Tag Archives: health

It’s MO time – please help!


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In my career fighting for the cure of prostate cancer, two organizations (besides the National Cancer Institute) have been outstanding partners. Movember was started by a couple of friends in a bar in Australia. This became the answer to a long standing jealousy of mine for something as popular and effective as the Susan G. Koman Foundation and Race for the Cure. I often refer to our prostate cancer journey when I lecture by noting how we “crawl for the cure” while our sisters are racing. In 2016, the NCI budget for breast cancer research was $519.9 million, more than twice as much as that for prostate cancer at $241 million. This, in spite of the fact that prostate cancer deaths this year are 3/4 as common (29,430) as breast cancer deaths (40,920). It’s not a contest really, since all cancer research is moving the field forward rapidly, but Movember has been incredibly helpful in sponsoring research and advocating for us.

The other organization, Prostate Cancer Foundation, shows how much a single individual with great connections and personal motivation can do. Michael Milken deserves enormous credit for his vision and leadership. I personally benefited from grants given out by the foundation, and even more from their amazing annual meeting that draws together prostate cancer researchers from around the world to share data and ideas. Dr. Howard Soule is a key factor in PCF’s incredible success and his name should be as well known as Susan G. Koman in my view.

I hope you will join with all of us in fighting for the cure in prostate cancer. Grow one, or support someone who is growing, and tell your friends. The progress and future has never been brighter, and our hairy upper lips should show it!

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Money, Medicine, and Me


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In an article appearing on Medscape on September 13, a Reuters correspondent cited a recent study published in the Lancet looking at doctors who tweet. Although tweeting is a form of social media I have not embraced, I did participate in an attempt to study its use in the ASCO meetings in this article. However, the Medscape and Lancet articles did cause me to think about transparency in this blog.

I began blogging at the invitation of an internet company looking for physicians who would provide content they could use. When they were successful enough, they began using pharmaceutical advertising, and I left them, choosing to pay for my own web presence on wordpress.com. However, I now realize that I should also disclose my other relationships with pharmaceutical companies. In the Medscape article, there is a reference to a government website where you can look up the payments and transactions I have with pharmaceutical companies. What it does not reveal is the nature of those transactions which I will herewith share.

In doing drug development, pharmaceutical companies rely on [mostly] academic physicians to perform clinical trials. These activities may involve grants to study drugs in the laboratory, grants to their institutions to offset the cost of data managers, IRB costs, and reimbursement for travel to discuss the ongoing trial or its publication with other physician/researchers. In the past, I have had support in all of these categories, most notably (in terms of career influences) in the development of leuprolide, the first new drug approved for treating prostate cancer in many decades back in ~1985. It was an amazing opportunity for a young faculty member to treat the first patients in the world with a new drug, eventually present the findings to the FDA, publish the results, and then participate in teaching the medical community about its use.

Since then, the landscape of disclosure has changed for the better. Now when my colleagues and I give presentations or publish articles we sign disclosure agreements revealing which companies we consult for, and there are annual reporting requirements to our academic institutions. In my case, the current companies I have consulting relationships with include Janssen (abiraterone, apalutamide), Bayer (rogaratinib), and Seattle Genetics (enfortumab vedotin). I also have founded (and have ownership interests in) Aurora Oncology, ProTechSure, and Gonex/Cedus, three startup companies attempting to move drugs we have worked on in my laboratory to the clinic. None of these relationships involve giving promotional talks, using company slides in education, or advocating for the drugs on this blog or elsewhere. For the large commercial companies they involve insuring patient safety in ongoing trials as an independent monitor.

I have expressed my concerns about the rapid increase in medical costs for cancer care here and here. I do not have a solution for this intrinsically difficult challenge in our capitalistic system, and I realize that my own consulting and entrepreneurial activities ultimately add to those costs. Indeed, the costs of prostate cancer detection and treatment in men over 70 is 1.2 Billion dollars every 3 years. The newest targeted agents and immuno-oncology agents are phenomenally expensive, often in the $8-10,000/month range which can result in severe economic distress even for those patients who have co-pay supplemental insurance. Eventually, American medicine, with all of its amazing basic science and translational science (bench to bedside research) will need to find a balance between the profit motives that drive innovation and the altruistic care that medicine embodies in its most noble applications. What is an extra 3 months of life worth, and what toxicities (economic or clinical) are acceptable to pay for that? We need to have honest discussions as a society, and importantly, with our own families about these questions, especially when we are facing the diminishing benefits of aggressive/expensive care in terminal illnesses.

 

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Filed under General Prostate Cancer Issues, Prostate cancer therapy, Targeted treatment

A perfect death


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This week in which the country will come together to mourn the passing of a true American original, John McCain, it might be worth considering our (your) own mortality. Even as the ongoing progress toward controlling prostate cancer is underway, it remains clear that “something else” will get us. As an example, in a study I was privileged to lead among patients with high risk prostate cancer, other cancers (many of which were caused by our adjuvant mitoxantrone treatment) were as likely to lead to death and prostate cancer was the cause of dying only ~20% of the time

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As oncologists, we face the “end of life” issues more frequently than most physicians, and certainly deal with the reality of death more than folks in most other professions. I distinctly remember one lovely woman in her 50’s who was very open in discussing her wishes. She wanted to die while lying on her favorite beach in Florida watching the sunlight sparkling on the ocean – not an easy thing to arrange (and it didn’t happen). My own fantasy would be to have a lovely vacation in Hawaii (without this week’s rain) with my entire family, say my good-byes as I put them all on the plane, and stay over an extra day to pay for the hotel and be sure all of my financial affairs were up to date – then die of a heart attack on the way home the next day. Perfect. The airline would be carrying my carcass home for the mere cost of a coach seat and I wouldn’t even have to suffer that long in the crunched position with no leg room.

Short of these fantasies, however, I recently undertook an exercise that anyone could do and I herewith commend to you as well. My wife and I were lucky enough to score tickets to the London production of Hamilton last February. In it, there were two numbers that grabbed me by the heart. First was Washington’s “teach ’em how to say goodbye” song, “One Last Time”. As with John McCain’s final commentaries over the past few months, Hamilton’s farewell speech written for Washington was masterful (as is Lin-Manuel Miranda’s reprise).

But the song that most moved me to tears (and action) was “Who Lives, Who Dies, Who Tells Your Story”. After listening to it about a dozen times, I realized that we all have a story. It may not be as honest/noble as John McCain’s, or as consequential as Hamilton’s or Washington’s, but for some small group of your relatives or children or grandchildren, your story will have special meaning. If you don’t write it, your memories of your father, your grandfather, your family in general will die with you. In my case, I read a couple of autobiographies, self-published, from friends/acquaintances and decided that their stories were highly personal, and not terribly interesting. But when I started writing the story of my own grandfather and father, and my story, it was a joyful experience of reliving many happy memories, and a way of reconnecting with my first love affair, our children’s births, and the many blessings that have come my way. The result is not a literary masterpiece, but I am going to have it bound and give a copy to each of my kids to gather dust on their bookshelves.

In the arc of history, some things have not changed. “Our days may come to seventy years, or eighty, if our strength endures; yet the best of them are but trouble and sorrow, for they quickly pass, and we fly away.” (Psalm 90:10). Although trouble and sorrow are a part of life (and of dying), there can be real joy in pausing to appreciate all life has given you. Carpe diem!

 

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Of Prostates and Teslas


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If you thought this might be an article about how your urologist shops for his/her newest fancy car, you are mistaken (sadly…). Nikola Tesla was a fascinating inventor and ultimately “mad scientist” at the turn of the last century. Every time you plug your cuisinart into the wall to chop something up, you are the beneficiary of his contributions to the alternating current coming to your kitchen and the motor driving the chopper. My favorite story (because of the local connection) was his laboratory in Colorado Springs, where he attempted to develop a method of transmitting power without wires. By creating YUUUGE electromagnetic fields, he could make lots of electrical things happen at considerable distances, including knocking out the power station for the city. Here’s a quote from the Wikipedia article:

He produced artificial lightning, with discharges consisting of millions of volts and up to 135 feet (41 m) long.[11] Thunder from the released energy was heard 15 miles (24 km) away in Cripple Creek, Colorado. People walking along the street observed sparks jumping between their feet and the ground. Sparks sprang from water line taps when touched. Light bulbs within 100 feet (30 m) of the lab glowed even when turned off. Horses in a livery stable bolted from their stalls after receiving shocks through their metal shoes. Butterflies were electrified, swirling in circles with blue halos of St. Elmo’s fire around their wings.[12]

Of course, for purposes of this blog, the key thing is that the strength of magnetic fields was named after him. When you get an MRI of your prostate, brain, or anything else, you are put into a machine with a superconducting magnet that produces 1.5 or 3 “T” of strength. At the risk of being completely wrong and oversimplifying, what happens in the MRI machine is that a strong magnetic field temporarily lines up the hydrogen atoms in the water that is 70% of “you”, and when these atoms “relax” they give off radio signals that can be converted to images. Details and images are here. Early on, my colleagues and I were fascinated by the possibility of using MR to investigate the prostate gland and published an article (completely ignored – cited only 3 times, so must not have been that important…) showing changes in MR that occurred after testosterone administration to castrated rats.

Now there are complex MRI protocols to image the prostate using techniques I don’t fully understand (multiparametric imaging) that give us remarkable pictures of the prostate gland. Here is one:

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Prostate gland with red arrow indicating a suspicious lesion that could be biopsied or followed closely.

As with any radiologic imaging technique, the skill of the radiologist as well as the equipment being used determine the accuracy of the MRI to diagnose a cancer.

While most of us learned how to “read X-rays” in medical school, it is beyond most clinicians to read MRI’s of the prostate. Fortunately, the radiologists have developed a system that helps us think about “how abnormal” some area of the gland is, called PI-RADS.  This can be very useful in thinking about what area to concentrate on when biopsying a patient, or in trying to determine whether surgery or radiation therapy should be altered if there is concern that the cancer is outside of the gland. An interesting question that is still controversial is whether the MRI could replace repetitive biopsies in a man who has chosen active surveillance. Particularly when combined with molecular techniques (see my previous blog here) to characterize biopsies, it may be that Tesla will be helping to do more than get you from one place to another or run your electric shaver. (Rock on, Elon Musk) To me, that is a pretty interesting outcome from knocking out all of the lights in Colorado Springs!

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What is going to kill me? – the cloudy crystal ball


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With an intense focus on prostate cancer, it is easy to overlook the reality of other causes of death or disability in making decisions about therapy. An example of this issue is the proliferation of molecular tests that have been validated to separate patients with “intermediate risk”, or “low risk” into “even lower” or “even higher” risk disease categories using a number of different gene expression profiles on the tumor or biopsy material. For example, Genomic Health offers the Oncotype Dx test that provides a “Genomic Prostate Score” that gives a patient who (based on clinical criteria such as PSA and number of biopsy cores positive) falls into a low or intermediate risk category another lab value (GPS) that can potentially be useful in making a decision about treatment. GenomeDx has a test that can evaluate high risk men after prostatectomy to more accurately predict metastatic disease at 5 years. There is a very balanced article on the challenges of using these tests (which are a potential step forward to be sure) in the real world of the clinic here.

However, in all of the excitement and marketing of these and other tests, a couple of key facts are often overlooked (and may be much more important in decision making). Prostate cancer is generally a slow disease anyway. Competing mortality looms large as patients get older. And most importantly, there are validated ways to put the “whole patient” into the picture before ordering these tests, whether they be a PSA, biopsy, or molecular analysis. The Charlson comorbidity index can be extremely useful in predicting survival and is barely ever mentioned in the molecular analysis literature/reports. It is a simple yes/no answer to whether a patient has any of these 12 conditions: diabetes, bleeding gastrointestinal ulcer, chronic lung disease, congestive heart failure, stroke, myocardial infarction, angina or chest pain, cirrhosis or liver disease, arthritis, inflammatory bowel disease, hypertension, and depression. In a lovely article published last year, the use of this analysis in relationship to prostate cancer mortality gave a vivid picture of prostate cancer mortality in the larger setting of 3533 men with prostate cancer. A snapshot of their data looks like this:

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Very often, the comorbid conditions lead to death from another cause. In my opinion (and in my practice), we too often ignore our ability to quantify the risk of dying from “something else” when we focus so intensely on the PSA or other tests in counseling patients about what to do. It is also true that patient perception of test results can vary dramatically. One patient with a “GPS score” of 10 might be reassured, while another will perceive it as “not low enough” and opt for aggressive treatment rather than observation. To some extent this exposes the fallacy of “we need to separate the issue of treatment from that of diagnosis” thinking. Until the crystal ball becomes crystal clear, management of prostate cancer will remain challenging and requires the kind of wholistic thinking that is often better done by primary care physicians or public health professionals than by prostate cancer docs, or their patients.

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Lengthen your telomeres this week


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For journal club last week, I selected an article that looks at length of telomeres as a prognostic variable for prostate cancer. Telomeres are DNA protein complexes that are added to the tips of chromosomes by an enzyme, telomerase, that carries its own little RNA unit and was involved in one of the authors (Elizabeth Blackburn) of the story below winning a Nobel prize. As you get older, the length of your telomeres shortens, eventually giving rise to loss of important chromosomal information that can lead to cancer. In the journal club article, it was found that men who had shorter and more variable telomere length in their prostate cancer or the surrounding tissue, had a higher chance of developing metastases or dying from their disease. Of course this is bad news, and you might think there is nothing you can do about it. Not so fast….

Blackburn and her colleagues at UCSF have been studying men with prostate cancer to see if exercise and diet can influence telomere length. In a 2008 study, they found that peripheral blood cells had increased telomerase after 3 months of improved diet and exercise intervention. In their most recent study, they find that the continuation of the diet/exercise program results in actual increases in the telomere length in the peripheral blood cells. Since these are men with low risk prostate cancer who are being followed on a study with active surveillance, we will also be learning how such improved life style affects other genetic changes in serial biopsies of the cancers.

For now, the bet is that (as usual) you will benefit from increasing your exercise program, dropping red meat from your diet, and probably watching less football and doing more hiking this week with your family as you celebrate Thanksgiving. I’m just saying….

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Cow’s milk – not your father’s drink of choice?


When I was a kid, my father, having grown up on a farm, was obsessed with having me drink lots of milk. There was a milk delivery service in Chadron, NE, that brought rich, fresh, whole milk to our door, and I recall drinking at least a gallon a week – sometimes twice that. I was told it would “build strong bones and healthy teeth”, especially during my pubertal years, when there is of course a growth spurt that does indeed require more calcium and good nutrition. (Hence the increased height of American children over the past century…)

But there is a dark side to this story. In an article in Medscape today, there is a lovely review of another pathway that stimulates prostate cancer, namely one that involves the PI3K-Akt-mTORC1 pathway. It is way beyond this blog to try and go into this pathway in any detail, but suffice it to say that the authors present a powerful (albeit very long) argument that leucine, a branched chain amino acid found in high concentration in cow’s milk stimulates this pathway and can lead to prostate cancer growth and metastases. I will reproduce here (and without permission….I wonder if that is needed in the blog world…) a couple of the figures that illustrate the point. (note I am not plagiarizing since I give you the link to the original article containing these figures)

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This figure illustrates how leucine interacts with the signaling pathways that might lead to prostate cancer or stimulate its growth.

Screen Shot 2013-01-28 at 12.37.55 PMThis figure demonstrates the increased consumption of milk products like cheese and milk that have occurred over time in western countries.

The bottom line here is that milk and cheese have a dark side and we should probably curtail our intake, especially in families who have high prostate cancer rates. It would be nice to go into all 250+ articles the authors cite, but trust me, their arguments are very well founded. Too bad, since I love cheese so much !

 

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