Posted on the New Prostate cancer Infolink today.
One of the best perspectives on AS that I have seen.
As one of our regular commentators constantly points out, active surveillance (AS) is not
for prostate cancer. It is a means by which to manage risk for prostate cancer progression in men with low- and very low-risk disease or higher-risk disease but a limited life expectancy.
Another way to describe this is that AS is a means by which to defer unnecessary treatment until it becomes necessary for men with low-risk and early stage disease.
As many of our readers will be aware, the “classic” candidate for AS is a man of 65 years or older who has a life expectancy of up to 15 years and has been diagnosed with Gleason 6, clinical stage T1c prostate cancer after findings showing a PSA of < 10 ng/ml, a negative digital rectal exam, and one or two positive biopsy cores with a limited percentage of tissue positive for cancer.
The premise behind AS is that a high percentage of these patients (of the order of 70 percent) will never demonstrate evidence of clinically progressive disease during their lifetime, and so treatment should be avoided if reasonably possible. This also implies that about 30 percent may well need treatment, and so all such patients should be carefully monitored in order to identify and act appropriately for those patients who show signals of risk for more aggressive disease (ideally confirmed by a higher Gleason score on repeat biopsy).
A recent commentary in “Beyond the Abstract” on the UroToday web site, however, tells us that at least some clinicians and researchers do not necessarily see things in quite this light. In this commentary, Pontes includes the statement, “The inadequacy of patient selection is one explanation for active surveillance failures.” By “failures” he is referring to men who need therapy after a period on AS.
Now we would argue that these patients are not “failures” at all. Indeed, precisely the opposite, these are men in whom AS has clearly identified a need for treatment after a period of careful monitoring. They are therefore successes! They are men in whom therapy has been deferred until there was evidence of need for invasive treatment (which was then either offered and rejected or offered and given). In the series of patients originally studied by Oliviera et al. (and on which Pontes is commenting), 93 patients met clinical criteria for AS (out of a total cohort of 406 patients) but were treated by radical prostatectomy. Of these 93 patients, 25.3 percent showed pathologic evidence of higher Gleason grade and 8.3 percent of higher stage disease on pathologic examination of the prostate post-surgery. (These are the patients Pontes is referring to as “failures” of AS.)
Pontes goes on to argue that “one third of patients that fulfill the criteria for insignificant cancer may actually harbor cancer with aggressive characteristics, implying that the current criteria of selecting patients for surveillance should be cautiously adopted. A reliable model to predict insignificant prostate cancer is needed, and until that happens, the prediction of clinically insignificant prostate cancer will remain a major problem in urologic practice.”
He appears to be missing the point of AS entirely. If and when we have “a reliable model to predict [clinically] insignificant prostate cancer,” we won’t need AS at all! AS is a technique that allows us, in the interim, to manage risk in those patients who we hope have clinically insignificant prostate cancer.
So what is a “failure” of AS? The “failures” are those patients in whom, despite careful selection and monitoring, there is progressive disease that does not allow for successful treatment of localized disease with curative intent at the time of evidence of increased risk. In Klotz’s series of patients, at 10 years of follow-up, only 17/450 patients or 3.8 percent have demonstrated prostate cancer-specific mortality (definitive evidence of a “failure” of AS). Also in this series, 117 patients received definitive treatment for localized disease after a period on AS; half of these 117 patients — 58/450 patients (13 percent) – subsequently demonstrated a rising PSA. These patients can also be defined as “failures” of AS (although that is arguable if they never ever demonstrated subsequent symptoms of progressive disease). It is not entirely clear how many of these 117 patients had chosen to have definitive treatment because of evidence of increased risk and how many elected to have definitive therapy because they “couldn’t deal with” knowing that they were living with prostate cancer — even though there was no good evidence of increasing risk.
Klotz’s series includes many men who were well under 65 years of age at the time they started AS. It is also worth noting that Klotz’s series reflects some of the earliest carefully monitored experience of AS. The protocol that he and his colleagues use today for entry into their AS series and the methods for monitoring of their patients has been adjusted over time.
The critical point here is that if the mindset of the treating clinician is that AS is a poor substitute for immediate therapy (as opposed to the optimal means currently available to defer or avoid unnecessary treatment), then that clinician may not be fully committed to seeing AS as a management technique that is in the best interests of the patient. It is true that we are still refining the criteria for selection of candidates for AS, but we have already, and clearly, shown the value of this management technique in thousands of men. Furthermore, in perhaps many patients on AS, pathological evidence of progressive disease at the time of death may still not be associated with any clinical evidence of a significant problem. If one dies of something else, with extracapsular extension of Gleason 7 prostate cancer that never had any symptoms and that one never knew about, then (at least arguably) treatment of that prostate cancer was still never necessary, and AS was a successful management technique
What should also be mentioned is that 1.7% of all those classified with low risk disease will die, regardless of treatment or time of treatment because of agressive varients. Also any treatment for low risk clinical Dxed PC is about 10% to 15% for all treatment options, about the mid range of the 13% documented failures in AS. It seems the risk of AS and the risk of immediate treatment are equal and As does not mean additional risk as some believe.