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Cancer: Prostate Message Board


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[COLOR="DarkGreen"]Hi especially Bob, but also kcon and fellow board members,

Bob, thanks for your thoughts in the third post on this thread, to which I'm replying below. One thing I love about this board is that it helps us exchange views and both fertilize and weed our own personal fields of what we think is true, and I believe these threads will have the key value of helping fellow survivors and their loved ones with their decisions. :cool: I've already learned at least a couple of new points from the responses on this thread. :)

The information in this post will probably not be enough to win you over to the view that AS can be appropriate for younger patients, but it does lay out some of the key considerations and evidence. I'll respond to your points in green. [/COLOR]

[QUOTE=shs50;4016225]Thanks to both of you for an erudite summary

[COLOR="darkgreen"]Thanks, and I hope the thoughts are practical as well. My feeling is that the Active Surveillance (AS) researchers are now giving us a good base of knowledge for our very practical task of making therapy decisions.[/COLOR]

of the Canadien and other leading A.S. programs from Jim and a very well presented critique of the perils of linear extrapolation for younger men by KCon.

[COLOR="darkgreen"]I have had to become so familiar with the nature of PSA doubling time (PSADT) because of my own case and therapy, that it is now practically second nature. Check out my previous post that responds to kcon's post; the extrapolation in my example is actually exponential instead of linear. (If you are a board reader who is not mathematical, hang on, the rest of the discussion is not so math centered.)[/COLOR]

The error potential of small deviations between assumptions and experience in any exponential extrapoplation is analagous to the effect of minute differences in the trajectory of a long range missile or the path of a comet.

[COLOR="darkgreen"]I am fully with you in recognizing that it may be somewhat difficult to pin down the PSADT, and that fact double underlines the worth of basing the PSADT on a series of tests from the same lab, using the same brand and kind of PSA test kit, if possible. Actually, like PSA both the missile and the comet follow a trajectory that to me is amazingly predictable. For patients after they choose AS, there is plenty of time to get a very firm grip on that PSADT as the months go by with their semiannual PSA tests.[/COLOR]

However both analyses failed to address the more subjective issues which to my mind are being bypassed completely by the advocates for A.S.programs:
1. The Canadian program is being run and funded by a country committed to a single payer government run system where managing health care expenditures is an equal if not paramount objective. The costs of health care practically drive the Canadian economy.

[COLOR="darkgreen"]Over the past nine years I've come to appreciate that Canada has an impressive number of highly talented and dedicated physicians working with prostate cancer; they have done some brilliant work, and I am grateful because I am one of the US beneficiaries of at least two of the trails they have blazed. :D :angel: However, I've also come to appreciate the tremendous negative power of bias, and, if the Canadian studies were the only evidence for AS, I would also be somewhat skeptical because of the concern you raise: possible bias due to the influence of wanting to make the Canadian single payer system work. Fortunately, that's not the case: the findings of the Toronto group are strikingly similar to findings from other major programs, mostly directed by surgeons, who you would think would be biased toward doing more surgery rather than encouraging AS. More below. [/COLOR]

2. Using chronolgical rather than the less objective but more valid physiological age as basis for entry and measuring points, discriminates against older men with longer life expectancies than chronologically younger men in poorer overall health and physical condition.

[COLOR="DarkGreen"]I see this as kcon put it - basically we are all agreeing. You yourself are the evidence that a healthy older man, who would not be considered a surgery candidate by many doctors, can do very well with surgery. I suspect that Johns Hopkins would have done the surgery for you if there were no other excellent centers around who had greater belief in the value of surgery for very healthy, older men.[/COLOR]

I question Jim's statement that its possible to predict that a low risk case won't become clinically significant for thirty years.

[COLOR="darkgreen"]Can't agree with you more! If that's how I came across, I sure did not mean to! I can say for certain that none of the major AS programs take that view either. In fact, their findings are remarkably consistent that, although a clear majority of well-selected and monitored AS patients will do very well with the program and appear to be able to stay in it long term, with the goal of staying until the end of their lives due to death from other causes, a substantial minority - around one third, will turn out to have more aggressive cases and will need timely treatment.

But this is a key point: the major AS programs (and I) are convinced that you can predict a reasonably strong likelihood that a low-risk case will stay low-risk, and also that you can be highly confident that you will be able to identify in time emerging cancer aggressiveness (or under-the-radar aggressiveness that was there from the start) with good monitoring; "in time" means in time to get one of the therapies that intends to cure the patient with likely odds of success in avoiding recurrence that are about the same as for those getting immediate treatment.[/COLOR]

I wonder whether anyone can make that call. As far as I know Dr. Scardino of Sloan-Kettering still uses the rule of thumb that there's a 50% probability of P.C. metastasizing when PSA reaches or exceeds 10 ng/ml.

[COLOR="darkgreen"]Bob, would you mind rechecking what Dr. Scardino has said about that? I'm thinking you have in mind local spread and invasion beyond the prostate capsule, rather than distant metastasis, where the cancer needs to hitch a ride in the lymph or blood systems. In contrast, I've heard (recollection here - not verifying) that it takes a PSA of around 100 before there is around a 50/50 chance of distant metastasis. The good news here is that external beam radiation, with or without hormonal blockade, can still be curative with prostate cancer that has broken through the prostate capsule.

Of course a concern about exceeding a PSA of 10 makes sense if you are do not want radiation and are highly interested in having surgery or cryo surgery, seeds alone, or any other strictly "local" treatment, since you need to have the cancer contained in the prostate if such local therapy is going to be curative.

That thinking about the importance of not exceeding 10 is based on the very well-known and probably universally used Partin Tables, developed by Dr. Alan Partin of Johns Hopkins. Let's take a look at what the tables say (version as of 2002 in my book (the "Primer"), which used the "new" 2001 version of the tables. For those who don't know, the Partin Tables predict the odds of post-surgery pathology results for OC (cancer that is confined to the prostate - what we hope to have), CP (cancer that penetrates the prostate capsule), SV+ (cancer that is already in the seminal vesicles), and LN+ (cancer that already involves the lymph nodes). The tables base the prediction on three factors: the PSA (broken into ranges of 0 - 2.5, 2.6 - 4, 4.1 - 6, and 6.1 - 10); the Gleason Score (ranging from 2 - 4, 5 - 6, 3+4=7, 4+3=7, and 8 - 10); and the Clinical Stage (based for the tables solely on the Digital Rectal Exam, with separate columns for stages T1c - the tumor cannot be felt, T2a - the tumor can be felt but involves half of a lobe of the prostate or less and does not extend beyond the prostate capsule (none of Stage 2 extend through the capsule), T2b - the tumor can be felt and involves more than half of one lobe but not both lobes, and T2c - the tumor can be felt in both lobes of the prostate; higher stages are not given because for stage T3 the tumor has already penetrated the prostate capsule so surgery alone would not cure the cancer).

I'll just recap here the table numbers for patients with Stages T1c and T2a, because major AS programs will usually recommend against deferring treatment to Stage T2b and T2c patients, and I'll also limit the recap to PSAs up to 10 and Gleason Scores of 5 or 6 basically for the same reason, and for simplicity because Gleason Scores of 2 - 4 are very uncommon these days and such patients have even better odds than Gleason 5 - 6 patients. (This is from the book "A Primer on Prostate Cancer - The Empowered Patient's Guide, Strum and Pogliano, pp. C1-C6.)

For PSAs ranging from 0 - 2.5 ng/ml & Gleason Score 5-6,
here is the percentage of the finding occurring:

Finding.....T1c.....T2a
OC............90......81 (Very high odds cancer is confined)
CP..............9......17 (Fairly low odds of penetration)
SV+...........0........1 (Virtually no chance SV involvement)
LN+...........0........0 (Virtually no chance nodes +)
----------------------------------------------------------------
For PSAs ranging from 2.6 - 4 ng/ml & Gleason Score 5-6

Finding.....T1c.....T2a
OC............84......71 (High odds of organ confinement)
CP............15......27 (Low odds of capsular penetration)
SV+...........1........2 (Virtually no chance SV involvement)
LN+...........0........0 (Virtually no chance nodes +)

----------------------------------------------------------------

For PSAs ranging from 4.1 - 6 ng/ml & Gleason Score 5-6

Finding.....T1c.....T2a
OC............80......66 (High/favorable odds of confinement)
CP.............19......32 (Fairly low odds of penetration)
SV+............1........1 (Virtually no chance SV involvement)
LN+............0........1 (Virtually no chance nodes +)

----------------------------------------------------------------

For PSAs ranging from 6.1 - 10 ng/ml & Gleason Score 5-6

Finding.....T1c.....T2a
OC............75......58 (Strong or better than even odds)
CP.............23.....37 (Fairly low odds of penetration)
SV+............2.......4 (Extremely low chance of SV +)
LN+............0.......1 (Virtually no chance LN involvement)

While these Partin Table odds of the patient's chances of organ confined disease with no spread range in favor from outstanding to substantially better than even, the AS programs actually can see the odds even more clearly. That's because the Partin Tables look at the big three - PSA level, Gleason Score and stage, but not at other factors the AS programs consider, such as PSADT, PSA density, number and percent of cores that are positive, free PSA score, and so on. You can see how the AS programs can greatly refine the odds that a man will be able to do well in an AS program.

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My fundamental skepticism of scientific advocates has me looking behind the published studies promoting AS for underlying agendas i.e. economic in the Canadian example or in J.H.'s case, consistent with their well known age based patient selection bias.

[COLOR="DarkGreen"]I too think we need to keep that grain of salt handy when reviewing scientific reports. However, I have read some of the reports from Canada and they strike me as sound in methodology and diligence, which is more than I can say for many studies. I'm also impressed that they are claiming impressive success rates, but they are not claiming sky-high success rates; that seems realistic based on what is known about the disease in low-risk patients. As for John's Hopkins, an institution that rejected me as a surgery patient (Thank God! - didn't know much then about how challenging cases limit options!), they see their position as not wanting to do surgery unless it will have a good chance of giving the patient a substantially favorable balance of benefits to side effects, and age and other health conditions play in that balance as well as the details of the patient's prostate cancer.[/COLOR]

Deferring treatment is a completely reasonable course for the truly older(physiologically as well as chronologically) and otherwise health compromised patient where the risk obviously outweighs the potential benefit of aggressive treatment. However for the younger healthier population it simply delays the inevitable for a few years and possibly to a time when surgery or other primary treatment will no longer be as effective or uncomplicated.

[COLOR="darkgreen"]Your "however" sentence is where the AS programs see the prospects for low-risk prostate cancer as bright instead of gloomy, but I suppose it is a "glass half full versus a glass half empty" kind of issue. While the necessity for treatment becomes inevitable for some of us, the major AS programs believe they can make good estimates of who those patients are, and which other patients have an excellent shot at deferring the need for treatment for many years, with a solidly based hope of deferring treatment for the rest of the patient's lifetime. :D :jester: :cool: They definitely believe that low-risk prostate cancer does not "inevitably" become a risk to life or welfare for all patients. What do you think of the evidence from the major AS programs that a clear majority of AS patients have been able to stay in the programs since the time when the patients joined the programs? (I've put a table with some key data below.) For some patients in AS programs, that means since 1995, as at least two of them were started in 1995, and one started in 1993; thus, some of the earliest patients have now been in the programs for 14 or more years and their cancers still show no indications of being anything but insignificant.

After a patient has been in an AS program for just one year, most of the AS programs are able to grind down the odds assessment much more finely, as they then have in hand a follow-up biopsy, as well as 6 and 12 month PSA scores and DREs, and they may have other observations and tests as well. Those assessments become even more precise when a patient has his second followup biopsy at the two year point, usually meaning there are three biopsies in the file (baseline, first year, and second year). The AS programs have been able to analyze their multiple biopsy statistics and get this additional combined clue for forecasting long-term success. Based on their AS patient databases of perhaps several hundred patients at each institution, as well as parallel data from other major AS programs, they have an excellent view of whether the patient is likely to be basically stable for the next follow-up period or is approaching the point where the cancer needs treatment soon so that it will not become incurable. In 2008, a number of leaders of AS programs and other researchers published a joint paper that highlighted key methods and findings. One of the tables they presented gave results from five programs. Here is a summary:

..................Patients.........Average........Percent
Program.....Reported.......Followup........Treated

UCSF.............321...............24.................21%

Klotz..............299...............64.................34%
Toronto at Sunnybrook (started 1995)

Hardie...........320...............23..................31%
Royal Marsden NHS Trust and Inst. of Cancer
Research, Sutton, Surrey, UK (started 1993)

Warlick...........80................42..................14%
Johns Hopkins

Patel..............88................44..................35%
Scardino, Memorial Sloan-Kettering, files

The arithmetic works out to a weighted (by percent of patients) followup of 37.36 months - more than three years. But what I find most impressive is the average followup of 64 months - close to 5 1/2 years, from the Klotz series at the U. of Toronto, Sunnybrook. Now the "average" in this table is the "median," meaning that half the patients fall below the value, and half above. That means that the Klotz series had, at the time of the study, about 150 men with longer followup than about 5 1/2 years in its series that started in 1995. Just about 1/3 (34%) had needed to be treated or later chose treatment, leaving 2/3 (66%), or about 197 men still in the program.

It does appear that problem cases - those that reveal themselves as more aggressive, can usually be spotted in just two years or so. If a patient makes it past that point - which typically includes the second follow-up biopsy, he has a significantly better shot at staying in the program long term. If he doesn't make it past that point, he is (1) getting treatment only two or so years later than he otherwise would have, (2) he has been monitored carefully and maintained his excellent chance for successful curative therapy, (3) he has maintained his quality of life for two or so additional years without having to bear the potential burdens an side effects of treatment, and he has gained the extra time during which therapies are likely to have continued to improve, giving him better options. :cool:

Probably the key issue in AS is, as you put it, whether it delays therapy "to a time when surgery or other primary treatment will no longer be as effective or uncomplicated." As results accumulate for the AS programs, it is looking more and more like a curative option is preserved. The other thread is a better place for those details. But that leaves a couple of questions in my mind for patients, especially younger patients: for those patients in AS programs who are determined to need therapy, for what percentages are the local options still open (surgery, seeds, cryo surgery) compared to the percentage needing radiation therapy that can reach beyond the prostate to achieve cure, and what percentage of these patients needing therapy will be able to have successful nerve sparing surgery compared to surgery that cannot spare the nerves. My recollection is that most of the patients who do have treatment in the AS programs choose surgery. I have seen no figures on nerve sparing success for those patients.
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Utilizing one's curative window is in my opinion too precious an opportunity to gamble on the odds derived from studies whose conclusions could be challenged or overturned tomorrow.[/QUOTE]


[COLOR="darkgreen"]I think I would see it the same way if there were only one or two small, short-term studies about AS, or if the success results were marginal or inconsistent among the set of major AS programs. To me, as of 2009, the accumulating evidence looks much too broad-based, long-term and consistent for there to be any risk that it will be overturned tomorrow, let alone in the next decade or ever. :cool: Are you aware of any serious challenge to the AS research? The only prominent physician specializing in prostate cancer that I know of who seems to be uncomfortable with the option of deferring therapy is Dr. William Catalona, a great prostate cancer surgeon and researcher. However, I haven't looked into the details of his views, and I'm thinking he may have become a supporter of AS in recent years, because of the accumulating evidence. If you know such details, or of a serious challenge to AS, would you mind telling me about it?

Take care,

Jim :wave: [/COLOR]





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