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, December 25, 2012

Merry Christmas!

Merry Christmas to you! Please check out these sites for prostate cancer info.

www.prostateoncology.com
http://pcribc.org/forum.php

 We are excited about 2013 and we'll see you in the new year.

Tuesday, December 18, 2012

Urologist and Radiation Therapist Attitudes toward Active Surveillance

BY MARK SCHOLZ, MD

In May of every year over 10,000 medical oncologists from around the world attend a 5-day meeting sponsored by the American Society of Clinical Oncology (ASCO) where preliminary results of the latest cancer research are presented.  Thousands of research projects are summarized and published in short 300-word abstracts.  What follows is a long quote of almost the entire abstract published in 2012 by Dr. Simon Kim from the Mayo Clinic:

“While active surveillance is well recognized as an acceptable treatment strategy for low-risk prostate cancer, the extent to which radiation oncologists and urologists perceive active surveillance as effective and routinely recommend it to patients is unknown. Therefore, we sought to assess the attitudes and treatment recommendations for low-risk prostate cancer from a national survey of prostate cancer specialists.
Methods: A mail survey was sent to a population-based sample of 1,439 physicians in the U.S. from late 2011 and early 2012. Physicians were queried about their attitudes regarding active surveillance and treatment recommendations for patients diagnosed with low-risk prostate cancer (PSA<10 ng/dl; Stage = T1c; Gleason 6 in one of twelve cores).
Results: Overall, 321 radiation oncologists and 322 urologists completed the survey for a 45% response rate. Most physicians reported that active surveillance is effective for low-risk prostate cancer (71%) and stated that they were comfortable routinely recommending active surveillance (67%). Urologists were more likely to agree that active surveillance is effective (77% vs. 67%; p=0.005) and were comfortable recommending active surveillance (74% vs. 61%; p=0.001) compared with radiation oncologists. Most physicians recommended radical prostatectomy (47%) or radiation therapy (32%), but fewer endorsed active surveillance (21%) for low-risk disease. After adjusting for physician covariates, radiation oncologists were more than eleven-times more likely to recommend radiation therapy, while urologists were 4.7-times more likely to recommend surgery and 2.1 times more likely to recommend active surveillance for low-risk prostate cancer.
Conclusions: Although active surveillance is widely viewed as effective by radiation oncologists and urologists, most urologists continue to recommend surgery, while most radiation oncologists recommend radiation therapy. Our results may explain in part the relatively low contemporary use of active surveillance in the U.S.”
My Comment: This study clearly documents that urologists and radiation therapists, while acknowledging that active surveillance is acceptable, overwhelmingly recommend surgery and radiation. Not surprisingly, the urologists recommend surgery and the radiation therapists recommend radiation. The study findings are remarkable because they were not generated by a third party. This report depicts urologist and radiation therapist behavior though a self-description survey. Clearly, broader acceptance of active surveillance will be impeded until the day when urologists and radiation therapist physicians are willing to act on what they know to be true about active surveillance rather than simply giving it lip service.   

 

 

 





Tuesday, December 11, 2012

The FDA and Its Firing Squad (Combidex Part 3)

BY RALPH BLUM


There are a number of things concerning Invasion of the Prostate Snatchers of which I am proud. Two in particular stand out.

First, that despite his full and demanding schedule, Mark Scholz and I were able to collaborate effectively to produce this book. I have received a whole heap of emails from men thanking us and pointing out that, as far as they know, it is the first time in the literature on prostate cancer where the voices of doctor and patient were heard speaking as peers, each presenting those aspects of the disease he considered of primary importance to the newly diagnosed.

Second, it was both surprising and gratifying to learn that Snatchers had been awarded the 2011 Nautilus Book Award Gold Medal for “Conscious Media and Investigative Reporting” as the result of our tracking down the FDA rejection of Combidex. Since many of you have not read our book, and I know of no other readily available report on that destructive process, I want to review it here as part of the Combidex story.

I was determined to find out why the FDA had rejected Combidex back in 2005. I started by tracking down Jerome Goldstein, the former CEO of Advanced Magnetics (Ad Mag), the Cambridge, Massachusetts company that had marketed Combidex. I found him through his golf club, the Country Club in Brookline.

         “So what do you want to know?” Goldstein asked.

         “What went wrong? Why did the FDA reject Combidex? And can I quote you?”

         “I’m retired now,” Goldstein said in a gruff voice. “so I suppose you can quote me.

Some of the blame was ours. Our application was too broad. We should have gone for disease specificity. But that’s only part of it. The FDA bureaucrats in ODAC were also to blame. ODAC—that’s the Oncologic Drugs Advisory Committee—has total control over the life and death of every new drug application. And because of ODAC’s decision, prostate cancer patients are dying and suffering needlessly.”

Ad Mag’s fatal error was that instead of specifying Combidex as a contrast agent for establishing lymph node involvement in one type of cancer—prostate cancer—they had tried to broaden its application to cover all cancers. They should have known better. Once it has FDA approval for a single “indication,” it is legal for doctors to use a drug “off label,” meaning, wherever, in their judgment, it is useful.

I asked Goldstein if it was possible to obtain a transcript of the ODAC meeting, and he told me that their meetings were a matter of public record. Then, in a low angry growl, he said, “Nobody should ever die from this disease. It’s a crime.” I was about to hang up, when he said, “You know I have prostate cancer. I was diagnosed two years ago. Gleason 6. My internist said I should do surgery or put seeds in.”

         “So what did you do?”

         “Nothing.”

         “Nothing?”

         “Well, not exactly nothing. I bought a new putter.”
 
Although the transcripts of FDA meetings are a matter of record, they are not that easy to find. What’s more, they are not indexed so you have to dig. When I finally read the minutes and watched a video of the March 3, 2005 ODAC meeting, it was painfully obvious that there was plenty of blame to go around. But the way Combidex—NDA Application 21-115—went down really pissed me off.

ODAC found lots to attack. One patient went into anaphylactic shock from the Combidex. They delivered CPR and epinephrine, but it was too late: the man died at the hospital thirty-five minutes later. The fact that this single death had occurred a decade earlier, and had resulted in an immediate shift in method of delivery—from injection, to dilution of the contrast agent in saline and use of slow infusion—did not reassure the FDA. When I went through the Combidex records, I learned that the man who had died was so eager to participate in the trials that he failed to disclose his allergic condition, or that he had gone into anaphylactic shock on other occasions. Ad Mag pointed out that the vast majority of test subjects had only very minor and transient adverse (mainly allergic) reactions and that only four out of 1,236 patients had experienced a more serious adverse reaction. There had been no further deaths and no serious side effects.
 
After interviewing several staff members at Ad Mag, I became very aware of the financial reality. Contrast agents are not economically viable. Subjected to all the same requirements as a drug, a contrast agent like Combidex can cost over $100 million to develop, and the likelihood of FDA approval is increased by having a narrow indication. But here’s the irony: the narrower the indication, the less chance the company will ever recoup its money.

And there is a fundamental problem with imaging substances in general. Contrast agents are regulated just like drugs: the same standards apply for a contrast agent as for an antibiotic used to treat a life-threatening infection. Apparently it takes an act of Congress to get contrast agents regulated differently from drugs, and so far that hasn’t happened. But it’s obvious that there need to be different rules for approving imaging agents. Just another disgrace. Add it to the list.

What a crock! A normal lymph node for somebody with breast cancer is no different than a normal lymph node for somebody with prostate cancer. Combidex is “taken up” only in normal tissue. If the tissue’s not normal, the contrast agent is not taken up, and you know there’s cancer.

So while it would appear that applying for a broad application not only made medical sense, it was the only hope Ad Mag had of getting their money back.

There’s a lot more to the death of Comidex. You’ll find it in two chapters of our book: Chapter 15, “Now Playing for a Limited Time Only: The Combidex Follies,” and more in Chapter 17, “Anatomy of an Assisted Suicide.”

I admit it. I’m pretty much obsessed with the fate of Combidex. But as some French person once said, Rien ne vaut un bon obsession . . . (“There’s nothing as valuable as a good obsession.”) And now I’ve found an ally (See prior Combidex blogs) in the courageous Prof. Jelle Barentsz

Combidex redux!

 

Tuesday, December 4, 2012

The Science Behind Active Surveillance

BY MARK SCHOLZ, MD

Active Surveillance versus the “Gold Standard”         
Ten years ago surgery was called the “Gold Standard,” the treatment to which every other kind of treatment should be compared.  Now you rarely encounter the Gold Standard argument to bolster surgery as the preferred treatment approach.  What scientific studies led to this change in perspective and why has it taken so long for this change to come about?
 
Finally, a Clear Answer
The final nail in the “Gold Standard” argument occurred in 2012, when the New England Journal of Medicine published a study by Dr. Timothy Wilt comparing the long-term outcome of surgery versus observation.1 Between 1994 and 2002, seven hundred and thirty-one men volunteered to undergo either surgery or observation based on a coin flip. 

No Benefit for “Good” Cancer, Modest Benefits for “Bad” Cancer
The average age for the whole group of men was 67. The median PSA was 7.8. The study ultimately concluded that here was no difference in prostate cancer mortality with either approach. Mortality was within the expected range of statistical variation (5.8% died in the surgery group and 8.4% died in the observation group).  A small survival benefit for surgery was seen in men with a PSA over 10.  (Mortality was 12.8% in the observation group and 5.5% in the surgery group.) Dr. Wilt also reported the side effects of surgery.
     
Even before Dr. Wilt’s report was published, Active Surveillance had been gaining mainstream acceptance in the medical community. Multiple, independently-published studies consistently reach the same conclusion that Active Surveillance is safe.  Some of these studies are briefly summarized in the next few paragraphs. The full abstracts are posted on our website at www.keepmyprostate.com. 

Do All Men Have Prostate Cancer?
One of the most compelling arguments for forgoing radical treatment is based on the fact that prostate cancer is simply too common in the general population to represent an imminent threat to life. Studies of prostate glands removed from men dying of unrelated causes show that by the time they die, most men harbor prostate cancer.1 That prostate cancer is incredibly common in the normal male population is also supported in another report from the New England Journal of Medicine where 4,692 healthy men over age 50 with a normal PSA (average 2.7) volunteered to undergo a simple six-core prostate biopsy.  The resulting biopsies showed that one-fourth of the men had cancer.2

Many Studies, Same Conclusion
Additional research has looked into comparing Active Surveillance with surgery. For example, a study from Johns Hopkins reported that life expectancy is only extended an average of 1.8 months by having immediate surgery.3  Another study in the Journal of Urology confirms that the grade of the tumor is an excellent method for determining which type of cancer is safe to monitor because prostate cancer mortality was almost nonexistent in 12,000 men with Gleason score of six or less  who were monitored for 12 years after surgery.4

Additional studies reporting the long-term outcome of Active Surveillance have been published: In a ten-year study of 1,000 men undergoing observation at Johns Hopkins Hospital, not a single man has died of prostate cancer or developed metastases.5 In another study of 450 men undergoing observation in Toronto that included some men with grade 7 disease, five out of 450 men died of prostate cancer.6

The Dark Side of Treatment
The idea of living with cancer may not seem at all attractive, but once the side effects of surgery are factored in, Active Surveillance starts to look really good. Unfortunately, the side effects of radical treatments like surgery are universally underemphasized by doctors and patients alike. Doctors downplay the effects of surgery because their years of working in the field accustom them to impotence and incontinence in their patients. The patients who have had treatment and are lucky enough to have had a good outcome, sing the praises of treatment because they took a radical step to remove their cancer and were fortunate to avoid bad consequences. The patients with bad outcomes are frequently too embarrassed to talk about their diapers and sexual incapacity.  They minimize the bad effects of the treatment and emphasize their gratefulness about “having been saved from cancer.”

The fact is that surgery and radiation cause permanent side effects with astounding frequency.  In a study of 475 men, four years after having surgery or radiation, less than 20% of men described their sexual function as returning to normal.7 In another study of 785 men, three years after surgery or seed implantation, less than 20% of men who had surgery and less than 50% of the men who had seeds described their sexual function as returning to normal.8 Unfortunately, to many people, all these statistics are an abstraction. Nevertheless, the tragedy of unnecessarily destroying even one man’s sexual identity cannot be calculated.

At First, New Thinking Always Seems Radical  
Let me close with an acknowledgement that Active Surveillance involves a totally new way of thinking. The very first conference to review the science of Active Surveillance was convened in San Francisco in 2007. At that time two hundred prostate cancer experts laid down the basic guidelines for Active Surveillance.  Doctors around the world are still being introduced to the idea of Active Surveillance. Believe it or not, some doctors have not even heard about it.  Inevitably, it takes time for people to change. Even so, that’s no reason for you to be trapped by outdated thinking.

Tuesday, November 27, 2012

Life After Combidex - Part 2

BY RALPH BLUM

If after my long association with prostate cancer, I could achieve one objective—strike one blow for all the thousands of men facing the uncertainty of lymphatic involvement—it would be to see the presently FDA scorned and excommunicated compound “Combidex,” restored to favor, in production and universally available for the Combidex MRI.


This contrast fluid consists of minute Fe nanoparticles (iron particles) that are injected into a vein in the arm. After 24 hours, metastases in lymph nodes (LN) that show less “uptake” of the iron oxide nanoparticles, are visible as a white structure in a dark background, whereas normal nodes display as black and are thus not distinguishable. The white metastatic lymph nodes light up like light bulbs in the darkness, and can hardly be missed by the radiologist.


I do my due diligence: regular PSAs. But lately, I have been anxious; concerned that my immune system is no longer doing its job as well as it did in the past. True, I have no compelling evidence that my cancer is “on the move,” changing color by Mark’s Blue Scale, edging from “Sky” to “Teal” to “Azure”, with each deepening “Shade” bringing heightened  “Risk.” And yet sometimes in the night I wonder: Is that a swelling I feel in certain lymph nodes?

What makes this a period of greater insecurity is the absence of my old ally “Combidex”.  It wouldn’t be that difficult to set my mind at ease about whether or not there is lymphatic involvement if, as I did five years ago, I could again take myself off to the clinic of Dr. Jelle Barentsz, Professor of Radiology at Radboud University in Nijmegen, The Netherlands, and undergo a Combidex MRI.

There are other tests available. But from what I’ve seen of the stats, either they don’t do the job the way Combidex did, or more research is required. Still, here are four you might want to check out. I confess that I am out of my depth here, reporting as a non-medical voice without pretension of authority or a guarantee of accuracy:

1. 11C Choline PET CT while effective to a point, is not good in detecting nodes <5 mm. In this regard, Combidex was clearly superior.

2. Feraheme (ferumoxytol) is not as effective going to normal nodes as Combidex, and thus has a significantly higher number of false positives! Anyone who uses this agent for nodal imaging should be aware of this, So again, this substance is not a good substitute for Combidex.

3. The new Prostascint Imaging (Indium-111: Labeled Capromab Pendetide) which shows promise (it is more specific PSMA) but is still in its early phases of testing. Indications are that  Prostascint may be useful to evaluate post-prostatectomy patients with rising PSA who have an otherwise negative or equivocal workup for metastases. Another potential role for Prostascint (controversial) is in the staging of newly diagnosed prostate cancer.

What is worth doing? My mind is preoccupied with thoughts of risk (doing nothing) versus trauma (the ghastly side effects). I have long thoughts about the “velocity of change.” I meditate about risk versus trauma. And I pine for Combidex.

Perhaps my Better Angels have been on the job. Because just as I finished this blog, I received a note from Dr. Barentsz in the Netherlands, informing me that maybe—just maybe—Combidex is about to stage a come back. And asking for my help. Did he ever come to the right man! I will lay out the strategy in my final “Life After Combidex” blog.

Hot dog! Combidex redux!

Tuesday, November 20, 2012

Provenge Treatment for Prostate Cancer

BY MARK SCHOLZ, MD

In 2010, Provenge was approved by the FDA, the first approved prostate cancer treatment that functions by enhancing the immune system.  Over the last couple of years Provenge has been gaining popularity with oncologists and urologists as well as with patients. What has been surprising to me is how slowly doctors and patients have warmed up to the idea of using the immune system to fight prostate cancer. For years my patients have been taking handfuls of Graviola, Shitaki mushrooms, Pau de Arco and Esiac tea because of unsubstantiated claims of immune enhancement. Yet, when the FDA approved an effective immune treatment that prolongs life I was surprised that my patients needed to be convinced to use it. 
Why, you might ask, is there any hesitation in the first place?  Well, Provenge is certainly different from other anticancer therapies at least in one very distinctive way:  Whereas the effectiveness of most treatments is signaled by a drop in PSA, PSA levels usually don’t decline after Provenge.  Having supervised more than a hundred Provenge-treated men, I have certainly seen exceptional cases with dramatic PSA declines. However, this is not the general rule. Most of the time PSA continues rising after Provenge. So people start wondering, if PSA is not dropping, how can Provenge prolong survival?  People forget that even though Provenge is administered over a six-week period, once the immune system is activated, it keeps functioning indefinitely; it’s the gift that keeps giving for the rest of your life.  Therefore, even if Provenge only slows disease growth slightly, the inhibitory effect keeps accumulating over time. So over a period of years, even a mild effect can become substantial.

If the hypothesis that Provenge is inducing a mild, long-lasting anticancer effect is correct, men take Provenge at an earlier stage (who have a longer projected survival) should receive a bigger survival benefit than men treated at a later stage. To test this thought, Dendreon, the manufacturer of Provenge, analyzed data from the original studies that led to FDA approval. Please note:  the researchers did not compare the survival of men treated earlier versus the survival of men treated later.  Obviously, men treated at an earlier stage live longer.  No, what they did is compare survival of Provenge-treated men with earlier-stage disease with similar-stage placebo-treated men.  They did the same analysis (Provenge-treated men versus placebo-treated men) in men with later-stage prostate cancer and in men with disease “in between” early and late stage.  Early stage—low-intermediate stage, high-intermediate stage and late stage—was defined by PSA levels of less than 22, 22-50, 50-134, and greater than 134 respectively. The table below summarizes the results of their analysis.

 
 
Patients Grouped by Baseline PSA 
 
 
 ≤22
22–    50
50–134
 >134
Number patients
128
128
128
128
Survival  months:
 
 
 
 
Provenge
41.3
27.1
20.4
18.4
Placebo
28.3
20.1
15.0
15.6
Survival Difference:
13.0
7.1
5.4
 2.8

 As can be seen from the table, all groups that were treated with Provenge showed a survival advantage compared to the same stage men treated with placebo.  However, when Provenge was given at an earlier stage, the survival advantages became larger. Men with the earliest stage (PSA < 22) lived 13 months longer than similar stage men who were placebo-treated. Men with advanced stage only lived a couple months longer than advanced-stage placebo-treated men. 
This pattern of improved survival with earlier stage disease seems to fit the hypothesis that the inhibitory effect of Provenge results in a progressively longer survival when its effects are allowed to accumulate over a longer lifespan.  Based on this data one would logically conclude that Provenge induces the biggest benefits when administered at the earliest possible stage.  In the real world, where Provenge is only covered by insurance for men who are hormone resistant and have metastases, men on Lupron who have a rising PSA should be vigilantly monitored with scans such as Prostascint, C11 acetate PET and Sodium Fluoride PET scans every 6 months to detect metastatic disease at the earliest possible stage. 

Tuesday, November 13, 2012

Life After Combidex (Part 1)

BY RALPH BLUM

A few days ago I got an email bemoaning the demise of Combidex, and asking for a review of the situation, including what replacements were on the horizon. So in this Blog and the next, I will attempt to shed some light on the matter.

The most common areas of prostate cancer metastasis are the pelvic or abdominal lymph nodes and the bones, but detecting whether the cancer has spread to the lymph nodes is a problem, because no truly reliable diagnostic test for lymphatic involvement is currently available.

In 2007, when my Gleason score had gone from 6 to 7 and the cancer had arrived in the left seminal vesicle, I traveled to the Netherlands for a Combidex MRI. According to the makers, Advanced Magnetics, Inc. (now AMAG Pharma), Combidex, the brand name for ferumoxtran-10, could “assist in the differentiation between metastatic and non-metastatic lymph nodes in patients with confirmed primary cancer who were at risk for lymph node metastasis.” How it worked was that metastatic lymph nodes showed less “uptake” of the iron oxide nanoparticles. Fortunately for me, all my lymph nodes were clear. However (and it’s a long story that I detailed in Invasion of the Prostate Snatchers) the Combidex infusion MRI, by far the most reliable (better than 90% accurate) diagnostic test for lymph node detection, didn’t make it past the FDA watchdogs, and AMAG Pharma discontinued the production of ferumoxtran-10. So the Combidex MRI is presently no longer available anywhere.

The primary FDA-approved diagnostic test for detecting lymphatic involvement is the ProstaScint scan. Given by an intravenous injection, ProstaScint circulates throughout the body and attaches to prostate cancer cells. The injection contains a small amount of low-level radioactive material that is absorbed by the cancer cells and shows up as “hot spots.” But the findings are subtle, with a high risk of false positives, and an absolute necessity with the ProstaScint scan is an extremely experienced interpreter.

Meanwhile in Holland, Dr Jelle Barentsz, Professor of Radiology, UMC  St. Radboud,  Nijmegen, has been working on a validation study of Feraheme (made of nano-particles of iron) as a lymph node diagnostic agent. Feraheme is the contrast agent with which AMAG Pharma replaced Combidex, and Dr. Barentsz’ study is to find out if Feraheme is as good a contrast agent as Combidex. Currently Feraheme is only approved for treating patients with iron deficiency anemia or chronic adult kidney disease.

We desperately need better tests. The ability of oncologists to accurately detect lymph node involvement could signify a huge step forward in staging and, therefore, in making optimal treatment decisions for men with newly diagnosed and advanced prostate cancer.

Thursday, November 8, 2012

A Breakthrough Study in Prostate Cancer

BY MARK SCHOLZ, MD

Ten years ago everyone agreed that surgery was the “Gold Standard” to which every other kind of treatment should be compared.  Now as we approach 2013, you rarely encounter the Gold Standard argument to bolster surgery as the preferred treatment approach.  What has led to the change in perspective and why has it taken so long for this change to come about?

Good Science Finally Leads to a Clear Answer
The primary cause for the changed perspective about surgery is the result of a well-performed scientific study published this year by Dr. Timothy Wilt in the New England Journal of Medicine.  The study has been a long time coming.  It was first conceived way back in the early 1990s when Dr. Wilt and others designed a definitive trial to test whether or not radical prostate surgery improves survival compared to observation. Even back then, researchers knew that prostate cancer can often behave benignly and were questioning the benefits of radical surgery.  Therefore, between 1994 and 2002 over five-thousand men were invited to participate in a study comparing immediate surgery with no treatment.  To make the comparison totally fair, individuals volunteering for the study had to be willing to have either surgery or observation based on the flip of a coin.  Most of the more than five thousand men who were invited to participate in the study refused. Ultimately, however, 731 men agreed to participate.

Modest Benefits for “Bad” Cancer, No Benefit for “Good” Cancer
At the start of the study the average age of the men participating was 67 and the median PSA was 7.8. After ten years the difference in prostate cancer mortality was essentially the same in both groups, i.e., within the expected range of statistical variation: 5.8% died in the surgery group and 8.4% died in the observation group.  However, subgroup analysis of the 251 men in the study who started off with PSA levels above 10 showed a modest improvement in survival for the men undergoing surgery: 5.5% died in the surgery group and 12.8% died in the observation group.

Validation of the Right Way to Look at Prostate Cancer
This picture of how different types of prostate cancer behave over long periods of time (having a high PSA for example versus having a low PSA) has been slowly forming in the minds of the prostate cancer experts over the years.  Dr. Anthony V. D’Amico, MD, PhD, Professor of Radiation Oncology at Harvard Medical School, is credited with developing the modern staging system that divides men into Low, Intermediate and High-Risk categories (At the PCRI we call them Shades of Blue, i.e., Sky, Teal and Azure).  Dr. Wilt’s study conclusively validates the fact that favorable prostate cancer—termed Low-Risk—can be safely monitored without immediate treatment, whereas men with High-Risk disease derive a modest benefit from immediate treatment.  His study also reported an intermediate outcome for the men with Intermediate-Risk disease: After 10 years, men in the Intermediate category showed no improvement in cancer survival with surgery.  However, there was a 10% lower incidence of metastases in the men with Intermediate-Risk who had surgery.   

Conclusion
Dr. Wilt’s study is an important breakthrough because it is the first modern, large, long-term, prospective, randomized study comparing treatment versus no treatment in men with relatively early-stage disease, i.e. diagnosed via PSA screening.  This study provides critically important scientific confirmation validating the policy of withholding radical treatment in men with Low-Risk disease.  The study also validates the predictive accuracy of the D’Amico staging system which functions by dividing men into Low, Intermediate and High-Risk categories.  Lastly, Dr. Wilt’s study provides a quantifiable measure of the degree of benefit associated with immediate surgery in men with Intermediate-Risk and High-Risk disease.  Using this information, individuals with High-Risk disease can better understand the rather modest survival advantages of surgery, and weigh them against the probable deleterious side effects, enabling them to determine for themselves whether or not they want to proceed with radical treatment.

Tuesday, October 30, 2012

Revisiting TIP (Testosterone Inactivating Pharmaceuticals)

BY RALPH BLUM

Why Does TIP Work?
Testosterone is the hormone that causes boys to become men at puberty. Prior to puberty, the prostate gland is roughly the size of a small marble. Then, when the teenage surge of testosterone occurs, the gland expands to walnut size and begins producing semen. This transformation occurs because the cells of the prostate gland are uniquely sensitive to the presence, or absence, of testosterone. Lowering the level of testosterone in the blood causes the cancer cells to shrivel up a die because the cancer cells are derived from prostate gland cells and retain the same dependence on testosterone for survival.

Long Term Results
One downside to TIP is that while it shrinks the cancer, it does not, ultimately, kill every last cell. However, it has been my treatment of choice for the past ten years. Studies done at Prostate Oncology Specialists, Inc. show that after twelve months of TIP the amount of residual cancer is usually too small to be detected with a lesion-directed biopsy using color Doppler ultrasound. In most cases PSA drops to near undetectable levels (mine dropped to 0.125), and TIP has the added benefit of having anti-cancer effects throughout the body.

When TIP is stopped, testosterone levels gradually return to normal, and a number of men require no further treatment. Some men require periodic treatment with TIP to keep their PSA levels under 5.  And other men, rather than continuing with intermittent TIP, decide to go for surgery, seeds or IMRT. However, even this latter group has bought themselves on average of five plus years before risking the intimidating potential side effects of more radical treatments.

Side Effects of TIP
Although no prostate cancer treatment is free of undesirable side effects, most of the side effects of TIP (weight gain, muscle loss, loss of libido)   are preventable with proper management. And loss of libido, unlike impotence, is reversible when TIP is stopped. Meanwhile, although some of the magic may be gone while on TIP, most men find that they can still enjoy sex (and give pleasure to their partners) with a little help from Big Pharma. Viva Viagra!
Final Thoughts
I can think of only three reasons why this non-invasive alternative to surgery and radiation is not more often the treatment of choice for men with Intermediate-Risk prostate cancer:

1)  Patients never hear that it is an option: Urologists usually don’t suggest TIP to men with Intermediate-Risk cancer as a viable alternative to their preferred treatments—surgery and radiation.

2)  Doctors are unfamiliar with the TIP option.  Finding an oncologist with experience in state-of-the-art methods of administering TIP is still a challenge.
3)  Most men are shocked and fearful when they are first diagnosed with prostate cancer, and it’s hard to resist the emotional appeal of “Just cutting it out”—especially when the risks of more radical treatment are sometimes glossed over.
Thankfully, in 2002, when I learned that my PSA had bumped up to 18.3, my fear of being sliced open, or fried by radiation led me to Mark Scholz, and TIP. And although I would not describe my experience as “a day at the beach,” I am deeply grateful that I chose TIP, and, more importantly, ten years later, I am still here!

Tuesday, October 23, 2012

The Un-Cancer

BY MARK SCHOLZ, MD

It’s easier to teach a proper golf swing to a true beginner than to someone who has previously developed bad habits that are now ingrained.  The young mind of a child learns a new language much more easily than the cluttered mind of the adult.  Good first impressions are valued so highly because we all know how hard it is to undo a bad first impression.  The biggest challenge of educating people about prostate cancer is overcoming their preconceived notions—what they already think they know about cancer.

What is prostate cancer?  Many say it’s harmless, that “you die with it, not from it.”  But how does that jibe with 28,000 deaths annually?  One reasonable conclusion is that prostate cancer occurs and acts in a variety of different ways. The Prostate Cancer Research Institute (pcri.org) recommends dividing prostate cancer up into five categories or Shades of Blue. This is helpful both for understanding the varieties of prostate cancer and for guiding the choice of treatment.

However, even though there are many forms of prostate cancer, this fact fails to convey how differently prostate cancer as a whole acts, compared to other cancers.  Why is it so important to understand this difference?  First of all, surgery—which is everyone’s first thought when they hear the word “cancer”—can have dire consequences.  For example, surgery almost always causes partial or complete impotence. Second, new research published by Dr. Timothy Wilt in the July issue of this year’s New England Journal of Medicine, shows that forgoing immediate treatment and embarking on a program of close monitoring known as “active surveillance,” has exactly the same survival rate as immediate surgery.  Bottom line: For far too many men, immediate treatment for prostate cancer is not only damaging, it is often unnecessary.

Forgoing treatment with something called cancer is certainly counterintuitive.  In order to support the case for monitoring, let’s compare the statistics for prostate cancer with those of colon cancer.

Prostate Cancer: 
The “Un-Cancer”
Colon Cancer:
A “Typical” Cancer
Difference
Factor
Deaths Annually
28,000
26,000
1 : 1
New Cases Diagnosed
241,000
73,000
3.5 : 1
Mortality Rate
8.5%
35.5%
4.2 : 1
Average Survival if Relapse Occurs
13 Years
13 Months
12 : 1


As the table shows, men diagnosed with colon cancer are not only three and a half times more likely to die from the disease, they die twelve times more quickly.  Unfortunately, almost all cancers—lung, pancreas, stomach, gallbladder, kidney, brain, bone, etcetera—approximate the behavior of colon cancer rather than prostate cancer.

The fact remains that it is logical for the general population to be terrified by the very idea of cancer.  When you consider all the different types combined, cancer is the second most common cause of death, just below heart disease. The risk of death from most cancers is high and if a cure is not obtained, death follows all too quickly. The unfortunate men who die from prostate cancer make the “news,” even though it may not be generally understood that it took 13 years for those men to succumb. However, the fact remains that there are 2.8 million prostate cancer survivors presently living in the U.S. That should be news too.

Ninety-one and a half percent of men diagnosed with prostate cancer will have a normal life expectancy, and will die of natural causes. The eight and a half percent who die from prostate cancer will live an average of 13 years, with this number expected to increase dramatically over the next ten years, thanks to continuing improvements in medical technology.  Treatment can definitely improve survival in selected cases.  However, it would seem that only men in the high-grade category are likely to benefit consistently.

The encouraging facts about prostate cancer outlined in this blog have been compiled to help men realize that survival rates with prostate cancer are extremely favorable compared to other types of cancer.  Now that studies show that survival with active surveillance matches that of immediate surgery, a great many men should take heart, and resist all efforts to rush into a treatment with such uncertain rewards but such predictable and devastating side effects. 

Tuesday, October 16, 2012

Harmony & Spirituality Practice Cultivating “Wa”

BY RALPH BLUM

Many years ago, I was invited to attend a breakfast fund raising event at the Bel Air Hotel in West Los Angeles. Ted Turner was attempting to squeeze donations from a room full of Hollywood moguls. The private dining room was filled with sunlight, and I remember sitting there, bored, zoned out and forking segments of my eggs Benedict around, when Turner’s Savannah chain gang growl poked a hole in my reverie: “I tell you, it’s spiritual,” he exclaimed. “And you know how I know it’s spiritual? Because I paid cash money for it.”

To this day, I have no idea what “it” was. But Turner’s logic—his working definition of “spiritual”—made me smile and stuck with me to this day. And while I’d rather steer the long way around when it comes to spiritual matters in general, I have become a devoted fan of harmony, as in feeling at peace. What the Japanese call Wa. Bottom line: I try not to regret anything that has already happened, and not to worry about what might happen. And in a way, I think this has played a role in my coming to terms with prostate cancer.

When discord hobbles me, throws off my vital signs, fogs up my reasoning, I feel it has a definite impact on my immune system. Efforts to counter mindless anxious behavior through breathing and light meditation may help, but in my case, only minimally. Instead, whenever I encounter discord, or more to the point, when I catch myself creating or contributing to the dissonance, I retreat from that discord as fast as I can. This happens in three steps:

First, I catch myself, recognize what’s happening, mark the moment: Blum, you’re doing it!

Second, I apply the brakes, stop what I am doing as best I can. Do whatever it takes to get into reverse and back away. I think of this step as “circuit breaking.”

Third, I substitute different behavior, consciously find a better way to look at what is disturbing my peace and serenity, my wa.

Example: Despite my expectations, my PSA has risen. And I’m suddenly scared s—tless my next Gleason score will have deteriorated from 3 + 3 to 3 + 4, and that I will start feeling pressure to “act,” to begin radical treatment. As a Remedy, I hold a conversation with myself,

Me:  How many years has your cancer been in the seminal vesicle?
Myself: About six.
Me: So six years out of the capsule?
Myself: Yup.
Me:  Is the cancer in your bones?
Myself: No.
Me: Well, how about the lymph system?
Myself: Don’t think so.
Me: So And how old are you?  
Myself: I’ve been around the sun 80 times.
Me: So in 10 years you’ll be 90?
Myself: You might look at it that way.
Me: And your cancer, basically untreated, has been stable for almost a quarter of a century.
Myself: Something like that.
Myself: So given hour history, what kind  of prognosis would you expect for the years to come. . . ?

The Q and A continues until I find myself relaxing, counting my blessings. This sounds like pretty simple-minded stuff. But not getting caught in the quicksand of negative emotions or behavior that is toxic, just staying in the “here and now,” is a spiritual practice that helps maintain Wa. I do my best to stay in the present moment. But when I slip, ASAP after the fact I review what has happened. I replay what happened in my mind with different features, focus on a better way to handle it next time. And some day perhaps I’ll find out what spiritual stuff Ted Turner paid cash money for. And place an order for myself. A baseball team. An ocean going racing yacht. A date  withJane Fonda. CNN. A day at the beach. . .

To each his own kind of Wa.

More to come.