The November speaker was our oldest and dearest friend, urologist Alan Treiman, who was instrumental in helping Jim Mullen establish the Man To Man program seventeen years ago. Dr. Treiman, as our medical advisor, has been a consistent lecturer every year since then. Somehow, he was assigned the same topic to speak on as our October guest, Dr. Gapin, namely how to handle recurrent prostate cancer (treatment failure). Since both speakers are excellent doctors and both are urologists who had the same training and read the same literature, their presentations were mirror images of each other. As newsletter space is precious, we refer you to the previous issue for details of treatment options and will pick up on Dr. Treiman’s presentation with his excellent summary and the question and answer period that followed. Here he is:

What type of things can we do for men who have a rising PSA following a radical prostatectomy? The gentleman in the second row was offered radiation therapy; but, where do we radiate? Naturally, we’ll go to where the prostate used to be, which can be determined by x-ray. Radiation does have some side effects whether you have a prostate or not. The rectum can be injured as well as the bladder and incontinence can be a consequence. There is a whole separate lecture that I could do on who should have radiation.

How well does it work? Should we combine hormones at the same time? There are many options to be considered. This is one of the reasons I tell younger (50s and 60s) prostate cancer patients to have their prostate removed, because if the cancer recurs then you can be radiated later. If you have radiation first, it is harder, much harder, to remove the prostate. If you are older, don’t have surgery but settle for radiation because statistics show that, regardless of outcome, you will still do well for 10 to 15 years.

We can also use hormone therapy after a radical prostatectomy. When do we commence that? That’s a matter of opinion. If a patient suffers surgical failure and he’s 85 years old, he’s a natural candidate for hormonal therapy. He might have to take hormones for only six to twelve months, time enough to get his PSA back down to 0, sparing him the necessity of radiation and it’s possible side effects. His PSA might take two to three years to go back up again.

What is the dilemma in terms of radiation? While we would like to think that we are smart enough to find the cancer, what if we can’t find it by biopsy? Should we still radiate somebody? That is very controversial. This gentleman (second row in the audience) had a biopsy and it showed where his cancer is, so we feel good about radiating it. Most of the time we do a biopsy and we can’t find the cancer, although we know it’s somewhere. A lot of guys will do radiation on a shotgun approach hoping to hit it right, but that’s certainly not scientific.

We don’t have a lot of long term studies comparing outcomes of patients who were radiated as salvage treatment and those who weren’t, but we’re working on it. But, here’s one from Sloan Kettering where they had over 500 patients from many centers around the country. This was a retrospective study (they looked back) analyzing men who had what was called “radiation therapy after radical prostatectomy” and found that two thirds of them completely responded; their PSA went back to 0.

I want to mention seminal vesicle involvement, the area behind the prostate. A lot of patients had seminal vesicles that contain prostate cancer cells and we don’t know this until we get the pathologist’s report following surgery. The problem is these men tend to do a little worse than the patients who had the cancer confined to the prostate itself. This is a group we might not consider for radiation therapy.

Enough of that, now let’s talk about hormonal therapy. Most of you know about this and that it’s very expensive. As with radiation, we’re not really sure when to start treatment; should the PSA be 2? 4? 6? There are some indications that earlier is better, but the final studies that we now have show that, despite when you start it after a recurrence, they all seem to do about the same. Should we wait until the patient has bone metastasis or should we start when the PSA is 0.2. We really don’t know the answer to that and I usually let the patient decide after we’ve discussed the plusses and minuses.

Clinical trials are currently underway to study early treatment with hormone therapy. The study’s conclusion is that they cannot find a survival difference whether the therapy is begun early or late. If you remember the slide from just a few minutes ago, the average time from metastasis to someone dying from prostate cancer is about five years, or more. There is no sense of urgency which is why some people say, why should I start the hormone therapy early? Why don’t I wait because we all know that the hormones could run out of steam because cancer cells become resistant to them?

And, here’s something interesting just to put into your memory banks and it comes from none other than Sloan Kettering. A study of theirs found out that if they did start very, very early with hormone therapy, there was a actually a small disadvantage to those patients who eventually got metastatic disease. We don’t know why that is, but if you think about it, the earlier you shoot your hormone bullet, the earlier you get resistant cancer. So, if you start a guy when his PSA is only 0.2 or 0.3, his PSA will go down to 0 very quickly, but the clock is then ticking because we know that 50% of those men might have a resistant cancer within two to five years. If you wait until someone’s PSA is 18 or 19 or he has bone metastasis, his PSA, most generally, will still go down to close to 0, but by now he is probably 10 years older than he was when his PSA was 0.2. When do we want to shoot the bullet, on day one or ten years later? There are studies under way which will tell us that.

And then there’s cryotherapy which, by the way, we are doing a lot of these days. It’s interesting to reflect back to when I was here five or six years ago giving a similar talk, we weren’t doing cryotherapy after radiation at all. Then, the machinery for that procedure was such that we were doing too much damage. Today, however, there have been significant improvements both to the equipment and to the surgeons and we’re quite busy with cryotherapy now.

Basically, what we’re doing is freezing the prostate, but that’s not all we can do. Earlier I discussed the problem of leaving some cancer behind in the seminal vesicles -- well, that’s something we can take care of with cryotherapy. We can actually insert probes into the seminal vesicles and freeze them too, just as we do the prostate. So, there are patients who have had radiation therapy, their cancer is back and even spread to the seminal vesicles, and we can help them.

We talked about people who have had a radical prostatectomy. We talked about people who have had radiation therapy. We never did get to the cryotherapy, but they are grouped in with radiation therapy patients. Since the prostate is still there with both radiation and cryotherapy as primary treatment, the salvage opportunities are the same. So, if the cancer comes back, what do we do with it?

If you’ve had a radical prostatectomy and your PSA is undetectable, we just keep getting PSAs. If, at some time in the future, it becomes detectable, then what do we do? Well, we have to confirm it, first of all. Then, if it’s a late failure (greater than two years since surgery) and your PSA doubling time is not rapid, it means you probably have a local occurrence of the cancer and you ought to consider radiation. If you have a PSA rise and it is an early failure since treatment, then we have to figure out where the cancer is located. Most likely, it’s not local but somewhere else in the body. So, we get a bone scan because that is the best we have; maybe a ProstaScint, maybe an MRI. If we find the cancer in a lymph node or a bone, you should probably go on hormone therapy. If the search is negative, then we have the dilemma of deciding what to do. Most patients are safe in waiting and seeing what happens. If you feel like you want to do something, a short course of hormone therapy is in order.

If your primary treatment was radiation and you have an undetectable PSA, we just keep following it. If it starts to go up, becomes detectable and the ascent is rapid, we do the staging workup and we either do nothing or hormone therapy. If the PSA is rising, but you are in one of those categories that doesn’t demand prompt attention, we can do a biopsy. If we find the cancer in the prostate, then we know it is local and we have three options: remove the prostate, cryotherapy or just keep watching..

For everyone experiencing recurrence, we have to go down pretty much the same path together and decide what to do. It is very complicated with decisions to be made every step of the way. Do I want treatment? Don’t I want treatment? What is the treatment going to mean to me? When should I start the treatment? We can help you reason out your options, but the final decision is yours.

Questions?

I don’t think it is that important, as most of the labs really do the same test. We have one in our office that is the same as Quest or DSI or any of the other labs. Since most use the same procedures and equipment, any variation is not going to be that much.

Nerve sparing is an option, but seminal vesicles are not and everybody removes them as part of the prostate. A millimeter isn’t that far and there are some limitations to the pathology. Obviously, your surgeon knowing your case and the Partin tables and based on his experience, decided that you were safer in the long run to have the nerves removed.

Ask this man here in the audience whose cancer has returned after so many years that question. No, all prostate cancer patients should continue to monitor their PSA. If it is normally undetectable, your annual physical with your family doctor should include this test as I’m sure he would insist. Should a rise be detected, that’s when you should return to your urologist. And, there’s always the possibility that you may encounter some other issues such as leakage or impotence and need to see me for those reasons. But, otherwise, so long as somebody does a PSA once a year, it doesn’t have to be a urologist. The problem could be that the primary care physician could lose sight of the fact that you had your prostate removed and when your annual test comes back as a 2.0 he tells you that’s normal. It could have been a busy day for him, or her.

Good question. The answer is, we don’t know. But, so it doesn’t drive us crazy we, meaning the urologic community, have picked the number 10. Where did we get that number? Well, that’s the PSA value at which we begin to worry about metastatic disease to the bones. The other guide that I use is the PSA velocity; how fast is it going up? For instance, if you come in to my office with a PSA of 2 and four months later it’s 8, the handwriting is on the wall and we’re not going to wait until it’s 10 or 12. You’re smart enough to know you need help right away.

I have other patients that I have to negotiate with because they hate the hormone therapy and it’s side effects which are well-known to everyone. Those side effects really rock a man in his 50s; think of what does to a patient who is 80 years old. They’ll come in and say, “hey, I feel pretty good, let’s go another six months” -- anything to avoid the side effects. The older men I have to be particularly careful with this as I can’t risk bone metastasis to the spine with them which could lead to paralysis or a broken hip. So, what I do is get bone scans in those cases, and if it’s positive, they’re on hormone therapy. In determining when to start, or restart, hormone therapy, several factors have to be taken into account, including the patient’s age as well his wishes in terms of lifestyle.

There are other alternatives such as going on Proscar and Casodex, which are antiandrogens, which won’t lower your testosterone like the hormones will, but will lower your PSA and you feel a little better. They will stop Lupron or Zoladex, but stay on some Proscar; and then the PSA goes up and they start on a regimen of Casodex.

Most of the time there’s no need for that, but there are specific reasons for checking it. One is when a patient is on hormone therapy and it starts to fail -- when his PSA begins to rise. Hormone therapy is a testosterone suppressor, a medical castration if you will, that keeps the PSA down. Why is the PSA going up? Is the suppression effect of the hormones failing? If the testosterone level is going up, the answer is yes, the cancer cells are becoming refractory to the treatment. With the use of these new Viadur implants that now administer Lupron for a whole year, [Ed. Year? Where did the monthly and quarterly injections go?] I need to get a comfort level that they’re really that good so I’ll order a testosterone check along the way.

Another reason is that I have a lot patients on intermittent hormonal therapy where I need to monitor their testosterone level because an increase in that will make them more prone to having their PSA go up.

Thank you. As always you’ve been a great audience and I appreciate the opportunity to be with you.

There was no business meeting in December which gives your editorial staff the opportunity to bring snippets of prostate cancer information from sources around the country and the world. Beginning with:

(From www.Medscape.com)

LONDON (Reuters) Sept. 28 - As many as half of the Viagra sold on the Internet could be counterfeit, British scientists say. They analyzed samples of Viagra sold on Web sites and found that some of the pills contained less of the active ingredient, or different components, than the top selling drug made by Pfizer. “On our initial estimate, around half of the of those Viagra samples could be counterfeit,” Dr. Nic Wilson of the University of London, told the British Pharmaceutical Conference. The bogus drugs were branded and labeled Viagra and came in identical packaging as the real thing.

The scientists are not sure whether wrong components in the bogus pills are harmful, but at the very least it is highly probable the fakes will not work. If the counterfeiters get the dose wrong and the fake pills contain too much of the active ingredient, sildenafil, it could be dangerous. “Part of the side reaction of sildenafil is increased heart pressure, so people could get heart attacks”, it was stated.

“If you go to a site that looks a bit wonky (sic), they are selling it cheap and you’ve got no address or idea where they are based, you’re chancing it”, was the warning. The scientists used a technique called near infrared (NIR) microscopy, which provides a more detailed picture of what is in a tablet and its active ingredients to separate the fakes from the real thing.

[Ed: Last issue we brought you the story of how the unscrupulous manufacturers of PC-SPES hoodwinked us and now this. Your health is worth the retail cost from a reputable supplier.]

High-risk prostate cancer patients who undergo a combination of hormone therapy, radioactive seed implant (also called brachytherapy) and external beam radiation therapy are shown to have an increased chance of cancer cure, according to a new study by researchers at Mount Sinai School of Medicine published in the August 1, 2004 issue of the International Journal of Radiation Oncology*Biology*Physics.

Historically, high-risk prostate cancer has been a therapeutic challenge for physicians, despite their efforts to cure patients by aggressively treating them with either surgery, brachytherapy or external beam radiation. Previous studies has shown the 5-year freedom from recurrence rates for high-risk patients treated with just one of these modalities to be between 0 and 50 percent, with up to half of these failures occurring where the original tumor was found.

To see if combining therapies would decrease recurrence rates for men with high-risk prostate cancer, 132 patients with high Gleason scores, high PSAs or who were at an advanced clinical stage were studied. A three-pronged approach that included brachytherapy, external beam radiation and hormonal therapy produced an 86 percent rate of freedom from recurrence after five years. In addition, 47 of the original 132 patients in the study had a prostate biopsy performed two years after the end of treatment and all of them showed no evidence of the cancer recurring.

“This is a very exciting study because it shows that this new approach of combining multiple therapies to cure prostate cancer can be very effective for men with aggressive forms of the disease,” said Richard G. Stock, M.D., lead author of the study and Chairman of the Department of Radiation Oncology at Mount Sinai. “The data also supports the theory that enhanced local control can improve overall disease control.”

In the past we’ve saturated these pages with the message that good food is good medicine (thank you, Eve Prang Plews for your wit and wisdom), and now we bring you another unheralded, and unproven, medical phenomenon. This from the Web site of the TV Channel MSNBC

To paraphrase a great old slogan for Guinness beer, “Sex isn’t just good, it’s good for you.” Okay, so maybe there’s some wishful thinking going on -- the science isn’t exactly ironclad -- but evidence is accumulating that the more sex you have, the better off you are.

There is one caveat, though. “We do not have good data to show a direct connection [to all-around good health]”. says Jennifer Bass, the head of information services at the Kinsey Institute for Research in Sex, Gender and Reproduction in Bloomington, Indiana. “We know that healthier people have more sexual activity, but we do not know which comes first.. Does the good health make you more willing to have sex, or does the sex have a positive impact?” [Ed. So far, this sure beats green tea, bioflavonoids and lycopene. Wait until you find out how many benefits are out there waiting for you.]

And, you Don Juans and adventurous ladies should know that the assumed health benefits of sex are generally thought to accrue to people in loving, monogamous relationships or those flying solo. Risky sex with lots of partners will probably do more harm than good. But while researchers try to nail down the impact on overall health, data is mounting when it comes to some specifics. Here are several potential advantages:

1. Easing depression and stress. Bass says this is pretty definite. “The release from orgasm does much to calm people. It helps with sleep, and that is whether we talk about solo sex or sex with a partner,” she says. But wait, there’s more. A recent study of college students at SUNY (Albany), suggests that semen acts as an antidepressant. Females in this study who were having sex without condoms (see safe sex caution, above) had fewer signs of depression than women who used condoms or abstained from sex.

“These data are consistent with the possibility that semen may antagonize depressive symptoms,” the authors wrote, “and evidence which shows that the vagina absorbs a number of components of semen that can be detected in the bloodstream within a few hours of administration.” I kid you not, ladies; semen is good stuff! It gives a shot of zinc, calcium, potassium, fructose, proteins -- a veritable cornucopia of vitality!

2. Relieving pain. Orgasm is a powerful painkiller. Oxytocin, a natural chemical in the body which surges before and during climax, gets some of the credit, along with a couple of other compounds like endorphins. According to a study by Beverly Whipple, professor emeritus at Rutgers University and a famed sexologist and author, when women come to orgasm, “the pain tolerance threshold and pain detection threshold increased significantly by 75% and 107% respectively.”

3. Boosting cardio health. I can’t resist another plug for semen. It’s possible that it can lower blood pressure. Other studies showed that sex might even protect against strokes caused because of its stress-relieving ability. But when we think of sex and the cardio system, we tend to think of poor Nelson Rockefeller having a heart attack in flagrante delicto. Well, not only does that hardly ever happen, but sex might actually protect the heart. A 2002 report from a large British population of men said “some protection from fatal coronary events may be an added bonus” of frequent sexual intercourse.

4. Countering prostate cancer. Over the past few years, several journals have published studies showing that the more ejaculations the better. Now the Journal of the American Medical Association (JAMA), no less, has reported that “high ejaculation frequency was related to decreased risk of total prostate cancer.”

5. Healing wounds. Some evidence suggests sex can be rejuvenating to the point of helping wounds heal faster. Several experiments have shown that oxytocin can help even stubborn sores, like those suffered by diabetics, to heal by regenerating certain cells.

6. Fighting aging. Maybe it’s the rejuvenation, maybe the happiness, maybe all of the above. One thing’s for sure: “Use it or lose it” is literally true. For example, post-menopausal women often suffer from “vaginal atrophy”, which is what it sounds like and can lead to all sorts of complications like urinary tract infections. What’s one way to prevent it? More intercourse. Sex is a form of exercise, after all, and like all exercise, it burns calories and can help settle the onslaught of the years. In fact, nursing home experts say they wish oldsters would have more sex.

Can sex really make you live longer? Maybe. In the same population of British men I cited earlier, researchers found a 50% reduction in overall mortality in the group of men who said they had the most orgasms. There was a dose response; the more orgasms, the better.

Of course, as Kinsey’s Bass reminds us, it could be that these blokes are just healthier and felt like having sex more often. But, since there’s no evidence that lots of sex is bad for you, what have you got to lose?

The author, Brian Alexander, is a contributing editor to GLAMOR magazine.

A recent report linking Vitamin E and increased risk of death is causing turmoil for a Seattle nonprofit that’s behind a long-term trial to determine if the vitamin can prevent prostate cancer. Seattle-based Cancer Research and Biostatistics is in the early years of a 12-year trial with a Texas-based cancer research consortium to determine if vitamin E or the mineral selenium -- or a regimen of both -- can reduce the risk of prostate cancer in men 55 and older. It’s the largest-ever prostate cancer prevention study.

But an analysis by doctors from Johns Hopkins University and other institutions concluded that high doses of vitamin E could trigger deadly heart attacks. And, as a result, during the past week those running the trial have been scrambling to reassure participants that the vitamin E doses are safe. Jack Crowley, president and chief executive officer of Cancer Research and Biostatistics, said he’s gotten a flood of emails from many of the 430 study sites across North America participating in the prevention trial. Crowley, and others, fear the vitamin E report could start an exodus among the 35,000 men taking part in the selenium and vitamin E cancer prevention trial (SELECT), which is funded by the National Cancer Institute.

“We’re worried about it. We are getting lots and lots of inquiries”, said Crowley, who said he has prepared a letter for the study sites pointing out flaws in the vitamin E report. He said there is no new research data in the that report posted November 10th on the Annals of Internal Medicine Web site. It analyzed data from 19 clinical trials using vitamin E, some dating back almost 40 years.

Crowley further stated the architects of the prostate cancer prevention trial were well aware of the past research, and the prevention trial is monitored by an independent panel of doctors. They say they are confident that the type and level of vitamin E doses in their trial (400 I.U.) are safe which Crowley himself, as a participant in the trial, is taking.

The prostate cancer prevention trial is one of more than 100 active clinical cancer trials that Crowley’s organization oversees, a role that includes designing the studies, developing protocol and managing and analyzing data, as well as doing the statistical research. Earlier this year, the National Cancer Institute awarded Crowley with a six-year, multimillion-dollar contract to continue analyzing data for the Southwest Oncology Group, the adult cancer clinical trials organization that launched the prostate cancer prevention trial in 2001.

A lot is riding on the prevention trial, which initial federal grant applications estimated could cost $172 million.

Prostate cancer is a leading cause of death among older men. The disease is particularly devastating among African-Americans, who have the world’s highest incidence of prostate cancer and the highest death rate from the disease. About 15% of the participants in the SELECT trial are African-American men.

“This is not chopped liver, this is a big deal”, said Dr. Charles Coltman, Jr., principal investigator for the clinical trial. “I’m not interested in having this trial mucked up by shyster science.”

Seattle, Wash., October 28, 2004 - Dendreon Corporation (Nasdaq: DNDN) today announced that the data from the final three-year follow-up of its completed first Phase 3 study (D9901) of Provenge ®, the Company’s investigational immunotherapy for the treatment of prostate cancer, showed a statistically significant benefit in patients with advanced prostate cancer who were treated with Provenge. Prostate cancer is the number one non-skin cancer in the United States and the third most common cancer worldwide.

The pre-specified 36-month final survival analysis of the double-blind, placebo-controlled study of Provenge in 127 patients with asymptomatic, metastatic, androgen-independent prostate cancer showed a statistically significant survival benefit in the overall intent-to-treat patient population, defined as all patients randomized in the study regardless of their Gleason score.

That survival benefit is greater than that observed with any type of treatment in any published Phase 3 study in late-stage prostate cancer. In addition, at the 36-month final follow-up, the percentage of patients alive in the Provenge-treated group is substantially greater than the percentage of patients who received a placebo.

Provenge is being further evaluated in an ongoing, pivotal Phase 3 trial (D9902B) under a Special Protocol Assessment agreement with the U. S. Food and Drug Administration. Provenge also has Fast Track designation. The double-blind, placebo-controlled trial is enrolling patients at leading cancer centers around the country. To learn more about the trial, go to www.dendreon.com