We did it!!


half moustacheHey everyone, your outpouring of support for my crazy moustache was incredible. I can’t thank you enough! Not only did you help me reach my $2500 goal, you blew the top off and raised over $5K. Today I share with you readers an “exclusive” – my Half Mast Mo in memory of the guys I have cared for and all the others who died fighting prostate cancer. It’s also a tributeto the goal Movember has set for cutting deaths from prostate cancer in half by 2030. Have a great December and know your generosity is truly humbling.

 

 

 

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Buddy, can you spare a …


Sorry for the intrusion, and I promise to write another blog after December 1 (my commitment for one/month). I’m thinking about discussing the HOX gene system which is fascinating – stay tuned. But for today, I’m shamelessly begging for 9 folks to contribute $25 to help me reach my Movember goal. If you can “spare the change”, please head on over to my website <https://mobro.co/michaelglode?mc=1&gt; and join in.

Many thanks to all of you who contributed this year and even encouraged your friends and family. Know that it makes a difference and we are on our way to beating prostate cancer!

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Lest we forget…


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Screen Shot 2018-11-12 at 11.28.18 AMOn this Veteran’s Day, we would be remiss not to thank the thousands of men and women who serve and remember those who have died in the cause of freedom. My parents used to take me to our local cemetery where the American Legion guys would solemnly fire a 21 gun salute at exactly 11AM and we would lay some flowers on the graves. Those were simpler times, before Viet Nam and all that has followed, but we still need them and I honor their service.

That said, I have wondered over the years how many thousands of men (and women) might have died from cancer caused by smoking that started when they joined the military. In searching for some information on this, I came across this article, actually from a “pro-smoking” magazine, that is a reasonably balanced history of tobacco in the military and admits to the relationship.

Focusing on prostate cancer, there is NO doubt that smoking increases your risk for developing the disease, and if you have prostate cancer, you definitely reduce your length of survival by smoking. I doubt there are many smokers who read this blog, but if you know someone who is fighting prostate cancer be sure to make them aware of this. It is probably one thing they could do (besides EXERCISE, EXERCISE, EXERCISE…) that could increase their survival… more than any supplement which we all continue to put false hopes in. In one (of many) articles evaluating the risk of biochemical relapse (rising PSA) after radical prostatectomy (N=6538) former (N=2086) and current smokers  (N=2214) were 1.5 times more likely to have relapse than never smokers (N=2238). If the men had quit > 10 years, their risk returned to the same as the never smokers.

So, if you know a vet (or non-vet) who is still smoking, thank them for their service, but give them a hug to encourage their smoking cessation.

 

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It’s MO time – please help!


To view this post on my blog site, sign up for future posts, and read more info relevant to prostate cancer, please click here. Donate to my moustache here. Even better, grow your own and get your friends to help out here. The more of us who join in, the wider the recognition of men’s health issues.

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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Rorshach and biomarkers


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Psychology, or for that matter being able to read others’ personalities, has never been a strong suit for me. Neither was art – I still am at the stick figure stage when drawing. It turns out that Hermann Rorshach was probably good at both. The question of what you see when looking at an ink blot seems relevant to the current status of biomarkers in prostate (and others) cancer. On the one hand, some biomarkers are fabulous – for example the Philadelphia chromosome, described in 1959, was the first unique cancer marker that ultimately resulted in a specific targeted treatment, imatinib (Gleevec), dramatically improving survival for patients with chronic myelogenous leukemia. PSA, on the other hand (our “favorite”) is not so great, and as I previously noted, may give rise to the “PSA Clock” effect in which patients ruin their lives by clock watching. But, as we know, it is remarkably useful as a weather vane. When a prostate cancer patient is being followed on any sort of therapy, going down is good and going up is bad.

Thus, there have been thousands of articles attempting to either make PSA interpretation  better, or to replace it with more sensitive or more accurate predictors of prostate cancer behavior. I reviewed some of these, and the challenges here. Today, yet another article on a rather “simple” biomarker, PTEN loss, showed up among the >20 prostate related emails I receive each day. Writing in European Urology, a group of well-known prostate cancer investigators looked at immunohistochemistry (using special stains to highlight a protein in cells under a microscope slide) to evaluate loss of PTEN, a tumor suppressor gene, in prostatectomy specimens. This simple test (in this particular experiment) was as good as the commercial Prolaris test that evaluates a panel of genes related to how fast cells are dividing in predicting biochemical recurrence (PSA relapse) or prostate cancer specific mortality. With PTEN loss, the chances of having a biochemical relapse (rising PSA) or developing metastases or dying in a 10 year followup period were significantly greater than if you did not have PTEN loss. A simple, inexpensive test might replace a more complicated one.

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Here’s where Dr. Rorshach’s psychological construct comes into play at so many levels. If you are the scientist looking through the microscope, do you score a loss when there is only faint staining? Are you sure you are looking at a cancer cell and not a normal cell or  a stromal cell, or maybe even an immune cell? If you decide on giving a score to each cell, say “1+, 2+, or 3+” staining, how do you add all those up?  How many cells should you examine? All parts of the tumor, or only the most aggressive (Gleason pattern ≥ 4) And if you can figure all that out, can you teach your colleagues to look at the same specimen(s) and come up with the same answer? These are the challenges we face when we move a lab experiment into the clinic (and they are well recognized by the authors).

But…there is more! Look at the graphs. Obviously you would rather be on the upper curve with PTEN present, but how bad is it really? At 10 years, only ~10% of the men had developed metastases or died in this study. Recognize that these men were a cross section of patients, median age 59, median PSA 5.9, 64% Gleason 3+3 and another 23% Gleason 3+4 with pretty low a priori risk (did we need the PTEN test to tell us?). So the real issue is whether you would want anything different done to you if you were one of the few patients with Gleason 3+3 and PTEN loss, just because you have this new information? And what would that be?? Radiation? Hormone therapy? How much and how long? -all in the psychology of looking at those curves. Some men might want nothing more done, while others would want “the kitchen sink” thrown at them, even if they had relatively little (and unproven) to gain.

So, medicine remains as much an art as it is a science (with no offense to my mathematical statistical colleagues). As the father of American Internal Medicine, William Osler, told his students, “Common sense in matters medical is rare, and is usually in inverse ratio to the degree of education.”

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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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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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