Wednesday, June 4, 2008

Even Better Odds

Long-Term Rates of Undetectable PSA with Initial Observation and Delayed Salvage Radiotherapy after Radical Prostatectomy.

Loeb S, Roehl KA, Viprakasit DP, Catalona WJ.

Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.

PubMed citation:

"The long-term rates of undetectable PSA associated with an SRT strategy were 83% and 50% for men with SM+/ECE and SVI, respectively. In the subset of 716 men who did not receive any hormonal therapy, the corresponding long-term rates of undetectable PSA were 91% and 75%, respectively."

91% long term rate of undetectable PSA. That's music to my ears, since I fall into that statistical group (positive margins, no hormonal treatment).


Jim Schlemmer said...

Hey Replicant.

I've been having trouble figuring out the results of this study.

First, it appears that they are not comparing ARP to SRP, correct?

I'm also a bit puzzled by how the "long-term rates of undetectable PSA associated with an SRT strategy were 83% and 50%" whereas "the 7-yr PSA progression-free survival rates with observation were 62% and 32%." Maybe it's a difference in what "undetectable PSA" means vs. "PSA progression-free survival rates," but long term seems like it should be longer than 7 years and so the higher rates are bit puzzling.

Also, what do you make of the rates for men who didn't do hormones? I can see how it might not help but how could that be such a benefit?


Replicant said...

Hi Jim.
You know, I was puzzled by this too, at first.
It was only after coming back to it later that I could grok it.
The way I understand it, they're saying that if you had positive margins and/or extracapsular extension, your 7 year odds of having undetectable PSA are 83% after salvage. If you had seminal vesicle invasion , your odds drop to 50% for long term success after SRT.

If you did NOT have radiation, but instead did observation, with positive margins/ECE your odds of being progression free would be 62%, but only 32% if you had SVI.

If you are not prescribed hormone treatment, and have salvage radiation, your odds actually go up. This part is a little puzzling, since it has been shown that hormone therapy can increase the effectiveness of radiation. However, I think this figure is picking up on the fact that men who are prescribed hormone therapy in addition to salvage radiation are often already at higher risk because of other factors.

In a nutshell, this study says to me that SRT increases your odds of being progression free 7 years down the road. The men who did best in the study had positive margins or ECE, but not SVI, and the ones who seemed to do VERY well were the ones who were pos margins/ECE, with no SVI, who did not get ADT.

This seeming negative effect of ADT is, I think, sort of an illusion. It does jibe with Andrew Stephenson's research. If you use his nomogram on, you see that ADT lowers the odds of success, but only slightly. Again, I think this is because a lot of men who get prescribed ADT in addition to salvage were in a high risk group because of high Gleason, rapid PSADT, etc.

Just my layperson's 2 cents.

Thanks for your comment!

Jim Schlemmer said...

Thanks. It's obvious now that I re-read it: SRT vs. observation. I guess I didn't make the connections between observation and watchful waiting.

The hormone explanation seems reasonable.


Replicant said...

I read a more detailed abstract of this on the AUA website. (I've also ordered a full text copy of the article for my own use).

It's not quite as rosy for me as I first thought.

On the AUA site (where they make poster sessions available for free) it says (all caps is my emphasis) "In patients with SM+/ECE, SVI, and LN+, the 7-year progression free survival rates WITH OBSERVATION were 62%, 32%, and 7%, respectively. AMONG THOSE WHO FAILED, 56%, 26%, and 0%, respectively, maintained an undetectable PSA for 5 years after salvage radiotherapy."

Okay. This means--using positive margin patients like me as an example--that 62% did not progress in 7 years of observation. Of the men that DID see their PSA rise during observation (like me), 56% seemed to have a good response to salvage radiation, at least out to 5 years.

Okay. So I'm back to progression-free odds in the neighborhood of 60% again, like Stephenson's research indicates.

Jim Schlemmer said...

Thanks for your updated thoughts.

"In patients with SM+/ECE and SVI, the 7-yr PSA progression-free survival rates with observation were 62% and 32%, respectively."

So this means that if you had SM+/ECE your 7-yr zero PSA rate was 62%. But that's for all Gleason scores combined, I'm guessing. My own score of 8 drops my number down to 57%, according to the S-K nomogram.

Among those who had PSA progression, 56% and 26%, respectively, maintained an undetectable PSA for 5 yr after SRT.

The long-term rates of undetectable PSA associated with an SRT strategy were 83% and 50% for men with SM+/ECE and SVI, respectively.

I'm still having trouble squaring these two statements. I mean, by definition, those that had SRT also had PSA progression prior to the SRT. And yet the 5-yr undetectable PSA rate is lower than the "long-term" rate.

The more I read the more I think that adjuvant is the way to go for me.

I spoke with a medical oncologist (friend of a friend) who summarized my situation in a way that I hadn't quite:

- no imaging done
- no lymph nodes taken
- gleason 8

So I'm wondering if maybe some imaging is in order. The surgeon still says that statistically he thinks lymph node involvement is remote, and indeed the S-K pre-op nomogram doesn't change much when I modify the inputs from Gleanson 7 to 8, even if I monkey with the clinical stage as well.


Replicant said...

Hi Jim.

I ordered and received the full text of that article, which is easier to understand in its full context. If you're interested, your local library should be able to get it for you at no charge or for a very low fee. That service is interlibrary loan, and it's a great way to get medical journal articles.

The 83% "cure" rate (their quotes, by the way) is a statistical construct. They're trying to estimate what the cure rate is for the following strategy overall, for the two different groups of men. Here's the strategy under consideration:

Wait until PSA rises before initiating RT after prostatectomy.

In other words, salvage.

They're saying that considering a group of men with SM+/ECE, without knowing anything else about them (Gleason, for example), overall those men have an 83% "cure" rate with this strategy. 83% of the men studied either never saw their PSA rise OR it rose but then it was knocked to a very low level from whence it never rose in the next 5 years.

And likewise, looking at men with SVI, this strategy is successful for some, but not most.

Anyway, we shouldn't read TOO much into this article. The authors noted some potential problems with their study, and the accompanying editorial in the journal was less than enthusiastic. Selection bias was just one of the problems, since this was not a randomized trial. Still, the editorial noted, the study was a step in the right direction to understanding this question.

Jim, good luck in your quest. I know how much the ambiguity and anxiety in such a situation can wear on a person.