Institute for Prostate Cancer Research

IPCR Director's Corner Newsletter October 2010

Director's Corner

Screening for Prostate Cancer - What's the Confusion All About?  

Welcome to the Institute for Prostate Cancer's inaugural newsletter -- the first in a series of commentaries on important issues about prostate cancer and how they might relate to the work of the IPCR. I hope you enjoy them — and I welcome your comments and suggestions.

The viewpoints in these commentaries are my own. Unanimity of opinion among the many, talented and multidisciplinary doctors in the IPCR is rare, with one exception; we believe we will make a contribution, and we believe we'll be around when we have cured, or at least dramatically controlled, this serious cancer.

And now, on to my first topic: prostate cancer screening.

Perhaps the most perplexing issue to survivor, layperson and expert alike is the controversy surrounding the early diagnosis of prostate cancer, called screening. You've all seen the recent headlines that shout that screening is harmful, that PSA is a bad test, and that early diagnosis doesn't work and is too expensive. Let me dispel these rumors, because that's what these headlines are: rumors.

In fact, diagnosing prostate cancer early is important and necessary!

Below are a few observations about prostate screening, as well as a few examples of how IPCR researchers are leaders in defining these issues. (For those of you who'd like to read more, see the end of this article.)

Bird flying out of fenced field. Turtle in fenced field. Rabbit hopping out of fenced field.

There are many types of prostate cancer. 

Years ago, I illustrated this fact by comparing prostate cancer to several animals in a fenced-in barnyard. The most important critters for our consideration here are the "turtles" and the "birds."

The turtles grow slowly and only escape (i.e., metastasize and kill) when they reach a certain size, and then only rarely. The birds grow at different rates, but always faster than the turtles. When they reach a certain size, they are apt to escape control. We know that, with prostate cancer, many more men have turtle-like tumors than bird-like ones.

With widespread PSA (prostate-specific antigen) screening in this country, approximately 250,000 men are diagnosed with prostate cancer each year; approximately 29,000 men die. With the turtle-bird model in mind, we say that most men die with prostate cancer rather than of prostate cancer.

What's at issue is excess treatment. With early diagnosis, doctors pick up way too many "turtles." If we treat all the cancer we find, we treat too many men, and because all treatments (e.g., radiation, surgery) have some side effects, there is a risk of causing needless harm.

Still, prostate cancer kills; it's the second-most deadly cancer for American men.

Making All the Difference   

The breakfast reminded us that cancer afflicts many of our families, and that progress toward a cure is both necessary and possible. Fortunately, the Institute for Prostate Cancer Research is well positioned to make such progress.

At last count, the institutions that comprise the IPCR (UW Medicine and Fred Hutchinson Cancer Research Center) are in the top 5 prostate cancer research institutions nationally in acquiring federal funding for our research. Considering that only 7 percent of the research grants submitted to the National Institutes of Health (NIH) are currently funded, this is an amazing ranking. Yet every major multidisciplinary prostate cancer research center needs considerable private support to function at a high level. 

This year, we plan to use most of the proceeds from the breakfast to fund pilot projects; we’re reviewing proposals even now. These are innovative, sometimes out-of-the-box ideas, often developed by junior researchers. Support allows these researchers to gather data needed to show proof of concept, a requirement before scientists can apply for more significant support, such as government grants. Providing the opportunity for a scientist to pursue new, high-risk, high-reward ideas is commonly what it takes for true innovation to occur in medical science. These projects have frequently made all the difference in the history of cancer research.

What's the value of screening?

The real question is this: does screening capture the "birds"? Does it prevent death from prostate cancer? And is it worth the cost?

With the therapies we have now for early disease, it sure looks like it! As delineated nicely by our own Janet Stanford, Ph.D., and her superb population science group, the death rate from prostate cancer has plunged in places where screening is widely practiced. Yet we need more proof, and, in medicine, that usually requires controlled randomized trials that are very expensive and take a long time.

What do we know from these trials?

The best trial on prostate cancer screening was done in Europe. It compared the prostate cancer death rate between men who were screened and men who were not. The good news is that they found that the group that received screening had between 25-31 percent fewer prostate cancer deaths (depending on how you interpret the data).

Looked at a different way, the study shows us that, to save one man's life, we now need to screen approximately 1,200 men and do approximately 200 biopsies (which will uncover 50 men who have cancer). Most of us believe that because the bird-type tumors take a long time to kill their host, these figures will be pared down significantly with longer follow-up. Still, that's a lot of unnecessary medical procedures, with accompanying costs, both financial and physical.

Is the PSA test any good? 

Once prostate cancer is discovered and the prostate is removed by surgery or destroyed by radiation, PSA is an outstanding blood test, one that can determine if cancer is still present.

When the prostate is present and alive, however, things are more complicated. This is because PSA is produced by both normal prostate cells and prostate cancer cells; in both kinds of cells, PSA leaks out into the blood (and it leaks more from the cancer cells unless the normal cells are inflamed). But cancer cells often make less PSA than normal cells. When all these factors are combined, deciding whether a man with a PSA level under 10 should get a biopsy makes for a complex situation involving complicated probabilities.

But -- make no mistake about it -- when properly interpreted by an expert, the PSA is a very valuable (though imperfect) test, one that helps physicians decide if a prostate biopsy is appropriate. Better biomarker tests need to be developed, ones that detect cancer more reliably, reduce the number of unnecessary biopsies, and pick up the "birds," rather than the "turtles." Many IPCR researchers, including Pete Nelson, M.D., Muneesh Tewari, M.D., Ph.D., and their associates, are looking for these biomarkers using very sophisticated technologies.

What should we think? and do? 

There are many treatment possibilities, ranging from doing no screening at all to biopsying everyone and aggressively treating all the cancers found. Hutchinson Center epidemiological statistician Ruth Etzioni, Ph.D., and her associates are known internationally for defining the consequences of a variety of options. This has allowed clinicians like me to develop more informed opinions about what to do.

As detailed in the editorial I reference below, I believe we should aggressively diagnose prostate cancer in all men who are likely (all things considered) to live 10 or more years longer. We should also aggressively treat men with "serious" cancers (e.g., those with high PSAs or with a lot of cancer in their prostate, particularly if the cancer looks aggressive under the microscope).

As for the rest of our patients (approximately 30-50 percent) we should watch them carefully; we call this active surveillance. Active surveillance entails regular exams and PSA tests, periodic prostate biopsies, and aggressive treatment for those men (about 30 percent) that get worse.

IPCR faculty, led by Dan Lin, M.D., and Pete Nelson, M.D., are leading the country in active surveillance and in finding better biomarkers to make this approach more accurate and less bothersome.

The exact approaches to early diagnosis and active surveillance will be topics of subsequent commentaries. For now, you can find out more by visiting the American Urological Association's website or the National Comprehensive Cancer Network'swebsite.

I hope this brief summary of a very complex subject is useful to some of you -- and that it gives all of you a sense of some of the interests that occupy the IPCR's many researchers. Finally, please accept my best wishes for a good and healthy summer.

For more reading on screening, see:
Lange, PH: Editorial comment on: Albertsen, PC: The unintended burden of increased prostate cancer detection associated with prostate cancer detection associated with prostate cancer screening and diagnosis. UROLOGY 75: 399 - 406, 2010. Copyright 2010

Join Us at the Survivors Celebration Breakfast

On Thursday, December 9, 2010, the IPCR is holding a very special event: the 2010 Prostate Cancer Survivors Celebration Breakfast. That morning, prostate cancer survivors and their families -- and members of Seattle's business and medical communities -- will come together to support prostate cancer research.

We're looking forward to the keynote speaker: Mitchell H. Gold, M.D., president, CEO and director of Dendreon Corp. Dr. Gold is a UW Medicine alumnus and a dynamic speaker, and Dendreon is a local biotech company that works on cancer treatment; they recently received FDA approval for a new therapy to treat advanced prostate cancer.

We hope you can attend the breakfast, perhaps even assemble a table or two. To learn more, please visit the breakfast's website. As event founder and Seattle businessman Steve Fleischmann says, December 9 is sure to be a powerful morning. We'd like to share it with you.

For more information about the Survivors Celebration Breakfast, visit the website or contact UW Medicine Advancement Special Events at (206) 543-7873 or meddev@uw.edu.

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