Duke, please tell us where you live and what prostate cancer books or
resources you already have, so we can refer you to some more specific
info, and maybe some local docs or groups.  It is good you are asking
your uro again, at least he was thinking of *treatment* instead of
whatever that onc thought.  The problem is that the uro referred you to
that particular onc, so obviously he has no idea who is a good PCa onc.

You need information from more sources than these 2 doctors.

This is not necessarily true.  It is often true but not always, not at
all.

Even then, one must define "work". It's not that hormones extend our
lives by 2-3 by years -- that's optimistic -- it's that we may LIVE
2-3-5-10 more years. The time ADDED to our lives by ADT (hormones) is
usually significantly less than those 2-3 years. But once one gets mets,
the downside of hormones begins to look much less threatening.

I.P.

RV>+++++++++++++>
Hello Duke,
Do not start your treatment with a pessimistic view of your present
situation.For many years, the medical profession had evidence that
demonstrate that the lower the tumor burden the better the response to
hormone suppression. This was clearly demonstrated by Crawford ED et
al(7). In this study, men were stratified by the degree of their cancer
progression. The response to combined suppression was as follows:
1. Advanced with major symptoms such bone pain, weight loss etc.
responded
for 8.5 months.
2. Advanced with minor symptoms, responded for 15.4 months.
3. Advanced with disease limited to lymph nodes, response was 4 years.

In this study, done more than a dozen years ago, even a significant
number of the
patients in the first group were responding after 4 years (about 10%).
About 30% to 40% of the patients with disease limited to lymph nodes
were still responding after 10 years. This is a clear indication that
deprivation response is directly proportional to the degree of disease
progression at the time of diagnosis and the tumor volume ratio of
androgen dependent/androgen independent cells.

More evidence of this is supported by Labrie et al (9) in a study in
which response to androgen deprivation was correlated to the number of
bone lesions at the initiation of therapy. Men with 5 or less bone mets
had the longest response.

These are known biological facts. Androgen dependent tumor cells die
when deprived of  androgens while androgen independent cells survive.
Why would anyone allow  androgen dependent cells to become androgen
independent when they could be killed by androgen deprivation applied
early in the first place?

Hormone suppression is known to prolong time to progression, but is it
possible that it could also extend survival? There are a number of
studies in which results indicate that early disease detection and
early hormone suppression not only postpone disease progression but
also improves survival.This is something that *fits* in the overall
picture of explaining the reduction in mortality experienced in the
U.S.A. since the mid nineties.

The old myth that patients diagnosed with advanced prostate cancer only
respond to hormone suppression for a year or two is simply a myth. In
this age of early detection and of earlier stages of advanced prostate
cancer at diagnosis this myth is no longer supported by the current
medical literature. This myth perseveres because of doctors that
believe that saving hormone suppression for later when bone mets
develop is perfectly fine. This IS NOT supported by current medical
evidence.

The real question then is the value of early versus delayed hormone
suppression. In the original VACURG study, DES at 5 mg caused many
vascular events causing  death. This study did not demonstrate a
survival advantage and in retrospect caused many clinicians to abandon
the use of estrogenfor the treatment of prostate cancer. In another
VACURG (STUDY II) study of men with locally advanced and  metastatic
disease, 1 mg of diethylstilbestrol (DES) was slightly more effective
than a toxic dose of 5 mg or a dose of 0.2 mg or a placebo. In a
reanalysis of the VACURG data, a subset of younger men with earlier
stages of prostate cancer when hormonally suppressed experienced a
survival advantage(1).

Similarly, The Medical Research Council Prostate Cancer Working Party
Investigators Group study(2) revealed a survival advantage to early
hormone suppression for locally advanced disease. The effects of
immediate vs deferred therapy was evaluated in 987 asymptomatic
patients in either Stage D2 or Stage C (T3) prostate cancer. Patients
treated early exhibited a marked decrease in comorbid events, such as
pathologic fractures, spinal cord compression, ureteral obstruction and
extraskeletal metastases.

Those on delayed therapy had twice the incidence of these events. The
reduction in these disease related events is enough evidence to justify
the use of early  therapy. However, additional support for early
therapy comes from survival data. Patients treated with early therapy
exhibited a small but significant increase in rates of both overall
survival and prostate cancer-specific survival. In patients with
locally advanced non metastatic disease, the benefit was even more
pronounced. The survival benefit increased over time; the survival rate
at 10 years of patients receiving early therapy was almost twice that
of patients receiving delayed therapy. This study clearly demonstrates
that the earlier the stage of the disease, the less tumor burden at the
initiation of therapy the better the results. This was a controlled
randomized clinical  trial.

Another example of the potential benefit of early hormone suppression
versus delayed we have the Messing EM et al study(3) in which immediate
androgen deprivation after RP with positive lymph nodes resulted in a
survival advantage for those treated early. At last follow up (median
of 7.1 years) 77% of those treated early were alive as compared to 18%
in the delayed group. As far as cause of death, 6.4% (3/47) patients
died of PCa. In the delayed group, 31% (16/51)  died of PCa. These are
significant numbers that support early versus delayed suppression.

Bolla M et al,(4) provided documentation that the combination of
hormonal therapy and radiation therapy is superior to radiation alone
in the management of T3 prostate cancer. In the Bolla study, 3 years of
hormonal therapy in combination with 6-7 weeks of external beam
radiation therapy (EBRT) resulted in a significant therapeutic benefit
over radiation therapy alone. Estimates of survival after 5 years were
greater following combined therapy vs EBRT (79% vs 62%). Furthermore,
85% of patients receiving combined therapy remained disease free,
compared with 48% of patients receiving EBRT alone.

Some have questioned whether radiation therapy contributed
significantly to the outcome and whether it is clinically necessary.
There is nevertheless a study done at M.D. Anderson that seems to
answer this question. Sagars GK et al (5), showed that therapy with
androgen deprivation treated patients had 58% failure rate at 5 years
while those on combined therapy (RT + HT) had a 10% failure rate. This
is not a randomized trial but it nevertheless supports the synergistic
value of hormone suppression with radiation therapy.

Recently D'Amico and coworkers (8) confirmed the synergistic value of
androgen deprivation added to radiation treatment. This study reduced
the deprivation period to six months and still obtained  an overall
survival benefit .

Another randomized control trial that supports the benefit of adjuvant
hormone suppression with RT is the Phase III RTOG Protocol 85-31(6). In
this trial there was 84% of the combined arm showing no evidence of
recurrence versus 71% in the RT arm at 5 years. More significant, the
real benefit was in patients with more aggressive disease (Gleason 8 to
10) in which at the 5-year mark, 66% on the combined arm survived
versus 55% in the RT arm.

In 1998, Granfors et al., reported the results of a controlled trial in
which 91 patients with surgically confirmed lymph node staged disease
were randomized to orchiectomy plus radiotherapy and radiotherapy
alone. Those patients on the RT alone arm that progressed were then
treated with androgen deprivation. Clinical progression was observed in
61% of those treated with RT alone and in 31% in those on combined
treatment. Mortality was 61% and 38% respectively. Disease-specific
mortality was 44% with RT and 27% in the combined therapy group.
Negative lymph node patients showed no significant difference in
survival. These results suggests that early androgen
suppression is better than delayed hormone suppression treatment  for
these patients.

Why would anyone advise men with advanced disease to postpone hormone
suppression until they become less responsive is hard to understand,
but this is what  happens in many instances. Men need to realize that
the there is a new paradigm for prostate cancer  in the PSA era.  Men
should not allow a physician or layman confuse them on this issue.
Don't allow an old myth that the response to hormone suppression
invariably is only 1 to 2 years, to detract from your quality and
extension of life if YOU decide to be treated as early as possible.

The value of early hormone suppression is not clear-cut, absolute or
proven case by these randomized clinical trials mentioned above, but
the existing evidence should not be ignored and physicians that project
a pessimistic stance to their patients need to revisit the latest
medical literature and get back on track for the benefit of their
patients.

RalphV
Sources:
(1) Byar DP, et al. NCI Monograph 7. 1988;165-170.

(2) Immediate versus deferred treatment for advanced prostatic cancer:
initial results of the Medical Research Council Trial. The Medical
Research Council Prostate Cancer Working Party Investigators Group. Br
J Urol 1997 Feb;79(2):235-46

(3) Messing EM, Manola J, Sarosdy M, Wilding G, Crawford ED, Trump D.
Immediate hormonal therapy compared with observation after radical
prostatectomy and pelvic lymphadenectomy in men with node-positive
prostate cancer. N Engl J Med. 1999;341(24):1781-1788.

(4) Bolla M, Gonzalez D, Warde P, et al. Improved survival in patients
with locally advanced prostate cancer treated with radiotherapy and
goserelin. N Engl J Med. 1997;337:295-300.

(5) Zagars GK et al., Management of unfavorable locoregional prostate
carcinoma with radiation and androgen ablation. Cancer 1997 Aug
15;80(4):764-775

(6) Pilepich MV et al., Phase III trial of androgen suppression using
goserelin in unfavorable-prognosis carcinoma of the prostate treated
with definitive radiotherapy: report of Radiation Therapy Oncology
Group Protocol 85-31. J Clin Oncol. 1997; 15: 1013  1021.

(7) 1: Crawford ED, Eisenberger MA, McLeod DG, Spaulding JT, Benson R,
Dorr FA, Blumenstein BA, Davis MA, Goodman PJ. A controlled trial of
leuprolide with and without flutamide in prostatic carcinoma. N Engl J
Med. 1989 Aug 17;321(7):419-24. PMID: 2503724 [PubMed - indexed for
MEDLINE]

(8) D'Amico AV, Manola J, Loffredo M, Renshaw AA, DellaCroce A, Kantoff
PW.6-month androgen suppression plus radiation therapy vs radiation
therapy alonefor patients with clinically localized prostate cancer: a
randomized controlled trial. JAMA.  2004 Aug 18;292(7):821-7.

(9)Labrie F, Dupont A, Cusan L, Gomez JL, Diamond P.Major advantages of
"early" administration of endocrine combination therapy in advanced
prostate cancer. Clin Invest Med.  1993 Dec;16(6):493-8.

Other supportive references:

Kozlowski JM, Ellis WJ, Grayhack JT Advanced prostatic carcinoma. Early
versus late endocrine therapy. Urol Clin North Am 1991 Feb;18(1):15-24

Mazeman E, Bertrand P. Early versus delayed hormonal therapy in
advanced prostate cancer. Eur Urol. 1996;30 Suppl 1:40-3; discussion
49. Review. PMID: 9072496 [PubMed - indexed for MEDLINE]