To do it early or deferred…some thoughts

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ralfinaz
Veteran Member


Date Joined Jan 2011
Total Posts : 735
   Posted 6/5/2011 5:14 PM (GMT -6)   
Androgen deprivation is not innocuous therapy and a decision to use it now or later needs careful consideration. One should not ignore the fact that the longer prostate cancer progresses naturally the more it inexorably advances to an androgen independent state on its own. Given enough time and growth factors the endpoint of untreated prostate cancer is androgen independence. These are known biological facts.

Some 20% of untreated advanced prostate cancer patients do not respond to androgen suppression. This implies that on its own the disease has become androgen independent BEFORE the disease is diagnosed or androgen deprivation is initiated.

As more men are diagnosed with earlier stages of prostate cancer including earlier stages of advanced prostate cancer, less men present with multiple lymph node or bone mets at diagnosis. This implies significantly less tumor burden and an opportunity for early hormone suppression to induce massive cell death in the androgen dependent portion of the tumor load.

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 20 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 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 multiple 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 estrogen for 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.

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

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 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.

We constantly hear, and rightly so, about the side effects of treatment.
We all need to know them in detail to be able to deal with them.
Do we ever hear about the symptoms and loss of quality of life
from untreated or untimely treatment in disease progression? Is allowing the cancer to invade the bone or organs inconsequential? Those who understand this dichotomy need to recognize that timely treatment/no treatment decisions can impact their lives in a significant way…to ignore it is far from reality.

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 alone
for 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.

(10) AARON J. MILBANK, ROBERT DREICER, AND ERIC A. KLEIN. HORMONAL THERAPY FOR PROSTATE CANCER: PRIMUM NON NOCERE

UROLOGY 60: 738–741, 2002

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]

Anderson JB. Early versus deferred hormone therapy. Eur Urol. 1999;36 Suppl
2:9-13. PMID: 10529560 [PubMed - indexed for MEDLINE]
Phoenix, Arizona
Surviving prostate cancer since 1992 at age 58. RP; Orchiectomy; GS (4 + 2); bilateral seminal vesicle invasion; tumor attached to rectal wall; Stage T4; Last PSA September, 2010: <0.1 ng/ml
Laughter is still the best medicine!
www.pcainaz.org/phpBB304

F8
Veteran Member


Date Joined Feb 2010
Total Posts : 3800
   Posted 6/5/2011 7:00 PM (GMT -6)   
interesting stuff.  thanx for posting.
 
ed
age: 56
PSA on 12/09: 6.8
gleason 3+4 = 7
HT, BT and IGRT
received 3rd and last lupron shot 9/14/10
2/8/11 PSA <.1, T= 6 ng/dl

Purgatory
Elite Member


Date Joined Oct 2008
Total Posts : 25380
   Posted 6/5/2011 7:09 PM (GMT -6)   
ralf, an excellent and scholarly piece on that perspective, no doubt, but how do you explain the opposing side, equally made up of oncology experts, that take the opposite view, and see more value in delaying HT use? This subject seems to be the twenty-million dollar question in the realms of advanced PC. And why it is difficult for patients in that situation to sort out, myself included.

david in scc
Age: 58, 56 dx, PSA: 7/07 5.8, 10/08 16.3
3rd Biopsy: 9/08 7 of 7 Positive, 40-90%, Gleason 4+3
open RP: 11/08, on catheters for 101 days
Path Rpt: Gleason 3+4, pT2c, 42g, 20% cancer, 1 pos margin
Incont & ED: None
Post Surgery PSA: 2/09 .05,5/09 .1, 6/09 .11. 8/09 .16
Post SRT PSA: 1/10 .12, 4/8 .04, 8/6 .06, 2/11 1.24, 4/11 3.81
Latest: 6 Corr Surgeries to Bladder Neck, SP Catheter since 10/1/9, SRT 39 Sess/72 gy ended 11/09, 21 Catheters, Ileal Conduit Surgery 9/10

Tony Crispino
Veteran Member


Date Joined Dec 2006
Total Posts : 8128
   Posted 6/5/2011 7:37 PM (GMT -6)   
Great job, Ralph.
I am very happy that you joined our site here. Your insight and experience are a blessing for us here. I saw you writing pieces before I elected to go with adjuvant therapies after my surgery results looked like yours. I sure am glad I found you out there doing what you do so well ~ helping men get through this stupid disease...

Always your friend,

Tony
Advanced Prostate Cancer at age 44 (I am 48 now)
pT3b,N0,Mx (original PSA was 19.8) EPE, PM, SVI. Gleason 4+3=7

Treatments:
Da Vinci Surgery ~ 2/16/2007
Adjuvant Radiation Therapy ~ IMRT Completed 8/07
Adjuvant Hormone Therapy ~ 28 months on Casodex and Lupron.
Undetectable PSA.

Blog: www.caringbridge.org/visit/tonycrispino

ralfinaz
Veteran Member


Date Joined Jan 2011
Total Posts : 735
   Posted 6/5/2011 10:26 PM (GMT -6)   
David,
Making a decision about androgen deprivation is never easy. From very early on in my disease process, I noticed that some men responded poorly or never responded to androgen deprivation. Why was that so? In investigating these men diagnostics, the key association was that they were diagnosed with advanced disease that had invaded their lymph nodes, organs or skeleton. In other words, the disease had progressed silently and finally for one reason or another they were diagnosed. I met several of these men and they all died within 18 to 24 months. This was very disturbing because at that point I had not realized that the natural progression of prostate cancer is from a mostly androgen dependent state to an androgen independent state.

In time I came to learn that the reason that androgen deprivation is not considered a curative treatment is because we are born with a prostate gland in which the vast majority of the epithelium is composed of androgen-dependent glandular cells, with lower numbers of androgen-sensitive basal cells and a limited number of androgen-independent basal stem cells.

These androgen-independent basal stems cells maintain their limited number and give rise to a subset of amplifying cells that are androgen-independent but androgen-sensitive. In the presence of physiologically normal levels of androgen (as in normal males) the majority of these androgen-sensitive amplifying cells differentiate into androgen-dependent glandular epithelial cells. Once the normal number of these androgen-dependent glandular cells is reached, their rate of cell proliferation balances their rate of cell death. In other words, a normal prostate contains a balanced, self-renewing number of androgen–independent, androgen-sensitive and androgen-dependent cells that are affected by the presence or absence of androgen. So even when all the androgen-dependent and androgen sensitive cells could be killed by androgen deprivation, the androgen-independent stem cells remain.

I mention all this because from the discovery of androgen deprivation as a treatment for advanced PCa, it is difficult for males and their physicians to accept this therapy. More so when results (as far as survival) are very variable as dependent at the stage of the disease at which the treatment is initiated. It is easy to understand the opposition. As one who has endured this treatment for almost 20 years, I can tell you that I understand very well and as such try to inform others of what I consider an advantage in early, intermittent therapy. It is just my opinion as a survivor…

RalphV
Phoenix, Arizona
Surviving prostate cancer since 1992 at age 58. RP; Orchiectomy; GS (4 + 2); bilateral seminal vesicle invasion; tumor attached to rectal wall; Stage T4; Last PSA September, 2010: <0.1 ng/ml
Laughter is still the best medicine!
www.pcainaz.org/phpBB304

John T
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Date Joined Nov 2008
Total Posts : 4223
   Posted 6/5/2011 10:49 PM (GMT -6)   
Ralph,
Excellent presentation of a contraversial issue. In all my readings I have never seen any evidence to support that waiting to do HT had any benefit. It baffles me that patients will do salvage treatments at the slightest rise in psa after primary failure, yet wait until tumor burden rises to the state where HT is not as effective before considering HT. Also never mentioned is that 30% of early patients have a very positive response to HT only needing one treatment course for long term regression. This is about the same effectiveness of all salvage treatments. It is also disconcerting to see many patients on HT that have very little knowledge of how to minimize the side effects and cardiac risks that HT entails.

JohnT
66 years old, rising psa for 10 years from 4 to 40; 12 biopsies and MRIS all negative. Oct 2009 DXed with G6 <5%. Color Doppler biopsy found 2.5 cm G4+3. Combidex clear. Seeds and IMRT, 4 weeks of urinary frequency and urgency; no side affects since then. 2 years of psa's all at 0.1.

zufus
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Date Joined Dec 2008
Total Posts : 3149
   Posted 6/6/2011 4:40 AM (GMT -6)   
Par excellence Ralph.

ralfinaz
Veteran Member


Date Joined Jan 2011
Total Posts : 735
   Posted 6/6/2011 9:28 AM (GMT -6)   
JohnT,
This issue will continue to be controversial. Like you mention, the application of therapy at the lowest possible tumor load is crucial. At that point the least amount of cells have turned to be androgen-independent or acquired metastatic potential and respond to deprivation the best. Men prefer to have a normal sex life. It is only human. Castration is an ominous word for any man. Male physicians tend to oppose this therapy while ignoring that a timely initiated and properly modulated to avoid irreversible damage the therapy could be beneficial to many. I do not see this changing in my lifetime or any soon thereafter… All we can do as survivors is present information for others to decide.

RalphV
Phoenix, Arizona
Surviving prostate cancer since 1992 at age 58. RP; Orchiectomy; GS (4 + 2); bilateral seminal vesicle invasion; tumor attached to rectal wall; Stage T4; Last PSA September, 2010: <0.1 ng/ml
Laughter is still the best medicine!
www.pcainaz.org/phpBB304

compiler
Veteran Member


Date Joined Nov 2009
Total Posts : 7203
   Posted 6/6/2011 10:02 AM (GMT -6)   
Ralph:
 
This is an excellent post, but it appears to be promoting one point: start HT early when the tumor burden is less. You've chosen a variety of studies that I assume back this view. Are there also many studies (recent) on the other side?
 
I have a feeling that this has been a very controversial question, but it is slowly being decided in favor of "sooner is better than later." Are we getting there? In fact, are we there yet? Has this information found its way to the average medico?
 
Just curious.
 
Mel

Old Sailor
Regular Member


Date Joined Aug 2009
Total Posts : 208
   Posted 6/6/2011 10:15 AM (GMT -6)   
Ralph, absolutely superb and comprehensive post.  Thank you.  After my failed RRP & SRT, my Mayo docs started me on Lupron on 11/26/10 when my psa reached 1.0.  They stated that they believed you had to hit the pc hard when tumor load and psa were low to get best results.  So far doing OK with psa and testosterone undetectable.  Side effects minimal except hot flushes which are largely controlled by Effexor.   The Old Sailor 

ralfinaz
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Date Joined Jan 2011
Total Posts : 735
   Posted 6/6/2011 11:14 AM (GMT -6)   
Mel,
The key is to start HT when the tumor burden is less and biologically more responsive to therapy. It is a very controversial issue as posted by JohnT. The question is that the studies presented tried to answer that. Some were randomized trials and they demonstrate a benefit in slowing down progression and disease-specific survival. Some demonstrate even an overall survival benefit.

In searching PubMed, I used terms like prostate cancer; androgen deprivation; early; deferred; survival benefit; randomized trial and such. The great majority of results supported early versus deferred. That is not to say that some studies like the following
(see beliw) showed a lesser benefit or no benefit. I must add that the majority of physicians that specialize in treating prostate cancer exclusively support early vs deferred therapy.

Am I biased? I admit that from the med literature and years of support group association with a variety of members with PCa, from attending Department of Defense Peer Review of PCa-specific research applications, I have developed an inclination to support early vs deferred. I do not see clear evidence that deferred androgen deprivation is in the same league as early deprivation in the intermittent form as far as progression, survival and QOL issues. It is just my very personal view.

1: Ross RW, Xie W, Regan MM, Pomerantz M, Nakabayashi M, Daskivich TJ, Sartor O,
Taplin ME, Kantoff PW, Oh WK. Efficacy of androgen deprivation therapy (ADT) in
patients with advanced prostate cancer: association between Gleason score,
prostate-specific antigen level, and prior ADT exposure with duration of ADT
effect. Cancer. 2008 Mar 15;112(6):1247-53. PubMed PMID: 18293426.


2: Studer UE, Collette L, Whelan P, Albrecht W, Casselman J, de Reijke T,
Knönagel H, Loidl W, Isorna S, Sundaram SK, Debois M; EORTC Genitourinary Group.
Using PSA to guide timing of androgen deprivation in patients with T0-4 N0-2 M0
prostate cancer not suitable for local curative treatment (EORTC 30891). Eur
Urol. 2008 May;53(5):941-9. Epub 2007 Dec 27. PubMed PMID: 18191322.


3: Studer UE, Whelan P, Albrecht W, Casselman J, de Reijke T, Hauri D, Loidl W,
Isorna S, Sundaram SK, Debois M, Collette L. Immediate or deferred androgen
deprivation for patients with prostate cancer not suitable for local treatment
with curative intent: European Organisation for Research and Treatment of Cancer
(EORTC) Trial 30891. J Clin Oncol. 2006 Apr 20;24(12):1868-76. PubMed PMID:
16622261.


4: van Andel G, Kurth KH. The impact of androgen deprivation therapy on health
related quality of life in asymptomatic men with lymph node positive prostate
cancer. Eur Urol. 2003 Aug;44(2):209-14. PubMed PMID: 12875940.

RalphV
Phoenix, Arizona
Surviving prostate cancer since 1992 at age 58. RP; Orchiectomy; GS (4 + 2); bilateral seminal vesicle invasion; tumor attached to rectal wall; Stage T4; Last PSA September, 2010: <0.1 ng/ml
Laughter is still the best medicine!
www.pcainaz.org/phpBB304

compiler
Veteran Member


Date Joined Nov 2009
Total Posts : 7203
   Posted 6/6/2011 12:33 PM (GMT -6)   
Ralph:
 
>>>>>>>>>>>>
 I must add that the majority of physicians that specialize in treating prostate cancer exclusively support early vs deferred therapy.
>>>>>>>>>>>>>>>>>>
That's quite a statement!!! If true, then I suspect it will filter down to the local doctors soon enough. My sense is that the statement is true, but I wonder if there is any data supporting that (like a survey?).
 
Also, you said:
 
>>>>>>>>>
 I do not see clear evidence that deferred androgen deprivation is in the same league as early deprivation in the intermittent form as far as progression, survival and QOL issues.
>>>>>>>>>>>>>>>>>>
I keep rereading this, and I'm not sure what you are saying. Are you saying that waiting before doing HT is just far inferior to doing HT early OR DOING IADT?
 
Another question for you. Obviously, given my stats (see signature), I am wrestling with doing ADT and I will consult an expert on that. But suppose my PSA indicates that SRT is working (ie: no PSA increase and maybe a decrease). Should one do ADT regardless?  This will be my big question for the expert (actually that will be answered without my having to ask it, I'm sure!). I know its been argued that one should do ADT before even doing SRT. For me, that horse is out of the barn.
 
 
Mel

ralfinaz
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Date Joined Jan 2011
Total Posts : 735
   Posted 6/6/2011 1:13 PM (GMT -6)   
Mel.
I have attended PCa conferences and Symposiums since 1996. I consider most participant speakers experts in PCa treatment. In all these years I have never heard anyone of them say to delay ADT when evident progression affects the patient. That might not cover all the PCa experts in the world, but provides me with evidence that they support that treatment.

Clarification: I believe that early ADT is superior to delayed therapy. I also believe that intermittent ADT is the way to minimize side effects without compromising risk of progression while on an off-cycle.

From your signature I see you are PSA recurrent after RP with a positive margin and have been treated with SRT finishing treatment last month. At this point in time it is too early to know your response to SRT. If your PSA were reduced to undetectable in the next few months, treatment with ADT would be overkill. On the other hand, if PSA response is poor or non-existing, that would be an indicator of systemic disease and for you to decide when to initiate a systemic therapy (ADT, chemo, clinical trial).

RalphV
Phoenix, Arizona
Surviving prostate cancer since 1992 at age 58. RP; Orchiectomy; GS (4 + 2); bilateral seminal vesicle invasion; tumor attached to rectal wall; Stage T4; Last PSA September, 2010: <0.1 ng/ml
Laughter is still the best medicine!
www.pcainaz.org/phpBB304

compiler
Veteran Member


Date Joined Nov 2009
Total Posts : 7203
   Posted 6/6/2011 1:34 PM (GMT -6)   
Ralph:
 
I was just about to send a lengthy response and the computer ate it.
 
So, I'll try a briefer version.
 
First of all, thanks for your complete responses.
 
Regarding the lack of a controversy about when to start ADT, it seems from reading this board that this is a major controversy. Others here have had a recurrence but are choosing to wait until their PSA rises to a certain level. Their local doctors seem to support that. This is not just an isolated case. So, while it does seem that this might be bad advice in the light of the latest studies, it does seem to be a grey area. According to you, it's not a grey area whatsoever. I'm not sure.
 
Also, with my situation, you mentioned ADT, chemo, or a clinical trial. Why would I do chemo in lieu of ADT? It seems the SE are even more dire with chemo. No? Also, why would I do a clinical trial? It seems that ADT could buy me a few years so that I could get the RESULTS of many of these clinical trials, and maybe some newer treatment too.
 
Finally, a questions I've asked before. PSADT is a big issue. Mine is 2 months. That's scary. But:
 
1) Does that indicate a poor prognosis for ADT? It would seem that the ADT prognosis depends more on the PC load (hence we would rather start it sooner rather than later) and  also on the ratio of sensitive vs. non-sensitive PC cells.
 
2) Is PSADT even that significant with very low numbers like mine. I know the MSK PSADT calculator does not take numbers less than 0.10 (yes, I can multiply everything by 10 and enter it)..
 
I've probably asked this before, but sometimes I forget the answers!
 
Mel

F8
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Date Joined Feb 2010
Total Posts : 3800
   Posted 6/6/2011 1:58 PM (GMT -6)   
>>Regarding the lack of a controversy about when to start ADT, it seems from reading this board that this is a major controversy.<<
 
from what i've seen here, most of the guys that put off early treatment are very adamant about not wanting the treatment.  in fact a couple have said that they will not subject themselves to HT evem if it means dying sooner.  i know this: there is no debate among my doctors about hitting the  cancer hard and fast for best results.
 
ed
 
 

age: 56
PSA on 12/09: 6.8
gleason 3+4 = 7
HT, BT and IGRT
received 3rd and last lupron shot 9/14/10
2/8/11 PSA <.1, T= 6 ng/dl

ralfinaz
Veteran Member


Date Joined Jan 2011
Total Posts : 735
   Posted 6/6/2011 3:39 PM (GMT -6)   
Mel,
Where in any of my posts I said the issue is not controversial? It is and that is the problem for many making decisions. I do not doubt that many doctors say to their patient to “save it for a rainy day”. Well, I feel that that is the wrong advice based on current medical literature since the PSA era.

If one has systemic disease, the available choices are ADT, chemo or a clinical trial. I did not tell you to have chemo or a clinical trial before ADT. I just mentioned the choices.

You said, “with a PSADT of 2 months do I have a poor prognosis for an ADT response?
After deciding on SRT (which I feel is a good decision) you at this point in time do not know what your doubling PSA time is. You and your doctors must have felt that there was a good potential for the cancer to be localized at the prostate fossa given your positive margin, no? I assume that imaging test showed nothing and the positive margin was the target. Targeted radiation with IMRT is/was the right choice for disease that was not defined as systemic at that point in the decision process.

Never mind about your present PSADT. You are looking at a good response from salvage IMRT and hopefully your post RT PSA will tell the story with decreasing numbers until reaching ZERO!

RalphV
Phoenix, Arizona
Surviving prostate cancer since 1992 at age 58. RP; Orchiectomy; GS (4 + 2); bilateral seminal vesicle invasion; tumor attached to rectal wall; Stage T4; Last PSA September, 2010: <0.1 ng/ml
Laughter is still the best medicine!
www.pcainaz.org/phpBB304

Tony Crispino
Veteran Member


Date Joined Dec 2006
Total Posts : 8128
   Posted 6/6/2011 4:30 PM (GMT -6)   
Ralph,
When I was researching what steps I was going to take after my surgery did achieve an undetectable PSA result, I was reading many of the studies you listed. In addition my oncologist was doing a great job of coaching me on the pros and cons of the future steps. He felt that early HT after failure was not the only option as well and suggested adjuvant HT. This was based on the fact that the cancer was at its weakest point since my diagnosis and the therapy would be far more effective than if we had waited for a rise in PSA. I took it a step further and asked if adjuvant radiation was a good idea. he said it does not come without a cost and the papers at the time were scant for a post-RP pT3b (seminal vesicle invasion) for it but that he said it would likely help. After mulling over the options and a possible chemotherapy clinical trial, I elected to go with the adjuvant therapies because I was being told that the sooner the better approach was in fact more effective.

It makes sense to me that if we are seeing a lot of papers about how adjuvant therapy with both radiation and hormone therapy are far more effective than waiting for biochemical failure, then so it likely means the earlier the better on salvage therapies as well.

As far as I am concerned the medical industry will always have controversy in advanced prostate cancer. But I feel that it is largely due to the fact that 50% of doctors are below the average doctor with their continuing education. In fact I know many in the advocacy who have been working and studying for decades that are in tune with the latest studies being released, but I find doctors who didn't know about them all. I have had some doctors who come to our UsTOO meetings where they are scheduled to speak, after I rattle off the months news, come up afterwards and ask about my resources for information. They said they were very impressed with my knowledge of the disease...And I know many non-doctors that are smarter than I am about prostate cancer.

Tony

Purgatory
Elite Member


Date Joined Oct 2008
Total Posts : 25380
   Posted 6/6/2011 4:45 PM (GMT -6)   
Ed, there may not be debate with your doctors, but there is with mine. I don't feel at all the subject is so black and white.
Age: 58, 56 dx, PSA: 7/07 5.8, 10/08 16.3
3rd Biopsy: 9/08 7 of 7 Positive, 40-90%, Gleason 4+3
open RP: 11/08, on catheters for 101 days
Path Rpt: Gleason 3+4, pT2c, 42g, 20% cancer, 1 pos margin
Incont & ED: None
Post Surgery PSA: 2/09 .05,5/09 .1, 6/09 .11. 8/09 .16
Post SRT PSA: 1/10 .12, 4/8 .04, 8/6 .06, 2/11 1.24, 4/11 3.81
Latest: 6 Corr Surgeries to Bladder Neck, SP Catheter since 10/1/9, SRT 39 Sess/72 gy ended 11/09, 21 Catheters, Ileal Conduit Surgery 9/10

logoslidat
Veteran Member


Date Joined Sep 2009
Total Posts : 5815
   Posted 6/6/2011 5:27 PM (GMT -6)   
Small point here, my previous points on this post are as confusing to the early risers and probably the late risers, as Ralphs presentation of his thesis is to me. I have read and reread the initial and later one and, maybe I am weary of all the back and forth, but , tho it sounded informative, frankly I did,t get it. probably me. One thing Ralph did say that I understood, was his history of research and symposiums, experts, lidat. And quite frankly, it brought to mind all the mapmakers prior to Columbus [ or was it Paul Revere }, saying, the earth round? What poppycock. I just hope , we don't have a case of new attire for the emperor here or in the medical profession. Tho fairy tales do have a universal application, hence there popularity to all ages. To clarify, not saying at all, that Ralph's thesis is a fairy tale, but it certainly is not chiseled in stone either. Not that you said it was!!
Diagnosed 8/14/09 psa 8.1 66,now 67
2cores 70%, rest 6-7 < 5%
gleason 3+ 3, up to 3+4 @ the dub
RPP U of Wash, Bruce Dalkin,
pathology 4+3, tertiary5, 2 foci
extensive pni, prostate confined,27 nodes removed -, svi - margins -
99%continent@ cath removal. 1% incont@gaspass,sneeze,cough 18 mos, squirt @ running. psa std test reported on paper as 0.0 as of 12/14/10 ed improving

F8
Veteran Member


Date Joined Feb 2010
Total Posts : 3800
   Posted 6/6/2011 7:37 PM (GMT -6)   
>>Small point here, my previous points on this post are as confusing to the early risers and probably the late risers, as Ralphs presentation of his thesis is to me.<<
 
your previous posts on almost every subject are confusing to me cool .
 
ed
age: 56
PSA on 12/09: 6.8
gleason 3+4 = 7
HT, BT and IGRT
received 3rd and last lupron shot 9/14/10
2/8/11 PSA <.1, T= 6 ng/dl

compiler
Veteran Member


Date Joined Nov 2009
Total Posts : 7203
   Posted 6/6/2011 8:43 PM (GMT -6)   
Ralph:
 
Just for clarification, I was advised by all my doctors NOT to do any scans/images. They said with a PSA of 0.27, the yield of any scans would be zippo and it might find all kinds of old man stuff (ie; arthritis) that would possibly need to be investigated and complicate matters, ending up with more radiation exposure and yielding nothing. So then they recommend lots of radiatiion exposure, SRT!
 
Mel

logoslidat
Veteran Member


Date Joined Sep 2009
Total Posts : 5815
   Posted 6/7/2011 4:29 AM (GMT -6)   
F8, I do respect your response and to quote myself, call me anything, just call me !!! Or to paraphrase a line from a country song. If you don't leave me alone, I'll find someone who will. Good fun ,no?
Diagnosed 8/14/09 psa 8.1 66,now 67
2cores 70%, rest 6-7 < 5%
gleason 3+ 3, up to 3+4 @ the dub
RPP U of Wash, Bruce Dalkin,
pathology 4+3, tertiary5, 2 foci
extensive pni, prostate confined,27 nodes removed -, svi - margins -
99%continent@ cath removal. 1% incont@gaspass,sneeze,cough 18 mos, squirt @ running. psa std test reported on paper as 0.0 as of 12/14/10 ed improving

ralfinaz
Veteran Member


Date Joined Jan 2011
Total Posts : 735
   Posted 6/7/2011 8:32 AM (GMT -6)   
Mel,
I understand that with a low PSA recurrence, imaging has a lower probability of detecting the presence of cancer. I thought that an endoscopic MRI would have been in order given the fact that a local recurrence was suspected. Hope you are getting over your fatigue.

RalphV
Phoenix, Arizona
Surviving prostate cancer since 1992 at age 58. RP; Orchiectomy; GS (4 + 2); bilateral seminal vesicle invasion; tumor attached to rectal wall; Stage T4; Last PSA September, 2010: <0.1 ng/ml
Laughter is still the best medicine!
www.pcainaz.org/phpBB304

BB_Fan
Veteran Member


Date Joined Jan 2010
Total Posts : 1011
   Posted 6/7/2011 11:09 AM (GMT -6)   
Ralph, this information is great. Thanks for posting it. I had HT with SRT, when PSA was only .5. I am just comming 12 months of ADT3 and hoping for a long vacation. I bought into the notion that early HT was the way to go after reading Dr Myers book, but recently have been second guessing myself. BB
Dx Dec 2008 at 56, PSA 3.4
Biopsy: T1c, Geason 7 (3+4)
Robotic RP March 2009
Path Report: T2c, G8, organ confined, neg margins, lymph nodes - tumor vol 9%
PSA's < .01, .01, .07, .28, .50. ADT 3 5/10. IMRT 7/10.
PSA's post HT/SRT .01, < .01
End ADT3 5/11 PSA < .01

ralfinaz
Veteran Member


Date Joined Jan 2011
Total Posts : 735
   Posted 6/7/2011 11:48 AM (GMT -6)   
Logo,
Sorry to have confused the issue for you. My point was that the key to slow down prostate cancer progression upon established recurrence, is to start HT when the tumor burden is low and is biologically more responsive to therapy. No question this is controversial and each patient must decide what and when to do it. I believe that early is beneficial and other might decide otherwise. And that is fine for that patient because these decisions are always very personal.

BB_Fan,
Never second guess your decision. Hope you have a super long off-cycle from ADT3. Something like not needing it again!

RalphV
Phoenix, Arizona
Surviving prostate cancer since 1992 at age 58. RP; Orchiectomy; GS (4 + 2); bilateral seminal vesicle invasion; tumor attached to rectal wall; Stage T4; Last PSA September, 2010: <0.1 ng/ml
Laughter is still the best medicine!
www.pcainaz.org/phpBB304
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