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PCU3|2002: Mary-Ellen
Taplin, MD
Edited comments by Dr Taplin
CASE 5:
57-year-old man with a rising PSA two years after external beam
radiation therapy |
History
This man was initially diagnosed in March 1999. At that
time, he had some induration on his rectal exam and a PSA
of 7.3 ng/mL. A biopsy confirmed Gleason 7 to 9 prostate cancer.
He enrolled in a clinical trial of external beam radiation
therapy in conjunction with hyperthermia. He received a somewhat
lower dose of radiation, 67 Gy, than we routinely use today.
In addition, he received six months of hormone therapy with
an LHRH agonist and bicalutamide.
He had a good response with a nadir PSA of 0.2 ng/mL. The
radiation caused nocturia, some frequency during the day,
and impotence. The six months of hormone therapy caused fatigue,
a reduction in mental clarity and memory impairment.
About two years after his primary therapy, his PSA had risen
to 1.8 ng/mL. Over the next six months, it rose to 2.8 ng/mL.
His radiation oncologist referred him for further evaluation.
On physical exam he had a palpable prostate nodule, and a
biopsy revealed recurrent prostate cancer.
Follow-up
I presented him with the options of standard hormonal therapy
(i.e., orchiectomy or an LHRH agonist), intermittent hormonal
therapy or testosterone-sparing hormonal therapy with bicalutamide
150 mg. At that time, cryotherapy was not available in our
institution. He chose bicalutamide 150 mg.
He also received low-dose prophylactic breast irradiation,
and he has not experienced any gynecomastia or nipple tenderness.
After one year of therapy, he has not had any side effects
other than infrequent, mild nausea. He has also been able
to maintain his libido. His PSA decreased from 2.8 to 0.2
ng/mL.
I see him every three months. Patients who are on bicalutamide
150 mg are followed regularly, as if they were on an LHRH
agonist, with visits every three or four months.
Case discussion
For several reasons, I felt it was important to consider
early hormonal therapy for this patient. His PSA doubling
time was less than a year, and he had biopsy-proven tumor
at the prostatic bed, which could cause urinary retention
in the future.
He probably could have been considered for cryotherapy.
We now have a couple of urologists in our area who are doing
cryotherapy. However, a recent report in the Journal of Clinical
Oncology suggests that patients with Gleason 9 and 10 prostate
cancer do not do well with cryotherapy. This patient had a
Gleason 9 tumor, so cryotherapy may not have changed the natural
history of his disease.
| Factors affecting
selection of patients for salvage cryotherapy after XRT
failure |
"We
believe that cryotherapy is not an optimal therapeutic
option for all patients with locally recurrent PCa after
XRT. On the basis of our current study, salvage cryotherapy
is more likely to fail in patients who have locally
recurrent androgen-independent PCa, a PSA level of greater
than 10 ng/mL, a Gleason score of 9 and 10 for the recurrent
PCa, or a pre-XRT clinical stage greater than T2. What
is not known is whether these patients would receive
a significantly greater benefit from another therapy
with curative intent, namely, salvage prostatectomy,
or other noncurative approaches such as early or late
androgen-deprivation therapy." |
| EXCERPT FROM: Izawa JI et al. Salvage
cryotherapy for recurrent prostate cancer after radiotherapy:
Variables affecting patient outcome. J Clin Oncol
2002;20(11):2664-71. Abstract |
Since he was actively working and playing golf, the patient
was interested in a type of therapy that would keep his quality
of life as close to normal as possible. The side effects most
often associated with bicalutamide 150 mg are breast enlargement
and nipple tenderness.
Given that he still had libido, he was interested in maintaining
it. Men without erectile function are still interested in
keeping their libido intact. It seems to be important for
their sense of self, how they feel about life and for their
spouses.
Although bicalutamide 150 mg is not FDA-approved in this
country for this use, we have a lot of experience with bicalutamide
50 mg in combination with a LHRH agonist. I have done studies
using the higher dose and treated about 50 patients with bicalutamide
150 mg, so I feel comfortable with its side-effect profile.
The studies done in Europe suggest that the efficacy of
bicalutamide 150 mg approaches that of standard hormone therapy,
although it may not be as durable. In most cases, at the time
of PSA progression, the majority of patients respond to an
LHRH agonist.
If he progresses, I probably will treat him with an LHRH
agonist. I could also offer him orchiectomy. But since he
did not like how he felt on his initial hormonal therapy,
orchiectomy would not provide the opportunity for intermittent
therapy. I probably would continue the bicalutamide at 50
mg a day for a month after the first dose of the LHRH agonist.
A small study in about 23 patients suggests that approximately
82% of patients with a rise in PSA while on bicalutamide monotherapy
can have a reduction in their PSA with secondary androgen
deprivation (medical or surgical castration). The duration
of that secondary response appears durable.
This gentleman seems to be handling his relapse well, psychologically.
He does not appear to be focused on death. Some patients ask
about their life expectancy every time they see me. But he
does not, and he seems to be living his life in a healthy,
productive way with his disease. |
Tolerability of bicalutamide and LHRH agonists
My overall impression is that muscle strength is better on bicalutamide
150 mg than an LHRH agonist, and anemia may not be as much of a
problem. Most patients on an LHRH agonist have a reduction in their
hematocrit to about 36% to 39%.
Generally, there is not much of a physiologic effect from the
reduction in hematocrit, but it may be a problem for patients with
concomitant conditions. In patients with anemia of chronic disease,
the addition of an LHRH agonist may take a hematocrit of 36% or
37% down to 32%. I think then it does become a practical issue.
Genetic counseling for men with prostate
cancer
During the initial visit, I take a family history to determine
who in the family has cancer and what types of cancer they have,
paying specific attention to prostate cancer. I find out how many
sons these men have and their sons’ ages. I strongly recommend
screening, starting at the age of 40, for the sons of men with prostate
cancer. I emphasize that screening requires both a blood test and
a digital rectal exam.
In families with multiple generations of prostate cancer victims
(i.e., grandfather, father and son), we certainly stress screening
as strongly as possible. The more relatives in the family with prostate
cancer, the higher the risk. The brothers and fathers of men with
prostate cancer should also be screened.
The impact of personal experience with illness
on clinical practice
I do not usually share this information with my patients, but
six years ago my husband was diagnosed with a low-grade brain tumor.
I have firsthand experience with how illness and difficult decisions
about surgery, radiation and medicine affect people, relationships
and outlook on life. Although I have been a practicing oncologist
for 10 or 12 years, I felt ill equipped to handle these burdens.
Through a variety of different avenues I have learned to deal with
these issues, and it has improved my skills as a clinical oncologist
incredibly.
I am willing to take more time to listen to patients. Before,
I made assumptions about who they were and what they needed. Now,
I hear and empathize with them better. I also have a much better
perception that the patient and his family often view this disease
and its treatments very differently. It is a cliché, but
prostate cancer affects an entire network of lives. Nobody teaches
you these things in fellowship or residency. The focus is always
on the patient, the surgery and the medicine.
Until you have confronted these burdens personally, it is easy
for a doctor to say, “You should do this” or “You
should do that." However, once you have lived with compromise,
you realize that there is no right or wrong. It was amazing to me
that we went to four different major medical centers and received
four different recommendations. It is difficult for patients to
figure that out.
Instead of telling patients what they should do, it is incredibly
important to provide information by telling them, "This is
what we know, and this is what we do not know. I can’t tell
you what to do, but you need to decide what makes the most sense
to you." Patients do not want to hear that there is not a correct
answer. They want decisions to be black and white, yes or no. Unfortunately,
the issues are too complex for that to be a realistic option.
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