) test. An anomalous (high) PAP, a high PSA (>20), a high Gleason score (8 or more), or a rapidly increasing PSA may be reasons that you want to make up your mind quickly, i.e., in two or three months. PC generally grows slowly! When all indicators are positive, you may take more time but keeping track of your PSA is fundamental.

12. Confirmation of your Gleason score may be crucial! You could need a second opinion from another pathologist’s examination of the biopsy cores, from one of the experts who look at prostate cancer biopsies exclusively5. Finding a GS of 7 instead of a GS of 6 (or vice versa) may influence your decision making process. Insurance or Medicare will usually cover a second opinion ($4-500). A second opinion is recommended for all men diagnosed with prostate cancer and in particular for those with a GS of 7 or less.

13. The urologist has another tool (his or her finger) that indicates how serious your cancer is. It is classified as follows: T1: cancer not felt with DRE: T1a or T1b: cancer in tissue removed by TURP; T1c: cancer in tissue removed by biopsy needles; T2: cancer felt with DRE, but still confined to the prostate (T2a/b: one lobe: T2c: two lobes); and T3 and T4: cancer is felt to be outside the prostate as well. This T+number is known as clinical stage, and it defines your cancer, together with PSA and Gleason score (GS). You may introduce yourself at a prostate cancer support group as a T1c, PSA 8, 10% core with cancer, and a GS of 6. Or as a T2b, PSA 9, 25% core and a GS of 7.

14. If you have a T3 or T4 classification, a high PSA (>10 and if your PSA is less than 10 but your GS is 8 or more), or have bone pain, expect your urologist to prescribe a bone scan. Such a scan will see whether the cancer has escaped the prostate and is in your bones (typically the back bone or the ribs). The cancer is now metastatic. CT (‘CAT’) scanning seldom provides any useful diagnostic or staging information when the PSA is less than 20 ng/ml -it is indicated rarely6. The scans are a few of the many procedures that may lead to a better staging of the cancer – see “A Primer on Prostate Cancer” by Stephen Strum and Donna Pogliano for additional procedures.

therapy

There are three responses considered by men just diagnosed with prostate cancer (PC): watchful waiting (WW), local therapy (treating the cancer in the prostate) such as radical prostatectomy (RP) or brachytherapy (‘seeds’), or hormonal therapy. Local or hormonal therapy may not be necessary for men with minimal disease because the chance that they will die of PC is small indeed; those men may opt for WW. About all men diagnosed with prostate cancer take medications (either prescribed or OTC: over the counter) that belong to the realm of alternative or complimentary therapy.

15. Watchful Waiting and Active Surveillance –
“Good risk prostate cancer, defined as patients with a Gleason score of 6 or less, PSA <10–15, and T1c–T2a, now constitutes 50% of newly diagnosed prostate cancer. For most of these patients, the disease is indolent and slow growing. There is substantial evidence that it does not pose a threat during the lifetime of most patients. The challenge is to identify those patients who are not likely to experience significant progression while offering radical therapy to those who are at risk”7.
“Twenty years ago, most men diagnosed with prostate cancer had advanced disease. Only about 25 percent of men were diagnosed with cancer that appeared to be confined within the prostate. Today, the story is nearly reversed: 75 percent of men diagnosed with prostate cancer have clinically localized disease. Today, some men are found to have minuscule amounts of cancer—smaller than 0.2 cubic centimeters, about the size of a pinpoint, captured by sheer chance during a biopsy. For some men, these are cancers that will never cause harm, and ideally, should never have been diagnosed. Which leads to a treatment dilemma: If this kind of small-volume cancer is diagnosed, what should happen? To treat, or not to treat? What should a man do? For some men, these are cancers that will never cause harm, and ideally, should never have been diagnosed. Which kind of cancer is it—the “good” kind that seems content to remain in the prostate and never causes harm, or the kind that will be less indolent over time, and needs to be nipped in the bud?”8
For a man in his forties or fifties, a very small tumor might be significant, but in an older man a very small tumor probably isn’t significant because of the time it takes for that tumor to grow and become dangerous. For men who are in their sixties or older, watchful waiting (WW) or expectant management (term used at Hopkins Univ.) or active surveillance (the name indicates more monitoring than with watchful waiting) may well be a rational approach. Criteria7 for such a treatment include a Stage 1c cancer (cancer detected because of an elevated PSA), free PSA > 15%, PSA density (=prostate volume divided by the PSA) < 0.15, Gleason score 6 or lower, cancer in only 1 or 2 cores, and less than 50% in each core. Watchful waiting is in some respects an unfortunate term: patients can be actively involved in battling their cancer. Their treatment can consist of eating less fat; more vegetables, more fruit and fish, and the use of supplements like vitamin E, lycopene, and selenium.They have their PSA monitored regularly. This is not just ‘waiting’. This is taking action, and this could be called aggressive watchful waiting (AWW).
Dr. Ornish conducted a small trial comparing two groups: one just waiting and the other one with a modified diet and stress reduction exercises9. The men all had PSA levels of 4 to 10 ng/ml and Gleason scores of less than 6. The experimental group ate an entirely plant-based low-fat diet that emphasized unprocessed whole foods. Participants also engaged in moderate aerobic exercise, stress management, and psychosocial group support. All men had declined conventional treatment. After one year, mean PSA levels decreased by 3% in the experimental group but increased by 7% in the control group. Dr. Ornish suggests that patients make comprehensive changes in diet and lifestyle, regardless of whether they have decided to have local therapy. Being on AWW does not exclude local therapy! The change from AWW to local therapy can be induced by a steadily increasing PSA, on the base of the speed of the increase, not on the absolute value (a steady increase from 4 to 6 over four years is worse than an increase from 9 to 11. One needs to determine the PSA doubling time (PSADT). A doubling time of one year implies that the PSA increased from 3 to 6 (or from 22 to 44) in one year. In a study10 with 231 patients on watchful waiting the median PSADT was 7 years (in 7 years, e.g., from PSA 5 to PSA 10). If the PSADT became less than 3 years the men were advised to have local therapy. Choosing (aggressive) watchful waiting is thus not necessarily a permanent decision. Whether postponing final treatment (for those who had watchful waiting followed by local or hormonal therapy) has an impact on the timing of death due to prostate cancer is unknown but appears unlikely in most cases.

16. Local Therapies –
Fortunately, relatively few men will have to choose between the various hormonal therapies. Most men have prostate cancer that points to a local therapy as the best choice. Those lucky men must still choose, but it is now between the various local therapies that will remove the cancer. But they should also consider watchful waiting or aggressive surveillance: the cancer might grow slowly and the objective will be to die with prostate cancer and not because of prostate cancer. There are choices to be made, and it is not obvious which choice is best. What makes it even more difficult is that the choice is also a reflectance of the personality of the patient, and this explains why two patients with the same diagnosis might choose two radically different therapies. And there are the limitations of the various insurance plans: HMO, PPO or Medicare. What appears to be needed is the answer to a few simple questions: Can local therapy be delayed for several months or should it be treated quicker? One study11 found that it doesn’t make a difference. Is a local therapy ‘better’ than watchful waiting? Is RP ‘better’ than brachytherapy? Is laparoscopic RP ‘better’ than a normal RP? What is meant with ‘better’? Less mortality? Less side effects such as impotence or incontinence?
More important than choosing a certain local therapy is the choice of who will do it: in general, the physician with the most experience will do a better job than the one with little experience, irrespective of the type of therapy. The patient should ask “How many (laparoscopic) RPs or how many brachies have you done in total, and how many this year?” We warn you: doctors don’t like these questions, partially because you may discover that the top physicians don’t necessarily live in Cincinnati. They may live in Detroit, Miami, NYC, (robotic laparoscopic RP), Baltimore, Columbus or Cleveland (RP), and Atlanta, Seattle or Sarasota (brachytherapy). One might prefer to go to Miami instead of staying in Cincinnati, but will the insurance pay for that?

17. RP, EBRT, brachytherapy and brachy+EBRT are most commonly chosen as local therapy of prostate cancer. One gets rid of the cancer! That notion is attractive, and its appeal should not be underestimated. But local therapy does not guarantee survival.

For an understanding what is meant with survival, look at the diagram10 to the left. It is part of a diagram that shows that men diagnosed with a Gleason score of 6 have a much better chance of survival than those with a Gleason score of 8, 9 or 10. The mortality of GS 6 men from non-prostate causes is greater than that from prostate cancer, opposite to the mortality in the GS 8-10 men. The diagrams are based on men who did not have local therapy. They were on ‘watchful waiting’ (WW). So how would they compare with men who had their prostate removed? That question is answered in a study12 in which 695 men (PSA < 50, no T3/T4, no positive bone scan) were randomly assigned to radical prostatectomy (RP) or watchful waiting. After 10 years the conclusions can be summarized in the diagram below, showing that there are more deaths from prostate cancer in men on WW than in men who had RP, but only in those younger than 65 years. If you are 65 years or older, it made no difference what therapy you had been assigned to as far as death from prostate cancer was concerned. But this does not imply that there were no differences between the two groups of men. Those on watchful waiting would have less impotence and incontinence that may result from a RP, but they would carry the considerable psychological burden that their cancer is still in them. Men on WW had also more treatment with hormonal therapy than men who had a RP: 177 of the 348 men in the watchful waiting group but only 110 of the 347 men in the RP group. The WW men didn’t begin hormonal treatment earlier: the mean time to such treatment was 4.5 years in the RP group and 4.8 years in the WW group.
Local therapy is a ‘no-brainer’ for high-risk patients or those younger than 65 years. The problem for these men is the choice between the various local therapies and whether hormonal treatment should be added as an adjunctive therapy (only for those with high-risk prostate cancer). And if hormonal therapy is to be added, what type of hormonal treatment: Zoladex (big needle)? Lupron (small needle)? Casodex alone? CHT? ADT3? Learn from other patients how they experienced the different treatments.
For men older than 65 years with low-risk cancer the choice is between local therapy and watchful waiting, knowing that it won’t make much of a difference, if any difference at all, as far as life expectancy is concerned.
There are, however, differences in the side effects of the various local therapies. Both RP and radiation therapy (EBRT and brachytherapy) have a major impact on the HRQoL (health-related quality of life). After RP the patient has maximum in negative side effects, but over time some of them disappear, while the side-effects after radiation are minimal but they increase in the course of time. Brachytherapy showed no benefit relative to RP or EBRT in a cohort of 1213 men at the VA in Ann Arbor (MI)13.

18. Recurrence after RP or Radiation -
Unfortunately, prostate cancer can come back after local therapy. In a cohort of 2091 men, all operated by Dr. Walsh – one of the best if not the best RP surgeon in the USA –, 16% had recurrence after 5 years, 28% after 10 years, and 39% after 15 years14. More than 1 of 3 men had recurrence! One easy method to predict recurrence is attaching a numerical value to various predictors15: PSA <6: 0 pts, 6.1-10: 1 pts, 10.1-20: 2 pts, 20.1-30: 3 pts, >30: 4 pts; GS 1-3/1-3: 0 pts, 1-3/4-5: 1 pt, 4-5/1-5: 3 pts; T stage T1/T2: 0 pts, T3a: 1 pts, Age <50 yrs: 0 pts, >50 yrs: 1 point. Sum the points and the following scores indicate the recurrence percentages in a group of 1,439 men who had undergone RP, after a median of 2 years: sum is 0: 1.3%, 1: 7%, 3: 18%; 5: 26%; 6: 37%; 7: 76% and 9: 100%. Radiation may be prescribed after recurrence, and/or hormonal therapy. The recurrence percentages after brachytherapy or EBRT appear similar to those after RP, but only in men with similar ‘statistics’: age, PSA, and Gleason score.

19. Hormonal therapy is at present the only treatment available for patients diagnosed with a positive bone scan, i.e., the cancer has spread into the bone (but is still known as prostate cancer, not bone cancer). The same treatment is for men who had a local therapy and had a recurrence: the PSA started to increase after being undetectable for a period that may range between a few months and dozens of years. Hormonal therapy is also commonly advised by physicians as an adjunctive therapy for those with high-risk prostate cancer: T3 or T4, Gleason scores of 8-10, a PSA >20, or a cancer that has spread to the lymph nodes. Adjunctive therapy is given in addition to a local therapy such as RP or brachytherapy. Finally, a small but rapidly growing group of men chooses to have hormonal therapy because they are not willing to undergo a local treatment, or to wait watchfully.
The treatment of men who need or choose hormonal treatment is based on the observation by Dr. Huggins (for which he received the Noble Prize) that prostate cancer, at least initially, needs testosterone to grow. No testosterone, no cancer growth. There are three hormonal therapies (HTs): a) stopping production of testosterone with hormones; b) blocking the action of testosterone, and
c) orchiectomy (removing the testicles) which can not be reversed. It is possible to combine a) and b) in CHT (Combined Hormonal Treatment) aka ADT2 (Androgen Deprivation Therapy). A good reason to combine the two is when testosterone, which should be measured regularly, becomes unacceptably high (>20 ng/dl) with a) alone. Hormonal therapy can also be administered intermittently: intermittent hormonal therapy or IHT (periods being on therapy are followed by periods off therapy)16. Unfortunately, most men’s hormonal therapy will fail in time (1-15 years).
a). Testosterone production is stopped by an injection (once a month, or once every 3 or 4 months) of a so-called LHRH medicine (either Zoladex or Lupron) or by estrogen patches. Zoladex or Lupron have the disadvantage that bones can become weakened (osteoporosis) and medications against bone loss (Calcium + Vitamin D, Fosamax or another bisphosphonate) will be necessary. Another option, and less expensive is estrogen patches that do not weaken the bones, but make the breasts sensitive. They also increase their size (gynaecomastia) which can be neutralized, however, with a cosmetic operation.
b). The access of testosterone to the cancer cells can be blocked with anti-androgen (AA) medications: Eulexin, Casodex or Nilandron. An AA protein, similar to testosterone, fits in the androgen receptor (AR), a messenger between a testosterone molecule and the cancer cell. The AA is sufficiently different from testosterone that no instructions from the AR will be forwarded to the cancer cells while the AA blocks the access of testosterone to the AR. The advantage of AA treatment is that libido and potency have a much better chance to survive as compared with LHRH treatment; the disadvantage of this treatment is that the preferred AA (3x50 mg Casodex) will cost $1,250+ per month. Casodex also causes gynaecomastia.
c). Orchiectomy has one advantage and two disadvantages. It is inexpensive as compared with LHRH or AA medicines, but not easily accepted psychologically. Another drawback of orchiectomy is that it excludes IHT. IHT is rapidly becoming more popular because it is easier ― libido and potency which normally disappear during hormonal therapy may return during the off-periods (periods without medications). Off periods may last longer if Proscar or Avodart is added17 to ADT2: ADT3.
Eventually, the cancer cells become sensitive to very small amounts of testosterone or they form androgen independent prostate cancer cells. Hormonal therapy will fail: AIPC (androgen independent prostate cancer). PSA begins to rise. This is not ‘the end’! There are several possible actions. First, the AA may be stopped because the androgen receptors have changed and consider the AA now as testosterone. The PSA goes down in 35% of all patients after the AA has been withdrawn. Ketoconazole (Nizoral or generic), aminoglutethimide (Cytadren), or estrogen patches (Climara or generic) can be prescribed by your doctor, and as a result the PSA might go down, staying down for many months. If the PSA keeps going up, chemotherapy can be considered as a solution but it will not extend life for more than a few months, and is therefore mainly given as a palliative medicine against pain.

20. Alternative therapy – most patients in our support group take various OTC (over-the-counter) medicines, including vitamin E, lycopene, and selenium. Studies have revealed that they influence the growth of prostate cancer: there was less cancer and less metastatic lesions in those taking vitamin E (in smokers; not necessarily in non-smokers)18; smaller cancers in those who took lycopene, and less prostate cancer mortality in men with high selenium. Numerous medications induce decrease of cancer in rats and mice, but there is no great urge to have clinical trials because those medicines are not patentable. A noticeable exception is green tea of which a clinical trial demonstrated19 the absence of success in men with metastatic prostate cancer. Of course, this fact does not include the possibility that green tea may work in men with an earlier disease stage. Soy and fermented soy (miso) are foods that may help, and other OTC medicines include curcumin, quercetin, and EPA & DHA (fish oil). Medicines that must be prescribed by a physician include calcitriol (Rocatrol), statin drugs (e.g., Pravachol), Dostinex, and NSAIDs such as Celebrex and Sulindac. These drugs have an impact on prostate cells in vitro (petri dish) and in vivo (rats and mice), but are without a clinical trial demonstrating an effect on prostate cancer in men. In addition to medicines, life style changes such as dieting, vegetarianism and stress reduction can be of help, in particular because they have an impact that goes beyond prostate cancer. Men diagnosed with prostate cancer die in about equal numbers of heart disease and prostate cancer, and life style changes do have an impact on heart mortality rates: if it won’t help for prostate cancer, it will at least help for heart disease! Acupuncture may help with pain.
In summary, about all men diagnosed with prostate cancer follow one or more of the various alternative therapies; as this does not exclude another therapy they should probably be known as complimentary or adjunct therapy. One of the most promising adjunct therapies is combining vitamins C and K3 100:1. In vivo tests were successful, and it is now waiting for the results of the first clinical trial20.

What to Do?

Men diagnosed with prostate cancer have to make many choices: aggressive surveillance or RP or brachytherapy? Hormonal treatment, and what type of hormonal treatment? Which physician to choose for brachytherapy? For RP? For robotic laparoscopic RP? One could argue that the disease management strategy for men diagnosed with prostate cancer, T1c, PSA <10, and GS 6, can be on more solid grounds if the diagnosis is followed by at least a few months on aggressive surveillance. These men can learn more about prostate cancer in that time period, and make better decisions.
All prostate cancer patients are encouraged to become knowledgeable about their disease: learning the basics, asking questions, reading the literature, and using the Internet. They’ll find themselves more at ease in their communication with physicians.
Share your feelings with your partner, and come to the PCNG meetings – we won’t give advice, but share our experiences, and you can learn from that. Stress and depression are common after diagnosis, but we think that selfempowerment through knowledge can be an excellent remedy. We wish you the best!

Books are, in our opinion, still an excellent source of information. “A Primer on Prostate Cancer” by Stephen Strum and Donna Pogliano is very good, and so is “Dr. Patrick Walsh's Guide to Surviving Prostate Cancer” by Patrick C. Walsh and Janet Farrar Worthington. Look for more titles at pcngcincinnati.org, in LINKS, category J.

References: 1 Int Braz J Urol. 2004 Mar-Apr;30(2):109-13 Miotto A Jr; 2 Eur Urol. 2003 May;43(5):528-34. Souverein PC; 3 Urology. 2004 Aug; 64, 311-5; Fradet Y; 4 Prostate. 2004 Nov 1;61(3):260-6. Postma R; 5 Pathologists for a 2nd opinion familiar to Dr. Stephen Strum: David Bostwick (VA) [800] 214-6628; Francisco J. Civantos (FL)[305] 325-5587; Jon Epstein (Hopkins) [410] 955-5043 or 410-955-2162; David Grignon (MI) 313-745-2520; Jon Oppenheimer (TN] [888] 868-7522; Dianon Laboratories 1 [800] 328-2666, and UroCor[800] 411-1839; 6 Urol Clin North Am. 2001 Aug;28(3):459-72. Moul JW; 7 Eur Urol. 2005 Jan;47(1):16-21. Klotz L; 8 Prostate Cancer Update, winter 2003, James Buchanan Brady Urological Institute, Johns Hopkins U.; 9 AUA Annual Meeting 2003, Abstract 286 Ornish D; 10 JAMA. 2005 May 4;293(17):2095-101. Albertsen PC; 11 J Urol. 2004 Nov;172:1835-9. Khan MA; 12 N Engl J Med. 2005 May 12;352(19):1977-84. Bill-Axelson A; 13 J Clin Oncol. 2002 Jan 15;20(2):557-66. Wei JT; 14 J Urol. 2003 Feb;169(2):517-23. Han M; 15 J Urol. 2005 Jun;173(6):1938-42. Cooperberg MR; 16 Oncologist. 2000;5(1):45-52.Strum SB; 17 ASCO 2005 Prostate Cancer Symposium, abstract 153, Scholz MC; 18 J Natl Cancer Inst. 1998 Mar 18;90(6):440-6. Heinonen OP; 19 Urol Oncol. 2005 Mar-Apr;23(2):108-13. Choan E; 20 J Nutr. 2001 Jan;131(1):158S-160S. Jamison JM.

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May 2005

20-Year Outcomes Following Conservative Management of Clinically Localized Prostate Cancer
Peter C. Albertsen, James A. Hanley, and Judith Fine.
JAMA (Journal of the American Medical Association), May 4, 2005, v.293:2095-2101.

            This article was published a few days before Adrian Boie’s death. Some of its major conclusions are summarized in a remarkable figure shown below.
Twenty graphs show the cause of death of men diagnosed with prostate cancer over a time period of 13 years. They died of prostate cancer (dark gray in the graphs) or something else (light gray).
The original study population consisted of 767 men of different age (vertical columns) and different cancer aggressiveness expressed as Gleason Score (horizontal rows). None of the patients had received radical prostatectomy or radiation therapy. Bone scan tests were performed on only 30% of the patients, so quite a few patients might have had advanced instead of localized disease. All patients began with watchful waiting, but many switched to hormonal therapy. Within 6 months of diagnosis 42% had received DES or had had an orchiectomy!
            Reading these numbers one realizes that a diagnosis of prostate cancer meant something strikingly different from what it means today, and that is because the PSA: the prostate specific antigen for which a test became readily available at about the time Adrian was diagnosed with prostate cancer.
            Nowadays PSA-testing results in diagnosing prostate cancer much earlier than twenty years ago, in particular in slow-growing cancers. The size of prostate cancers identified by PSA testing has decreased steadily since the mid eighties, and the net effect is that prostate cancer mortality will be less in patients diagnosed with prostate cancer today. More men are nowadays diagnosed with a relatively low Gleason score and less advanced cancer than 20 years ago, and earlier diagnosis finds cancers that are less significant. The average Gleason score is now considerably less than it was when Adrian was diagnosed.
            The Gleason score in the 767 men, diagnosed between 1971 and 1984, is closely related to the mortality due to prostate cancer. This becomes obvious when studying the mortality rates. Those can be expressed as prostate cancer deaths per 1000 person-years: 6 per 1000 person-years for a Gleason score of 2-4 (138 patients), 12 for GS 5 (118), 30 for GS 6 (294), 65 for GS 7 (137) and 121 for GS 8-10 (80). Death because of prostate cancer is rare in men with lower Gleason scores and common for those with the higher scores.

Adrian would have been in the 60-64 years column and the 8-10 Gleason score row. He did far better than the great majority of the patients depicted in this graph, and this gave him the opportunity to lead our prostate cancer support group in Greater Cincinnati to success. Thank you, Adrian!

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April 2005

Highlights from the 2005 ASCO Prostate Cancer Symposium

      During three days last February oncologists attended in Orlando (FL) a Prostate Cancer Symposium sponsored by ASCO (American Society of Clinical Oncology), the Prostate Cancer Foundation, the American Society for Therapeutic Radiology and Oncology, and the Society of Urologic Oncology.
      Three hundred and eleven abstracts of the presentations were published, and they are now all on line at the ASCO web site (C8 in pcngcincinnati.org/links). I read all abstract titles, and when the title appeared interesting I read the abstract. What was read is summarized below. Reference to the abstracts is made by number--clicking on this number will show the abstract when this newsletter is read 'on-line', at pcngcincinnati.org. The abstracts have also been collected in a file.
      There are also more highlights in the online edition of this newsletter than in the paper edition―in the paper edition are the highlights of the highlights.
      The symposium had 8 sessions in a logical order. First the Risk Factors and Prevention were discussed (29 abstracts), than Screening and Diagnosis (29). Localized Disease (86) was followed by Locally Advanced and Recurrent Disease including Climbing PSA (35), Androgen Deprivation therapy (aka Hormonal Therapy)(17), Refractory Hormonal Therapy (46), New Therapeutic Developments (15), and finally, the Biology of Prostate Cancer (54).

-----Risk Factors and Prevention
    In the first session two abstracts quantified what we already knew: don't be overweight (BMI >25) or obese (BMI > 30) (Body Mass Index is the weight in kilograms divided by the square of height in meters). In abstract 6 the data from the Physicians Health Study were used. Among 22,071 US male physicians aged 40 to 84 years at baseline in 1982, 2,144 were subsequently diagnosed with CaP, of which 233 (11 %) died of CaP during 21 years of follow-up. Among the 2,144 men diagnosed with CaP during the follow-up, 3.4% were obese and 39.1% were overweight at baseline. Adjusting for age at diagnosis and smoking status, obese men had a 2-fold higher risk and overweight men had a 30% higher risk.
    It was already known that HRQOL (Health-Related Quality Of Life) is a function of education but the results were slightly suspicious because the access to diagnosis and treatment was often not the same. In a new study (abstract 21) 237 men all had access to the VA Healtcare System.
    There was no difference between the educational groups in baseline PSA, Gleason score, T-stage, or BMI, although men with less education were significantly more likely to be diagnosed at an earlier date. However, patients with less than a high school diploma reported lower HRQOL at baseline, a steeper decline at 6 months post-treatment, and remained significantly lower at 12 months post-treatment than patients with some college and patients with an undergraduate degree or higher.
    Smoking (11) is not good either. Of 1787 patients, five years after diagnosis, 75% of previous and non-smokers but only 65% of current smokers were alive. After 10 years 10% of non-smokers but 22% of current and previous smokers had a cancer other than prostate cancer (e.g., bladder cancer)
    The next abstract (22) had information that I never expected: the type of treatment a prostate cancer patient receives is partially a function of the insurance he has. Compared to Medicare patients, men in the Veteran's Administration system were more likely to receive brachytherapy than radical prostatectomy, while patients with PPO insurance were less likely to receive brachytherapy.(OR=0.57 95%CI 0.38-0.86). Men with PPO and HMO insurance were less likely to receive hormonal therapy when compared to patients insured by Medicare.
-----Screening and Diagnosis
    In the first abstract in this session (32) we read about a new tool that may distinguish between the tigers and pussycats in prostate cancer. A first attempt (see March '05 PCNG Newsletter for details) to make that distinction is based on the following: PSA density less than 0.15 ng/mL; the Gleason sum 6 or smaller; cancer in fewer than 3 of the 6 cores obtained on biopsy, and less than 50% cancer in each positive core. Using this information 74% of all insignificant tumors could be identified.
    A better distinction would be welcome, of course, and the one discussed in abstract 32 is with a bloodtest. According to the authors the “PSP94 level” was able to distinguish patients with high-grade disease. “PSP94 levels may also identify patients with lethal forms of prostate cancer”. I like 'tiger version of prostate cancer better than the term they use!
    Are any newly diagnosed patients in Cincinnati staged on the base of their PSP94 level?
    Another abstract (35) presents data about the success of screening for prostate cancer in the Quebec Province in Canada. In Quebec (and also in Tyrol, Austria) screening with PSA and DRE resulted in less prostate cancer deaths, speaking strongly in favor of screening. However, there is a study (BMJ 2002;325:740-743 Grace Lu-Yao, Peter C Albertsen, et al. see our March 2003 PCNG Newsletter) showing that prostate cancer mortality in Connecticut and the Seattle area were about the same whereas screening was much more prevalent in Seattle than in Connecticut. So the last word has not been said about screening.
    I am, as most prostate cancer patients are, in favor of screening, although I notice that education of the men both before and after screening is commonly scanty at best. PSA and DRE are made but what the findings signify is not always explained clearly. Anyhow, in the paper on screening in Quebec the decrease in prostate cancer mortality between 1991 and 2002 is the most significant in Montreal (from 66.5deaths per 100,000 men to 42.9) and Quebec City (from 74.2 per 100,000 men to 37.7). The latter city is the only one that has been involved in a mass prostate cancer screening program coupled with clinical trials of early treatment of the disease.
    The questions have remained the same over the last years: screening: yes? no? if there is cancer: what treatment? RP? Radiation? WW?. There are several screening trials and treatment trials but there is only the ProtecT study (29) combines screening with treatment. 500,000 men aged 50-69 years will be randomized to participate in the ProtecT treatment trial or in the routine care comparison arm.
    Men in the ProtecT treatment trial are invited to take the PSA test. If the level exceeds 3.0 ng/ml, they are invited for biopsy. Those found to have localized prostate cancer are consented for randomization between radical prostatectomy, radical conformal radiotherapy (EBRT) and aggressive surveillance.
    By October 2004, 150,000 men have been randomized to the ProtecT treatment trial (42,000) or the comparison arm (108,000). In the trial, 42,000 men have received PSA tests, 4,000 a raised PSA level and biopsy (c. 10%), 1,102 cancers detected (c.2% tested) and 550 have been randomized to radical prostatectomy, radical conformal radiotherapy or active monitoring.
    The effectiveness of treatments will be determined by survival at 10 years. The strong points of this trial are the combination of screening and treatment, and the large numbers. The results will be 'robust'. But why can the men choose EBRT, and not brachytherapy?
    Many men have their PSA measured annually. Why not after 2,3 or 5 years? Good question, answered in a study (33) of 5387 men aged 45-80 years with a PSA less than 3 ng/ml and no prostate cancer at their first screening visit. Those men had 35,425 consecutive annual follow-up visits.
    The time to a PSA more than 3 ng/ml significantly decreases with increasing baseline PSA--- men with a PSA >1.5ng/ml should be screened every year but men with a PSA lower than 1.0ng/ml at baseline could wait 4 to 5 years before being retested.
    How many biopsies should a urologist take? The answer to this question is given in a study presented in abstract 41: the number of biopsies could be a function of the prostate volume!
    Three hundred eighty three patients had an average positive biopsy rate of 41.5%. The best indicator for finding cancer was not the initial PSA nor the age of the patient, but the VBR: prostate Volume/Biopsy Rate. Assuming that the prostate volume is 28 cc (about average), the cancer detection rate is then with 14 cores 47% (VBR 2= 28/14; one core for each 2cc of prostate volume), with 7 cores 40% (VBR=4) and 27% (a VBR of 5).
    Biopsies can discover pussycat or tiger (=aggressive) cancer. Whether it will be one or the other can be based on the speed with which the PSA is doubling: when it doubles fast the chance is large that there is an aggressive cancer. The authors of abstract 61 define an aggressive cancer when the Gleason Score is 8, 9 or 10. They studied 406 patients who underwent 1,069 biopsies. Aggressive cancer was in 41 patients (10.1%).
    If the PSA was doubling in less than 2 years, the detection rate of aggressive cancer was 42.2%, but if it was more than 5 years, the detection rate of aggressive cancer was only 3.0%. “Patients at low risk of harboring aggressive prostate cancer could reduce unnecessary biopsies and potentially reduce the over-treatment of prostate cancer”.
-----Localized Disease
    Laparoscopic radical prostatectomy (LRP) has been around for about 6 years in the USA, and robotic laparoscopic RP (RLRP) was introduced in Cincinnati last year. How do they compare? Data on 331 LRPs and 191 RLRPs were reviewed (99). There were no statistically significant differences between the two groups. Three men in the LRP group and zero men in the RLRP group were converted to open prostatectomy and the median operative time was 4.4 hours for the LRP group and 3.4 hours in the RLRP group.
    The median number of days to complete continence in the LRP group was 118 days vs. 41 days in the RLRP group. Robotic prostatectomy appears not only better than regular laparoscopic prostatectomy, but is also much easier to learn.
         Another study (123) concludes, based on a retrospective review of 1707 patients treated from 1992 to 2004, that brachytherapy and radical prostatectomy are equally good for low-risk prostate cancer patients. However, in intermediate and high-risk patients brachytherapy had better control rates. The addition of external radiation with or without LHRH neoadjuvant therapy (Lupron, Zoladex, etc) improved biochemical control rates in intermediate and high-risk brachytherapy patients.
    Which factors predict satisfaction with the treatment of early prostate cancer? 560 men were surveyed before treatment, immediately after choosing therapy and at intervals thereafter (101). The men chose external beam radiation (EBRT) most often (51%), with 38% RP, 10% WW or hormonal therapy, and 2% other treatments. 'Compared to RP patients, men choosing EBRT were older, had more high-grade tumors and T3 tumors. They were 8 times as likely to cite quality of life after treatment as their treatment goal and conceded a greater role for the doctor in making a treatment decision. WW patients were still older, but did not have high-grade or T3 tumors.'
    Patients underestimated the side effects of their chosen treatment compared to other men, but over 80% of men were satisfied with their decision.
    This a rather strange set of men. Nobody choose brachytherapy? But the 80% appears quite reasonable to me. After all, one cannot redo any treatment, and to accept this notion and think positive about it is obviously the best response.
    At our meetings patients are asked to share their data but only a few can say something about their PSA velocity before diagnosis. PSA velocity is the rate of PSA rise. In study 68, if it was less than 1 ng/ml per year patients were free of cancer at 5 years, but if it was more than 1 ng/ml only 78% were free of cancer at 5 years.
    The results of the study presented in abstract 106 are truly amazing. The authors conclude that 13 months of TAB (Triple Androgen Blockade: Lupron or Zoladex + Casodex or Eulexin + Proscar) followed by Proscar alone should be explored “as a safe and viable alternative to surgery, radiotherapy or brachytherapy in patients with local disease.” Median age was 67, mean baseline PSA was 11.1 ng/mL (range 0.39-59.8) and median Gleason score (GS) of 7 (range 4-10). High risk PC (PSA > 20, or GS > 7, or T3 stage) was documented in 59/183 (32%) of men.
    At a median follow-up of 75 months (range 48-156; first 100 patients) mean PSA is 3.3 ng/mL. Mean current testosterone is 487 ng/dl. A second cycle of AD has been initiated in 14/183 men; all 14 of these men have high risk PC. One man developed metastatic PC and died from progressive resistant PC. No man with low- or intermediate-risk local PC has received a 2nd cycle of AD to date. Five men have proceeded with deferred local therapy 3-6 years after TAB. Disease specific survival is 99.4%.
    The conclusion is that a single 13 month cycle of TAB combined with Proscar maintenance provides excellent long-term control and management of local PC, including in men with high-risk local PC. This triple androgen blockade with Proscar continuing is also known as the Leibowitz treatment after one of the authors of this abstract.
    A similar study is described in another session of the Forum, but is discussed here (153). The authors (Drs. Lam, Scholz, Strum and others) treated 100 patients with IHT: Intermittent Hormonal Therapy. That is, a period of androgen deprivation therapy (ADT) was followed by a period without ADT but with Proscar (60 patients) or without Proscar (40 patients). Patients went back on ADT when the PSA rose above either 2.5 in the Proscar group or 5.0 in the no-Proscar group--the median time off with Proscar was 24.0 months versus 8.7 months without Proscar.
    Thirteen men have developed androgen independent PC. The patients had a similar diagnosis as those of Dr. Leibowitz (median baseline characteristics were age 66, PSA 15, and Gleason score 7), and one wonders how it was possible that one group (Leibowitz) needs only one treatment with ADT, and the other group (Lam et al.) more than one treatment.
    In abstract 64 the HRQOL (Health-Related Quality of Life) of RP patients is compared with that of EBRT patients, all with clinically localized prostate cancer. Approximately 10.6% of the 47 RP patients and 2.9% of the 49 EBRT patients were incontinent at 2 years; 26.5% of EBRT and 6.1% of RP patients had bowel dysfunction at 2 years, and at 2 years sexual dysfunction was more prevalent in the RP than in the EBRT group (70.2% versus 61.2%). Still, there was no decrease in the general HRQOL, except in the first month after RP.
    Satisfaction with the treatment decision as a function of the income of the patient is the topic of abstract 80. Their conclusion is that income levels may affect access to prostate cancer information and that more effort must be made to improve patient education and treatment information for lower income patients. Knowledge is power, and an empowered patient understands the issues better and will be more easily satisfied with his treatment decision.
    Empowering patients is one of the major tasks of the PCNG.
    In abstract 129 our Dr. Barrett is the senior author of an abstract addressing the question what PSA a patient should have after brachytherapy. Between 1995 and 2002, 148 patients had Iodine seeds implanted. The median age of the patients was 67 years (range 45-84); the median Gleason score 6.07
    (2 - 8), and the median pre-treatment PSA 6.7 ng/ml (1.6 - 17 ng/ml). All patients were followed continuously with a median follow-up time of 55 months (24 mo.-104 mo.). A nadir PSA level of 0.5 ng/dl is associated with a 91% likelihood of biochemical disease control.
    These results are considerably better than those of the 1992-2000 group of 200 patients described in Dr. Barrett's 2001 abstract (see June 2001 PCNG Newsletter): only 52% achieved and maintained a nadir of less than 0.5 ng/ml.
-----Locally Advanced and Recurrent Disease (including Climbing PSA)
    COMPARE (Comprehensive Observational Multicenter Prostate Adenocarcinoma Registry) will document the treatment decisions and outcomes for men with rising PSA levels following RP or radiation (168). Progression will be assessed using biochemical, radiological, and clinical changes including QOL.
    COMPARE is an observational registry which examines clinical, pathologic, and sociodemographic effects on treatment decision-making and outcomes. Race, age, education, literacy, zipcode, marital status, and insurance access (in addition to clinical correlates such as grade, stage, and Gleason score) will be assessed in 3750 men. As of October 2004, 264 sites qualified for the registry.
    It is amazing is what had to be done to get collaboration from those 264 sites:7,728 sites were contacted, and 19,163 telephone contacts made. I wonder whether there are any sites in Greater Cincinnati.
    Local therapy can be followed or preceded by hormonal therapy (=ADT - Androgen Deprivation Therapy); the late ADT after local therapy has been shown to be beneficial for intermediate and high-risk patients whereas ADT before local therapy (“early ADT”) has not been of much help. What about early chemotherapy?
    In abstract 169 a study is described in which 48 men had at least 1 cycle of chemotherapy prior to surgery - we will have to wait a long time before it is known whether 'early chemo' might become advisable for high-risk patients.
-----Androgen Deprivation Therapy
    Hot flashes are part of hormonal therapy. Placebo-controlled trials have shown that 25% of patients respond to placebo treatment. A much larger percentage, 73% responds to acupuncture treatment (155).
    Bone Mineral Density (BMD) decreases during the first 12 months of hormonal treatment, but it decreases considerably less in men who have a higher BMI (Body Mass Index) and taking calcium and vitamin D supplements and drinking at least 1 glass of wine per day (148). Being overweight is thus not all bad, and the daily glass of wine I drink because it is good for my heart turns out to be good for my my bones as well!
    An exciting trial at Memorial-Sloan Kettering in NYC is described in abstract 145. Patients with a rising PSA received six cycles of treatment during four weeks: three weeks of Lupron + Taxotere followed by one week of Androgel (a gel that rubbed in the skin increases testosterone). PSAs as low PSA as< 0.05 ng/ml following prostatectomy or < 0.5 ng/ml following radiation were achieved in some patients.
    We have to wait and see whether this short-term Intermittent ADT/Chemo therapy with a testosterone boost during the ‘off’ period will be effective, but the preliminary data presented in abstract 145 are promising indeed.
    Reading a study is most exciting when it can be applied to one's own situation. I have had a Zometa

*November*		Food Supplements Taken by Dr. Myers; First Clinical Trial of Dark Chocolate
*October*		Will Rogers, Garrison Keillor, and Prostate Cancer
*September*		Prescription Drugs from Canada
*August*		Your PSA is 0.8; my PSA is 1.1, and his PSA is 2.3 - what does that mean?
*July*		What is New in Prostate Cancer Research and Treatment? AUA Meeting San Antonio, TX
*June*		Your PSA is High - What Next
*May*		20-Year Outcomes Following Conservative Management of Clinically Localized Prostate Cancer
*April*		Highlights from the 2005 ASCO Prostate Cancer Symposium, Orlando (FL)
*March*		Hormonal Therapy in Early Prostate Cancer & What is Insignificant Prostate Cancer?
*February*		Normal Range of PSA is NOT 0-4 ng/ml & News from the Active Surveillance Front
*January*		Active Surveillance with Selective Delayed Intervention Using PSA Doubling Time for Good Risk Prostate Cancer