| Tracks 1-18 |
| Track 1 |
Introduction |
| Track 2 |
Risk of prostate cancer-specific
mortality after biochemical
recurrence |
| Track 3 |
Selection of patients for early
hormonal therapy |
| Track 4 |
Importance of regular surveillance
for patients with lower-risk
disease |
| Track 5 |
Predictive value of PSA doubling
time for prostate cancer-specific
mortality |
| Track 6 |
Factors influencing the early
initiation of therapeutic
interventions |
| Track 7 |
Use of combined androgen
blockade versus LHRH
monotherapy |
| Track 8 |
Salvage radiation therapy with
or without combined androgen
blockade |
| Track 9 |
Clinical use of intermittent
androgen deprivation |
|
| Track 10 |
Paucity of clinical trials evaluating
therapy at PSA relapse |
| Track 11 |
Role of high-dose bicalutamide
for patients with PSA-only
recurrence |
| Track 12 |
Commonly asked questions about
the management of PSA relapse |
| Track 13 |
Efficacy and tolerability of
docetaxel in hormone-refractory
metastatic disease |
| Track 14 |
Use of docetaxel for patients with
high-risk, PSA-only disease |
| Track 15 |
Impact of obesity on the
development and natural history
of prostate cancer |
| Track 16 |
Counseling patients about lifestyle
and dietary changes |
| Track 17 |
Cardiac and bone health in
patients receiving androgen
deprivation therapy |
| Track 18 |
Ongoing studies evaluating the
effects of obesity and diet on
prostate cancer |
|
|
Select Excerpts from the Interview
Track 2
DR LOVE: Can you discuss the data from your study that evaluated
predictors of prostate cancer-specific mortality in patients with PSA-only
relapse?
DR FREEDLAND: The study we did with Alan Partin and Patrick Walsh
(Freedland 2005) observed patients who underwent radical prostatectomy at
Johns Hopkins and experienced PSA failure. Of those men, we eventually identified a cohort of 379 who had clean doubling times, and we knew their
long-term outcomes. The mean follow-up after surgery was 10 years — in
some men, it was out to 15 to 20 years after surgery.
We evaluated which parameters within the first year or two were the best
predictors at the time of recurrence — doubling time, how quickly the PSA
became detectable to the 0.2 ng/mL level, the Gleason score and several other
factors (1.1).
The doubling time was the key driving factor and by far the strongest
predictor. But we also found other factors that were important: how quickly
the PSA became detectable, the time to PSA recurrence (three years or less
versus greater than three years) and the Gleason score.
Track 6
DR LOVE: Can you describe a typical clinical scenario in which you think
patients are not being treated early enough?
DR FREEDLAND: One situation may be if a patient has had a radical prostatectomy
and within a year experiences recurrence with a PSA level of 0.2 ng/mL
that is 0.4 ng/mL three months later; you’re now worried that his doubling
time is three months, but the PSA values are low, and you’re not 100 percent
confident.
After a couple of doublings the PSA level is up to 0.8 ng/mL, and data with
salvage radiation therapy from Andrew Stephenson (Stephenson 2006) and
others indicate that radiation therapy works best at low PSA values — 0.2,
0.3 ng/mL — and it probably works best when you use it with combined
androgen blockade, although that is purely speculation based on when we treat
with the prostate intact.
If you have a patient who has a PSA recurrence and is young and healthy and
you’re worried that he is going to be at risk of dying — you’ll want to be
aggressive in this case, and I would use combined androgen blockade with
radiation therapy.
Track 7
DR LOVE: What prompts you to use combined blockade as opposed to
LHRH agonist monotherapy?
DR FREEDLAND: This stems from extrapolations. We don’t have great data for
the salvage setting. We don’t even have great data for LHRH versus combined
therapy when the prostate is intact.
Therefore, we are extrapolating from the metastatic data, which indicate
approximately a 10 percent survival benefit for combined androgen blockade
using the nonsteroidal anti-androgen.
It’s extremely unlikely that combined androgen blockade will be worse for
that short period — six or 12 months — and the possibility exists that it may
be better. So I tend to give it the benefit of the doubt.
Track 13
DR LOVE: What’s your take on the data that have come out over the
last couple of years on chemotherapy for prostate cancer, specifically the
docetaxel data in metastatic disease?
DR FREEDLAND: Two large studies (Petrylak 2004; Tannock 2004; [1.2]) that
were published in The New England Journal of Medicine showed that, relative to
treatment with mitoxantrone and prednisone, which was the FDA-approved
standard of care for men with hormone-refractory metastatic prostate cancer,
treatment with docetaxel and prednisone every three weeks resulted in a two-month
survival advantage — from about 16 months to 18 months.
How important is a two-month survival benefit? Rather than ask that
question, the way to consider this is that we have a drug that we know works
in the latest of late stages — hormone-refractory metastatic disease, a year and
a half to live — and we see benefit.
A study that was published in the Journal of Clinical Oncology (Goodin 2005)
showed that for men with PSA recurrence, docetaxel by itself is active, so we
have an active drug that improves survival in the late to latest stages. Now
the key question is, if we use this earlier, can we achieve a similar, 15 percent
survival benefit?
If we treat when the patient has five years left to live, can we see nearly a year
— eight, nine months — improvement in survival? Docetaxel has gotten the
medical oncologist interested in clinical trials for prostate cancer, and previously
we weren’t seeing a lot of those.
Track 14
DR LOVE: Are there any situations with PSA-only disease for which you
could see justifying the use of chemotherapy off protocol?
DR FREEDLAND: I believe that’s reasonable, especially in the hormone refractory
setting. Frankly, at this point we don’t have alternatives. I strongly
support clinical trials, and clinical trials exist for men with hormone-refractory
PSA recurrence, so a lot of options are available.
Most of the trials are built off docetaxel, so it would be docetaxel with X
versus X alone and docetaxel with Y versus Y alone. The docetaxel data have
changed the face of clinical trials. Historically, the design was always X versus
placebo. Now everything has to be compared to docetaxel or combined with
docetaxel.
Select publications
