On Tuesday night a panel of three respected local doctors presented updates in their fields and answered questions for our Us Too support group. One was a urologist, one a radiation oncologist, and the third was a medical oncologist. None specialize in prostate cancer, but all have many prostate cancer patients in their practices.

It was very interesting that both the radiation oncologist and the medical oncologist each chose to emphasize as one of his updates the importance of PSA velocity in assessing the seriousness of prostate cancer. Just a few years ago, PSA velocity was acknowledged as something to consider, but it hardly ranked with the number of cores and percent of cores and the percent of each core that was cancer, let alone with the big three: baseline PSA at diagnosis, the Gleason Score, and the clinical stage.

The change is mainly due to two research papers written by teams led by the well-known prostate cancer researcher/physician Dr. Anthony D'Amico. The first, published in the New England Journal of Medicine in July of 2004, demonstrated that, for radical prostatectomy patients, whether the PSA increased by up to 2.0 or more than 2.0 in the year prior to diagnosis was a strong indicator of seriousness of the case and was independent of the baseline PSA, Gleason Score and stage. Having such a high velocity PSA resulted in many times greater death rates from prostate cancer. :( The second, published in July of 2005 in the Journal of the American Medical Association, showed a similar impact of a PSA velocity of greater than 2.0 on patients who elected radiation therapy. :( I've reviewed complete copies of these papers, and the risks are even higher if the cancer can be felt (and not much different if the cancer cannot be felt :) ).

I've noticed that at least two other research teams confirmed these findings.

What this means is that we should pay attention to our PSA doubling time (PSADT) in the year prior to our diagnosis, if we have the PSA results needed to calculate the PSADT, as most of us do. (Not me, though, but it's a cinch mine was greater than 2.0 since my baseline PSA at diagnosis was 113.6.) Some of us who don't have precise information about it can make good estimates: we don't have to get an exact velocity, we mainly need to know whether it was up to 2.0 or greater.

There is good news as well as bad news here. While we now have an additional factor to indicate higher than normal risk considering the other factors, the reverse is also true: if our PSAV was less than 2.0 in the year prior to diagnosis, especially if it was much less than 2.0, that is an indicator that we will probably do better than the statistics indicate based just on the more established factors, particularly the baseline PSA, the Gleason Score, and the clinical stage. :angel:

We should also remember that having a PSAV greater than 2.0 before diagnosis need not put us in the middle of the bull's eye. With knowledge that we are at greater risk, we can make decisions that improve our chances. :cool:

If you want to read abstracts of these studies, go to our free, taxpayer supported US Government website www.pubmed.gov, and search for " "Preoperative PSA Velocity" OR "Pretreatment PSA Velocity" AND Risk of Death from Prostate Cancer AND d'amico [au] ". In fact, you can click on the pages icon with the green heading to get a free complete copy of the paper. To read just the abstract, click on the authors lists.

It is remarkable that this change in understanding of pre-diagnosis PSAV has penetrated the consciousness of doctors treating prostate cancer patients in so short a time. :)

Jim

Did the study recommend any specific treatment options for patients whose PSA velocity was >2? Should treatment now consist of a combination of modalities rather than just one? What about patients who only had RRP and are still PC free?

Did the study recommend any specific treatment options for patients whose PSA velocity was >2? Should treatment now consist of a combination of modalities rather than just one? What about patients who only had RRP and are still PC free?

The RP study did not make specific recommendations about treatment options except the RP study said, in the ever cautious and tentative words of medical studies, "For these men, who are otherwise in good health, watchful waiting may not be the best option. Randomized clinical trials are needed to identify a treatment that improves survival among these men." At least one of the major Active Surveillance programs is working a PSAV standard into its approach for selecting suitable candidates for Active Surveillance. To me it seems obvious that hormonal blockade therapy would most likely help, and perhaps follow-up radiation might also help the RP patients.

The RT study noted that the standard of care for higher risk men is RT plus hormonal blockade therapy, based on evidence from two clinical trials. The RT study suggests that men who appear to be otherwise low in risk, not counting a PSAV > 2.0, would benefit from being treated like higher risk patients.

Regarding men who had an RP and are still PC free, they may have been cured. Having a doubling time greater than 2 doesn't condemn a patient to recurrence after an RP, it just means his odds of recurrence are higher. Normally roughly 30% to 40% of all RP patients will recur in time, but, as we know, case characteristics make a big difference. (Also, many recurrences will be quite mild -- virtually as good as a cure, though a lot more worrisome, especially before we had the Freedman research from Johns Hopkins that told us how to separate the lambs from the wolves, recurrence wise.)

Looking just at the effect of having a PSAV in the year prior greater than 2.0, Figure 1.A. the study shows recurrence of nearly 30% at just the first year, almost 50% at the end of the fifth year, and nearly 60% at ten years. That's a lot higher than the overall average. On the other hand, 40% of men with a PSAV >2.0 are still recurrence free at the ten year point, and, when you look at the plot of failures by year, you see that the recurrence "curve" becomes nearly flat, suggesting that not many recurrences will happen after the ten year point for these men.

In contrast, men with lower PSAVs than > 2.0 in the year prior to diagnosis had recurrence rates at the 10 year point ranging from about 30% for those with a PSAV <= .5/year, about 34% for those with a PSAV from .51 to 1.0/year, and about 40% for those with a PSAV from 1.01 to 2.0 per year, and all three curves were essentially flat (suggesting more recurrences were unlikely) at about the seven year point for the first two and a little after the eight year point for the 1.01 - 2.0 group.

For those of us in the PSAV >2.0 group, Figures 2.A, 2.B, and 2.C present how clinical stage of T1c versus 2a, PSA of <= 10 or >10, and Gleason of <= 6, 7, or 8-10 affect outcome of PSAV >2.0 men.

RT patients are in the same circumstances.

It sure makes sense to me that men with a PSAV of greater than 2.0 in the year prior to diagnosis should also support whatever treatment they have with a conscientious program of diet/nutrition/supplements, exercise and stress reduction.

Jim

...

The RT study noted that the standard of care for higher risk men is RT plus hormonal blockade therapy, based on evidence from two clinical trials. The RT study suggests that men who appear to be otherwise low in risk, not counting a PSAV > 2.0, would benefit from being treated like higher risk patients.

... Jim

It's also important to remember when the patients in the studies were treated. For example, the 1,095 patients in the RP study were treated between 1989 and 2002. While we now know that it pays to add hormonal blockade to RT for higher risk men, it was not known for most of the years during which the men in the study were followed. In fact, results of the two clinical trials that established the RT plus blockade standard were not published until 2002 (Bolla) and 2004 (D'Amico - not the RP study he led in this thread). Neither the RP nor the RT study makes clear what other care the patients had after they recurred, but urologists during the time of the study generally distrusted hormonal blockade, believing it would work for only a short time, so it may well be that few patients were treated with blockade, and those that were may have been treated late in the disease, when blockade is less effective. Also, modern blockade techniques such as intermittent triple blockade were just getting a foothold during the latter part of the RP study period, making it likely that few if any patients were so treated, and chemotherapy for prostate cancer was not yet very effective. The same patients would most likely do much better if they experienced recurrences and were treated with therapies available today. :angel:

Jim