FORT LAUDERDALE, Fla--The key feature of prostate cancer that distinguishes
it from most other solid tumors is the large discrepancy between annual
incidence (about 250,000) and mortality (about 41,000).
"This means that there are many patients who are at risk for overtreatment,
and we need to refine the prognostic features that tell us which patients
are going to be in which risk category," said Randy Milliken, MD,
in his presentation of the updated prostate cancer guidelines at the 2nd
annual meeting of the National Comprehensive Cancer Network (NCCN).
Dr. Milliken, of the M.D. Anderson Cancer Center, was standing in for
Christopher Logothetis, MD, chairman of the prostate cancer guidelines
committee and professor of genitourinary medical oncology at M.D. Anderson.
Coming up with a prognosis that will guide the treatment choice requires
looking at two "biological clocks," he said--that of the cancer
(determined by the staging workup) and that of the host (life expectancy).
The consensus view is that after diagnosis (based on PSA, DRE, and Gleason
score), if life expectancy is less than five years and the patient is asymptomatic,
"one should not bother to do a single additional test," Dr. Milliken
Prostate cancers staged as T1A disease are incidental cancers that are
neither palpable nor apparent on imaging apparent, and the treatment recommendation
is watchful waiting. "But in some cases, even these cancers may be
appropriately treated if life expectancy is good and other factors suggest
that the disease may not be biologically indolent," Dr. Milliken said.
Such factors include Gleason score greater than 7 and PSA greater than
10 ng/mL after transurethral resection.
The bulk of prostate cancers are potentially curable (stage T1 subgroups,
stage T2A, B and C). The first task in deciding on treatment in these patients
is to consider the probability that the patient will have organ-confined
"Approaches based on assessments of probability of cure are going
to become increasingly important as we think about how to steer patients
toward definitive local therapy," Dr. Milliken said.
He cited, for example, the work done at Johns Hopkins by Dr. Patrick
Walsh. More than 1,000 consecutive prostatec-tomy patients were stratified
by preop-erative PSA level, Gleason score, and pathologic stage, and a
table was created showing the likelihood of freedom from recurrence after
prostatectomy based on these factors.
Once the probability of organ-confined disease is determined, "the
next question to grapple with is the issue of life expectancy," he
said. The combination of these two factors will determine treatment (no
treatment until symptoms, radiotherapy, or prostatectomy).
In patients with advanced disease, androgen ablation, radiotherapy,
or both is recommended, with androgen ablation alone for the most advanced
The exception would be patients with T3A disease, for whom prostatectomy
may be considered if they have low volume disease and Gleason score less
than 7. "Patients with these favorable features may have about a 40%
chance of cure with surgery," he said.
For patients who were initially observed and have a limited life expectancy,
the guidelines recommend that therapy be withheld and, consequently, that
surveillance be withheld until the patient has symptoms.
If the initial decision was to observe, but life expectancy is greater
than 10 years, then the recommendation is to measure PSA twice a year and
consider annual biopsy "because of the well-described tendency for
the Gleason score to change with time," he said.
For patients who had definitive therapy, PSA should be checked twice
a year for five years and then annually along with a digital rectal exam.
"The lead time that PSA gives you in this setting is quite good, at
least seven months or longer," Dr. Milliken said, "and so a PSA
every six months seems to be adequate to preserve the appropriate therapeutic
For patients who are initially metastatic, surveillance is more extensive
and frequent. "One thing to point out is that antiandrogens do have
a certain tendency to upset the liver," he said, "and in patients
taking these drugs, we think that the liver function test should be checked
occasionally (every month for three antiandrogen cycles)."
For patients with uncharacteristic presentations (visceral disease or
lytic bone metastases), biopsy is recommended. "These are red flags
for a high probability of some histologic variant, such as small-cell carcinoma,
for which cytotoxic chemotherapy may, in fact, be the preferred treatment,
and it should be given earlier rather than later," Dr. Milliken stressed.
A member of the audience asked why the guidelines for salvage workup
call for a biopsy at the prostate bed in patients who have failed radical
prostatectomy or radiation therapy, even though they have a positive DRE
and an increase in PSA.
"The main reason is to look for histologic variance," Dr.
Milliken answered. "At M.D. Anderson, we've accumulated a large number
of patients with relapsing cancers, especially those that relapse as a
large mass in the pelvis, where the biopsy clearly shows neuroendocrine
differentiation, and that implies a very different treatment strategy."
He added that "the point is well taken that this may not be absolutely
necessary as part of the workup of every such patient."
Primary Salvage Therapy
The guidelines endorse salvage radiotherapy or androgen ablation for
patients who have failed prostatectomy and have negative bone scans, but,
conversely, salvage prostatectomy is not recommended for those who have
"Obviously, there are individual patients for whom salvage prostatectomy
is appropriate, but it should never be the first option," Dr. Milliken
said, sparking a member of the audience to suggest that it was not the
guidelines' intent to make salvage prostatectomy an option at all, except
in the case of clinical trials.
Dr. Milliken agreed, reiterating that salvage prostatectomy is not on
the main treatment pathway of the guidelines. "I was trying to make
a conciliatory remark because we all have seen patients who are many years
out, have no detectable disease outside the pelvis, are still young and
in good shape, and I think that for some of these patients, a salvage prostatec-tomy
makes a certain amount of sense."
In patients with positive bone scans, androgen ablation is the standard
of care. "At the top of the list is orchiectomy, which continues to
be the simplest, cheapest, and most definitive way of achieving androgen
ablation," he said.
If the patient and physician opt for an LHRH agonist, "there is
increasing recognition that this should be coupled with a measurement of
the serum testosterone a couple of months later," Dr. Milliken said.
"If serum testosterone is high, then you can either suggest to the
patient that he have an orchiectomy or add an antiandrogen."
At the first sign of rising PSA, the antiandrogen should be withdrawn.
Once androgen-independent progression is documented, options for symptomatic
palliation include local radiotherapy, glucocorticoids, or a trial of cytotoxic