Newsletter Features 2002

November 2002

Diagnosis of Prostate Cancer

From: “A Primer on Prostate Cancer” written and compiled by Donna Pogliano (2000):

..A vast array of testing procedures is available to correctly assess the character and spread of any particular prostate cancer. Most patients will not need all the tests that are available, but most doctors will honor an informed patient's requests for any testing that seems reasonable. Some insurance companies or HMO's may not agree to pay for all the available tests.

It is vital that everything that can be known about your cancer be discovered BEFORE you make a treatment decision. That way, you will have the confidence that the treatment you undertake will be the best choice of treatment for your particular situation. Many doctors will stress that with the current available treatment options, you have ONE chance at a cure if you have organ-confined disease. And they will not be responsible for making that choice for you, since you need to live with the consequences of your decision for the rest of your life.

THE PSA

The first test, used primarily as a screening procedure since 1990, is the PSA blood test. Blood is drawn and tested for the presence of "prostate specific antigen," a marker in the blood that indicates the presence and extent of cancer activity. PSA is actually an enzyme made by prostate tissue. Its purpose is to dissolve the proteins that cause semen to clump. Further investigation to determine if cancer is present is usually recommended if the PSA is over 4, and some doctors feel that 2.6 merits monitoring on a six-month basis to see if there is an upward trend. This will be discussed in more detail below.

Free PSA testing can easily be used to weed out some of the patients with PSA's above 4 that are not cancer-related. Free PSA testing (see further information later in this section) can rule out benign prostate hyperplasia (BPH), but not prostatitis.

At minimum, before undergoing a biopsy, you should have your PSA tested several times. There is considerable variation in test results depending on the lab and assay used, so you need several readings to arrive at an average. Refrain from ejaculation at least 48 hours before the blood draw, and do not do anything else that massages the gland for one week prior to the blood draw, such as using a bicycle or exercise bike, or riding a motorcycle. It is thought that these activities can temporarily raise your PSA, and could result in unnecessary concern or inappropriate testing based on distorted PSA results.

Some men with elevated PSA should routinely follow up with a Free PSA test to help rule out causal factors other than cancer. This is another type of blood test which might avoid needless biopsies if used more regularly. However, this test is only reliable for PSA's of between 4 and 10. Recent studies indicate the lower level of reliability may be 2.5.

Also, after the first elevated PSA and before a biopsy, some experts recommend that you be tested for prostatitis, or inflammation of the prostate. If this condition is found, it can be treated with antibiotics, such as Cipro, usually prescribed for a month or more. Prostatitis can be a noncancerous cause of an elevated PSA. Be sure to wait at least six weeks after the condition is cleared up and medication is discontinued before rechecking the PSA. Benign Prostate Hyperplasia (BPH) is a result of an enlargement of the prostate, which also elevates PSA levels. Symptoms can mimic those found in some cancers, but this is a treatable, noncancerous condition.

An often-unused approach to PSA evaluation relates to what the PSA levels are doing over time. Malignant processes relate to persistent cell growth and production of specific proteins. With prostate cancer, this would relate to PSA production. If the rate of doubling of the PSA (PSA doubling time or PSADT) or the rate of increase in PSA (PSA velocity or PSAV) is abnormal, then prostate cancer is more likely present than not. PSADT should be longer than ten years to rule in a benign process. PSA velocity should be less than 0.75 ng/ml/year on the test results to rule out prostate cancer. These are adjunctive tests and are not absolute criteria for or against malignancy. However, they are valuable tools and their principles apply to all malignancies.

DIGITAL RECTAL EXAM

Digital rectal exam (DRE) is used in combination with PSA testing to determine if there is any evidence of a palpable tumor. The doctor will insert a gloved finger inside the rectum to feel the gland. This isn't as bad as it sounds. It may help you to keep in mind that women are routinely poked, pummeled and invaded in an effort to maintain good health. You can deal with this.

The digital rectal exam (DRE) will be a factor in establishing the Clinical Stage of your cancer, which will help to assess your situation and enable you to describe your condition in a way that others who know what staging means will understand. The TNM system is used internationally at this time to describe the cancer and it's spread. "T" describes the tumor, whether or not it can be felt, how large it is and whether it occupies one or both sides of the prostate. "N" stands for nodes and describes whether or not the cancer has spread to the lymph nodes. "M" stands for metastasis, and indicates whether or not the cancer has spread to other organs or tissues. A full description of TNM staging designations is available on the Internet. See the Resource List later in this primer under "Quick Reference".

FREE PSA

If PSA is between 4 and 10, requesting a test for "free PSA" also termed fPSA or PSA II might help to rule out cancer as the cause. Clarifying the reason for the elevation could spare the patient the intrusion of a biopsy. This test is a different type of PSA blood test, which can be used to help rule out noncancerous enlargement of the prostate gland, called BPH or benign prostatic hyperplasia. BPH can also cause elevated PSA readings. This test yields a "% free PSA" number. The lower the number, the more likely you are to have prostate cancer. A high limit of 25 or more would indicate that the man might not have cancer. This test should be done routinely if PSA is elevated between 4 and 10, before making a decision regarding undergoing a biopsy.

BIOPSY OF THE PROSTATE

If a biopsy is done, it should consist of at least six needle sticks, placed in separate, well-labeled vials so the pathologist can draw conclusions based on the locations from which the samples were taken. Some studies indicate that a ten or twelve needle biopsy approach shows an overall increase in cancer detection of as much as 35% and is recommended.

The biopsy results will yield the Gleason grades. This is a subjective analysis by a pathologist of how the prostate cancer appears in the sample (biopsies) as compared to normal cells. The number will be between 1 and 5 for each Gleason grade, the higher number indicating a more aggressive cancer. The Gleason "score" or "sum" will be derived from adding the two grades. The first number indicates the predominant grade; the second number is the second most predominant grade. The predominant Gleason grade has to be at least 51% of the total picture seen under the microscope. The secondary Gleason grade has to be at least 5% of this same picture. This is stated as, for example, (3,3), which is the most common Gleason score. A Gleason score of (3,4) indicates that anywhere from 51% to 95% of the specimen is Gleason grade 3 disease and that anywhere from 5% to 49% of the specimen has a secondary pattern of Gleason grade 4 disease. Gleason grades 4 and 5 disease are important NEGATIVE prognostic indicators for the extent of disease and the clinical course of prostate cancer.

Tissue samples taken during biopsies are preserved and retained, making it possible to send the samples to an expert prostate cancer pathologist for review and confirmation. Experts in assessing prostate cancer biopsies are available at specific labs, such as UroCor, Inc. and Dianon Laboratories, and at certain major medical centers. Samples from all over the country can be sent to these artists for "second opinions". Don't be afraid to ask for this additional assurance that your Gleason is correct, because this will be a MAJOR factor in your decision making process. If your Gleason is inaccurate, you may overtreat or undertreat your cancer based on erroneous information!

In every struggle the only ones who can truly grasp your fear, your pain, your grief,
and your stamina that may sometimes fail are those who share the battlefield with you.
It is no different when the enemy is prostate cancer,
and the fight is for your integrity as a man as well as your life
from www.phoenix5.org/battle.html

Cancer and Prostate Cancer Citations from Cincinnati compared with citations from Columbus, Cleveland, Indianapolis, Pittsburgh, and Ann Arbor

Last month Steve C., an acquaintance in Louisville, drove to Detroit, and had an RP (radical prostatectomy) in the morning of October 17. That same day, in the afternoon, he drove back to Louisville. This was not an RP as usual! It was a “robotic/laparoscopic” prostatectomy done by Dr. Mani Menon at the Vattikuti Urology Institute at the Henry Ford Hospital in Detroit.

“With this robotic laparoscopic procedure, the patient's pain, blood loss and recovery time in the hospital and at home is significantly reduced. In addition, the procedure eliminates the large incision that is used in the traditional surgical method. "It's almost like the movie 'Fantastic Voyage,'" said Mani Menon, M.D., director of the Vattikuti Urology Institute. "It's as if you are diving into the patient and you have these very tiny and precise instruments that allow you to manipulate tissue with great precision."” 1)

Steve had learned about the existence of robotic/laparoscopic RP through a web search. He learned, after doing a search with ‘laparoscopic prostatectomy’ in Pubmed 2) that laparoscopic operations had been pioneered in Europe, and that such operations were also done in nearby Detroit. He cancelled his appointment for an RP in Louisville, and went to Detroit - this nicely illustrates the reality of medical practice today. Some patients, after diagnosis of prostate cancer, and in addition to the advice they get from their local urologist/radiologist/oncologist, will collect additional information. Then they may make a choice different from what they would have chosen a few years earlier, when all this information would not have been available.

We, Kees DeJong and Fran Stanton, both chose to go to Sarasota in Florida for treatment, for several reasons. First, our health insurance plans allowed us to do this. Not all health plans are like ours - but if you are on Medicare, going to Sarasota would be an option. Second, Dr. Dattoli and his colleague Dr. Sorace are specialized in brachytherapy; they have an excellent reputation, and tend to work on the more difficult cases. They have treated thousands of prostate cancer patients, and the equipment in their clinic is top-of-the-line. Another reason for going to Sarasota was because Dr. Dattoli had published his clinical results, and he is also one of the authors of an authoritative book on brachytherapy that came out recently. Publications are important: they apparently influence what patients do; they partially control the flow of grant money, create an institution's reputation, and make it possible to compare medical institutions or even cities. How does our city, Cincinnati, compare with other cities in the region?

We counted the number of citations on cancer and prostate cancer from seven cities: Cincinnati, Columbus, Cleveland, Indianapolis, Pittsburgh, Detroit, and Ann Arbor. Actually, the citations are counted by MEDLINE, the National Library of Medicine's electronic data base, also known as PUBMED. This database contains bibliographic citations and author abstracts from more than 4,600 biomedical journals published in the United States and 70 other countries. The file contains over 11 million citations dating back to the mid-1960's. Of these, 1.44 million citations are on cancer and 38,700 (2.7%) of those are on prostate cancer. If one enters as keyword 'prostate cancer' and 'Cincinnati', all citations on prostate cancer and with Cincinnati in the address of the first author would be listed after clicking on 'Go'.
PubMed added in the late eighties an address to the name of the first author, and therefore only information from the last 10 years, last 5 years and last 2 years was collected respectively (on Nov. 9, 2002). It took about 45 minutes to collect the numbers shown in this table (with an ADSL connection), and to enter them into a spread sheet. First we looked at how many citations there were about cancer or prostate cancer (column with 0). Then we entered the name of the city, first without key word, and then with cancer or prostate cancer as keywords.

What are our conclusions?

1 – Looking at the numbers obtained without a key word we obtain an impression of the total research activity in medicine in each of the seven cities. They cluster in two groups: Cleveland, Pittsburgh and Ann Arbor in one group, and Cincinnati, Columbus, Indianapolis, and Detroit in the other group. The first group published about twice as much as the second group.

	years	0	CVG	COL	CLE	IND	PIT	DTW	Ann Arbor
no	2		2,592	2,698	5,147	2,526	4,837	2,489	4,644
keyword	5		6,016	5,919	11,949	6,000	11,368	6,141	10,781
	10		10,726	10,621	20,831	10,996	20,645	11,209	19,929

keyword:	2	130,539	218	375	756	342	596	409	612
Cancer	5	316,460	586	822	1,823	926	1,496	1,073	1,475
	10	570,520	1,162	1,366	3,205	1,737	2,804	2,012	2,705

keyword:	2	6,191	3	14	66	25	39	75	108
Prostate	5	14,118	9	31	139	47	73	178	205
Cancer	10	22,954	21	45	191	58	107	330	285
0:NoLocationSpecified
CVG:Cincinnati;COL:Columbus;CLE:Cleveland;IND:Indianapolis;PIT:Pittsburgh;DTW:Detroit

2 – The citation numbers obtained with cancer as key word become more meaningful if we compare those numbers with all citation numbers originating in a particular city. This way we might learn what percentage of the total effort in medical research is dedicated to cancer.

	CVG	COL	CLE	IND	PIT	DTW	Ann Arbor
1992-1997	12%	12%	16%	16%	14%	19%	13%
1997-2000	11%	14%	16%	17%	14%	18%	14%
2000-2002	8%	14%	15%	14%	12%	16%	13%

During the 1992-1997 period 12% of all medical publications originating in Cincinnati was about cancer. In the 1997-2000 period 11% was on cancer, but in the last two year it was only 8%. During the same periods the effort in the six other cities was 15, 15 and 14% on average. There is thus less output of cancer research in Cincinnati than in the other cities, in particular during the last few years.

3 – What is the percentage of prostate cancer citations of all citations on cancer?

	0	CVG	COL	CLE	IND	PIT	DTW	Ann Arbor
1992-1997	3.5%	2.1%	2.6%	3.8%	1.4%	2.6%	16.2%	6.5%
1997-2000	4.3%	1.6%	3.8%	6.8%	3.8%	3.8%	15.5%	11.2%
2000-2002	4.7%	1.4%	3.7%	8.7%	7.3%	6.5%	18.3%	17.6%

During the 1992-1997 period 3.5% of all publications on cancer were about prostate cancer. During the last two years it was 4.7%, a major increase! It is obvious, from this table, that prostate cancer in Detroit and Ann Arbor is one of the major or perhaps the major cancer type being studied in those cities: the effort is about four times the average effort. In Cleveland, Indianapolis, and Pittsburgh the prostate cancer effort about doubled during the last two years. And in Cincinnati? It shrank from about half in 1992-1997 to less than a third of the average effort in 2000-2002.

The number of PubMed citations is in all likelihood correlated with various other assessment parameters to determine the standing of a medical center, such as research grants, number of clinical trials - in summary, the quality of medical care in a city. Prostate cancer patients in Cincinnati have, reason to travel to another city!

The decline of cancer research in Cincinnati during the last few years is worrisome from our perspective. The decline of prostate cancer research is even more worrisome. Two years ago, one of us wrote to Dr. Steger, president of UC, expressing concern about Cincinnati’s decline in prostate cancer research. His response was that "…the UC Medical Center has to focus its research and resources to be excellent in its efforts…." Apparently, excellence at UC in one area implies negligence in another area. The area in which we are most interested is definitely in the latter category.

Steve is doing fine.

KD & FS

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October 2002

Questions and Answers About Metastatic Cancer

From the National Cancer Institute

1. What is cancer?

Cancer is a group of many related diseases that begin in cells, the body's basic unit of life. The body is made up of many types of cells. Normally, cells grow and divide to produce more cells only when the body needs them. This orderly process helps keep the body healthy. Sometimes cells keep dividing when new cells are not needed. These extra cells may form a mass of tissue, called a growth or tumor. Tumors can be either benign (not cancerous) or malignant (cancerous).

Cancer can begin in any organ or tissue of the body. The original tumor is called the primary cancer or primary tumor and is usually named for the part of the body in which it begins.

2. What is metastasis?

Metastasis means the spread of cancer. Cancer cells can break away from a primary tumor and travel through the bloodstream or lymphatic system to other parts of the body.

Cancer cells may spread to lymph nodes near the primary tumor (regional lymph nodes). This is called nodal involvement, positive nodes, or regional disease. Cancer cells can also spread to other parts of the body, distant from the primary tumor. Doctors use the term metastatic disease or distant disease to describe cancer that spreads to other organs or to lymph nodes other than those near the primary tumor.

When cancer cells spread and form a new tumor, the new tumor is called a secondary, or metastatic, tumor. The cancer cells that form the secondary tumor are like those in the original tumor. That means, for example, that if breast cancer spreads (metastasizes) to the lung, the secondary tumor is made up of abnormal breast cells (not abnormal lung cells). The disease in the lung is metastatic breast cancer (not lung cancer).

3. Is it possible to have a metastasis without having a primary cancer?

No. A metastasis is a tumor that started from a cancer cell or cells in another part of the body. Sometimes, however, a primary cancer is discovered only after a metastasis causes symptoms. For example, a man whose prostate cancer has spread to the bones in the pelvis may have lower back pain (caused by the cancer in his bones) before experiencing any symptoms from the prostate tumor itself.

4. How does a doctor know whether a cancer is a primary or a secondary tumor?

The cells in a metastatic tumor resemble those in the primary tumor. Once the cancerous tissue is examined under a microscope to determine the cell type, a doctor can usually tell whether that type of cell is normally found in the part of the body from which the tissue sample was taken.

For instance, breast cancer cells look the same whether they are found in the breast or have spread to another part of the body. So, if a tissue sample taken from a tumor in the lung contains cells that look like breast cells, the doctor determines that the lung tumor is a secondary tumor.

Metastatic cancers may be found at the same time as the primary tumor, or months or years later. When a second tumor is found in a patient who has been treated for cancer in the past, it is more often a metastasis than another primary tumor.

In a small number of cancer patients, a secondary tumor is diagnosed, but no primary cancer can be found, in spite of extensive tests. Doctors refer to the primary tumor as unknown or occult, and the patient is said to have cancer of unknown primary origin (CUP).

5. What treatments are used for metastatic cancer?

When cancer has metastasized, it may be treated with chemotherapy, radiation therapy, biological therapy, hormone therapy, surgery, or a combination of these. The choice of treatment generally depends on the type of primary cancer, the size and location of the metastasis, the patient's age and general health, and the types of treatments used previously. In patients diagnosed with CUP, it is still possible to treat the disease even when the primary tumor cannot be located.

New cancer treatments are currently under study. To develop new treatments, the National Cancer Institute (NCI) sponsors clinical trials (research studies) with cancer patients in many hospitals, universities, medical schools, and cancer centers around the country. Clinical trials are a critical step in the improvement of treatment. Before any new treatment can be recommended for general use, doctors conduct studies to find out whether the treatment is both safe for patients and effective against the disease. The results of such studies have led to progress not only in the treatment of cancer, but in the detection, diagnosis, and prevention of the disease as well. Patients interested in participating in research should ask their doctor to find out whether they are eligible for a clinical trial.

DEFINITIONS:

lymphatic system (lim-FAT-ik SIS-tem)

The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes, and lymphatic vessels (a network of thin tubes that carry lymph and white blood cells). These tubes branch, like blood vessels, into all the tissues of the body.

biological therapy (by-o-LAHJ-i-kul)

Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Some biological therapy agents may act directly on cancer cells to block their growth. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy.

(Original article is from the NCI Web site at http://cis.nci.nih.gov/fact/6_20.htm. Definitions are from the National Cancer Institute dictionary at http://cancer.gov/dictionary/)

Diagnosis is like being awakened in a completely foreign country.
You discover you don't know where you are and you don't have a map.
Worst of all, you don't know the language, so you can’t ask any questions.
Nor do you don't know the food, the customs or even the weather.
Now you must travel in it and survive.
But how?
How can you do this -- or even make decisions -- when you can't speak the language and don't have a map?
Our convener, Robert Young, has created a first-of-its-kind Prostate Cancer Glossary book-let to help anyone navigate and survive the vocabulary jungle. It will serve the newly diagnosed as well as the "old timer."
It is 68 pages, with over 800 terms, synonyms, abbreviations and slang words defined, just like those above. It is also fully cross-indexed, plus there are full pages in the back (appendices) that take up basic issues like the prostate (illustrated), PSA, grading (illustrated), staging (with a chart of all stages), resources (books and organizations) and more.
Robert is offering complimentary copies to libraries, non-profit organizations that deal with prostate cancer, practicing urologists or oncologists, professional medical/health writers and prostate cancer support group facilitators.
Contact him at his Phoenix5 Web Site www.phoenix5.org, or call 513-321-1693.

A Phase III Clinical Trial of Zometa: Success? Failure?
by Kees DeJong, Prostate Cancer Support Group Member

I am a so-called ‘poor prognosis“ also known as “high-risk” patient. Diagnosed in 1996 with a PSA of 24 and a Gleason score of 9, I have, however, been doing fine, thanks to (intermittent) hormonal therapy, with the addition in the past year of EBRT (external radiation) and brachytherapy (seed implantation). A poor prognosis implies that the chances that I will die of prostate cancer are considerably higher than they are for a patient diagnosed with a PSA of 8 and a Gleason score of 6. I thus worry about becoming “hormone refractory” (PSA increases while I am on hormonal therapy), and about the spreading of the cancer into the bones.

The rise or fall of the PSA can be followed with a regular blood test, and tumors in the bone can be seen on bone scans. I have had many blood tests and many bone scans! The PSA has been rising recently (which was expected as I am off hormonal therapy at present), and the bone scans have been “clean”, at least most of them. But one report read as follows: “The left sacra ala lesion persists and could represent a tumor, with arthritis less likely but not excluded”. Sentences like these worry me, and I go to each successive bone scan with considerable trepidation.

What can one do if there is cancer in the bone? Radiation therapy or surgery is possible, but the patient can also take medications. This year one medicine, Zometa, was mentioned more than any other medicine. It was a hot topic in the bulletin lists of prostate cancer patients, and Dr. Waterhouse (my oncologist) was excited. Zometa can be given to patients with bone lesions, but it can also be used in patients who might easily get bone cancer, in patients like me. According to my good friend Wil de Jongh Zometa is now being prescribed in Germany for most highrisk patients, even those without any spread of the cancer to the bone. All paid by their insurance.

I wanted Zometa! Dr. Waterhouse kindly prescribed it, but subsequently learned that the insurance wouldn’t pay the $1,350 as I did not have well-established bone lesions. That in itself is good news, whereas not getting Zometa would be bad news if it could be shown that Zometa could indeed prevent the occurrence of bone lesions. But how can this be established? With a clinical trial, of course.
Such a clinical trial (about Zometa preventing the spreading of prostate cancer in the bone) has not yet been done. However, another clinical trial, about Zometa reducing skeletal events, was published a few weeks ago. The article describing this trial is quite technical: see extracts from the article on page 5. Below it are comments from the editors of the Journal where the article was published.

The FDA approved Zometa in February of this year against bone metastases. At the time the FDA committee cautioned, however, that Zometa did not appear to be a "home run." The Zometa clinical trial did not provide a clear demonstration of net therapeutic benefit according the editorial quoted above. In addition, the rather minor though statistically significant reduction in skeletal-related events (see figure) may have been observable only because 4 mg (not 8-4 mg!) patients have been compared with placebo patients who did not take medicines against osteoporosis but calcium and Vitamin D. All 643 patients in this study were on hormonal therapy (either through orchiectomy or Lupron/Zoladex) at a time that it was already rather well known that hormonal therapy may lead to osteoporosis.

I have been on Fosamax since 1997, as have many other patients because bisphosphonates such as Fosamax or Aredia (pamidronate) lead to a reduction of skeletal events. The clinical study compares Zometa patients to calcium-Vitamin D patients ----- a better study would have compared Zometa patients to Aredia/Fosamax patients. I think that this can be another reason why Zometa is not recommended as a standard therapy.
----
P.S. I changed insurance companies in 2003; what would I do if they would allow administering Zometa? I would take it! One never knows.

Extracts from:
Journal of the National Cancer Institute - Vol. 94, 19, 1458-1468, October 2, 2002:

A Randomized, Placebo-Controlled Trial of Zoledronic Acid in Patients With Hormone-Refractory Metastatic Prostate Carcinoma -- Fred Saad et al.

We studied the effect of a new bisphosphonate, zoledronic acid (= Zometa), which blocks bone destruction, on skeletal complications in prostate cancer patients with bone metastases...Patients with hormone-refractory prostate cancer and a history of bone metastases were randomly assigned to a doubleblind treatment regimen of intravenous zoledronic acid at 4 mg (N = 214), zoledronic acid at 8 mg (subsequently reduced to 4 mg; 8/4) (N = 221), or placebo (N = 208) every 3 weeks for 15 months.... A greater proportion of patients who received placebo had skeletal-related events than those who received zoledronic acid at 4 mg (44.2% versus 33.2% placebo...) or those who received zoledronic acid at 8/4 mg (38.5% versus 33.2% placebo.…) …Pain and analgesic scores increased more in patients who received placebo than in patients who received zoledronic acid, but there were no differences in disease progression, performance status, or quality-of-life scores among the groups. Zoledronic acid at 4 mg given as a 15-minute infusion was well tolerated, but the 8-mg dose was associated with renal function deterioration. Conclusion: Zoledronic acid at 4 mg reduced skeletal-related events in prostate cancer patients with bone metastases.

The median time to cancer progression… [was] 84 days for patients in each treatment group. There were no statistically significant differences between patients who received zoledronic acid and those who received placebo ... indicating that zoledronic acid had no apparent effect on the ... PSA.

[Comment: The article points out that the main effect of the Zometa infusion was in the reduction of skeletal-related events, defined as “pathologic bone fractures (vertebral or nonvertebral), spinal cord compression, surgery to bone, radiation therapy to bone (including the use of radioisotopes), or a change of antineoplastic therapy to treat bone pain.”]

The above article was preceded by editorial comment in the Journal of the National Cancer Institute, Vol. 94,19,1422-1432,Oct. 2,2002

Editorial: Should Bisphosphonates Be Used Routinely in Patients With Prostate Cancer Metastatic to Bone? Christina M. Canil, Ian F. Tannock:

“...several features of the study should lead to caution in accepting this result as sufficient evidence to introduce zoledronic acid into standard practice for the treatment of patients with metastatic prostate cancer.... Thus, this study with zoledronic acid has not provided a clear demonstration of net therapeutic benefit.

Analyses of the cost-effectiveness of using pamidronate in patients with breast cancer have shown that its use is associated with high incremental cost per adverse event avoided. Zoledronic acid (Zometa) is a more expensive agent than pamidronate (Aredia), and the incremental cost of preventing each skeletal-related event in patients with prostate cancer is likely to be high and outside a range that would be regarded as cost-effective. The study by Saad et al. adds to the evidence that bisphosphonates have some activity in reducing the incidence of skeletal-related events in men with metastatic prostate cancer but with some added toxicity. Zoledronic acid is a reasonable option for patients who do not respond to alternative therapies and who are at high risk for bone fractures or spinal cord compression, but currently zoledronic acid cannot be recommended as a standard therapy for men with prostate cancer and metastases to bone."

"....Some patients join clinical trials out of desperation, others to advance medicine, others are seeking therapeutic value...Only 5% of clinical trial patients will benefit .. but 85% state their reason for entering a phase I trial was expectation of therapeutic value. Who is to blame if they get sick--or even die?".... (Time Magazine, April 22, 2002).
what is a clinical trial?
Every drug is tested first 'in vitro', that is, in test tubes and petri dishes, and 'in vivo': on mice, rats, dogs, monkeys, etc. But the new drug must be also tested on real live people before it becomes an approved drug. This happens in clinical trials: research studies done to find better ways to prevent, diagnose or treat a disease.
Usually, when someone says clinical trials, he or she thinks of cancer - however, only one third of all clinical trials deal with cancer. Less than 10% of those are on prostate cancer (about 170), and only 17 clinical trials can be entered in Cincinnati.
Please, come to our 9/25 meeting and learn more about
clinical trials in Cincinnati.

Most prostate cancer patients don’t want to hear about clinical trials. Only a few patients will enter a clinical trial in Cincinnati, and most of us will never have to consider participation in a trial. That is the good news. But we know that stage II patients with a Gleason score of 6 and a PSA of 6 may have recurrence (rise of PSA) and that after a few years on hormonal therapy the PSA may rise again: the cancer has become refractory. Of course, the cancer of most ‘6-6-RP’ patients will remain in remission –but we all understand that this is not certain.

So-called high-risk patients (PSA >20, Gleason score >7) have a greater chance to be confronted with recurrence or becoming refractory. We both are such patients and certainly interested in clinical trials. Our information comes from the physician, of course, but we don’t wait, and have started looking around. And this means using the Web.

The major source of information is the NIH (National Institutes of Health), and about the same information can be downloaded, using prostate cancer and Cincinnati as key words, from two different sites within the NIH: www.clinicaltrials.gov/ (NIH’s NLM: National Library of Medicine) (22 trials) and www.nci.nih.gov/search/clinical_trials/ (NIH’s NCI: National Cancer Institute-PDQ) (17 trials). The NLM’s list is longer, partially because it has more trials to prevent prostate cancer than the PDQ list. Other differences are in the titles: the NLM uses informal titles, and the NCI uses the official titles of the clinical studies. The latter are easier in the evaluation of a clinical because all important key words are in the title, such as phase and randomization.

From PDQ: Phase I trials: These first studies in people evaluate how a new drug should be given, ...how often, and what dose is safe. A Phase I trial usually enrolls only a small number of patients, sometimes as few as a dozen. No phase I trials in Cincinnati.
Phase II trials: A phase II trial continues to test the safety of the drug, and begins to evaluate how well the new drug works. Phase II studies usually focus on a particular type of cancer. Four phase II trials in Cincinnati.
Phase III trials: These studies test a new drug, a new combination of drugs, or a new surgical procedure in comparison to the current standard. A participant will usually be assigned to the standard group or the new group at random (called randomization). Phase III trials often enroll large numbers of people and may be conducted at many doctors' offices, clinics, and cancer centers nationwide. Thirteen phase III trials in Cincinnati.

There is one study in Cincinnati whether selenium may prevent prostate cancer; all other studies are about treatment. The randomization requirement in phase III trials can be a major obstacle for entering patients if they prefer to be in the ‘new group’, not in the ‘standard group’. This may explain, at least partially, why only 3% of cancer patients participate in clinical trials. “Why are patients reluctant to enter trials? Some patients fear that the trials are to satisfy the need to publish, or financially reward the doctor/institution vs. trying to advance the medical science of cancer treatment. ... Many patients are reluctant because their insurance refuses coverage for the experiment, or any adverse ramifications thereof. Other patients are reluctant to do the required ‘cleansing’ required for trial entry. Also, many reports reflect that the patients who do enter trials are unclear about the objectives of the trial“ (Bill Aishman in Don Cooley’s site www.cooleyville.com/cancer/cactpar.htm).

But “such concerns expressed by respondents who chose not to enter a clinical trial were not borne out by those who participated. The vast majority of patients who had participated in clinical trials said their experience was positive. Ninetyseven percent said they were treated with dignity and respect, and received excellent or good quality care. Eight out of 10 said they were not treated like guinea pigs and were not subjected to more tests and procedures than they thought necessary. Three out of four said they would recommend participation in a clinical trial to someone else with cancer.” (www.nci.nih.gov/clinicaltrials/developments/doctors-barriers0401)
Yes, we would consider participation in a clinical trial!

Reading in the NCI’s PDQ site we came across this article which, although it deals with breast cancer patients, may be equally valid for prostate cancer patients.

For more than a decade, conventional wisdom has held that participation in a support group can extend the lives of breast cancer patients. This belief was largely based on the results of a single study, published in 1989, which found that women with advanced breast cancer who participated in a support group lived about 18 months longer that those who did not.

Now the results of a new study challenge this conventional wisdom. The new research, published in the New England Journal of Medicine on December 13, 2001, found that patients survived about the same length of time whether they took part in a support group or not. However, support group participation did improve patients' mood and perception of pain.

Between 1993 and 1998, Canadian researchers recruited 235 women with metastatic (advanced) breast cancer who were receiving treatment at cancer centers across Canada. Two thirds of the women were randomly assigned to attend a therapist-led support group that met for 90 minutes once a week. The remaining women did not participate in a support group. Upon enrollment in the study and at intervals for the following year, the women completed questionnaires that asked about mood and pain.

Women who received group therapy survived for an average of 17.9 months, compared with 17.6 months for the control group that received no therapy -- an insignificant difference. However, women who received group therapy reported less worsening of pain and had significantly lower scores on measures of depression, anxiety and bewilderment. Women who were highly distressed when they entered the study benefited from group therapy more than women who were initially less distressed...
Do these findings mean support groups for cancer patients are a waste of time? Emphatically not, say two experts. Two things can be concluded from the new research, Rowland and Rosenstein agree.

• Support groups help many <breast> cancer patients cope better with the symptoms, pain and stress of their disease, improving their quality of life.
• No <breast> cancer patient should feel guilty about not wanting to participate in a support group.

"A myth has been perpetuated that if I just go to a support group I'll feel better and live longer," says Rowland. "That's probably not the case. Support groups vary enormously. They can be very helpful for people who feel comfortable in a group, but they aren't the answer for everybody. These new findings take the pressure off survivors who may feel they have to join a support group." ...

Two breast cancer survivors who have participated in support groups think it misses the point to focus on whether or not taking part in such groups helps patients to live longer. "People join support groups for the psychosocial and quality-of-life benefits," says Diana Rowden, 49, of Dallas, Texas, who was diagnosed with early-stage breast cancer in 1991. "It helps with pain and symptom management and it gives you coping skills, as well as tips on communicating with your doctor."

Six-year survivor Cindy Geoghegan, 41, of Wilton, Conn., thinks access to quality of care influences survival more than support group participation. "I never went to my support group thinking this is something I have to do or I'm not going to get better," she says. The value of support groups, she believes, lies in the opportunity they provide for patients to share experiences and coping strategies with people who understand what they are going through. "But not all support groups are equal, and some people are group joiners whereas others are not."

Talking With Your Doctor
(Adapted from an article on the American Cancer Society website)

Introduction

A good relationship between you and your doctor is an important part of good health care. You must be able to communicate well with each other so that your needs are met. Cancer treatment often means that you will have more than one doctor. You may even have a cancer care team. Although you may get information from several sources, it's a good idea to choose one doctor to be your main source. This will be the doctor you turn to with your concerns. This doctor may or may not be the one you see most often. Only you can choose which doctor will be your main source of information. We offer the following to help you make the choice that's right for you. You should feel at ease with your doctor. A good relationship with your doctor is worth the effort it takes to create it. This means taking the time to ask your questions and make your concerns known. Likewise, your doctor must take the time to answer your questions and listen to your concerns. If you and your doctor feel the same way about sharing information, and making choices, you are likely to have a good relationship. What is the first step toward creating good communication with your doctor?

Ask Yourself, How Much Do I Want to Know?

You may want to know a lot of medical details about your illness. Some people feel more in control of what is happening to them when they know all of the facts. Decide whether or not knowing many details about your diagnosis and treatment would be helpful for you. If it would, let your doctor know. Or you may want only the overview. It disturbs some people to be told too many details. They may want simple directions - what pill to take or what their treatment will be and when it will be done. They feel overwhelmed by medical details and would rather leave most decisions to the doctor. Don't be afraid to tell your doctor how much or how little information you want.

Sharing Information

Everyone has a different style of communication. That's why the perfect doctor for one person may not be a good match for another. Consider what you value in a doctor. Some people feel more comfortable with a physician who will share information in a clinical and businesslike manner. They expect their doctor to be the medical expert rather than a friend. Other people want their doctors to have an excellent "bedside manner." They value a physician who can attend to their patients' emotional health as well as to their medical needs. Many people whose illnesses require longterm treatment prefer this kind of friendly relationship with their physician. After you have thought through what you want as a patient, the next step is to look at how you communicate with the doctor you have chosen.

Remembering What Your Doctor Says

Remember, it's hard to listen well and understand complex information when you are anxious or afraid. Even if the doctor is very thorough, you may not hear or remember what is being said. There a

*November*	1. Diagnosis of Prostate Cancer 2. Cancer and Prostate Cancer Citations from Cincinnati compared with Citations from Columbus, Cleveland, Indianapolis, Pittsburgh & Ann Arbor
*October*	1. Questions and Answers About Metastatic Cancer 2. Navigating the Vocabulary Jungle 3. A Phase III Clinical Trial of Zometa. Success? Failure?
*September*	Clinical Trials /Support Group
*August*	Talking with your Doctor
*July*	The Physician as Patient: the Story of Dr. Charles Myers
*June*	Hormonal Therapy as Primary Therapy
*May*	Patient Empowerment
*April*	NYT article on P.S.A. (April 9, 2002)
*March*	1. Vitamin D and Fosamax are effective against osteoporosis! 2. The Army Wants YOU
*February*	Recurrence after Radical Prostatectomy
January	Lycopene