Tag Archives: cancer screening

Dear Abby, my PSA…


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If you are a reader of this blog, it is likely that you or a close friend/relative has dealt with or are dealing with prostate cancer. Hence, you have become the “expert” in your family or book club or similar for people who know your story. One of the most frequent questions I encounter in such circumstances is a question about someone’s recent PSA. As an example, an 86 year old otherwise healthy cardiologist recently called me asking what to do about his  PSA that had gone from 4-ish to 6-ish during the last 2 years.

There are a few generalizations that seem to apply to most of these queries. First, the PSA increases at a fairly predictable rate with age. As a crude rule of thumb, I tell patients/friends that it should be less than 2 when you are 50, less than 3 when you are 60, and less than 4 when you are 70. A recent article in JAMA illustrates this point nicely. In the PLCO cancer screening trial, 10,968 men aged 55-60 had a baseline PSA drawn and were then followed with various screening strategies for prostate, colon, or lung cancer. Among the men with baseline PSA of <0.99, the incidence of developing clinically significant prostate cancer in the next 13 years was only 1.5%, whereas if their baseline PSA was 2-2.99, the chances increased to 10.6%. The authors concluded that ” These findings suggest that repeated screening can be less frequent among men aged 55 to 60 years with a low baseline PSA level (ie, <2.00 ng/mL) and possibly discontinued among those with baseline PSA levels of less than 1.00 ng/mL.” What to do for my octogenarian cardiologist friend is more complicated, of course.

A second generalization is that if someone has chosen to follow his PSA more closely, say on an annual basis, because they have read enough about screening to feel that regardless of the controversy, they wish to do so, they should plot their data. A column of numbers is much harder to interpret than a visual graph. There is an easy way to do this by entering the data on a website like this one: Doubling-Time.  It is also important to realize that different labs may give slightly different values on the same patient – particularly challenging if one is trying to torture the data in the lowest ranges of detectability (<0.2).

Thirdly, and related to the plotting approach, for any given patient with known metastatic prostate cancer, the absolute value of PSA may be less important than the rate of change (doubling time). A rising PSA that goes from 3 to 6 in 6 months is of greater concern than someone with a PSA going from 150 to 160. Of course having a lower value generally means a lower cancer burden, but I once had a patient enjoy elk hunting during the later stages of his disease with a PSA over 2000. He had relatively few symptoms in spite of his advanced disease.

Lastly, and related to my aging cardiologist friend, there’s a lot more to know than the PSA in most cases. When I asked him what his urinary habits were (unchanged) and what his rectal exam revealed (he hadn’t had one), I suggested he should visit a urologist for a more complete picture. If you biopsied his prostate, there is probably >50% chance of finding cancer at his age, but the key question is whether it would be a “clinically significant” cancer (Gleason score >3+3=6, or multiple cores positive etc.) In addition, one now has the opportunity to do pre-biopsy tests such as Select MDx, PHI, or ExoDx with newer tests being developed all the time to try and NOT find patients with low risk disease who might never need any sort of treatment.

So, at your next cocktail party when a friend asks about PSA, you can gently explain the complexities you are all too familiar with, and hopefully guide them in the right direction. And if you are interested in more blogs, I recently discovered Snuffy Myers’ blog site, Prostapedia, that has numerous blogs from highly respected prostate experts with great ongoing updates. Happy New Year and most importantly EXERCISE!

 

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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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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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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:

Screen Shot 2014-06-19 at 9.15.54 AM

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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No surgery or radiation. Just make my PSA go down!


To read this blog on the website and have access to subscribing and older posts click here. What if you could avoid all of the well-known side effects of surgery or radiation and just take hormone therapy? (aka Androgen Deprivation Therapy or ADT) Given the incredible power of the PSA value to drive thinking of both physicians and patients, this question makes a lot of sense. >95% of patients will have a PSA response to ADT, usually in the form of GnRH agonists (e.g. Lupron, Zoladex, Trelstar, etc) or antagonists (Firmagon, Plenaxis) You might imagine that dropping the PSA would be all that is needed in some men and if they didn’t have too many side effects (weight gain, hot flashes, muscle weakness) they would benefit from the treatment.

A study just reported looked at 3435 men treated in this way between 1995 and 2008 to determine if such treatment would reduce death from prostate cancer and compared them to 11735 men who did not receive such treatment. The age ranged from 35 to >80 and as you might suspect, there was a statistically significant tendency to use treatment in older individuals, in men with higher PSA at diagnosis, and in those with higher Gleason scores. Anyone who received radiation or surgery within the first year after treatment was excluded from the analysis. The bottom line is that there was no effect of using such treatment. To quote the authors, “Our main conclusion is that PADT does not seem to be an effective strategy as an alternative to no therapy among men diagnosed with clinically localized PCa who are not receiving curative-intent therapy. The risks of serious adverse events and the high costs associated with its use mitigate against any clinical or policy rationale for PADT use in these men.”

This study adds to the complexities surrounding prostate cancer diagnosis and treatment. Screening and treating patients with surgery or radiation after age 65 may not produce any positive results in the large screening studies, or at the least, you have to treat a significant number of men who would not need treatment to save one life. While you can make the PSA go down with ADT, it also does not save any lives. Such is the challenge of whom to diagnose, whom to treat, and how to best treat anyone who you think does need treatment. On this blog you will find many entries on these issues, and as I have stated before, when you ask men who are dealing with the disease, they virtually all think their treatment either saved their life or was given too late – illustrating the difference between a population and an individual view. The silver lining is that whether you are diagnosed with pca before you die or not, regardless of treatment choice, you are more likely to die from something else.

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Shift work and PSA values


I just came across this article because the editors at Medscape send around interesting articles on prostate cancer when you sign up for them. It seems likely to me that this is not a red herring, but the accompanying editorial goes into the issues of more holistic prostate cancer screening – with the intent to try and figure out who might really benefit rather than just screening all men over age 50. If you could reduce the denominator in some way by eliminating men who have the “usual, non-threatening” “cancer” (with a nod to all the articles suggesting we should change the nomenclature for Gleason 3+3 disease), screening might make more sense and be of greater benefit. Until then, it’s still caveat emptor.

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PCPT rides again – finasteride (proscar) to the rescue?


Today’s NEJM has a great article written by our colleagues who headed this study designed to ask whether taking finasteride could reduce the incidence/death rate of prostate cancer. This is the same group that reported on fish oil being a risk as I have previously discussed. The main finding of the PCPT trial was that taking finasteride (Proscar™) could reduce the rate of prostate cancer, BUT that there were more high grade cancers in the group taking the drug compared to placebo. As a result of this finding (which has been the subject of extensive discussion and speculation…for example one analysis suggests that this is an artifact of making high grade cancers easier to find because the prostate volume shrinks by about 1/3 in men on finasteride), the FDA issued a warning against taking finasteride or dutasteride. In the article released today, the investigators reported on the long term outcome of the study. As usual, the results are creating much discussion, and differing points of view. Overall there was NO DIFFERENCE in the death rate among men taking finasteride vs. placebo. 78% of men in each group survived 15 years. Moreover, there was no difference in the death rate among men who did develop cancer regardless of whether they were on finasteride or placebo. The investigators suggest this means it is reasonable to take finasteride to reduce the incidence of men who must deal with a diagnosis. Of course another approach (favored by the U.S. Preventive Services Task Force) is not to screen at all (remember all the patients in the trial were being screened by psa testing). Based on these considerations, I think it would be reasonable to recommend finasteride as a preventative in men who have a positive family history. Purists would point out that this has not been tested and would require a prospective trial before making such a recommendation. Where is Diogenes when we need him???

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