Showing posts with label Patrick Walsh. Show all posts
Showing posts with label Patrick Walsh. Show all posts

Friday, August 9, 2019

Yes, "Every Cancer Patient Is 1 In A Billion" -So Why Can't Some Of Us Just Co-Exist With The Cancer?



Robert Nagourney ('Every Cancer Patient Is One In A Billion',  WSJ,  July 22, p. A15) is correct when he writes:

"We now know that cancer is a disease of altered cell survival, not excessive proliferation. That is, cancer doesn’t grow too much, it dies too little. Applying cell kinetics, we can trace a newly diagnosed colon cancer back to its first cell. This reveals that a cancer that has spread to the liver by the time it’s diagnosed may have its origins some 30 years earlier yet remain undetectable with current diagnostic techniques for well over two decades. The same holds true for pancreatic, lung and other tumors. By the time many patients are diagnosed, they have unknowingly lived more of their lives with cancer than without. "


Which knocks out  the trope that cancer is an "uncontrolled over growth" of cells. In reality, it is cells not 'clocking' out and dying on schedule.  Let's go to the image shown at the top.  This highlights what happens to a cell when a specific protein (p27) messes up its death- cessation time.  To be specific, in one particular shape the protein prevents cell division, in another it won't.  In the latter case there is the potential for what we call cancer - the cell ceasing to terminate.

 Given a cancer can take decades to be detected it begs the question that if this is the case then why not just allow for continued co-existence? Say as opposed to carving it out - leaving much damage in the wake, or burning it out (by radiation), or freezing it out, e.g. by  insertion of cryotherapy probes at -90F ,


Why not just live with it and done?  Well, because to most cancer patients it represents an 'invader' and foreign invaders are not to be tolerated. So one carves, burns or freezes them out. But if they've already been there for years, maybe decades, then why not let them remain longer- so long as these cells don't pose mortal threats - say invading critical organs?

Hell, advanced prostate ("metastatic")  cancer patients already do this once the cancer has resisted all standard treatment approaches and therapies - as indicated above.  They snatch extra years by resorting to hormone treatments  such as androgen deprivation therapy (ADT) generally suppressing testosterone - the key "food" for prostate cancer cells, see e.g. .  

https://www.youtube.com/watch?v=KtIfsvQh2qI


This is despite there being a faction of cells known as "hormone treatment insensitive" that keep on growing.  As pointed out  by Hopkins urologist Patrick Walsh in his book Dr. Patrick Walsh’s Guide To Surviving Prostate Cancer’. p. 338):

"Hormonal therapy does two things: it stops cells from making PSA, and it shrinks the hormone sensitive cell population.  Thus, a man's PSA falls and it takes longer for his bone scan to become positive for metastases.  But it doesn't stop the clock. The hormone insensitive cells keep right on growing silently."

But the main issue for the advanced patient is to prevent the "mets" as seen in the PET scan below,  from wreaking havoc by spreading to major organs:
No photo description available.
From getting out of control, causing bone fractures and the like or getting into critical organs like the liver.

Nagourney's other point is equally important (ibid.):

"Cancer cells are normal cells that distort physiologic stress responses to succeed under conditions of deprivation. Drawing on genetic elements, either mutated or normal, they configure a new biology: the cancer phenotype. Since there are some 1,000 cancer-related genes and each cancer requires up to three distinct gene alterations to succeed, every cancer patient is literally one in a billion. It’s reminiscent of Tolstoy’s observation: “All happy families resemble one another, each unhappy family is unhappy in its own way.”

Note the numbers:   1,000 cancer-related genes, and up to three distinct gene alterations to succeed.   Do the combinatorial math and every cancer patient is like a 1 in a billion manifestation.   This belies the "manfiest complexity" of the disease as Nagourney puts it but also indicates the "one size fits all" treatment response to most cancers (e.g. surgery, chemo, radiation) is passe.  This is given the one size fits all template is based on the error of applying population statistic to an individual for whom the gene(s) involved and alternations call for something totally different.  As the author describes the situation:


"The physician’s role is to discern what makes each patient unique, but few take the time to find out. While gene profiling offers hope, cancer has proved much more complex than the sum of its genes. The study of human tumors at the tissue level suggests that it may be possible to reverse-engineer the process by moving away from top-down genomic analyses toward bottom-up cellular studies. The Physical Sciences Oncology Network is applying physical principles to cancer medicine to explore the dynamics of human tumors in three dimensions. One concept is that in select patients less may be more, since responses can be prolonged using intermittent dosing.

Cancer-cell defenses can now be examined in the laboratory by using drugs, gene-targeted agents and inhibitors of cellular metabolism to probe human tumor biology. We can ask: What cell survival process is your cancer using? More important: Can it be targeted therapeutically? If the answer is yes, and a drug or combination is identified, the patient would likely respond favorably—twice as likely in fact. But if the answer is no, treatments would be more likely to cause suffering without benefit."

Which is sad.  The last is especially germane whether we're talking about a patient like my brother Mike (who died in June last year) offered chemo and radiation to get "a few months" more from stage 4 liver cancer, or a prostate cancer patient having to make the choice to get hormone therapy to extend life - even at the risk of getting Alzheimer's disease.    These considerations have been raised in a forthcoming  book ('The First Cell, and the Human Costs of Pursuing Cancer to the Last') by Dr. Azra Raza

 Most telling is the author's response to one cancer patient for whom a 2-drug chemo combination had provided a remission that's lasted ten years. When the patient asked him "You mean I'm not going to die?"  He responded:  “No,  you’re not sick. You just have cancer.” 

In other words, having cancer and dying from it may actually be two mutually exclusive propositions.   The trick is to decide or determine which one applies in the case of a  particular individual.  For my own part I have decided for the time being to live with the existing cancer given I am asymptomatic.  At such time that changes, say manifesting in bladder obstruction or bone pain, then it will be time to go the ADT route.  But I am hoping that can be postponed as long as possible!

See also:

Cancer Treatment at the End of Life- 

https://www.nytimes.com/2019/08/05/well/live/cancer-treatment-at-the-end-of-life.html

Excerpt:


"Although slightly more than two-thirds of cancer patients treated in the United States are cured, this is mostly the result of early detection and combinations of surgery, radiation and chemotherapy treatments developed decades ago, Dr. Azra Raza, director of the Myelodysplastic Syndrome Center at Columbia University, wrote in her forthcoming book “The First Cell, and the Human Costs of Pursuing Cancer to the Last.” In fact, experts suspect that some cancers discovered through early detection would never have become fatal even if they had not been treated.....As Dr. Raza wrote, most new cancer drugs add mere months to a patient’s life at an agonizing physical and financial cost

The decision today is more complicated that in decades past because some modern treatments are less toxic than traditional chemotherapy and because there are now ways to counter, though not necessarily eliminate, the devastating side effects of many treatments."

And:\

Latest Medical Finding: Hormone Treatments Put Pr...

Tuesday, July 9, 2019

Latest Medical Finding: Hormone Treatments Put Prostate Cancer Patients At Higher Risk Of Alzheimer's Disease

Brane Space: Latest Medical Finding: Hormone Treatments Put Prostate Cancer  Patients At Higher Risk Of Alzheimer's Disease
PET-scan showing extent of bone metastases in a prostate cancer patient. Each dark area represents actual prostate cancer cells, i.e. in the spine, pelvis, neck etc.  Such evidence would definitely indicate the need to begin ADT or other hormone therapy.

As I noted in my June 3rd post, as a prostate cancer survivor unsure of how many years he has left, or what the disease is doing now (though the last PSA test did how the velocity slowing  from 0.21 ng/ml / mo. to 0.12 ng/ml/ mo.) I am trying to take an open minded approach combined with a realistic one.  Basically this means (and my wife and primary care doc agree) postponing any hormone treatments until I become symptomatic.   This decision actually was based on advice from leading Hopkins urologist Patrick Walsh, in his book Dr. Patrick Walsh’s Guide To Surviving Prostate Cancer’.


Therein he wrote (p. 338):

"If you have metastases to bone, bone pain, or a large mass of cancer that is obstructing your kidneys or bladder, you need to start ADT right now.    In this situation it's the right course of action - one that can make a huge difference in your quality of life and can protect your body from the ravages of cancer.

But what if you have no cancer in your bones  and no sign that anything is wrong except a rising PSA level after surgery or radiation - or the presence of cancer in your lymph nodes- and you feel fine?   Many doctors would advise you to start hormonal therapy as soon as possible.  Others - and I'm in this group - believe that in most cases there is no evidence that starting hormonal therapy immediately, as opposed to later, will prolong life.

Hormonal therapy does two things: it stops cells from making PSA, and it shrinks the hormone sensitive cell population.  Thus, a man's PSA falls and it takes longer for his bone scan to become positive for metastases.  But it doesn't stop the clock. The hormone insensitive cells keep right on growing silently."

The last sentence makes an important point, and as Dr. Dr. Walsh goes on to elaborate:

“A drug or hormone therapy that targets only one kind of cell won’t have any effect against another variety so the one size fits all approach doesn’t work here. Plus some of these cells have learned to be resistant and to grow in the absence of male hormones…so the drop in PSA may be misleading. These are called androgen independent or androgen sensitive cells.” 

 Adding:


“When male hormones are shut off, the PSA making process may indeed stop, but this doesn’t mean the cancer cells are dead or have stopped growing.”

Now, a study out of the University of Pennsylvania’s Perelman School of Medicine supports this recommendation by Dr. Walsh.  The study, in JAMA Network Open, included 154,089 men whose average age was 74 and who had diagnoses of prostate cancer. Of these, 62,330 received ADT  and the rest did not. The study found a link between drugs commonly used for hormone therapy and an increased risk of developing dementia.as well as Alzheimer's disease.


The study adjusted for socioeconomic status, age, race, severity of prostate cancer and other factors.
The lead author, Ravishankar Jayadevappa, an associate professor at the University of Pennsylvania Perelman School of Medicine, said that for advanced cancer, ADT. can be a lifesaving treatment and should not be avoided because of any increased risk for dementia. But, he said, “Patients with localized cancer should be looking at the risks of dementia, and possibly avoiding A.D.T.”

I totally concur with that but with the additional proviso: that patients with NO  evident symptoms should also be looking at the risks, and not just from cognitive disability.  With diabetes running in my family, and having seen its ravages, I can't simply adopt a therapy to fight a cancer while not recognizing the other - perhaps greater- threat.   (Currently, through the use of diet I am keeping the a1c and blood glucose under relative control, but it's still rated as "pre-diabetic")

Back to the UPenn study:  In an average follow-up of eight years, the scientists found that compared with men who had no hormone therapy, one to four doses of ADT was associated with a 19 percent increased risk for both Alzheimer’s disease and other forms of dementia, and the risk increased with the number of doses. At five to eight doses the increased risk was 28 percent for Alzheimer’s and 24 percent for other dementias.  Since most advanced prostate cancer patients are given doses every 6 months, and this could go on easily for 5 or more years, that threshold is easily crossed.

Further, the  University of Pennsylvania researchers found that 22-percent of prostate cancer patients who received ADT were later diagnosed with dementia compared to 16-percent who did not receive ADT. As well, 13-percent of ADT recipients developed Alzheimer’s disease compared to 9-percent who did not receive the hormone therapy.

Though this hormone-blocking therapy - first discovered in the 1940s -  has been proven highly effective for slowing prostate cancer, it comes with a number of risk factors including:  increased risk of depression, strokes, diabetes, cardiovascular disease, bone density loss (with attendant fractures)  and progressive cognitive decline.

The UPenn study was cited by at least one member of the prostate cancer survivor's group to which I belong, as he wrote:

"This study has convinced me that I'd rather die from prostate cancer than take ADT overly long and get dementia or Alzheimer's!"

An extreme statement but I agree with him, after seeing the ravages of Alzheimer's and dementia on three close family members (Krimhilde, my sister-in-law, the most recent).  So, as I told my primary doc I plan to postpone beginning ADT until I become symptomatic, and then plan to cut it off after  6- 12 months by which time the most PCa grievous symptoms should subside and before profound cognitive incapacity arises.

This news is definitely a wake up call for prostate cancer patients, many of whom are pushed into hormone therapies much too early - and often as an accompaniment of other treatments, i.e. radiation.

See also:

https://www.youtube.com/watch?v=KtIfsvQh2qI

And:

https://www.pcf.org/c/adt-what-you-really-need-to-know/