DR ROBERTS: I was diagnosed with prostate cancer in 1999, and my Gleason score was nine (4+5) and my PSA had doubled in the year before.

It was considered to be locally advanced and surgery was not recommended. I was initially treated with intensity-modulated radiotherapy (IMRT) at about 71 Gray.

I also received maximum androgen blockade before and after the IMRT, so it was about six months of treatment and then I didn’t receive any kind of treatment for about 18 months before I had a PSA relapse.

At that point I went on leuprolide, and that was the worst experience of my life because of the weakness and the chemical castration.

I remember meeting with my radiation therapist when I was undergoing treatment. I was chemically castrated at that point. He said, “How are you?” I said, “Fine, for a eunuch,” because that’s exactly what I felt like.

DR LOVE: Can you talk a little bit more about what was going on and why you felt so bad?

DR ROBERTS: The hot flashes were intolerable. I had to stop wearing ordinary shirts and sweaters and start wearing cardigan sweaters so I could get out of them faster without breaking out in a sweat. I was examining a patient, and I would suddenly start to sweat; the same thing happened in bed at night. Weight gain and redistribution was also a big issue. I was a competitive tennis player and I couldn’t beat anybody anymore, which was not easy to take.

I don’t know whether this is related or not, but I developed a supraventricular tachyarrhythmia. I haven’t heard anybody else mention that, but I had one spell of SVT, and constant PACs that were rather annoying. I had no history of heart trouble — it could have been a coincidence but it occurred while I was on Lupron.

Last year I listened to the Prostate Cancer Update series and learned about Laurence Klotz’s work with intermittent therapy. I have two friends who are urologists at Brown University, who thought it might not be a bad idea to go on intermittent endocrine therapy since I was having such a tough time with the antiandrogen. So I stopped everything.

I had my last injection in May of 2003 and since then I’ve had a PSA and a testosterone level every two months. After about five months I began to feel like a human being again. I still had erectile dysfunction, but I wasn’t a eunuch.

I had a very passionate relationship with my wife prior to all this, and then she became a good friend, sort of a buddy. I couldn’t stand that feeling. After I got off of the leuprolide, we became lovers again. I did not have good erectile function, but that is a small part of the whole thing.

Since then, I’ve been watching my PSA, and in the last month it has tripled. It was 1.6 two months ago and it went up to 4.2. Next month or the month after I’ll be getting my next PSA and I have to decide what to do at that point. I won’t go back on leuprolide. I’d rather die. Bicalutamide monotherapy has been suggested, and I’d be happy to hear any comments or suggestions from any members here.

DR LOVE: What’s your wife’s perspective on this right now?

DR ROBERTS: She wants me around as long as I can be here.

DR LANGE: Alan, as a medical person, do you have any theories on why your reaction to androgen deprivation was so extreme compared to some other men who say, “Ah, it’s nothing.”

DR ROBERTS: Sure, because I was so much more macho! (Laughter from the group.) No. I have no idea.

DR LOVE: Do you have any theories, Paul?

DR LANGE: No, but I’d just like to get every one of these people an FMRI or something, to figure it out.

DR LOVE: Do you think this is unusual? Is it uncommon to see men who are totally miserable on androgen deprivation?

DR LANGE: I see it a lot, but I see more who say, “Ah, no big deal.” And I’ve never been able to postulate why that is, other than the fact that it’s endocrinology and something to do with neuroendocrinology.

DR LOVE: Judd, how would you think through this situation?

DR MOUL: It might have something to do with androgen levels when the person starts the therapy, but that’s too simple, and I’m sure it has been studied to see if the initial testosterone level has anything to do with the complex androgen receptor pathway.

We’re learning more about the antiandrogens — different ones behave differently. A lot of other things impact the androgen receptor — other molecules — and that’s just starting to be elucidated.

We don’t know anything about hot flashes or why they occur. It’s another example in which we don’t really understand the physiology.

DR ROBERTS: I took progesterone when I was desperate and it worked. It stopped the hot flashes so I could manage.

DR LOVE: What about bicalutamide 150 in this situation?

DR MOUL: Most of the patients, the younger ones who had libido and sexual function at the beginning of therapy, seemed to be able to maintain that, or at least to continue to respond to Viagra or one of the other agents. I have never seen a patient who had hot flashes on bicalutamide 150.

The question is: If a guy is on that therapy for a long period of time, will he gradually lose his ability to respond sexually?

Or will he gradually lose libido over time? I don’t know if that has been studied, but in the short term, the younger guys seem to be able to maintain their function in that regard.

DR LOVE: Alan, you talked about trying intermittent therapy, but that’s still going to involve going back on androgen deprivation.

DR ROBERTS: Based on what I hear, I probably would be willing to try high-dose bicalutamide.

DR SCHELLHAMMER: Another alternative is multiple transdermal estrogen patches, and follow your testosterone to see how many you need to put on each week. It’s relatively inexpensive. The cardiovascular side effects are abrogated by bypassing the liver, so that certainly would be less expensive and you wouldn’t have some of these other side effects, except the gynecomastia, which you can preempt with radiation.

DR LOVE: Have you actually utilized that in your practice, Paul?

DR SCHELLHAMMER: I have not as primary therapy, but as secondary hormonal therapy in individuals already on an LHRH agonist, so you don’t have to put on as many patches. They already have a castrate T level.

I can’t tell you a percentage but I’ll say a third, in a small experience, have a dramatic PSA response. We knew estrogens had effects on prostate cancer cells other than the endocrine axis, and I think that it’s a reasonable thing to try in elderly individuals for whom you want to avoid more toxic therapies.

DR ROBERTS: But patients will still be castrate?

DR SCHELLHAMMER: Yes.

DR LANGE: One has to remember that the patches are estradiol, not DES. DES still hasn’t been put into any kind of a formulary.

I happened to be involved in discussions that involve the FDA, about getting estrogen re-approved for delivery in a manner other than through the compound pharmacies. They are not making it easy.

DR ROBERTS: What about the idea of continuing some type of intermittent therapy, such as high-dose bicalutamide or estrogen patches for eight months or so?

DR SCHELLHAMMER: It would be an entirely new arena because intermittent Casodex has never been studied.

DR ROBERTS: If the PSA is any indication, you would at least have that to follow.

DR SCHELLHAMMER: Correct. That’s what you’re treating. But your PSA doubling time is worrisome, so treatment is something you need to strongly consider, however you decide to embark.

DR SHUMAN: I don’t know if it’s been published yet, but preliminary evidence indicates high-dose Casodex resulted in an increased incidence of death. It’s not clear what those deaths were due to, but I would be more cautious about going that route.

DR LOVE: Judd, you were one of the reviewers for that paper, correct?

DR MOUL: Yes. I don’t know if it’s out yet, but it will be published in the Journal of Urology. It’s by Peter Iverson. As a reviewer of the paper, I couldn’t make heads or tails of it.

The bottom line is that the patients with localized prostate cancer who went on Casodex in the Scandinavian watchful waiting part of that international trial had a higher overall death rate than patients with localized prostate cancer who were on placebo. No clear reason exists to explain why.

No one type of death predominates — a multitude of deaths occurred — yet it is statistically significant. At this point, the clinical relevance of this is uncertain because it’s just a matter of a few deaths making the one arm statistically significant.

I think they’re reporting it to alert people. I studied that paper carefully but it was not a show-stopper for me. I would still use Casodex in a patient at high risk who really needed it.

I would, however, be reluctant to use it in a patient who didn’t really need it, such as a patient at low risk for whom watchful waiting would be appropriate.

DR ROBERTS: The difference between absolute risk and relative risk reported in the literature is large, and we have to be very careful when we review studies, as to what we’re considering.

For example, if you consider the risk of breast cancer in women who are taking estrogen, the relative risk is about 28 or 29 percent.

But if you consider the number of patients per 10,000 per year on estrogen who develop breast cancer, it’s extremely small. In this particular case, I don’t know whether the difference between relative and absolute risk is significant.

DR ROBERTS: The one thing I am curious about is why I developed an atrial arrhythmia. It hasn’t been reported and I haven’t heard of anybody else having that happen. It could have been just total coincidence.