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PCU 4|2002: Peter
R Carroll, MD
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 Peter
R Carroll, MD |
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Professor
and Chair,
Department of Urology,
University of California, San Francisco
Program Leader,
Program in Urologic Oncology,
Mt Zion Cancer Center,
University of California, San Francisco
Interim Chief of Urology,
Mt Zion Medical Center,
University of California, San Francisco |
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Edited comments by Dr Carroll
Cancer of the Prostate Strategic Urologic Research
Endeavor (CaPSURE)
CaPSURE is an observational registry being conducted at about
35 sites — mainly community physicians’ offices —
around the United States. Consecutive patients with prostate cancer
of all ages, stages and treatment modalities are enrolled. The objective
is to evaluate prostate cancer treatment trends and outcomes.
I believe that CaPSURE is providing a representative picture of
prostate cancer care in the United States. When we compare the outcomes
in CaPSURE to those at academic medical centers, they are reasonably
close. We see a stage migration — lower stage disease, lower
median PSA, younger patients with more favorable disease.
Prostate cancer treatment patterns
We are detecting rather remarkable changes in treatment patterns,
over time. Currently, 30% to 40% of men are still treated with radical
prostatectomy. Another 30% may receive radiation therapy alone or
in combination with hormonal therapy. The rest are either observed
or treated with hormonal therapy.
There are many more men with low-risk prostate cancer now being
managed with brachytherapy and fewer with radical prostatectomy.
The number of patients being observed is relatively stable —
about eight percent. Men with intermediate-risk prostate cancer
are being treated with radiation therapy and radical prostatectomy.
In men with high-risk prostate cancer, more hormonal therapy is
being prescribed.
CaPSURE has noted two other treatment trends — more neoadjuvant
hormonal therapy in combination with radiation therapy, and the
use of hormonal therapy as primary therapy in men with nonmetastatic
disease in all risk groups. This trend is greater in patients with
high-risk (high grade or volume) disease.
Currently, in the United States we are not seeing the use of antiandrogens
as primary therapy very frequently. However, I think that this is
going to change, and we will see more bicalutamide given as primary
therapy. My sense is that bicalutamide monotherapy will be used
in patients with highrisk (high grade and volume) localized disease
(M0), who do not want or are not candidates for standard therapy.
| CaPSURE database:
Use of primary androgen deprivation therapy (ADT) in 1,485 consecutive
prostate cancer cases |
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RP = radical prostatectomy, RT
= radiation therapy
DERIVED FROM: Meng MV et al. Contemporary pattens
of androgen deprivation use for newly diagnosed prostate cancer.
Urology 2002;60(suppl 3A):7-12. Abstract |
Primary hormonal therapy for prostate cancer
Increasingly, older men with comorbidities and high-risk, nonmetastatic
prostate cancer are initially being treated with hormonal therapy
— an intermittent LHRH agonist or bicalutamide monotherapy.
The effect of hormonal therapy on the primary tumor is more durable
than on metastatic disease.
In a patient with an estimated survival of five years or less,
based on age and comorbidity, aggressive local therapy will not
make a difference. We can control prostate cancer well with systemic
therapy, certainly in the three- to five-year range, in patients
with low- or intermediate-risk disease and even high-risk, nonmetastatic
disease.
For patients with M0 disease, data suggest that bicalutamide 150
mg and an LHRH agonist are both reasonable options. Bicalutamide
seems to preserve health-related quality of life, sexual function
and bone mineral density compared to an LHRH agonist.
Management of patients with biochemical relapse
This is the largest group currently receiving hormonal therapy.
First, biochemical progression must be confirmed with another PSA,
and it is also important to get a sense of the PSA kinetics —
the rate and timing of rise. The primary disease characteristics
should also be considered. Those two factors — more than imaging
— allow you to determine the approach to treatment.
The typical patient with a local recurrence has Gleason 7 or less
with a late failure (after two years), PSA doubling time more than
10 months, and no seminal vesicle invasion or positive nodes. The
typical patient with systemic recurrence has Gleason 8 to 10 prostate
cancer, PSA greater than 20 and early failure (before two years).
There may be a tendency in some physicians to ignore the importance
of biochemical recurrence, but one should have an honest discussion
with the patient about the treatment options and trade-offs.
These patients are candidates for either clinical trials or systemic
therapy. Outside of a clinical trial, patients failing systemically
are candidates for hormonal therapy — an LHRH agonist (continuous
or intermittent) or bicalutamide. One needs to have a careful discussion
with the patient about what they can expect from one form of treatment
or another.
Bicalutamide 150 mg is a reasonable treatment option for the patient
who wants to maintain sexual function and understands the risk of
gynecomastia. Most men do not find gynecomastia a real issue. For
men who are physically or sexually active, declines in physical
and sexual function seen with LHRH agonists may be a bigger trade-off.
Management of patients with high-risk prostate
cancer
I consider combination therapy in patients with a high probability
of failing local therapy. One option is surgery followed by adjuvant
radiation or systemic therapy. Another option is neoadjuvant hormonal
therapy followed by 3-D conformal radiation therapy to the prostate
and regional lymph nodes.
Currently, we have a trial comparing chemo/hormonal therapy to
hormonal therapy alone in patients with node-positive disease. However,
the most common type of treatment for this situation is hormonal
therapy — either bicalutamide 150 mg or an LHRH agonist.
When discussing hormonal therapy with these patients, I tell them
that early therapy may delay progression and provide a survival
benefit, but we do not know how early is early. Most patients will
delay hormonal therapy and monitor their PSA.
CASE 2:
49-year-old man with Gleason 4+3 prostate cancer |
History
The patient was recently divorced, in a new relationship
and ignoring a prostate cancer diagnosis. His parents came
for a consultation with me and audio taped it for him. Ultimately,
another urologist on the East Coast and I evaluated the patient.
There was no family history of prostate cancer. His PSA was
16 ng/mL, and he had 90% of the cores involved with Gleason
4+3 prostate cancer. His bone scan was negative. He clearly
had locally advanced disease on palpation, and we demonstrated
by ultrasound that there was invasion at the base of the seminal
vesicles. His quality of life and sexual function were good.
Follow-up
He is currently undergoing hormonal therapy with an LHRH
agonist. He will also receive bicalutamide, for at least one
month. A radiation oncologist has evaluated him for 3-D conformal
radiation therapy.
Case discussion
TREATMENT OPTIONS:
Based on his PSA, Gleason score and the number of positive
biopsies, he was considered a high-risk patient. I thought
the likelihood of this patient being cured with radical prostatectomy
was quite low. He was not a good candidate for monotherapy
and required combination therapy. His choices were either
surgery with a node dissection followed by adjuvant therapy,
or neoadjuvant hormonal therapy and radiation to the prostate
and pelvis.
He elected neoadjuvant hormonal therapy and radiation therapy.
Despite his high risk of nodal involvement, a lymph node dissection
was not necessary. We were going to treat him with the full-field
radiation, whether or not the nodes were involved.
In terms of hormonal therapy options, he was offered an
LHRH agonist or bicalutamide monotherapy. I told him, “We
have the most information with the LHRH agonists, and the
decision to use an LHRH agonist is not permanent. We can start
out with a one-month injection, and we can change forms of
hormonal treatment in the future.” Even though bicalutamide
monotherapy might not interfere as much with sexual function
and quality of life, he decided to receive an LHRH agonist.
In patients who are strongly averse to an LHRH agonist,
I switch them from an LHRH agonist to bicalutamide monotherapy,
just to keep them on some form of hormonal therapy. In this
patient, I would use an LHRH agonist, evaluate his response
and tolerability, and then make a decision about bicalutamide
later.
The timing and duration of hormonal therapy is negotiable.
Normally, for high-risk patients, we treat for two years.
In this situation, because of PSA monitoring, there is the
opportunity to, perhaps, treat him for a shorter period of
time and then restart. We have negotiated with this patient
to start an LHRH agonist and monitor his PSA, tumor volume
and tolerability of therapy.
My sense is that he should be on hormonal therapy for at
least 8 to 12 months, and after that, it might be negotiable.
If he tolerates therapy well, I think he should continue.
If his quality of life is impaired, then maybe we will stop
it, follow his PSA kinetics and consider treatment if his
PSA rises in the future.
PSYCHOSOCIAL ISSUES:
For young patients, prostate cancer is not on their radar
screen, and the overwhelming concern in this man’s life
is death from prostate cancer. He was consumed with the idea
that he would die shortly and that he had no future. He is
at high risk, but I told him that I felt very confident that
he was going to have a response — that the PSA was going
to go down, tumor volume would go down — and that radiation
and hormonal therapy was going to affect his cancer favorably.
Men in this situation need to understand that, and that at
the same time, we’re working hard through research to
look at novel treatment strategies.
At this point, I think he’s coping very well. This
is also a situation where you want to make a solid commitment
that you’re going to be there not only now, but that
you have a treatment plan in place for later if current treatment
therapy fails.
His significant other is very supportive, and her expression
of that support was very important to him. Most significant
others are more risk-adverse than the patient themselves and
want more aggressive treatment than the actual patient. They
want to leave no stone unturned for cure, even though they
understand that might impact quality of life.
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Impact of psychosocial intervention to improve
coping skills
We have an ongoing randomized trial evaluating the role of psychosocial
intervention to improve coping skills in patients with prostate
cancer. Patients are randomized to receive psychosocial intervention
focusing on coping skills with a psychologist, or to receive no
intervention.
The primary endpoints are health-related quality of life, emotional
well-being and fear of cancer recurrence. Secondarily, we will look
at differences in PSA outcomes, but that will not be evaluated for
many years. It may be that psychosocial intervention correlates
with other things, such as how people seek additional treatment.
Prostate cancer management strategies
I think there is going to be a great paradigm shift in two areas
of prostate cancer, relatively soon. First, there are some patients
who are being overtreated. This is supported by two recent clinical
trials and data from CaPSURE.
Certain older patients with comorbidities and low-stage, low-volume
and low-grade prostate cancer may be watched and treated selectively
based on parameters of progression — PSA change or selective
biopsy at 24 months. At UCSF, we are conducting clinical trials
to evaluate initial surveillance and selective therapy for low-risk
patient populations.
On the other hand, we may not have been aggressive enough in high-risk
patients. So, we will assess combination and novel therapies in
those patients. In one patient population we will treat less aggressively,
and for patients with intermediate- and high-risk prostate cancer,
we will treat more aggressively.
Select publications
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