Part 2. So Why So Many Biopsies?

 BY RALPH BLUM

 

“No More Unnecessary Biopsies . . . ” The first four words of the sub-title of our book, Invasion of the Prostate Snatchers,” are a clear statement of our objective. I am no fan of biopsies. At the same time I know that a biopsy is an essential diagnostic tool when appropriately used. The problem is that too many doctors schedule an immediate biopsy if there is only a slight rise in PSA, when it would be more appropriate to explore less invasive diagnostic methods first.

The Liability Factor: More and More Biopsies

One million men are biopsied annually in the United States. Yet only about one in five will be diagnosed with prostate cancer, and the majority of those will have Low-Risk disease—the type that will never become life threatening. Even so, most of these men will undergo some form of radical treatment. Having a biopsy is like opening Pandora’s box.

Doctors know that biopsies actually miss cancer about 20% of the time, especially in men with enlarged prostates. Which is one reason why, when an initial biopsy is clear of cancer, urologists often want to perform a second or even third biopsy, in order to confirm their initial findings. Naturally urologists are concerned about missing cancer in their patients; they don’t want to be responsible for a delayed diagnosis. They are also concerned about their vulnerability to lawsuits. In 2010, according to the Physicians Insurers Association of America (PIAA) the leading cause of malpractice claims against urologists was the failure to diagnose prostate cancer in a timely manner.  When in doubt, perform the biopsy.  “Better safe than sued.” So the number of biopsies continues to mount up.

If you and your doctor have done your due diligence, and the indicators suggest the possibility of an aggressive cancer, you need to get a biopsy. Transrectal Ultrasound (TRUS), preferably with color Doppler, is the most common method used to provide visual guidance for biopsy. A small ultrasound probe, inserted in the rectum, emits sound waves that bounce off the prostate and return to the probe with an image that is developed on a TV screen. Since cancer cells produce less reflection of the sound waves (a condition referred to as hypoechoic) the area will look different from normal prostate tissue, and thus show the urologist the precise locations to biopsy. The procedure, usually done in the urologist’s office, lasts approximately 20 minutes, should cause minimum discomfort., Total it up: a million of those procedures produces a gross revenue approaching half a billion dollars annually. Prostate cancer is a multi-billion dollar a year industry and growing. A significant portion of that industry’s growth is biopsy driven.

Prostate Oncologists: A Special Breed

After reading my first Biopsy blog (To Biopsy or Not to Biopsy—That is the Question) my screenwriter friend, Harvey Frost, reminded me that he was diagnosed with metastatic prostate cancer in 1996, and warned twice by his urologist that he had less than 5 years to live. “Since then,” Harvey told me, “I have been treated at USC’s Norris Cancer Center by a world class prostate oncologist. I was sentenced to death from prostate cancer when I was in my forties. Well, I plan on dying from something else in my 80s—no, make that my 90s!”

My best advice to any man newly diagnosed with prostate cancer is to find himself a prostate oncologist, if only for a consultation. The problem is that out of more than 15,000 medical oncologists practicing in the continental US, fewer than 60 appear to have taken a particular interest in prostate cancer, which makes them almost as rare as hen’s teeth. And even if the nearest prostate oncologist is 150 miles from where you live, make an appointment for a consultation, pack a lunch, gas up, and go!

Bottom line, when a biopsy is recommended, do your own research, and be aware of what you’re getting into. If there is any indication that your cancer is the aggressive type, a biopsy is still the best diagnostic tool available.  

Harnessing the Immune System to Fight Cancer

BY MARK SCHOLZ

Using the immune system to fight cancer is a rapidly advancing area of research. The immune system (as it relates to fighting cancer) is made up of three components: 1) regulatory cells (T_Regs), 2) killer cells, and 3) detector cells otherwise known as dendritic cells.  Dendritic cells activate the killer cells and help them “home in” on the cancer. 

Over the last 30 years, immune treatments have proven disappointing time after time due to a failure to address the immune system’s natural propensity of self-regulation. Self-regulation—inhibition of immune over-activity—is a normal aspect of immune function that prevents diseases such as lupus or multiple sclerosis. 

However, recent research reveals that some cancers, prostate cancer being one of them,  “cloak” themselves from immune attack by “kidnapping” T_Reg cells and using them as a shield to diminish or  inhibit killer cell activity.  This new understanding provides a good explanation of why the immune system fails to attack and eliminate cancer. Rather than being a type of weakness, immune inactivity is a type of blindness. 

Two new treatments, one that is already FDA approved and another that is in Phase III trials, are designed to counteract this blindness; they are Ipilimumab and Provenge.  Ipilimumab is a new drug from Bristol Myers that blocks an “on/off switch” on the surface of T_Reg cells. When the switch is in the on position T_Reg activity is up-regulated, suppressing the immune system. When the switch is locked in the off position by Ipilimumab, the inhibitory action of the T_Reg cells is taken off line. Ipilimumab was approved by the FDA in March 2011 to treat advanced melanoma. Preliminary studies of men with advanced prostate cancer have shown some dramatic results. In addition, Dr. Eugene Kwon from the Mayo Clinic has reported surprisingly good results against advanced prostate cancer using small doses of Ipilimumab in conjunction with hormone blockade. Presently two phase III trials of Ipilimumab in advanced prostate cancer are ongoing.*

Provenge was FDA approved to treat advanced prostate cancer in 2010 after two separate phase III trials showed that Provenge-treated men lived 20% longer than men treated with a sham infusion. Provenge works by providing a cancer “scent” (via a common cancer protein called PAP) to activate the dendritic cells and enable them to better home in on the cancer. Provenge is the ultimate individualized therapy because dendritic cells are filtered from the blood of each patient and exposed to PAP in the laboratory.  Each patient’s own activated dendritic cells are then reinfused back into the blood stream.

As exciting as both these intelligently designed therapies are as stand-alone treatments, the irresistible next step is to use them together. It is natural to assume that the effectiveness of a well-tolerated treatment like Provenge will be further enhanced when used in combination with a therapy like Ipilimumab that will keep the regulatory defenses of the T_Reg cells in check. I contacted Bristol Myers this week to inquire about the status of research into the effectiveness of a Provenge/Ipilimumab combination. I was assured that such a study is in the works and anticipated to become a reality in the near future. 

*Prostate Oncology Specialists is conducting two Ipilimumab trials in advanced prostate cancer.  Parties interested in participating in one of these trials in Marina del Rey, may contact Jennifer at (310)827-7707 or jennifer@prostateoncology.com. Additionally, you may visit http://ResearchForProstateCancer.com

Who's Afraid of a PSA?

BY RALPH BLUM

The straight answer? Every guy who’s ever been told his PSA was elevated for his age, and that he needs to have a biopsy. Because from that point on, things can happen fast. It’s the prostate cancer version of baseball’s famous Tinker-to-Evers-to-Chance double play—PSA Test-to-Biopsy-to-Surgery.

The PSA is a simple blood test for prostate-specific antigen, a protein produced by normal prostate cells. Cancer cells, however, produce more PSA per unit volume than benign cells, so an elevated PSA can be cause for concern. Since 1986, PSA testing, although not perfect, has served as the gold standard for widespread screening and early diagnosis of prostate cancer. Controversy arises from the fact that, at the first sign of an elevated PSA, your family doctor is likely to send you to a urologist who will almost certainly perform a biopsy—all too often opening the door to unnecessary radical treatment.

Avoiding False Readings 

There are other factors besides prostate cancer that can influence PSA test results. Here are some of them:

BPH: Benign prostatic hyperplasia, prostate enlargement caused by age or infection, induces an elevated PSA not indicative of cancer. 

Infection: Consider the possibility of infection. Some years ago, when my PSA spiked unaccountably from 7.4 to 20.3, my wife, Jeanne, who is a medical intuitive and practices Traditional Oriental Medicine, suggested to our family doctor that he put me on a course of the antibiotic Cipro. Which he did, and after ten days my PSA had dropped back to 9.25.

The 48 Hour Rule: It is possible that strenuous exercise, heavy lifting (like lugging suitcases through airports), sexual activity, and even bicycle riding before a PSA test will negatively effect the result. However, a false elevation is guaranteed if you get your PSA checked immediately following a Digital Rectal Exam (DRE) or too soon after intercourse. So don’t have a blood test for at least a week after a DRE, and avoid ejaculation for 48 hours before the test. 

Inconsistent Lab Work: Standardization of tests, or assays, from one lab to another, is still lacking. This makes comparisons between PSA tests done in different labs unreliable. If you have two or more PSA tests, make sure they go to the same lab for analysis. 

If any of these factors apply in your case, ask for a repeat PSA. 

When a PSA Makes Good Sense 

Early PSA testing makes the most sense if you fall into any of the following categories:

Family History: If you have a family history of prostate cancer, it’s advisable to begin PSA testing at 40 and repeat the test at six-month intervals.

African Americans: All African-Americans are advised to begin tests by age 40 regardless. The death rate from undiagnosed prostate cancer for African-Americans is currently two-and-a-half-times that for Caucasian men. This is partly for genetic reasons, and partly from reluctance to submit to a DRE—85% of cancers occur in the peripheral zone of the prostate gland, and therefore can be felt by the doctor performing the exam. A DRE is an essential diagnostic procedure.

Men Over 75: Nowadays, men over 75 are apt to be spared testing entirely. So you can always avoid the anxiety, and have a good time. On the other hand, you might just go for the PSA test anyway, and while you’re at it, have a thorough physical. I know a number of grateful men who never would have discovered that they had a serious heart problem or high blood pressure, if they hadn’t started with a PSA check. How long has it been since your last physical? 

The Politics of PSA Testing 

The best clinicians do not mindlessly screen all of their male patients. They decide which men should be tested based on age, symptoms, family history, expected longevity, general medical condition, physical examination findings, and—a significant factor—the patient's own request for the test. The goal of early detection remains to identify patients who have clinically significant cancers at a time when treatment is most likely to be effective.

Remember that, ultimately, the big decisions are all yours to make. Trust is crucial. So never hesitate to go for a second opinion. Bottom line, regardless of its shortcomings, the blood test for prostate-specific antigen is still the most useful and widely available method for detecting the presence prostate cancer. And if you want an encouraging statistic, here’s the really good news for men over fifty: 28 out of 30 of you who are reading this blog, and who do have prostate cancer, will die with it, not of it.

As you probably noticed, there is no “MD” after my name. Which means that my experience, my facts, and my emotional involvement are open to scrutiny and comment. In these blogs, I will be writing about matters that I know are of concern to men with prostate cancer, and to those who love them. You don’t need an MD after your name either, to point out something I’ve missed, or correct me if I’m off base. I welcome any PSA questions, advice or stories—reassuring or cautionary—that you’d care to share.

Sex, and Life after Surgery

BY MARK SCHOLZ, MD

After prostate surgery only 5-15% of men describe their sexual function as unchanged.¹ And I’ll venture that zero percent describe it as improved. For an average man with good preexisting sexual function, the best surgeons preserve some level of function about half the time—with the aid of copious Viagra. (Just so you know, the medical definition of function is anything adequate to “be stuffed in.” Seriously!) And erectile dysfunction isn’t the only way to ruin intimacy. Dr. John P. Mulholl, author of the excellent book, Saving Your Sex Life: A Guide for Men with Prostate Cancer, has coined the term “climacturia” to describe the distressing news that, after surgery, some men ejaculate urine rather than sperm.

Prostate Cancer Surgery is Difficult, Robotic or Otherwise
These sad results are not due to lack of effort. Over the last five years, prostate operations are up 50%. Every year, more than 70,000 men are taking a ride on the wild side.² The primary reason for all the excitement is robotic surgery. Can the robotic approach justifiably claim any advantages over older methods? Yes, scars are smaller; hospital stay is shorter and serious bleeding less frequent. However, for all its popularity, studies confirm that robotic surgery serves to preserve bedroom bliss just as poorly as the older standard techniques.

What About the “Average Surgeon?”
Quality control for prostate cancer surgery is nonexistent. The above statistics are for the most practiced and skilled surgeons.  Studies show that with average surgeons, results vary widely. For example, at reputable large academic institutions the likelihood incomplete removal of the cancer varies between 11 and 50%!³

What then might we anticipate from the “silent majority” of urologists at the community hospitals? If the number of operations is any indication, we need to be seriously concerned. In New York for example, for the whole year of 2005, one in five urologists only performed a single prostatectomy, while 80% of the urologists did less than 10.⁴ 

Does Surgery Save Lives?
The frightening risks of prostate surgery would certainly be justified if survival was increased dramatically. Yet despite an explosion in the use of surgery, prostate cancer death rates in the United States have only improved about half of a percent compared to 30 years ago. And experts aren’t entirely sure that surgeons can take credit for these slight benefits. Estimates indicate that on average surgery adds at most a couple months to a man’s life expectancy.

If Not Surgery, What?
Almost any other kind of treatment—seed implants, radiation, focal cryotherapy, hormone therapy, or active surveillance—is just as effective as and considerably less dangerous than surgery.  Consider that prostate cancer is the only remaining type of cancer where surgeons (urologists) are acting as the primary doctor. Men with other common cancers, say of the lung or colon, benefit by consultation with cancer experts called medical oncologists. Beware of indulging your initial gut reaction to “just cut it out.” Instead of saving your life from cancer, all you may be accomplishing is the eradication of your sex life.    

1. Harin Padma-Nathan, Journal of Urology, Abstract 1402, 2003.
2. Barbash, Gabriel, New England Journal of Medicine, 363:701, August 2010.
3. Eastham, James, Journal of Urology, 170:2292, December 2003.
4. Savage, Caroline, Journal of Urology, 182:2677, December 2009.