radiation with and without Casodex

 

Thought some of you might be interested in this, from UroToday:

  http://www.urotoday.com/index.php?option=com_jentlacontent&view=enhanced&id=42184&Itemid=57

  Effect of anti-androgen therapy (AAT) with bicalutamide during and after radiation therapy (RT) on freedom from progression and incidence of metastatic disease in patients following radical prostatectomy (RP) with pT2-3,N0 disease and elevated PSA levels

This study evaluated patients post radical prostatectomy with pT3N0 or pT2No and positive surgical margins and an elevated PSA. Freedom from progression and incidence of metastatic disease in these patients, following radical prostatectomy with an elevated PSA, was assessed. Patients were randomized to 150mg bicalutamide or placebo plus 64.8Gy RT. Patients were stratified by margin status, nadir PSA level, and entry PSA level. 771 patients were randomized and median age at entry was 65 years. PSA nadir after radical prostatectomy was <0.5ng/ml in 87% of patients, and PSA at entry was <1.6ng/ml in 87% of patients.

Median followup was 7.1 years and over 95% completed RT. 84% completed taking bicalutamide, compared with 95% completing oral placebo. The primary endpoint was overall survival. GU and GI toxicities were similar among the two study arms. Late gynecomastia occurred in 89% of bicalutamide treated patients. OS was 91% in the treated arm exceeding the 86% in the placebo arm. The FFP was 57% for bicalutamide vs. 40% in placebo. For Gleason scores ≤6, 7, and >8 the FFP for the bicalutamide and placebo arms were 63% vs. 50%, 55% vs. 39%, and 56% vs. 26%. This was beneficial in those with positive surgical margins and higher Gleason subtypes.

Presented by William U. Shipley, MD at the 2011 Genitourinary Cancers Symposium, General Session I: Emerging Trends in the Characterization and Treatment Decisions of Newly Diagnosed Prostate Cancer - February 17-19, 2011 - Orlando World Center Marriott, Orlando, Florida USA

Zufus - I don't know.  The answer given from time to time on this board --do radiation in isolation so we can see to what extent the radiation is succeeding,  without conflating factors -- does not personally resonate with me, if there is evidence that the combined impact of two modalities has been shown to deliver superior results.  But I am not a doctor, and not even a very bright guy, so my views on this stuff are probably best taken with a grain of salt.

John -- my doctor started me on lupron two months before BT and IGRT.  is the study saying that adding HT to radiation is not a "gray area" ?

ed

"The FFP was 57% for bicalutamide vs. 40% in placebo. For Gleason scores ≤6, 7, and >8 the FFP for the bicalutamide and placebo arms were 63% vs. 50%, 55% vs. 39%, and 56% vs. 26%. This was beneficial in those with positive surgical margins and higher Gleason subtypes. "

So for high-risk G-8 patients, the ADT produced a 56% Vs 26%, who were free from progression...

No wonder my R-doc INSISTED on HT as part of his treatment plan...

Johns last post is very important.

The primary end point is supposed to be overall survival yet the statistical data is measuring biochemical failure. Which of course means more time is needed to show us if in fact there is a survival benefit to salvage anti-androgen therapy with Casodex.

Shipley is working with my doctor on this study. We hopefully will see that delaying biochemical failure will also improve survival.

Good post...

Tony

mel -- yes .

John T  -- i agree.  i also think that when you've got a chance for a "cure" you go for it.  i don't understand statistics but i know they can be misleading.  it seems to me that anything that knocks back or stops the cancer is going to make you live longer, and that's my goal.

ed

>>Still too many conflicting reports and opinions at the pro level about adding or not adding HT in the mix.<<

there's no conflict at my doctor's office. never one bit.  my doctor told me i'd have a 60% chance of needing SRT and he said with that in mind he didn't think surgery was a good choice for me.  also, because i had a high volume of cancer he recommended a combination treatment -- HT, BT and IGRT.  also my prostate is very small, making me a VG candidate for seeds.

now with all due respect your doctor's may think differently and there may indeed be a gray area but there was never any doubt or conflict with any of my doctor's regarding what was best for me. none whatsoever. 

i should add that my doctor believes that HT is overused and at first he recommended six months of lupron, which because of the way scheduling fell turned into nine months.  my radiation oncologists  -- there are three  of them -- all agreed that short-term-HT would be beneficial to me.

and i'm one to err on the side of "overtreatment".

of course we don't know if the treatment worked but i should have a better idea before the end of the year.

ed

Ed, I don't doubt the wisdoms of your doctors, or their advice to you. Wouldn't pressume to do that to you or anyone else.

I can't imagine, if you were being literal, that anyone was gunning to be on HT, lol. I don't really think its a monster, and for some guys here, its not that bad of a ride for them. You could say the same for SRT, for many - just a couple of months of treatments and a short bout of side effects, for me, it was a living hell and I am still paying the price and it didn't work.

Looks like we are about 3 years apart. I don't any kind of death wish in particular. Just 3 years ago, I was still riding a motorcycle at speeds to 155 mph on narrow windy roads here, probably had a higher level of pending death from that habit than PC has been for me so far.

David

John, just thinking about the "stats" side of your post. Could the 4% death rate still be more, in that many more men are being diagnosed do to PSA testing than in the past. More diagnosed, more cases, more reported deaths? No facts to back this.

Ed,
I think that PC falls into three catagories.
1. Non agressive PC that will never hurt you in your lifetime.
2. Very agressive PC that regardless of treatment will cause death in a short number of years. (Think varients or G9 or 10)
3. Intermediate PC that if caught in time treatment can prolong life for many years.
If 50% -60%of all DXed pc is in the 1st catagory and 5-10% is in the 2nd catagory then we can only affect overall survival in 30% -45% of the patients. We know that approximately 30% of intermediate risk patients fail primary treatment. Therefore 21% -31% benefit from treatment. Unfortunately we can't tell which individual patients will benefit and which will not with any degree of certainty. If we want to move the end number we can only influence the 30% of intermediate risk patients that fail primary treatment. We can prolong the life of high risk patients and those that fail primary treatment, but we can't affect the end number of deaths from PC to any great extent with the treatments we have today.
This is why I think that the 4% hasn't changed much over the years regardless of psa testing and all treatments we have.
JT

>>>3. Intermediate PC that if caught in time treatment can prolong life for many years.<<<

John,  are you saying that we'll die of cancer anyway? i think that remains to be seen in cases that have been treated aggressively with modern treatment. 

ed

Ed and Fairwind.
Prostate cancer is a spectrum that goes from indolant to extremently agressive. The D''Amico risk classifications are just lines drawn at places along that spectrum. Of course there are high risk patients that will survive; we cannot determine an individual's outcome, but we can make generalizations about risk catagories. As a group 70% of intermediate risk cases will be cured and 30% will suffer reoccurrances. The number of high risk cases caught early that are cured is about 45%.
There are a number of high risk cases at the far end of the spectrum that will not be cured regardless of treatment and time of DX. Age is a very important factor as many of those with high risk PC will die of something else simply because they are reaching that point in thier lives. If people didn't die from other causes and lived to be 100 then we would have many more prostate cancer deaths. The low and stable death rate from PC is due more from patients reaching old age and dieing from something else. The 10 years survival rate is close to 100% ,so the chances of a patient dxed in his 60's or 70's dieing from something else is very high.
What I was attempting to do was to give an explaination of why I think the rate of deaths from PC has remained stable at 4% for the last 20 years in spite of all the advancements in testing and treatments. I think that this is an important question. We can't affect the death rate by treating the highest number of PC patients, those in the low risk catagory, because they don't die. The majority of high risk patients fail treatment so we can prolong life, but not cure.
As Tony mentioned the end point is overall survival. As many studies point out that the treaments seem successful, but overall survival never goes up, Why???
I'm just "blue skying" here trying to think out of the box. If one of my companies kept adding expensive equipment and increasing their research or marketing budgets without increasing profits I would be all over the managers to justify what they were doing or trying to find out what wasn't working and why.
JT

Does the 4% relate to the number of deaths divided by the number that have PCa? If 32,000 die this year from PCa, at a 4% death rate it means some 800,000 have PCa. With 220,000 new cases a year I don't think this is correct. There should be probably twice that many of us with PCa.

Fairwind, your calculation is the total number of deaths in a year divided by the number newly diagnosed that year, which is not the overall death rate.

From all causes some 2,500,000 males die each year in America. 4% of that figure would be 100,000 deaths. So it is not this number either.

John T, how is the 4% death rate determined?