Tag Archives: PSA

Improving our focus


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I have had two life changing experiences in focusing. The first was when my wife discovered the Myers-Briggs personality classification system and found I am a “strong P”. This meant I couldn’t help it when I was on my way to take out the garbage, noticed a light had burned out, put the garbage down and went to get a light bulb, but found that there was a spot on the carpet that needed cleaning and finally found the carpet cleaner but an hour later wondered why there was a garbage sack in the hall. Prior to her discovery, she just thought I was an idiot, but she became [somewhat] more tolerant of the foibles when she could “classify” me. The second was when I had my congenital cataracts removed and new lenses inserted in my eyes. It was a whole new world of color. I had been living in a fish tank with scum on the glass and “wow, the world is really pretty!” was my response when I took the patches off the next morning. “Trees have LEAVES!”

Focus in understanding prostate cancer is becoming clearer as well. For several decades we have known that the Gleason scoring system is pretty darn good at predicting the cancer’s behavior, adding a lot to what we knew when there was only the digital rectal exam… “Oh, oh, that feels like a really big tumor” or “Maybe I’m feeling something but I can’t be sure”.  Then came the number of biopsies positive, the percentage of each core, differentiating 3+4 vs 4+3, and now an avalanche of new molecular markers, briefly reviewed here. Combining the old standby risk categories with the newer methodologies has been challenging.

A recent paper in the JCO provides us with one way of integrating the old risk categories with the newer molecular classifications. Using the widely adopted risk categories of the NCCN, the authors added to this, one of the more mature molecular classifiers, the 22 gene Decipher™ scoring system to reclassify (focus) a new model to predict outcomes. As I explained previously, these genetic tests are typically developed looking at the level of gene expression in biopsies or in removed prostates in a group of patients for whom an outcome is known (examples include prostate cancer free survival at 10 years or freedom from metastases at 5 years). The investigators (or companies) then go to a different institution or collection of biopsy material and see if their gene expression model developed from the first group accurately predicts the outcome in the second group. This is called “validation” of the test. Decipher has done all of this. The question is how it might change the risk classification of the “old” system.

This figure illustrates how it plays out when a large number of institutions collaborate to study the information gained and develop a new model.Screen Shot 2018-04-28 at 10.16.05 AM

As an example of how this can be used in the “real life” clinic, we are often faced with a patient who has a “favorable intermediate” prostate cancer. Let’s say this is a 75 year old man with excellent health. Should we advise that he adopt a “watchful waiting” strategy, given his age and the relatively low risk? By adding the genomic test, you can see that 27% of the time, this might be a bad recommendation. Similarly, in the unfavorable intermediate group, 40% of patients are moved into a high risk category. Such a patient might be well advised to “do more” (example: more prolonged ADT with radiation, or use of brachytherapy in addition to external beam radiation if they had chosen radiation therapy as their preferred treatment modality).

These kinds of improved focus will allow investigators to do better studies prospectively as well. In breast cancer it is already a standard of care to do molecular classification of certain stages and types of tumors, allowing women to make far better decisions on whether (for example) to take chemotherapy in addition to surgery/radiation. In prostate cancer, where I have been concerned that we aren’t “racing for the cure“, rather we are “crawling for the cure”, it looks like we may be catching up. Research is the answer – sign up and contribute!

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Filed under General Prostate Cancer Issues, Prostate cancer therapy

No pain, no gain?


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One of my patients last week had a heartfelt discussion regarding the survival benefit of ADT vs his quality of life. He enjoys body building and showed me some pretty dramatic pictures of himself during his last ADT cycle (on intermittent therapy) versus now, when he had been off treatment for ~6-9 months. Added to his concern was his decline in libido and sexual function during ADT, a common complaint especially among younger patients. The question of quality vs quantity of life was,of course, utmost on his mind.

Starting from the initial diagnosis, every (maybe that should be every !!) prostate cancer patient will experience a decrement in quality of life. Those who elect “watchful waiting” will nevertheless experience anxiety regarding the shadow of CANCER following their footsteps. Sure, you can put it out of your mind, but turn around and there it is, like the neighbor’s unwanted cat stalking you. Then there is the anxiety over what the next PSA will be. And if on active surveillance, what will that next biopsy show?? These issues are both real, disturbing, and often under-appreciated in the discussions surrounding screening…”we should still be screening, but not treat the men who don’t need it…” Really? What about the 80% of men who die at age 90 with prostate cancer at autopsy who never had to deal with the shadow? (The inevitable counter-argument is, “yes, and what about those who had early detection of a high grade cancer whose life was saved?”)

We also tend to ignore the impact of competing mortality in our discussions. “Sure you had a stent placed last year, and you already survived that small colon cancer, so why wouldn’t we be aggressive in treating this new problem?” Dr. Sartor provided an elegant discussion of this in an editorial on the PIVOT trial you can read here. Whatever the flaws in that study, it remains clear that we are not very good at predicting the non-prostate cancer “future” for our patients, and the older you are, the thinner the ice gets regardless of how many marathons you run.

When patients choose one form of primary treatment vs another, they are weighing the different side effect profiles of surgery or radiation as much as which is “most effective”. I often give patients a copy of this article from NEJM and encourage them to spend some time looking at the graphics in Figure 1 to get some idea of what they will face in the way of side effects from treatment. As any honest physician would tell them, treatment will involve side effects, some permanent, in the best of circumstances.

In the setting of more advanced disease, for example a patient who presents with metastases outside the pelvis, the recent CHAARTED and STAMPEDE trials both suggest an advantage to the earlier use of docetaxel chemotherapy in combination with ADT as opposed to ADT alone. These data suggest that “pay me now or pay me later” analysis favors the “pay me now” approach in terms of overall survival. But at what price for quality of life? Fortunately most chemotherapy side effects are reversible, but distinctly unpleasant, potentially making the equation something like “4 months of misery to provide 14 months of longer life….not all of which will be great anyway”.

Even in the very advanced setting, there is some evidence that greater toxicity results in improved survival. A recent analysis of the TROPIC trial of cabazitaxel suggested that the patients who had the most “toxic response” in terms of dropping their neutrophil count benefited the most in terms of overall survival.

While all of this seems incredibly negative (for which I apologize), the history of oncology as a field has been the incremental improvement in survival AND the development of newer treatments that provide such advances with diminishing toxicity. Pediatric leukemia, as discussed extensively in “The Emperor of All Maladies” is a great example of how pioneering patients and physicians worked together to find cures and reduce side effects. We may only be at the beginning of such achievement in prostate cancer, but with the advent of the newer hormonal and imaging agents, increasingly sophisticated surgery and radiation, vaccines and immunotherapy, and even the chemotherapies now available, we have  no doubt reached the end of the beginning. Onward!

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Filed under General Prostate Cancer Issues, Prostate cancer therapy

Yay…Movember is here. Let’s kick Pca


Hi friends and relatives (those who will admit it…),

This Movember, I’ve committed my upper lip to help change the face of men’s health by growing a moustache, now I need your support at http://mobro.co/michaelglode.The Movember Foundation is the leading global organization committed to changing the face of men’s health. I’m passionate about this cause because too many men are dying unnecessarily from prostate cancer. In 2014, more than 233,000 men will be diagnosed with prostate cancer. Even better, join our team and donate to yourself and invite your friends/family to the cause! Our team is here: http://us.movember.com/mospace/index/search/?q=university%20colorado

 The Movember Foundation is working tirelessly with an urgent goal in mind: accelerating breakthroughs in prostate cancer research that will benefit patients and their families. Movember is achieving this with the formation of the largest, global alliance of prostate cancer researchers and clinical specialists, who are tackling the toughest prostate cancer challenges. I had the privilege of hearing the updates on the research they have been sponsoring last week at the PCF retreat. More progress in the last 5 years than in the previous 25. Take a look there for updates/posts yourself!

I need your support to fund this important work. Together, we can create a world where no man dies of prostate cancer.

You can donate by:

– Donating online at http://mobro.co/michaelglode (and follow the pathetic growth of my not-so-manly moustache…)

– Writing a check to ‘Movember’, referencing my registration ID: 5798901 and mailing it to:  Movember, P.O. Box 1595, Culver City, CA 90232

You can learn more about the important work and impact Movember is having at: http://us.movember.com/programsThere’s a lot riding on this moustache, thank you for your support!

 Mo Bro Michael Glode

http://mobro.co/michaelglode

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Filed under General Prostate Cancer Issues

Oh, no! My PSA is going up….do something….


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One of the most frustrating and frightening things that can happen to a prostate cancer patient is for there to be a recurrence of the PSA after he thought he had been cured by surgery, radiation therapy, or both. This is entirely understandable. It is no picnic to go through those treatments in the first place, and when the PSA is clearly going up, it can only mean (with very rare exception) that there are still cancer cells lurking somewhere in the body. The rate of the PSA rise can predict how long it will be until something shows up on a scan, and on average, this is about EIGHT years. The median time to death from prostate cancer after a PSA recurrence is 16 years.

For >95% of patients there is something that CAN be done to stem the rise in PSA. That is to go on hormonal therapy (androgen deprivation, ADT) which will drop the PSA, often all the way to undetectable levels, in over 95% of patients. Voila! Both patient and physician feel much better emotionally. But for the patient, there is a significant price to pay. Namely the hot flashes, loss of energy, weight gain, bone calcium loss, lack of libido and further decrease in sexual function to name a few. The question is whether this is “worth it”.

A study to be presented in the next few weeks at ASCO’s annual meeting, suggests it won’t make much difference if you start ADT early versus waiting until metastases, or perhaps even symptoms occur. Utilizing the CaPSURE database, the investigators evaluated over 2000 men who had PSA relapse. The estimated 5 year overall survival (87% vs 85%) and 10 year overall survival (72% vs 72%) were the same regardless of whether the men received immediate or delayed ADT. The same was true for death from prostate cancer…no significant difference. There are of course other considerations that may come into play like treating those patients who have highly aggressive disease earlier because one knows that there will be metastases within a year, or the patient simply can’t live with himself knowing his PSA is going up.

In my experience, it is the exceptional patient who is willing to go play golf or travel or enjoy his grandchildren and forgo PSA testing on a regular basis. I have trouble even convincing my patients to extend their PSA testing to 6 months from 3 months. The question is, does it make any sense to watch this “number”, any more than it would to have cardiac catheterization every 3 months to follow the slow but inexorable accumulation of calcium in your coronary artery? Or what about the 0.01 mm increase in your abdominal aortic aneurysm? Or the accumulation of two more tangles in the Alzheimer plaque in your brain. Just because we CAN measure PSA so easily certainly doesn’t mean we SHOULD, and I have seen far too many men let this number ruin their otherwise healthy lives.

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Filed under General Prostate Cancer Issues

The silent majority


Yesterday the US Preventive Services Task Force released information that it will recommend against routine PSA testing for prostate cancer. Predictably, there has been a firestorm of responses, mostly criticizing this finding. The most vocal critics are prostate cancer patients and advocates, including their physicians. As a physician who has cared for several thousand prostate cancer patients and a member of this community, I think it is appropriate to chime in. However, what I am about to say will not set well with many. Here is an inconvenient truth: If you live long enough, you will probably develop prostate cancer. 55% of men in their 50’s and 64% of men in their 70’s have prostate cancer when their prostates are carefully examined at autopsy. And the frequency goes up from there. These men are the silent majority – the ones who had no treatment, remained continent and potent in many cases, did not have the anxiety of knowing they had cancer, and lived a full life, dying from some other cause. In fact, prostate cancer accounts for only 4% of all deaths in men. The patients who have been diagnosed and successfully treated ALL feel that prostate cancer screening saved their lives. Most of us who treat prostate cancer or participate in screening for it would like to believe the same thing. Indeed there are some retrospective studies like the famed Tyrol, Austria study that would make us believe that prostate cancer screening is having a major effect. And yet, as I previously blogged on screening, randomized trials suggest that if we save lives at all, …1) It is only in men under 65 and 2) you have to screen and treat a very large number of men (with all those side effects), to save even one life. This controversy will not go away soon, and we all await the day when molecular testing can tell us which cancers we can safely ignore, even if we find them “by accident” on screening. Until then, I think it is perfectly reasonable to salute all of our men who have lived into their 70’s and 80’s, especially those 50% walking about who have prostate cancer and don’t know it and will never miss nor be harmed by NOT being treated or screened. They are the silent majority in this debate.

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