"PSA density" etc.

Hi folks, I'm new to the forum and think I have a fairly unusual case. Here is some background: I'm 73 and in quite good general health. My PCa diagnosis was just a few weeks ago. My PSA had shown gradual increase over the last 10 years or so and most recently reached 4.3 with approx. 10% free. I've had two TURPs in the past. At age 49 and again at 59. Both of these were for BPH and no cancer was found in those cases. Those TURPs are possibly the reason my prostate is small (around 18cc) which means greater "PSA density" (.22 approx.).

The biopsy which confirmed my diagnosis was done by taking just 6 cores. "Because the prostate was so small," according to the urologist. Every one of those cores showed positive for adenocarcenoma. Each also had Gleason 6 (3/3). Lowest % involvement was 50%. Highest was 90%. The other 4 were at 60%, 65%, 70%, and 70%. So this means I have a small prostate that is apparently very involved but with fairly low grade cancer. I'd like to know more about what such widespread involvement may mean. And what are the implications of my higher PSA density? The Partin tables seem generally to use only an unadjusted PSA number and the Gleason score.

A DRE, done prior to biopsy, indicated palpable tumor but, according to the urologist, no sign of tumor beyond the prostate. So it seems I am probably stage T2c, right? Or do the other features of my case point to likely spread beyond the prostate despite the DRE?

I'm having the pathology report redone at Johns Hopkins and also Prolaris genetics/molecular testing. Those results should be back shortly. Any other suggestions as to getting a better picture? Can MRI be of likely value?

Once I do have as clear a picture as possible I will move toward a treatment or AS decision. Since I'm still early in the process I'll be getting additional medical opinions, of course, but I very much look forward to any input from HealingWell participants.

Thanks!

Welcome. First of all, based on what you posted, you already sound like a "well-educated" (about PC) patient, which is a great start. Get your results, including the JHU reading of your biopsy slides before jumping ahead. Great that your general health is good at 73; life expectancy will likely factor into your next steps. Be aware that MSKCC (basically the gurus for all things PC) guidelines are:

PSA testing should end:
*At age 60 for men with a PSA level that is still ≤ 1 ng/ml
*At age 70, unless a man is very healthy and has a higher than average PSA level
*At age 75 for all men

Thanks to each of you!

I've really appreciated this site. That long initial thread for the newly diagnosed is excellent!

First to JNF: Yes, I'm anxious to see what the reread of my biopsy might tell me. But I'm especially concerned that I seem to have such extensive involvement of every core. And with a small volume prostate.
I really want to know if I can have any hope for AS approach if the Gleason still comes back at 6. There just doesn't seem to be a lot out there about the diagnostic relevance of high core % involvement, etc.

Now Jack H.: I do understand those PSA testing suggestions and am definitely aware of the huge over-treatment problem. I just obviously don't want to miss an exception where action is called for.

And Whip: I agree that it seems I'm at T2c. And I'm delighted (though with obvious regrets for what this means to you personally) that you have knowledge about what it means to have multiple core involvement. My extent on this score is even more extreme, though, right? I've yet to see anything quite so total as my level of involvement. You used that phrase "unfavorable intermediate risk". Do you have a source on that? As I think I said earlier, I'm having a very hard time finding sources that discuss the implications (I know it's only statistical but that's all we have to go on, right?) of PSA density, percent of cores involved, and percent of involvement in each core.

Unfortunately, if AS is not reasonable I'm being told brachytherapy is not an option due to past TURPs. True?

I'm told RP is the gold standard but the huge side effects, especially if I already have to deal with ECE, are not attractive. I hate the idea of two plus weeks with catheter just for starters. (And that's the least of my worries, I know!)

I'm really interested in what you had to say about the restaging MRI possibility. How good are these now? I have a teaching/research hospital within 100 miles. Could they actually do accurate detection of tumor spread? I've been told there are just too many false negatives and even false positives.

BTW, can you tell me more about the difficulties posed by small prostates and getting clear surgical margins, especially at apex? Maybe you have another reference on that topic you could provide?

I guess this is enough for now. Sorry for the very long post but you've been a huge help!

Thanks to all of you!

"You used that phrase "unfavorable intermediate risk". Do you have a source on that?"

This is a new category that was accepted this year by NCCN. NCCN deemed those with favorable intermediate risk PC as candidates for active surveillance. It's based on the analysis by Zumsteg et al. below:

A New Risk Classification System for Therapeutic Decision Making with Intermediate-risk Prostate Cancer Patients Undergoing Dose-escalated External-beam Radiation Therapy

"I'm having a very hard time finding sources that discuss the implications (I know it's only statistical but that's all we have to go on, right?) of PSA density, percent of cores involved, and percent of involvement in each core."

There's been many studies on those topics. Epstein (at JH) condensed them all into a set of criteria, called the "Epstein criteria" that Johns Hopkins and a few other institutions (but not all) use to define optimal candidates for active surveillance. In addition to low risk PC (GS 3+3 and PSA<10 and stage T1c/T2a), the patient fulfills the following criteria: PSA density<.15 andfewer than 3 positive cores and ≤50% cancer in any core. NCCN calls someone who meets all of those criteria "very low risk." The significance of very low risk PC is that NCCN recommends active surveillance as the preferred therapy for them. (NCCN is an organization of many of the top tertiary cancer care facilities that pretty much defines the standard of care).

According to the NCCN standard of care, you are ruled out of active surveillance on the basis of stage and % positive cores, which puts you in the "unfavorable intermediate risk" category.

The 3 basic NCCN categories - low risk, intermediate risk and high risk - are defined on the basis of Gleason score, PSA and stage. The other risk factors you mentioned are subsidiary to those, and are not wholly independent of them. Their only use is in helping to define the subcategories I mentioned.

NCCN isn't the only risk stratification system, just the most widely used one in the US. There are others; e.g., CAPRA. And there are many nomograms that give estimates of risk based on large databases.

"I'm told RP is the gold standard"

Only if you talk to a uro-surgeon. That's why we recommend talking to specialists in each field.

"I'm really interested in what you had to say about the restaging MRI possibility. How good are these now? I have a teaching/research hospital within 100 miles. Could they actually do accurate detection of tumor spread? I've been told there are just too many false negatives and even false positives."

3T MRIs are as good as we have for staging, but they are not as good as examining the prostate after surgery. I don't know how many is "too many" for you, but they are pretty good at seeing ECE - it does not directly detect cancer itself, just the bulges caused by tumor penetration, which is what you care about for restaging. Don't get that confused with multiparametric MRIs which is a different thing with different uses altogether (i.e., for targeted re-biopsies and AS protocols).

'I'm being told brachytherapy is not an option due to past TURPs. True?

As I said, LDR brachytherapy may be precluded - and you should talk to an LDR brachytherapy specialist about that and not take my or anyone else's word. However, HDR brachytherapy may still be a good option. SBRT as well. You have to talk to specialists in each of those.

can you tell me more about the difficulties posed by small prostates and getting clear surgical margins, especially at apex

Unlike the rest of the prostate, the apex doesn't have much of a capsule around it. Tumors there are apt to grow into the muscle walls of the underlying prostate bed, and are the primary cause of positive surgical margins. Unlike at other places, the surgeon can't simply cut wider to get it all as that would insure permanent incontinence. It's particularly problematic with small prostates with large tumors that easily spread there. That's why I think your urologist may want a staging MRI to get a better look before committing to cutting you open. It doesn't matter as much with radiation - the treatment margin will encompass it all.

Wow! What a great thorough response from Tall Allen! (Sorry I referred to you by my own pseudonym in that last post! Glad you figured it out)

I'll check out the Zumsteg reference for sure. I am aware of the NCCN system, of course, but not of this later adjustment.

I did discover the Epstein (JH) work you mention. And I do recognize that it places me at a higher risk (not likely AS) category. Alas. What still confuses me, I guess, is that my Gleason 6 is so strongly low risk for aggressiveness. I've even seen studies arguing that Gleason six should not be called Ca. Of course, the redone pathology may not support G6 and I may be underestimating the importance of those "subsidiary" risk factors. That's the problem.

Don't you get the feeling that JH, Epstein, Walsh, et. al., are all pretty uro-surgery biased? And, of course, if they do get clear margins and side effects are ok, then all is really great. But.....

So, I am really interested in getting some better imaging to decide on stage. Deciding stage after surgery is kind of beyond the point, right? By then you've already got all the side effects to contend with! (I do appreciate your input about MRI used for other purposes than restaging, by the way)

I will definitely check out that HDR brachytherapy possibility you mention and the various RT possibilities. Can you tell me anything about the side effects and general down side of RT? We have local availability of "Calypso" targeting technology and "SmartArc" RT. I do like the idea of avoiding the immediate trauma of surgical recovery (especially that darn catheter for two weeks!) but longer term problems from RT don't sound like fun and if I don't take the surgery route I lose the chance for that quick (relatively) definitive "we've got it" possibility.

Finally, thanks a lot for the clarification re possible apex margin problems. That does push hard in the direction of MRI imaging clarification, for sure. I definitely do not like the prospect of long term incontinence problems!

Thanks, again, for all your input!

For Tall Allen, especially,

Your latest input is again much appreciated! I am working through all the details and it may take some time (no,surprise there, right?).

I have read all of that sticky you reminded me of. Indeed, it was what most persuaded me to join this forum for further input, in the first place. But it is easy to forget things, so I'm not surprised that I may be asking about things covered there.

I really need now to look into imaging options (for more accurate staging) and also start talking with other docs re the various treatment options (my primary uro type is clearly an RP type with 700 +\- surgeries done) so I'll get plenty of support for that option from him. Your point about the added seriousness of SEs if adjuvant RT is used on top of RP is very important. I say I'm a health 73 year old but I'll bet I'd feel not nearly so healthy if I went through that combo!

I did not realize there was a difference between low and high dose brachytherapy approaches, by the way, and was simply told by the uro doc mentioned above that my prior BPH TURPs and the small prostate ruled out any brachytherapy. You may have additional thoughts on this topic and other references?

Right now I'm still waiting for the redo of my biopsy pathology assessment (at JH) and that Prolaris report. I was told two weeks ago that those were being ordered. Once I have those in hand I should be able to bring a more thorough file with me to my appointments with other docs.

Whippoorwill

Ok, good idea but isn't there a bit of a circularity problem: The specialist whose specs I would most want to follow is the one who fits my chosen treatment approach. But that staging imaging is what I need to choose treatment.

Further thoughts?