The Case for Progression in Untreated Prostate Cancer

These days there is a national reaction to over diagnosis and over treatment in the prostate cancer world. The reaction has been to not recommend the PSA test in asymptomatic men. Fortunately many still believe in its value, but unfortunately, prostate cancer can progress without symptoms and in adopting such recommendation, if successful, it will lead to diagnosing PCa at more advanced, more difficult to treat stages of the disease. With longer male life expectancy there is a high probability that disease mortality will increase.

No question that there is a need to educate both patients and their physicians in the biology and the potential for prostate cancer to progress. The true natural history of untreated prostate cancer has not been clearly exposed to the population There is a long history to refer back to in places where localized treatments were seldom used after a PCa diagnosis. Why are they mostly ignoring that history? See here:
www.healingwell.com/community/default.aspx?f=35&m=2230814

Here at the Mayo Clinic a noted PCa pathologist (Dr. Bostwick) did a PCa progression study in men with incidental adenocarcinoma detected at the time of the transurethral resection of the prostate (TURP). It showed that with time the disease dedifferentiated and patients progressed to more aggressive cancers. This is a significant study. See here: jnci.oxfordjournals.org/content/90/14/1105.2.full

Before the introduction and commercialization of the PSA test PCa was mostly diagnosed at the presentation of symptoms. Before the commercialization of the PSA test, in the absence of symptoms, physicians had a positive digital rectal examination (DRE) and later an elevated prostate acid phosphatase (PAP) test to trigger a manual transrectal biopsy. If the biopsy was positive a bone scan was prescribed to determine the stage of the disease. Prior to the widespread use of the PSA test 70% of men diagnosed with prostate cancer were diagnosed with advanced stages of the disease. Now, because of more frequent use of PSA and DRE, 70% of men are diagnosed with earlier stages. There is no question that PSA and DRE are responsible for this shift in stage at diagnosis.

If such is the case and more men these days are diagnosed with earlier stages of the disease it is understandable that in the absence of the PSA test or any testing, the stage at diagnosis will increase and revert to the recent past level. If this really happened here some 20 years ago how can anyone support that the great majority of PCa will not progress through different stages of aggressiveness from well differentiated to poorly differentiated in a huge number of cases when the disease remains occult and untreated? In other words, why without PSA testing the disease can progress and with PSA testing it doesn’t?

I would like for someone to provide a logical explanation why the PCa progression rate in the absence of PSA testing would be different 20 - 25 years ago to the present. Age at diagnosis cannot be ignored in this equation. It is fundamental. To believe that the process of dedifferentiation is not involved and that we are born and diagnosed with GS 6 that in most cases that will not progress (while untreated) is unrealistic and not supported by the natural history of untreated PCa or today’s clinical evidence.

I agree that most PCa is slow growing and in a good number of cases involving older men with a limited life expectancy, postponement or avoidance of treatment is an option. I am not so sure that the same is true for a great number of younger men with a life expectancy of 20 to 30 years. In the future with more supporting evidence (with more mature trials), such men can assume AS safely if those clinical trials show that there is little risk of progression and by they have better means to detect such progression than they have at this time.

The problem is that we are not there yet...at least not across the board. There is too much difference of medical opinion and too few studies with a high population and long followup to safely support AS in younger men (men in their 50s). Believe it or not AS should be a good option for many men if the process could be more generally supported by physicians. What is lacking is long-term clinical support and a well-defined protocol.

Do not take this post as an anti-AS one. It is a cautionary post for many newly diagnosed young men that come to HW these days. As more well populated trial results mature we will have more certainty in promoting AS for younger patients. We are not there yet...

RalphV

"Prior to the widespread use of the PSA test 70% of men diagnosed with prostate cancer were diagnosed with advanced stages of the disease. Now, because of more frequent use of PSA and DRE, 70% of men are diagnosed with earlier stages. There is no question that PSA and DRE are responsible for this shift in stage at diagnosis."

Ralph, I think the main reason at least for this statistic is the shear increase in the number of people whom have been diagnosed. Prior to the PSA testing era, less than 70k men per year were diagnosed. But today we see 230k men per year are diagnosed. Mostly earlier. So in agreement with your point, it is important to acknowledge that the PSA test has simply found more men with asymptomatic disease and that there has been little increase of symptomatic cases, at least by general population percentage. Still your point is valid though. We have seen that 40% decrease in the men actually dying from PCa and it is in part because of screening. Other factors for the decrease in mortality rates are that we do indeed have better treatment options. But still many options would not work well if they were not utilized while we have a local versus systemic disease. So from a standpoint in support of screening, we can benefit from screening, and from a standpoint of over treatment or over diagnosis, we can really counter the USPSTF recommendation with restraint, and better tools in the future...

All the best, sir. You are still one of my heroes and always will be...

Tony

David,
There are many men that won't process that data well. While in the management of tumors the earlier the better is always best. But managing the human is vitally important. Still I side with screening, but not all men will benefit from it, in fact most won't. And I acknowledge that fact. But most men diagnosed early will and that too is a fact. But I really press onward for a better screening method and that's where the ball lies with screening for PCa.

Tony

tony, liked your answer, but what did you mean, "many men that won't process that data well". what data?

I want better screening tools developed too, to tell indolent from aggressive from day one, that would help on the overtreatment side of the equation.

david

David,
As a live support group leader I have met many men that were diagnosed with minute detection of PCa and they not be able to cope with that Dx. Calling me a 2:00am fearing that they are dying and yet they are clear candidates for taking their time and learning before they rush to treatment. Their QoL sapped by fear of the worst possible scenario with the data they have processed. Conversely, many men make irrational treatment decisions based on "surface" data that needs to be further analyzed and options fully understood.

Tony

tony,

got you now. sometimes I miss the obvious.

thanks

david

Tony,
The point in question is not the difference in incidence between the time that PSA was not available and the time it became available. The PSA test has increased incidence. The point I am making is the difference in the stage of the disease at diagnosis. In the past, the cancer progressed silently until it presented some symptom. By then, the cancer was advanced and typically more difficult to treat. BTW, in 1985 the incidence rate was 115/100K and now is 150/100K. No doubt that PSA testing is the cause.

The shift in stage at diagnosis is another matter. When no disease marker is available, the disease can progress undetected(if not symptomatic) to a more advanced stage. That is why some 25 years ago most men (the cited 70%) were diagnosed with advanced PCa. The opposite is true today when early detection is available. The point of my post is that disease progression cannot be easily ruled out when men are diagnosed young and hear that GS6 does not progress in most cases when untreated. I do not think that this has been clinically proven at this point in time. Remember we are talking untreated PCa here. Did you read Dr. Bostwick’s study cited in the original post? He concluded:
“In summary, men with untreated stage T1a prostate cancer are at risk of clinical progression of cancer”

Many men with progressive PCa do not die of the disease, but progression has health consequences that are typically ignored. It is not only the dying of the disease, but what the disease can do to patients while progressing. As science improves survival for coronary/vascular disease, diabetes and other diseases associated with age that kill men prematurely, more men will eventually die of PCa. Counting on those diseases should not be an excuse to prevent a PCa death...

Keep up your good PCa work at the National level!

RalphV

Ed [oops I said Ralph at first],
I'm saying that not knowing is better for some guys certainly not most. Anecdotally, I am the same as you. I was screened without knowing I was screened and for that I am thankful. I was so darn close to your case I took it a step or two further. I was advanced to the seminal vesicles and had the scraping to the rectum with a 4+3=7 case. In many ways I can argue that I wish I had been diagnosed sooner, but I wasn't. It wasn't in the cards for me. I was 44, and still in 2006, the doctor was working outside of guidelines in running the PSA test on a 44 yo man.

Ralph, you've been at this a long time as a wonderful live support group leader, and advocate leader since the early 90's. I know you have had to have heard somewhere along the way of men whom stated that they wished they had never been treated. Never been diagnosed even.

To me it hasn't been that rare of an occurrence.

I dunno. Maybe I just see a different fish to fry. We need better education for men. Better screening methods. Better the ability to understand the psychology of each man diagnosed and provide the necessary caring and support before he has goes into a decision. To go along with better therapies and better understanding of AS.

Maybe if every doctor entered a screening event with these thoughts in mind, the USPSTF stands idle about screening instead of recommending against it.

Tony

Post Edited (TC-LasVegas) : 3/12/2013 11:58:52 AM (GMT-6)

David,
In your reply the "for me" part is the key subject of my comments. We all can relate to our own experiences. We have a harder time adjusting to others experiences and perspectives. The understanding that what works for "me" does not always work for others come into play quickly and often when you run a support group.

I don't understand why my position on Dx and screening is an issue. I speak in support of early education of men to understand this disease. I speak in support, with a rational eye, of screening. But let's not argue the obvious. We need a better tool to deliver the indolent versus aggressive cancer. Anything else is subject to debate and I have my position in support of a better Dx.

Tony

Post Edited (TC-LasVegas) : 3/11/2013 11:48:30 PM (GMT-6)

Ralph, I always enjoy reading your thoughtful and knowledgeable posts.  Thanks for this latest, and I find myself in complete agreement with just about every point you've made. 

I'm sure there are some men, maybe a lot of  men, who, for a variety of reasons, regret being tested or "screened" for prostate cancer.  I imagine the same is true for other cancers as well. For example, I'll bet a lot of guys who get a bad result from a colonoscopy wish they had never submitted to that test.  Sure, they probably would have eventually died of colon cancer, but they would not have had to endure the re-section, the chemotherapies, and the other medical procedures that follow a diagnosis of colon cancer. 

Before anyone objects to that analogy, let me point out that I realize that a diagnosis of colon cancer is different from a diagnosis of prostate cancer, but my point is that we've all met guys who would rather deal with the disease, even if it leads to a shortened life, than put themselves and their families through the grind of cancer treatments.  Or, at least they profess that to be the way they feel.

Or, consider coronary artery disease.  If I'm told I have a vessel that is 65 percent blocked, where do I go from there?  Do I do nothing?  Do I insist on treatment?  Do I trust a regimen of diet and exercise to minimize the problem and keep my alive?  It's sort of the same dilemma faced by someone diagnosed with PCa, Gleason 6, organ contained.  Treat or not treat?  Know or not know?  Yet, while we would probably applaud the guy for getting his arteries roto-rooted out, we sometimes tell the Gleason 6 guy who chooses surgery that his decision was a knee-jerk reaction, made too hastily and without medical justification.  These are not easy decisions, and there are no clear "rights" and "wrong."

I've always been skeptical when I've read that a Gleason 6 does not de-differentiate into a Gleason 7 or worse.  That doesn't jibe with my very limited understanding of biology and cell activity.  I suspect cells do de-differntiate.  I have no proof of that, but my gut says it's likely true.

Maybe in a generation a lot of the questions we currently face will be answered, but we'll always have guys who will say, "I wish I hadn't found out I had prostate cancer."  That won't change.

tony,

couldn't imagine anyone arguing against better testing and diagnostic tools.

david

iSpark said...
My Uro told me that if I was 65-70 years old, he would not recommend any treatment for my G7 PC, and that I would most likely die of other causes before the PC killed me.

Since I was 47 at DX, he recommended treatment because in all likely hood I would live long enough that the PC would kill me.
He said I may have 10-15 years if I did nothing at all as far as treatment.

I think age plays a big factor in The Case for Progression in Untreated Prostate Cancer.

I'd like to be a fly on the wall when your uro tries telling a healthy 65 year old that it's OK not to have any treatment for his G7 PC because he'll last 10 to 15 years anyway!

We'd all LIKE to have done nothing, but what we'd prefer to do and what seems the smart thing to do are often two different things. Best of luck to you, James. At your age, you should come through the surgery fine and the side effects should be short-lived and extremely manageable.