You are here: Home: PCUTT1 | 2007: Management of PSA-Only Relapse

Select Excerpts from the Discussion

Tracks 21-23

DR LOVE: Steve, can you discuss your study evaluating the relationship between mortality and PSA doubling time following prostatectomy?

DR FREEDLAND: The PSA doubling time was calculated within the first two years after a PSA recurrence. Few men received hormonal therapy until the time of metastasis. Therefore, it is largely a natural history story (Freedland 2007; [2.1]). The question would be, if you take those men with PSA doubling times of less than three months and treat them with early hormonal therapy, will we see a better outcome? I don’t know the answer.

In Anthony’s study published in the JNCI, he evaluated patients — from the CaPSURE and the Center for Prostate Disease Research databases — who were treated with radiation or surgery.

It was a much larger study than ours, and the median survival in patients with a PSA doubling time of less than three months was six years (D’Amico 2003). If you look at our study, the median survival was also six years.

DR OH: In looking at Steve’s data, I am surprised that patients with a longer PSA doubling time had so many prostate cancer deaths. In patients with rapid PSA doubling times — where your data parallel Anthony’s data — my guess would be that the practices are completely different at Hopkins and in the community in terms of when to initiate hormonal therapy. There’s potentially no difference in outcomes. I’m not comparing the studies, but I don’t think there seems to be an impact in those patients.

This brings up the question that perhaps, paradoxically, the benefits of hormonal therapy may actually be more dramatic in patients with moderate PSA doubling times.

If the patient’s PSA is rapidly doubling, it may not matter whether you start hormonal therapy when the PSA is one or 10 or 20 ng/mL, but if a patient’s PSA is doubling every 12 months, maybe it matters a lot. It may be that hormonal therapy is not being used enough.

DR LOVE: Steve, what about the use of intermittent hormonal therapy for patients with PSA-only disease?

DR FREEDLAND: I’m not a huge fan of intermittent hormonal therapy. In the man with a rapid PSA doubling time, the time off therapy — meaning the time he has a normal testosterone level — is extremely short. He actually derives a relatively low benefit.

I believe the patients who do have a significant quality-of-life benefit are the ones who, when their testosterone levels come back, stay off therapy for a year or two. In my experience, those are the patients with long PSA doubling times in whom I’m hesitant to use hormonal therapy in the first place.

For some patients, intermittent hormonal therapy would be better than continuous therapy because they don’t need any treatment — some need continuous therapy. If you take “all comers,” you’re going to see no difference between intermittent and continuous hormonal therapy. If you risk stratify, however, I believe we can identify the group of patients that needs continuous hormonal therapy and the group that probably doesn’t need any.

DR KLOTZ: We conducted a 100-patient prospective Phase II study of intermittent treatment, which was recently published (Bruchovsky 2007, 2006), and a lot from that study relates to these comments.

First, you can predict the off-treatment interval, in part, from the baseline PSA. The patients who do best are the ones who have a baseline PSA that is below 10 ng/mL (Bruchovsky 2007). Second, the PSA nadir is a huge predictor for the off-treatment interval and time to androgen-independent progression (Bruchovsky 2007).

DR LOVE: What about Steve’s point about PSA-only disease and, for example, a patient with a rapid PSA doubling time?

DR KLOTZ: For me, there are three groups of patients. The patients with a PSA doubling time that is less than three or six months should receive continuous hormonal therapy. The group with a slow PSA doubling time should have delayed hormonal therapy, which could be intermittent.

For the group in the middle — those with a PSA doubling time that is between six and 15 months — androgen deprivation therapy is warranted. However, no benefit of long-term, continuous hormonal therapy has been demonstrated. So other than for the patient with bad disease, I typically don’t continue hormonal therapy beyond one or two years.

Track 25

DR LOVE: I’ve seen a change in the last couple of years in the approach to patients with hormone-refractory, PSA-only disease. Two or three years ago, I didn’t hear much support for considering chemotherapy in these patients. I believe a lot of it is related to your work, Steve, on PSA doubling times and the idea that we can pick out the bad tumors and be more aggressive. What are your thoughts on that?

DR FREEDLAND: If you have a patient with hormone-refractory, PSA-only relapse, especially with a rapid PSA doubling time, you know what the future holds. If we have an effective therapy and our mantra is, “Effective therapy used earlier should be even more efficacious,” I don’t see a reason to hold that therapy.

Track 26

DR LOVE: What about the side effects of chemotherapy, specifically docetaxel? What’s your take, Dan, in terms of how docetaxel affects quality of life?

DR PETRYLAK: The data from TAX-327, which evaluated the quality-of-life parameters for docetaxel versus mitoxantrone, are telling. The quality-of-life parameters improved more with weekly and every three-week docetaxel than with mitoxantrone (Tannock 2004; [2.2]).

It’s different in an asymptomatic patient when you’re not trying to treat bone pain and other issues. My general experience, however, has been — if you support the patients properly with growth factors and other measures — docetaxel is fairly well tolerated.

DR OH: If we properly select patients, we may not be making them feel better, but we’re not making them miserable either. We’re making them feel a little worse than they otherwise would in exchange for the probability that the longer-term picture might be better.

We don’t have data in this setting, but we know the time to metastasis is short in patients with rapid PSA doubling times. So, if a patient’s PSA is doubling quickly in the absence of metastatic disease, even if he feels well, I believe docetaxel is a legitimate option to discuss, although it’s not a standard practice.

Track 29

DR LOVE: How do you compare the quality-of-life impact from chemotherapy and androgen deprivation therapy?

DR FREEDLAND: I believe it’s different in a lot of ways, but a lot of fatigue occurs with both therapies. Hormonal therapy dramatically affects quality of life, and we probably underestimate its effects.

DR OH: Docetaxel probably has greater global quality-of-life issues than hormonal therapy. Hormonal therapy is still a well-tolerated treatment, in general. I want to clarify that chemotherapy is not commonly used to treat patients with nonmetastatic, hormone-refractory disease. It’s becoming more of an issue because men are increasingly receiving hormonal therapy in the absence of any metastatic disease.

In this setting, we’ll often use second-line hormonal therapies — antiandrogens, ketoconazole, et cetera — in an effort to control the disease without having to use chemotherapy right away.

However, in a selected group of patients with aggressive, hormone-refractory prostate cancer, I don’t believe it’s wrong to have this conversation with the patient. In general, our surgical and radiation therapy colleagues ask us as medical oncologists, “Why aren’t you using this treatment? It makes no sense not to.”

Medical oncologists in the community have to balance this in the absence of data. They may say, “How do I take a patient who’s feeling well and decrease his quality of life in the absence of data?” It’s a fair point.

For many patients, once they have metastatic disease — whether they’re symptomatic or asymptomatic — that’s justification for chemotherapy. There is a survival benefit in that group of patients with metastases (Petrylak 2004; Tannock 2004; [2.3, 3.2, 3.3]).

In the patients with nonmetastatic disease, if they have a rapidly doubling PSA, it’s predictive of time to metastasis. In that setting, if you’re delaying chemotherapy by six months, is it meaningful to an extremely anxious young patient? My feeling would be that you’re not buying much for that man by delaying chemotherapy.

Select Publications

Home