THE "NEW" PROSTATE CANCER INFOLINK

Who is really a candidate for active surveillance (AS) as opposed to early treatment for prostate cancer that is supposedly localized is not yet well-defined. Indeed, it may not even be possible to come up with any “absolute” guidelines for eligibility for AS based on the diagnostic and prognostic tools we have at this time. However, one of the things that we don’t seem to be taking into account in analyzing the value of AS is the value of not needing immediate intervention for the patient (i.e., “deferred” treatment).

Catalona and his colleagues recently published data on the outcomes of men who might theoretically have been eligible for active surveillance (AS) but who actually underwent immediate radical retropubic prostatectomy (RRP). In their abstract, they write that, “AS protocols are designed to spare the potential morbidity of treatment to patients with low-risk prostate cancer.” This is completely true, but for the patient an AS protocol also does something else. It gives him — and often his spouse – time to be certain that they are making the right decision. In other words, from the patient’s point of view, active surveillance addresses two possibilities:

• The possibility that he really does have indolent disease that will never need to be treated and
• The possibility that he does need treatment — but not immediately

So let’s look at what Catalona and his colleagues showed from their analysis of their extensive database of patients. (We assume that is this Catalona’s own series of patients, which is now over 5,,a but that is not stated in the abstract to the paper, so we can’t be certain of this.)

They used three separate sets of proposed eligibility criteria for AS:

• Clinically localized disease, Gleason ≤ 7, and no significant comorbidities (as defined by Patel et al. in 2004, who do refer to these criteria as criteria for “deferred therapy”)
• T1b-T2bN0M0 disease, Gleason ≤ 7, and a PSA level ≤ 15 ng/ml (these are the Sunnybrook criteria, as defined by Choo et al. in 2001)
• Simple stage T1c prostate cancer (defined by Mohler et al. as long ago as 1997)

It is perhaps a pity that Catalona’s group did not include the most restrictive set of criteria established for AS — the Epstein criteria used at John’s Hopkins — but this may not have been technically feasible.

The authors then analyzed how many men in their series of patients would have met each of the three sets of criteria outlined above, and compared that result to (a) the pathological findings in these patients immediately after surgery and (b) the long-term outcomes of the patients. They showed the following results:

• 3,959 of their patients met the criteria defined by Patel et al.
• 3,536 met the Sunnybrook criteria
• 2,330 met the criteria of Mohler et al. (i.e., they were simply T1c at diagnosis)

We do not have a copy of the full paper to refer to, and we assume that in the full paper the authors break down the pathologic results by category, but what the abstract says is that, overall:

• 3 to 4 percent of these patients (regardless of category) had a Gleason score of 8-10
• 16 to 19 percent had positive surgical margins
• 15 to 18 percent had extracapsular tumor extension
• 3 to 5 percent had seminal vesicle invasion,
• 0.4 to 1 percent had lymph node metastasis
• The 5-year progression-free survival rate ranged from 84 to 89 percent.
• Metastasis occurred in 0.1 to 1.2 of patients
• 0.1 to 0.9 percent died of prostate cancer
• A Gleason score > 6 was the strongest predictor of biochemical progression

Now we should immediately point out that you can’t just “add up the numbers” and say that between 37 and 47 percent of the patients had non-localized disease at the time of diagnosis. For starters, it is safe to assume that there were patients who had (say) extracapsular disease and seminal vesicle invasion and/or positive lymph nodes.

Secondly, we have no idea whether the results would have been much different if half of these patients had had their surgery deferred for a year while they decided what to do — and indeed some of them may well not have had their surgery until a year or more after their initial diagnosis.

The conclusion drawn by the authors is that, “A substantial proportion of men who might have been considered potential AS candidates had aggressive tumor features at RRP and/or progression.” (“The glass is half empty!”)

The conclusion drawn by The “New” Prostate Cancer InfoLink is that at least 50 percent of these patients showed no aggressive tumor features at the time of surgery (“The glass is half full!“). The fact that 11 to 16 percent of the patients did progress after surgery and that at most 1.2 percent of them (47/3,959) went on to have metastatic disease after treatment means nothing in terms of the validity of active surveillance because we have no information on how they might have done if they had either had no treatment at all or if they had deferred it for a year or more.

The place we certainly agree with Catalona and his colleagues is when they state that, “the accurate identification of patients with truly indolent PCa at the time of diagnosis remains challenging.” We also agree with them that any patient diagnosed with Gleason 7 disease needs to think very hard about his options. However, what we also believe is that these data help to demonstrate the very real potential of active surveillance to defer treatment (even if you have Gleason 3 + 4 = 7 disease)  – maybe for just a year, but maybe for ever — if we could just get closer to a good set of eligibility guidelines. And if you are 70 or older, or you have other clinical history that significantly impacts your normal life expectancy, the more sense some form of expectant management seems to make for many of us.

Filed under: Management Tagged: | active surveillance, expectant managemt, outcomes