Tag Archives: biopsy

23 & You – Genetic tests for pca


The genetics of prostate cancer are daunting, but there are now a range of tests available that could be used at almost every stage of the disease IF you can deal with the answers you are likely to receive. Generally these tests are the product of science that goes something like this: A complete molecular picture is taken of all the mutations or all the genes expressed in a series of prostate cancer patients diagnosed years ago. For these patients “all you need to do” is go back to the paraffin blocks that were saved for each patient, extract the DNA/RNA and quantify gene expression and any mutations that can be detected. A decade ago, the technology for doing this was daunting, but now it is relatively easy. Once you have the gene expression profile, you can ask a computer to look for gene expressions that correlate with a certain outcome. For example, you take 500 patients from one center for whom the outcome is known…50 patients are dead, 32 from prostate cancer…70 patients developed metastases by 5 years…these 315 patients are alive and well with no evidence of recurrence…etc. Let’s say there are 50 genes that show changes in expression or mutation. Do we need all 50 to forecast what happened to the patients in that group? No. A computer algorithm can keep testing combinations and permutations of genes and reduce the 50 to a smaller number. We can either let the computer pick the final genes, or we could start with genes we think are related to tumor progression and then do the reduction. In the end, we have a small number of genes with characteristics that accurately separate the patients into “good” and “bad” groups and everything in between. We now take our gene panel, reduced to something like a computer chip and apply the test to 500 patients at another institution blinded from what actually happened to those patients. If our algorithm works, we should be able to accurately predict what happened to those patients in the next 5 or 10 years. If it works, our testing system has been validated, and we can begin offering the test to newly diagnosed patients at some stage of illness. For example, a Gleason 3+4=7 patient might fall into a group where surgery produced a 90% chance of being cured at 10 years, or a 40% chance depending on the gene expression. BUT…and this is key…what to do about the result is still a complex decision for both patient and physician. If you are a Gleason 3+3=6 patient and with no treatment at all you have an 85% chance of “cure” at ten years, is that good enough? What if it is a 95% chance? Will that make you more comfortable choosing no treatment, or do you want to be cured at any cost (impotence, incontinence, other side effects of radiation or surgery)?

As none of these tests has been proven in a prospective study – that is, using the tests to do something like even more aggressive therapy in a group of high risk patients, we are still in the early stages of understanding how and when to use them. Fortunately, my colleague, Dave Crawford and some colleagues have put together an excellent website to help patients/doctors understand the tests. http://www.pcmarkers.com has a list of most of the available tests and you can see what results might look like before you and your physician decide to send one off. This is a rapidly evolving field however, and not every test that is being commercialized is listed, and at big centers, there are always new tests being developed.

Finally, as with all of medicine, the payment systems/insurance coverage is crazily complex. Only today, I received an email with the “news” that a cardiologist/congressman, Rep. Buchson has introduced a bill called the “Prostate Cancer Misdiagnosis Elimination Act of 2017” that uses DNA profiling to make sure the tissue being tested is yours. You could theoretically apply this test to ANY cancer biopsy of course, so why prostate cancer? Then there is the motivation…call me cynical, but I suspected that the good congressman, meddling in medicine, might have a local connection, and sure enough, the company that markets the test is from his home state, Indiana. Not to say it isn’t important to know that tissue being tested comes from the correct patient or that the test isn’t a nice application of the kind of technology that identified OJ’s blood, just that we live in interesting times where medical technology is rapidly consuming more and more of our tax/insurance/personal dollars. Personalized medicine will depend totally on this type of technology and can be incredibly expensive. Whether it saves money or consumes it may depend on how many “worthless” (for that patient…and is a treatment with only a 5% chance of working really worthless??…not if you are in the 5% group) treatments are avoided and at what cost. I don’t have the answers. Hopefully this blog at least helps you begin to understand the current molecular diagnostic landscape.

2 Comments

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

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


To view this post in my blog allowing you to sign up and make comments, please click here.

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.

7 Comments

Filed under General Prostate Cancer Issues

Active Surveillance – NIH draft statement


Not to put too many blogs up this week, but  a very well balanced article was just published and includes input from my friend Lori Klotz, whose articles have been at the forefront of doing active surveillance. He tried to get an international trial going that would provide some definitive evidence that this is a reasonable alternative. In the trial, men with low-volume Gleason 6 disease were asked if they would sign up to be randomized between immediate therapy versus going on an active surveillance program. We had the protocol open for about two years and could only find 1 or 2 men willing to participate. When you read THIS ARTICLE, you will see that the study was really important, since a significant portion of men go on to get treatment anyway, and that some studies suggest lower survival with this approach. On the other hand, those being watched do not suffer the side effects of definitive therapy. As with screening, there will be no “final answer”. However I really like this statement as an informational piece that I can give patients who are considering this approach. We also still offer targeted focal therapy at our institution as a possible “in between” treatment option – an interesting approach that is still very early in terms of knowing the long term consequences of this treatment. Mike Landess took this approach and has made a nice video blog of his experience. One of the major unanswered questions in all of this is what the optimal formula for followup should be. For example, PSA’s every 3 months, or should it be more often? Should you initiate treatment based on some absolute number, or a change in the doubling time? Should you biopsy every 2 years, or should it be 18 months? What about doing mapping biopsy on everyone who wants to consider active surveillance? So many questions and so little time !

2 Comments

Filed under General Prostate Cancer Issues