IADT3since2000

We have a closely related thread now ongoing - "Effectively Preserving Curative Options- Active Surveillance for Prostate Cancer" - in which the role that the patient's age makes has come up in discussing the decision whether to pursue Active Surveillance (AS) for prostate cancer instead of immediate treatment. I hope that discussion continues, but because age is such an important factor in the thinking of the major Active Surveillance programs in the US and world, and because their approaches differ substantially, I thought it deserved a separate thread.

Here's the essence of what I know about it: while most AS programs strongly prefer older patients, at least one is comfortable with patients who are at least 55 years old, and at least one will take truly low-risk patients of any age, and that program is led by a doctor who is arguably the leading guru for AS. He also has a well thought out rationale for his position.

Most of the AS programs prefer that their patients be older, with the later 60s and older considered ideal. On the flip side, for older men and those with significant, likely life-shortening other health conditions, the major AS programs are willing to go with higher-risk case characteristics. This is all kind of logical - the risk of treatment versus benefit of treatment balance is tilted toward higher risk and lower benefit for older patients with low-risk cancer. Obviously, if you are 70 years old and have a prostate cancer that is very unlikely to become a serious threat or burden on your life for at least 30 years, but with a risk of side effects of treatment that can be substantially higher and more intrusive and burdensome for many men as they become elderly, the net likely value of getting treated declines. Similarly, if a man has, for example, diabetes that is difficult to control and serious heart problems, especially if he is elderly, a low-risk case of prostate cancer is not likely to be a significant threat to his life or well-being, and possible complications from prostate cancer surgery (such as blood clots) or other treatment may seriously aggravate other health conditions . There is strong agreement among the AS programs that AS is a highly attractive option for such men.

But the real issue, still controversial and without an abundance of information yet, is what to do about younger men who have case characteristics that all suggest very low risk prostate cancer. Now that many men are being screened with PSA and DRE exams at a fairly young age, it is increasingly likely that men will be diagnosed with cancers that would never have affected them in their lifetimes and would not have been noticed except for the screening. I'm expecting that many more younger men will be screened because the prestigious and influential American Urological Association just revised its guideline to recommend that all men be screened by age 40, with even earlier screening for men at high risk, such as by having a couple or more "first-degree" relatives (like fathers, brothers) who were diagnosed with prostate cancer, especially in their 50s or earlier. I'm expecting that an increasing number of men with very low risk prostate cancer will be diagnosed in their early fifties, forties or even thirties.

I got some insight into this issue when I attended the IMPaCT Conference ("Innovative Minds In Prostate Cancer Today"), held in Atlanta in September 2007. Attendees were invited from among the researchers whose research projects over the past ten years had been supported by funds from the Congressionally Directed Medical Research Program (US tax dollars) managed by the Department of Defense for the Government, from among survivor representatives (like me) who had helped evaluate proposals for at least two years, and from prominent prostate cancer scientists and physicians. One panel discussion included three representatives from major AS programs, Dr. Laurence Klotz from the U. of Toronto (Sunnybrook), Dr. Fritz Schröder from the Erasmus University Medical Center (Netherlands), and Dr. Christopher Warlick, recently from the Johns Hopkins program, but having moved to the University of Minnesota. After each commented on their AS program, I got to ask what minimum age they looked for in their patients, mentioning that I had read that Dr. Schröder's program was comfortable with men as young as age 55. The question stirred a lively discussion among the panelists.

I thought that the Johns Hopkins program under Dr. Carter focused on patients in their mid-60s or older, but Dr. Warlick said that 44% of their program participants were younger than age 65, with the age ranging from 46 to 82, with an average age (median: half older, half younger) of 66. My impression is that most of the major AS programs have preferences for age that are similar to the Johns Hopkins program, targeting men in their 60s, especially latter 60s, and older.

Dr. Schröder confirmed that his program had an age minimum of 55. He also said that about 500 patients were now in his AS program.

However, Dr. Laurence Klotz, from the University of Toronto, Sunnybrook, really caught the audience's attention when he stated that he was comfortable with prostate cancer patients of any age for AS, but adding that the Toronto program takes an even more detailed look at risk factors and does even more observant monitoring for younger men, at least at in the patient's early years in the program.

Of course I cannot speak for Dr. Klotz, but, having heard him on the panel, having listened to and studied one one of his talks, and having read some of his papers, I can give an informed estimate of what his program would do with two young example patients, both 37 years old, who would be considered to have apparently low-risk prostate cancer based on the usual key combination of PSA, stage and Gleason Score. Let's say both got early prostate screening exams because of a mild concern with family history of prostate cancer, and based on some concern because of the DREs, coupled with their PSAs which were elevated compared to norms for their ages, both were given biopsies. Both patients have a PSA of 2, have Gleason Scores of 6 (3+3) confirmed by expert pathologists (with no other concerns in the biopsies), and are Stage 2a (can be felt in the prostate, but only in half a lobe or less). Patient A has a PSA that increased from 1.8 in a baseline test, to 1.9 a year later, and 2.0 the next year. Only one of 12 cores was positive, with cancer in only 5% of the core. His free PSA reading was 20%. Patient B has a PSA that increased from .4 in a baseline test to 1.0 a year later, and to 2.0 a year later; 3 of his 12 cores were positive for cancer, with percentages of cancer of 25%, 40% and 45% in the three cores; his free PSA test value was 16%.

Careful patient selection is key to all AS programs, but especially for younger patients in the Toronto program as described by Dr. Klotz. It's clear to me that Patient A is very low risk in all key case characteristics, but that is not at all true of Patient B. Consider the PSA doubling time PSADT(velocity). Patient A has a favorable encouraging PSADT of 13.17 years - think about it: it's going to take his PSA 13.17 years to double! - (158 months), or .1 ng/mL of PSA per year. Assuming the rate stays constant, as is typical, starting from a PSA of 2.0 at age 37, he will be 50 before his PSA reaches 4.0, about 63 before it reaches 8.0, 76 before it reaches 16.0, and 89 before it reaches 32.0. (Twenty percent of patients in the Toronto program have PSADTs of 100 years or more, as I recall the figure! ) In sharp contrast, Patient B has a rapid doubling time of just 10.34 months! When he is still 37 it could have doubled to 4.0, climbed to 8.0 when he is 38, to 16 when he is still 38, to 32 when he is just 39 (60 years earlier than for Patient A), and so on. And let's not forget the biopsy cores: even though just 3 cores are positive for Patient B, none exceeding 50% cancer in any core, which are numbers that look decent for the average low-risk patient, that is not such a good picture for a very young patient. The free PSA percentages, used in the Johns Hopkins program, might also help project the courses for these patients. Patient A has a free PSA that is close to that for men with healthy prostates; in contrast, while Patient B, at 16%, is above the 15% threshold that triggers concern at Johns Hopkins, he is close to that threshold.

As I understand it, the Toronto program would probably be comfortable with Patient A as an Active Surveillance patient; in accordance with their policies, he would be given extra monitoring in the early years, compared to that given to older AS patients, to make sure his prostate cancer was behaving in a way that lined up with the early favorable clues. In sharp contrast, I believe the Toronto program would strongly recommend treatment in the near future to Patient B. In fact, unless an older patient like Patient B, with his fairly rapid PSADT, had a relatively short life expectancy, I suspect the Toronto program would recommend treatment to him, too.

Dr. Klotz makes the reasonable and generally accepted point that careful screening of men at relatively young ages, followed by efficiently done 12 core (or more biopsies), is going to pick up some small cancers that some of these men would not have noticed for their whole long lifetimes if they had not had screening. However, he also maintains the position that we now have the ability to actively surveil these cancers and provide timely, highly effective treatment if they become aggressive. The Toronto program is finding that the chance that prostate cancer will suddenly become very aggressive for truly low-risk men is extremely remote, as I understand it. The program is also finding that many men are enjoying the benefits of AS for long years. All that makes good sense to me, but I'm sure many of us hope his program will do a special report on how well younger men have fared.

While all the heads of the major AS programs are highly respected, well-known physicians and medical leaders, I've heard several expert doctors say that Dr. Klotz is arguably the leading expert in AS. For me that makes his position regarding the minimum age carry extra weight.

Jim