DR SCHELLHAMMER: My Gleason sum was high and I had biochemical failure within a year. After a lot of discussions with urologists, it seemed that distant failure had occurred, because of the high score, the rapidity of the rise and the fact that my pathology with regard to local extension was excellent. My tumor had negative margins and I had negative seminal vesicles, so the likely presumption was that the disease had a systemic component.

At that time, Dr Taplin was just coming out with some of her early information about the combination of chemotherapy, the taxanes, and androgen deprivation, and I thought it was perhaps a good schema to think about. Even though the toxicity profile of taxanes is acceptable, it’s still considerable, so I decided to proceed with radiation therapy and androgen deprivation, without chemotherapy.

If I had a systemic component and my scans were all okay, then perhaps hormonal therapy would be effective in synergizing with the local therapy for local disease, as well as perhaps systemic disease. I took complete androgen blockade for six months using both an LHRH agonist and 50 milligrams of Casodex® (bicalutamide) as an antiandrogen, and I did not have particular difficulty with hot flashes. These were present, but certainly not debilitating.

I didn’t have to change my shirt or night garments, but I did have rather significant fatigue and I thought my ability to add and subtract (or at least to multiply) was somewhat less, so my cognition was decreased. It became clear that I was a laboratory for how we are driven by our hormonal environment, because my libido and sexual interest just evaporated to the point that even the prettiest damsel didn’t even negotiate a look.

Fortunately, after the six-month regimen, my testosterone level eventually rose and I’ve recovered, but it’s impressive how you are a product of your hormonal environment when it is suddenly altered.

DR FAGAN: This is very interesting because I had a Gleason 9 and no local extension, yet my PSA was present and doubling in a very short period of time. I had not had a preoperative CT scan so Mary-Ellen Taplin insisted that I have one, which I did. Everything else was negative, but I had two nodes — one large obturator node on each side, which is probably where my PSA was coming from.

I chose docetaxel and exemestane and hormonal ablation. My testosterone now is about 90, but at one point it went down to 30. Normal is in the 600 to 800 range, so I’m still in that phase.

I had terrible, horrible, awful hot flashes and they occurred frequently. It’s interesting when you talk about mentation. My wife noticed some changes. I’m 81, so I thought maybe it was my age that was causing it, and that may be part of it, but I’m sure the treatment contributed to it.

DR LONG: I’m just a country urologist but we used to treat people with DES (diethylstilbestrol), which would not result in hot flashes. Then we’d treat them with Lupron® (leuprolide acetate) and so forth. I know most people do not give any sort of female hormones to these patients.

I take Zoladex® (goserelin acetate) myself, and I take estradiol daily because after about three months on Zoladex, working full time all through this period, one afternoon I just felt like a wilted plant. I started taking estradiol and all these things disappeared.

Physical contact became an important part of my relationship again, and I do appreciate pretty girls walking down the street, so I’m curious why more people do not receive some sort of female hormone replacement when they’re on Lupron and so forth.

DR SHUMAN: Tom Beer at the University of Oregon has begun to do some research on transdermal estrogen patches, which have been studied more intensively in Europe.

One of the reasons for embracing this as a potential alternative to the LHRH agonist is that preliminary evidence indicates less of a deleterious effect on mentation with the estrogens, possibly even a beneficial effect in terms of osteoporosis, and because it’s transdermal, the risk for thromboembolic disease does not appear to be increased.

Another potential benefit of transdermal estrogen is that it would be infinitely cheaper than an LHRH injection, but the patches are not currently available in this country. The available patches are too low a dose so patients must use multiple patches, which is impractical.

So far no pharmaceutical companies have been interested in pursuing this, but hopefully the prostate SPORE mechanism that Paul and I belong to will study this as an alternative to the LHRH approach.

Why differences exist between using estrogens versus LHRH is not clear, but it is clear that abundant androgen receptors are present in the brain and the estrogens cross the bloodbrain barrier. Considerable research is needed to develop treatments for men who are forced to be on some kind of hormonal therapy.

DR LANGE: As with testosterone, the estrogen patches are not terribly convenient. The gel form of testosterone has changed everything, and I think the same thing will happen with estrogens, not to mention cognition and osteoporosis. The only downside is gynecomastia, but we have some interesting ways around that, besides pretreatment radiation.

DR LOVE: What about the issue of antiandrogen monotherapy with 150 milligrams of bicalutamide? This has been a fascinating story evolving over the last couple of years. At the AUA meeting, we had a think tank of clinical research leaders, and antiandrogen monotherapy was one of the topics. Patients are aware of the controversy about selection of primary local therapy, but I’m not sure they’re as aware of some of the controversies about timing and selection of hormonal therapy.

During the think tank Bill See discussed the issue of 150 milligrams of bicalutamide in the EPC trials and the various side-effect profiles. Laurence Klotz did a presentation on maximum androgen blockade, which was very interesting.

Judd, you did a presentation there about timing of intervention in terms of PSA relapse. Would you review the issues about timing and selection of therapy, and how can we involve patients more in making the best decision for themselves?

DR MOUL: It’s a very controversial area and, like so many other areas of prostate cancer, we do not have a lot of randomized trial data to go on, which makes it difficult to practice evidence-based medicine. Randomized trials suggest a benefit from traditional early hormonal therapy in men who have lymph node metastasis after radical prostatectomy or men with traditional metastatic prostate cancer.

We have absolutely no randomized trial data in patients with biochemical recurrence, and they are the most common patients who are going on hormonal therapy.

We published a paper based on data from the military database evaluating a whole bunch of guys who had biochemical recurrence. We compared the ones who received early hormonal therapy to the ones who received late hormonal therapy. Again, it was not randomized.

We found evidence suggesting that early hormonal therapy seems to benefit the guys who have high-risk biochemical recurrence, delaying the development of bone metastasis; however, our follow-up was too short to show survival benefit.

In the overall group of patients with PSA recurrence, we were not able to demonstrate any benefit. The doctors out there who are anti-early hormonal therapy can look at our data and say, “Ha! Told you so. There’s no benefit to early hormonal therapy.” On the other hand, for patients with high-risk disease, early hormonal therapy offers some benefit.

DR LOVE: Paul, you chose to be treated with MAB even though a minority of men in your situation are being treated that way. I was impressed by Laurence Klotz’s presentation in which a comparative analysis — including a lot of your data — suggests that using MAB with bicalutamide may offer a 20 percent improvement in mortality compared to an LHRH agonist alone. What are your thoughts on that and why do you think more men aren’t receiving that type of therapy?

DR SCHELLHAMMER: I think the reason more men are not receiving it is financial, budgetary and economic. If antiandrogens cost a nickel or a dime or a quarter a pill, my personal conviction is that everyone on androgen deprivation would be taking CAB. The large meta-analysis experience of the randomized trials shows an overall survival benefit that may be small, but is statistically significant, and it’s in a group of elderly men for whom an overall survival difference is quite impressive because of the other competing causes of death.

No trials have compared combined androgen blockade with Casodex to LHRH monotherapy. With some statistical manipulations, which some individuals find distasteful but has precedence in FDA-reviewed trials, as much as a 20 percent reduction in death occurs with that combination versus monotherapy.

I believe we should take every little incremental benefit we can and apply it as a standard. In answer to your question, the economics certainly become a big obstacle because of the cost of the drug and the fact that it’s not covered by many insurance carriers.

DR LOVE: Colleen, to me, this is a unique situation in cancer. Dr Klotz drew cost-benefit analogies to other types of interventions in cancer and showed data suggesting that MAB is comparable, maybe even better in terms of calculations of dollar per life saved, etcetera. What are your thoughts on that?

DR LAWTON: I couldn’t agree more with Paul’s comments about finances. This isn’t a small financial impact. It’s a huge financial impact. Many of these elderly individuals are on fixed incomes and they just don’t have the resources to consider that.

Paul is right, the data support combined therapy if you look at the meta-analyses, yet the differences aren’t huge. Very often, the wives are making these choices, or I watch the wife say to the husband, “Yeah, you know, that’s really going to impact us.” And they have the option of going on an LHRH agonist, which is Medicarecovered, or paying out this big dollar amount for MAB and they choose the LHRH agonist and say, “Well, the benefit isn’t really that much, so I’ll probably be fine with that.”

DR LOVE: This may be a men versus women, breast cancer versus prostate advocacy issue. I believe that if something like this were going on in breast cancer, it would be on the front page of the New York Times every day. Yet I don’t hear people talking about it.

Do you think the option of MAB should be presented to men who are going to be receiving hormonal therapy, or are physicians not bringing it up because of economic issues?

DR MOUL: I agree 100 percent with Paul and Colleen. I experienced it firsthand in just the last six weeks. My previous practice was in a socialized setting where the antiandrogens were covered, and we basically gave the patients the benefit of the doubt. Virtually all patients went on combined androgen blockade because of the modest but real survival difference.

The corporate culture, if you will, in my new practice setting is that the doctors basically just make the assumption that the patients don’t want it and don’t want to pay for it. When they put a patient on hormone therapy, they just write a prescription for 10 or 12 days of oral antiandrogens to block the flare, and don’t even bring up the option. They just assume the patient is not going to want to bear that cost.

DR LOVE: Shouldn’t that be the patient’s decision? I see you shaking your head, Gus.

DR MAGRINAT: This is like aromatase inhibitors costing $400 or $500 a month in breast cancer. I always tell my patients, “Look. This is a marginal improvement, but it is an improvement; fewer side effects, a little bit more benefit, but much more costly. If you can’t get it, we’ll try to get it for you,” because the companies do have programs to provide the drug to indigent patients.

I discuss it with them, and they make the decision. “No, I really can’t afford it. I don’t want to try.” In those cases, we may use tamoxifen, which is not bad at all. But the cost of Casodex may be overwhelming.

DR MOUL: Monotherapy with bicalutamide is even worse. In my previous job I used a lot of Casodex 150. I was kind of patted on the back, because in the socialized system, when I tripled the dose of Casodex 50 and gave that to a patient and avoided an LHRH agonist, believe it or not it actually saved our healthcare system money. We have no incentive to do that outside that socialized setting. In fact, I have not yet prescribed Casodex 150 in my new practice.

DR LAWTON: Just so that we don’t think that Casodex 150 has no complications, about 75 percent of patients on Casodex 150 get gynecomastia. We ran an RTOG trial in which patients with a postoperative rising PSA underwent postoperative radiation with or without Casodex. It was a placebocontrolled trial but, clearly, you could tell the patients on Casodex because the gynecomastia was very obvious. My point is that Casodex is not without side effects.

The other side of the LHRH story as far as side effects are concerned, having had my dad on it both long-term and now intermittently, is that some people really tolerate it exceedingly well. He virtually has no hot flashes. And my dad, God bless him, he’d complain about it, if he had hot flashes.

And my mother, as far as their intimate relationship is concerned — they don’t get specific about sex but my mom would say that my dad’s actually more affectionate now, more sensitive, than he ever was before.

DR LOVE: The theme that has been adopted in a lot of other cancers — and, again, I keep coming back to breast cancer — is trying to involve the patient in these kinds of decisions. With regard to a lot of the things that we’ve talked about today, I don’t see patients with prostate cancer as involved in their own treatment.

It bothers me, looking at it from the outside. People can make whatever decisions they want, but to have the decisions made for them — I’m not sure that’s the way it ought to be.

DR SHIMM: Some of it may be an age issue in the sense that breast cancer patients tend to be a little bit younger, probably a little bit less deferential to physician authority. Breast cancer and prostate cancer afflict patients in a wide range of ages but, in general, prostate patients are older and maybe a little more inclined to just nod their head and go along and not ask questions.

DR SCHELLHAMMER: It’s also rather difficult when you advise the patient that taking a pill in addition to their shot can add a perceptible and measurable benefit. You become a semantic, word-crafting wizard trying to avoid a situation whereby they feel they are jeopardizing their survival because of money. You don’t want them to have that angst, but they need to be aware that this therapy exists.

And then you ask, “Does your insurance plan cover?” And they say, “No.” And then you are faced with saying, “Well, it’s going to cost you too much.” And they’ll say, “Well, ‘too much’ for life is not within my vocabulary or thought process.” And then you mention the cost and they say, “Well, we might not be able to pay the rent.”

It’s a time-consuming and discouraging conversation. I often have my nurse go in first and find out what their insurance situation is right from the get-go. Then I make a bit of an arbitrary decision that, if they don’t have any coverage, I’m not going to go into detail about this added expense, other than to maybe mention it peripherally.

DR LOVE: Colleen, you were talking about gynecomastia. Could you comment on what methods can be used to decrease the chance of that happening?

DR LAWTON: We can give low-dose radiation therapy preemptively to prevent gynecomastia from occurring. Once the gynecomastia has occurred, we can prevent it from getting worse.

Often, we can eliminate the pain issues but we can’t reverse the gynecomastia, so if a patient is going to take Casodex 150, my bias is we ought to do it sooner, rather than later.

DR LOVE: Paul, does gynecomastia occur with CAB?

DR SCHELLHAMMER: It’s a rare event and I did not have that problem.

DR MAGRINAT: Going back to your comment on information release, in medical oncology, we frequently have treatments that patients cannot afford and we always tell them about it. It’s just a different way of doing things. Whether it’s better or worse, I don’t know.

I have a patient with true Philadelphia chromosome-negative CML and no one will pay for his Gleevec® (imatinib mesylate). But he responds to Gleevec so he actually spent $1,800 of his own money to buy a couple of months of Gleevec, and it worked.

Whether he can keep it up or not is going to be his and his family’s decision. I can’t obtain it for him. No one will pay for it.

That happens all the time with bone marrow transplantation. A transplant might really make a difference to a patient, but they don’t have insurance to cover it. It’s a terrible situation, but you didn’t create it and it’s not your ultimate responsibility.

I am more concerned about taking responsibility for providing information to a patient who comes to me for information. I lay it all out on the table. It is unfortunate and hard to deal with, and it may be unjust, but I don’t take that responsibility.

DR MOUL: I was really struck by what Paul said, and I didn’t know his full story until today, with regard to his radiation.

It struck me that in settings such as his, with a Gleason 8 and a patient who has a relatively rapid recurrence, I have been very pessimistic about radiotherapy. Perhaps I’m doing patients a disservice.

On one hand, we don’t have any randomized trial data to suggest that it’s beneficial in that setting. On the other hand, I recommend hormonal therapy without any problem in that situation without randomized trial data.

I have bashed postoperative radiotherapy in similar settings, but I’m going to try to be a little more empathetic with my patients in the future.

I honestly can’t say what I would do if I were diagnosed with prostate cancer, although I was also struck to hear that the “C” word has such an emotional impact — even among physicians who know a lot about prostate cancer and know that it’s a whole spectrum of disease.