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:

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...

Into The MRI Machine and Out - What I Saw, and Learned

Top: Image of MRI scan using 3T machine identifying possible carcinoma sites. Below right: MRI machine similar to the one I was in yesterday.


Yesterday afternoon I experienced my first MRI scan done as a prostate exam recommended by my oncologist in San Francisco.  This was after the post treatment PSA recently spiked to 6.0. See e.g.

http://brane-space.blogspot.com/2016/05/post-treatment-psa-spikes-to-60-not-so.html


In the wake of seeing these results the UCSF oncologist ordered an MRI exam, as opposed to a prostate biopsy and with good reason: given the tissues of the prostate have already been exposed to high dose (Ir 192) radiation, (1920 cGy) they will be scarred and much more susceptible to hemorrhage.

In addition, MRI technology has proceeded so markedly in the last ten years (due to what is called faster development of "echoplanar surfaces" - or MRI image slices) that the MRI can now actually find and grade carcinomas that occur there.  The key has been the development of  more powerful 1.5- and 3-Tesla scanners where Tesla refers to the magnetic field strength. (1 T = 10,000 Gauss). The machine that scanned my pelvic region was 3T or fifteen times greater than the magnetic field of the most powerful sunspots.

The result has been a quantum leap in signal to noise ratio (or "SNR") with the SNR increasing with magnetic field strength. Thus, the 3T (and 1.5T) machines  are ideally suited to the task of scanning for prostate lesions.

According to one radiology website:

"Current receiver coil technology includes pelvic phased-array coils with or without the addition of an endorectal coil. The endorectal coil adds approximately an order of magnitude to the available SNR  and also allows for the use of small fields-of-view (FOV) for some critical applications"

In other words, the radiologists conducting the exam seek ever greater enhancement of SNR by use or coils (pelvic phased and endorectal) by using ancillary devices that play the same role as a radio receiver or antenna. The pelvic array coil - which was used on me (at Penrad Imaging in the Springs) -is somewhat like one of those protective pads dentists put on you when taking dental x-rays except these are filled with coils to  receive radio frequency inputs from the MRI.  In the MRI case it is fitted snugly around your waist before you go into the machine

The endorectal coil is actually a thin wire inserted inside a balloon filled with 50 ml of air to fix the coil to the prostate for better reception of the radio frequency waves and superior SNR. However, much of the literature so far disputes these ERCs improve imaging that much over what an external pelvic coil delivers.

In my case, at Penrad, only the outer pelvic array coil was used not the ERC, and I was glad for that - given the use of the latter too necessitates having an enema first, then having the ERC inserted inside a condom. Thus, according to the same radiology site noted above:

"the endorectal coil is highly preferred, even though it adds discomfort, time, and cost to the MR exam"


Anyway, after arriving I was greeted by a young blonde woman who allowed Janice to accompany me and took my paperwork which included ensuring I had absolutely no metal artifacts anywhere in me (like implants or pacemakers) or on me. Next, I had to assure her I was not claustrophobic - because many people freak out when being put into an MRI for the first time, given the tightly confined space (6" from your face). Also, you can't move at all during the process when can take from 20 minutes to an hour. So you're basically "trapped" in that space for up to an hour - but you are handed a little "squeeze" alarm in case you do panic.

After taking all my insurance and other data down the young woman escorted me to a changing room and told me I had to remove all my clothing and put them in the locker provided - which she pointed to. She then opened another door and showed me the two sizes of surgical gown. Already, with all this huff and puff, I was starting to get nervous that I might have to be "introduced" to the ERC! Fortunately that was not the case, and as the woman left Janice helped me into the stupid gown - which was the only thing covering me.

After finishing I peered outside to see three young women all seated in their own gowns but allotted more clothing (like shoes, etc.) than I was. I balked at first going out, but Janice accompanied me staying close so none of the women could see too much. So in that condition I had to sit and wait with these women until called. Janice kept my mind off my embarrassing state by using her Ipad to bring up different restaurants to go to afterwards.

After twenty minutes or so my name was called, whereupon I was walked to the MRI room and assisted onto the table. My head fitted snugly into a cushioned support and my legs were raised on the MRI table, as the pelvic array coil was spread on top. I was then given earphones and chose some piped in music (60s rock) to drown out the loud 'banging' sound of the MRI. (It was somewhat like being in a giant tin can with huge hammers banging different tones while you lay still).

The scanning began and I enjoyed the music but found it difficult to catch a breath. Finally, after about 16 minutes I tried to slowly inhale and exhale when the operators stopped and warned about taking deep breaths. So she had to run those slices over again. Then about ten minutes later the scan suddenly stopped once more and I was asked to please use the rest room just outside as the MRI scans were picking up gas (trapped in the rectum) obscuring the images. I complied and returned after expelling roughly two loud farts.

Assisted back onto the MRI table, the scanning resumed where it left off and was completed in about ten minutes with no further issues. I was told the imagery - on a CD- would be sent to my primary doc and would be available in about 1-2 days. I then ambled back to the waiting room - where Janice was- to change back into my clothes. From there it was on to the Texas Roadhouse restaurant where we enjoyed two excellent steak dinners.

What happens next will depend on what the MRI scans show. I told Janice that at the least they will likely show the same 6 cancerous cores - at grade T1C - that were first detected in my standard biopsy 4 years ago. (The MRI, of course, is unable to render the Gleason score).

Basically, if the imagery shows the disease is "indolent" I plan to adopt a wait and see approach, probably continuing with the PSA tests and getting the occasional MRI. But NO more biopsies for the reason already given.

If the cancer (adenocarcinoma) is found to have spread I will then wait until evidence of metastasis - before considering androgen deprivation therapy (ADT) since new research finds little difference in benefit between initiating it right away and once bone metastasis has arrived. The advantage of ADT - even if used in cycles (which I will likely do because of the nasty side effects, e.g. depression, loss of memory, metabolic disease, cardiac problems, high BP etc.) is to lessen risk of bone fractures. Once the cancer spreads to the bones further metastasis naturally will weaken them and increase fracture  risk.

But as I said, I am opting here for life quality as opposed to quantity. My will has already been revised and the estate lawyer is working on the final draft including a revised living will and advanced directive "to take into account what occurred in the Terry Schaivo case". The primary change in the will was to the beneficiaries and also a more exhaustive accounting of assets.

I may have two years left or ten, I don't know and can't say. But the only choice any of us has is to keep on keeping on and try our best to live each day to the fullest  - as we define that term.


To see a video explanation of the MRI process. including the sort of sounds you hear:

https://www.youtube.com/watch?v=DZTXa4qerI4

Testosterone-Blocking Cancer Drugs Linked To Much Greater Alzheimer's Risk

While we're on the topic of prescription drugs and costs, we can also consider the set referred to as "anti-Androgen" or "testosterone-blocking". These are usually prescribed by oncologists after a treatment "failure" -  defined in the case of radiotherapy as three successive PSA increases after the defined PSA nadir (or lowest reading). Since treatment such as radiation often leaves tissues a "mess" it isn't generally a good idea to barge in with a radical prostatectomy - so anti-Androgens are prescribed to cut off the testosterone feeding the tumor.

As Dr. Mark Scholz observes in 'Invasion of the  Prostate Snatchers', p. 42:

"testosterone fuels prostate cancer growth  and prostate cancer is the only type of cancer susceptible to testosterone inactivating pharmaceuticals"

It is also true that anti-Androgens can be prescribed for men who've been biopsied and found to have localized prostate cancer but opt not to go for the extreme treatments like surgery or high dose brachytherapy - such as I had in 2012. It is now estimated that a half million American males are on these drugs for one or the other reason.

The Androgen deprivation therapy - also known as chemical castration - lowers levels of testosterone and other male hormones that can fuel the disease but can also wreak havoc including: a higher risk of cardiovascular disease, diabetes, high cholesterol, loss of muscle mass and impotence.

Now we learn males on this therapy probably need to also do more watchful waiting for Alzheimer's disease.

According to a WSJ article ('Alzheimer's Danger Seen in Prostate Drugs', p. A3, Dec. 10), a new study published in the Journal of Clinical Oncology found that men taking testosterone-blocking drugs had an 88 percent increased risk of  developing Alzheimer's disease compared to those not taking such drugs.

The researchers from Stanford and the University of Pennsylvania searched electronic medical records from Stanford Health Care in Palo Alto, CA and Mt. Sinai Hospital in New York City. They identified 16, 888 patients with "non-metastatic prostate cancer" between 1994 and 2013. Of those:

"Nearly 2,400 were treated with anti-Androgen therapy and they had an 88 percent increased change of being diagnosed with Alzheimer's disease in the next three years than those who weren't"

According to one urologist from Brigham and Women's Hospital in Boston, while this therapy "can extend survival when used with radiation in some cases", he also warned:

"But we should never use androgen deprivation therapy alone for localized prostate cancer".

My view is perhaps it shouldn't be used at all, especially after reading and reviewing How We Survived Prostate Cancer: What We Did and What We Should Have Done ...by Victoria Hallerman. Hallerman writes of her husband who had brachytherapy and also the anti-Androgen treatment. She notes that basically, he was reduced to weeping at the slightest provocation and also losing the ability to think clearly. To me it showed the wisdom of me not adding this to my own high dose brachy treatment.

One is led to ask: 'What is the quality of life if it means getting Alzheimer's?' You are better off croaking earlier from the cancer than be converted to a living vegetable.