Mark Scholz

Mark Scholz
Authors of the Invasion of the Prostate Snatchers, Ralph Blum and Mark Scholz, MD bring you a weekly Prostate Cancer Blog from Marina del Rey, CA and Los Angeles, CA.

BLOGGERS: MARK SCHOLZ, MD & RALPH H. BLUM

The co-authors of Invasion of the Prostate Snatchers, blog alternate posts weekly. We invite you to post your comments.

Tuesday, April 15, 2014

The Art of Being a Patient

BY RALPH BLUM

In an essay entitled Complications: Surgeon’s Notes on an Imperfect Science, Atul Gawande, surgeon, writer and professor at Harvard Medical School wrote: “Just as there is an art to being a doctor, there is an art to being a patient. You must choose wisely when to submit and when to assert yourself.”
 
This advice is especially important if you have just been diagnosed with prostate cancer. Because prostate cancer is so common, and in most cases so slow growing, that to submit to any form of radical treatment could be a huge mistake, and hugely detrimental to your quality of life. Yet most doctors you consult will advocate some form of radical treatment. It’s what they know, what they do. And it goes against the grain for both doctors and patients alike not to treat cancer.
 
But prostate cancer is unique among cancers because the mortality rate is so low. Autopsies reveal that more than 50% of older men have the disease, live with it, and die from something else—sometimes without ever knowing they had a life threatening condition. Furthermore, the life expectancy of men with recurrent prostate cancer stretches out well past a decade. And yet the radical prostatectomy, one of the most complex and challenging surgeries because the prostate is located in absolutely the wrong place for a simple surgical solution, is still the most widely recommended treatment option. It is also the most unnecessary, and the one most likely to leave you incontinent and/or impotent.
 
My own experience with urologists has not been a happy one. Twenty years ago, a doctor who wanted nothing but patient compliance, told me that if I did not agree to immediate surgery I would be dead in two years. His recommendation and prognosis were not only wrong, but in my opinion violated the ancient medical precept incorporated in the Hippocratic Oath: “First do no harm.”  Fortunately I was not the kind of patient to be easily intimidated.
 
A significant part of any doctor’s job is to create a relationship based on trust, confidence and hope. And as patients, our job is to put ourselves in charge of our recovery. It is our job to do the research, and give ourselves permission to say “No” if we feel the recommended treatment—for what ever reason, or simply instinct— is not right for us.  My decision not to be intimidated by what, in effect, was a death threat, but to monitor the cancer and take the time to educate myself, has given me many years of quality time with my wife that almost certainly would have been lost or diminished if I had committed to immediate surgery.
 
Doctors have busy lives. They believe in what they do. But often they tend to treat the disease and not the patient. Traditionally we’re encouraged to go along with whatever they recommend, and asking questions, or refusing to follow advice is unpopular.  But this passive attitude does not serve us well. The feisty, “difficult,” assertive patient, the one who challenges the doctor, is the one who has the best outcome.

Tuesday, April 8, 2014

Prostate Cancer Clinical Trials

MARK SCHOLZ, MD

Clinical studies are primarily performed on men with advanced prostate cancer (the Royal Shade of Blue). Why?  The FDA.   FDA only approves new drugs when survival is proven to be prolonged compared to similar men treated with a placebo. The FDA’s insistence on a survival endpoint forces pharmaceutical companies to limit their research to men with a short life expectancy. If survival has to be the endpoint and the study participants live a long time, the cost of performing the study goes up exponentially.

Undergoing experimental therapy with a new medication is reasonable consideration when standard treatment is either no longer working or is causing unacceptable side effects.  However, it’s rare for doctors to recommend an experimental medication before other FDA-approved drugs on the market have been tried.  The commercially available treatments already proven to extend survival are Lupron, Provenge, Xtandi, Zytiga, Xofigo, Taxotere and Jevtana.

Getting Involved in a Trial Can Be Challenging

Eligibility requirements for participation can be rigorous. Trials have carefully specified pretreatment and health status criteria: Eligibility may be denied if the patient is either too sick or not sick enough, if there is too much previous treatment or not enough previous treatment. Criteria are pre-specified so that the final results of the trial are not skewed by a lack of uniformity among patients.  Other requirements designed to achieve trial uniformity include stopping all other anti-cancer medications and the use of placebos, both of which at times may be at variance with a patient’s best interest.
An additional challenge is finding the right trial that matches a patient’s need. The clinical trials landscape changes quickly.  New trials are initiated with limited fanfare and close as soon as they have met their pre-specified number of participants. Trials available at one center may not be so at another.  Another difficulty patient’s face is how to determine the effectiveness of a prospective study drug. Is it likely to work or not?  Due to a study drug’s newness, its functional characteristics are often unclear to patients and doctors alike.
There are different types of study designs to consider each with different goals.  Phase I studies, for example, are primarily designed to learn more about a drug’s side effects. Phase I studies sequentially escalate medication dosages up to determine the point of dosage intolerability. Phase II studies treat a group of patients at a fixed dosage to get a preliminary sense of a drug’s response rates. Phase III studies are the final step that leads up to FDA approval.  Phase III trials are the placebo-controlled trials.
The Business of Clinical Trials
Patients contemplating participation in a clinical trial should be aware that the clinical trial world functions like a business.  It’s funded primarily by the pharmaceutical industry. As such, doctors working in academia are highly motivated to find participants in their research.  If trials are not completed in a timely fashion funding for new trials will be harder to come by in the future.
Participating in a clinical trial has become more attractive over the last ten years as the pharmaceutical industry has made significant strides toward understanding cancer.  Now that they have access to cancer “blueprints” it’s feasible for brilliant biochemists to design “software patches,” new drugs that are far more effective and far less toxic than what has been traditionally available.  However, patients need be careful they don’t mistake a “new” drug for being an “effective” drug.  Despite the tremendous advances in research, most phase I and II drugs still fail to meet minimum standards of clinical effectiveness and never even advance to phase III testing. Sadly, many of the potential prostate drugs that have been tested in Phase III studies over the last ten years have failed to meet the FDA minimum threshold of showing a survival advantage.
Dr. Scholz is the Principal Investigator at Prostate Oncology Specialists - a list of the active trials are found at http://www.prostateoncology.com/clinical_trials

Tuesday, April 1, 2014

IMRT: The Gift that Keeps on Giving

BY RALPH BLUM

By 2013, I had lived with prostate cancer for almost 25 years without submitting to any form of radical treatment. I was fortunate that my cancer was the non-aggressive, slow moving variety. And over the years I became a strong advocate of a “Die with it not from it” policy.

I learned early on that a “Whatever you say, doc,” attitude can be dangerous, and I knew that the longer I could simply monitor the cancer and use the time to educate myself about the disease, the better off I would be. However, the main reason I resisted radical treatment was the book Mark Scholz and I wrote with the sub-title: “No More Unnecessary Biopsies, Radical Treatment or Loss ofSexual Potency.” I reckoned I’d better practice what I preached.

Then, a little over a year ago, when my PSA suddenly spiked to 26 for no reason I could determine (like BPH or an infection), I figured the cancer was finally on the move. And maybe, after all these years, my immune system was no longer the staunch ally it had been. Mark was reassuring. My cancer hadn’t changed—it was still the non-aggressive type. Which meant the odds of surviving were pretty much in my favor if I decided not to submit to treatment. Still, “To treat or not to treat” remained the question.

After determining that the cancer hadn’t spread to my lymph system or to my bones (big relief there!), I couldn’t help wondering if perhaps I was pushing my luck by sticking to my credo. And to tell the truth, I was getting tired of living with cancer. So as I am no fan of surgery, and anyway at my age (81) it was not an option, I decided to go for a cure with IMRT, Intensity Modulated Radiation Therapy.

It is now almost five months since I completed 45 sessions of IMRT, and I could not be more pleased with the results. At first, I was dismayed to see a rather snail-slow descent of my PSA. Then I learned—and this is the really big news—that cell death, or apoptosis, continues after treatment for another year to a year and a half. According to Lisa Chaiken, MD, an admirable and patient teacher, who is in charge of St. Johns Hospital’s IMRT program, “The cancer cells turn over slowly. More and more die off with the passage of time. There is an immediate impact of the radiation—the damage, is done—but the process takes time."

And get this: the cells only die when the time comes for them to divide! In trying to participate in the creative process of replication, cell death, apoptosis, is the result.  The cancerous cells are actually committing suicide: How’s that for irony?

To confirm with visual evidence what is taking place, I’ve been to see radiologist Duke Bahn, MD and compared his various ultrasound images of my prostate: the multiple red tributaries indicating angiogenesis (the flow of new blood to the tumor), once as thick as a busy river delta, are now reduced to a scattered few!

An unexpected bonus for me from undergoing IMRT is a new understanding of PSA function, about which I was always uncertain in the past. Now that I understand the process, the behavior of my PSA—post-treatment—makes total sense: As the cancerous cells die off, the PSA falls. I am now almost five months post treatment, and my PSA has dropped from 26 to 17 to 7.8 and a week ago, in the most recent PSA, to a gratifying 2.8! A level I haven’t seen in a quarter of a century!

Technically speaking, I still have prostate cancer. But my cancer is terminally feeble, itself waiting for the final cut by the Grim Reaper of cancers.

IMRT is truly the gift that keeps on giving!

Tuesday, March 25, 2014

Shades of Blue, Trying to Simplify a Complex Situation

MARK SCHOLZ, MD

How can one disease be so vast?  Actually, it really isn’t one disease; there are hundreds of variations: Prostate cancer can be slow or fast growing, responsive or unresponsive to treatment, metastasizing early or not metastasizing at all.  In fact, selecting treatment for prostate cancer would be simpler if these extreme “either-or” types of examples I just cited were common. In reality, most men’s cases are not so extreme, they lie somewhere in the middle.  Selecting the best treatment, one that matches each variety of prostate cancer, is a really big challenge. Therefore, the process begins by trying to understand the disease as well as we can.

Characterizing the Disease
People often assume that differences in the way cancer behaves—life threatening vs. benign—comes from observing the same illness at different time points.  What’s often misunderstood is that distinct varieties of prostate cancer also exist. It’s not all one disease. This doesn’t mean that the stage of disease is unimportant. It’s just not the whole picture.  Patients frequently ask, “Am I stage A, B, C, or D?” without realizing the lettering system is just a description of what the surgeon feels during his finger exam. PSA and the Gleason grade are just as important as the stage of the disease. What can be confusing is that no single element comprehensively defines the disease. For example, one man with a higher PSA may do well while another man whose PSA is low may do poorly.

A Widely-Accepted Classification System
Therefore, a classification system to help predict cancer aggressiveness requires a “grid” that incorporates multiple prognostic elements—the letter-stage, PSA, Gleason and scan results.  Dr. Anthony D’Amico from Harvard is credited with developing the modern system that uses PSA, Gleason and stage to divide newly-diagnosed prostate cancer into low, intermediate and high-risk categories.

Building on the D’Amico system, and to further highlight the differences between categories, the Prostate Cancer Research Institute (PCRI) has named the risk categories with different Shades of Blue* and expanded the grid to include two more categories: men with disease relapsed after treatment with a rising PSA and men with metastatic disease or disease that has become resistant to hormonal therapy.

The Five Shades of Blue:  



Sky for low-risk
Teal for intermediate-risk
Azure for high-risk
Indigo for PSA-relapsed disease after treatment
Royal for men with metastases or hormone resistance

Does the system separate men into distinct categories?  Yes. For example, in a study published by Dr. Timothy Wilt in the New England Journal of Medicine, 731 men volunteered between 1994 and 2002 either to have immediate surgery or observation alone.  The subsequent outcome showed higher cancer mortality with in men in a higher-risk (Azure) category compared to Sky or Teal. It also showed an 8% improvement in ten-year survival rates for men in the Azure category when they underwent surgery (rather than observation).  Surgically-treated, intermediate-risk men (Teal) showed a 10% reduction in the incidence of metastases compared to the men who did not have surgery. Men in the low-risk category (Sky) showed no difference in mortality or metastases with or without treatment. Dr. Wilt’s study, therefore, went beyond merely validating the predictive ability of the D’Amico staging system. The study also provided a measure of the degree of benefit associated with doing surgery.

General Treatment Recommendations

While there are no absolute rules for treatment, as a starting point, here are some general guidelines:

Sky (low-risk): observation or monitoring with active surveillance

Teal (intermediate-risk): monotherapy, limiting treatment to a single therapy such as IMRT or surgery or brachytherapy

Azure (high-risk) combination therapy with IMRT, brachytherapy and hormone blockade

Indigo (relapsed-disease): Treatment intensity tailored to the location in the body of the relapsed disease and to the PSA doubling time rate

Royal (advanced-disease): Multimodality immunotherapy, hormonal therapy, chemotherapy and radiation sequentially or in combination

The message is that before treatment can be selected what we are treating needs to be accurately defined.  The starting point, therefore, is to begin with dividing prostate cancer into five broad categories or Shades of Blue.  By doing this, the number of treatment options can be narrowed down and finding the right treatment becomes easier.