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

Tuesday, August 27, 2013

Xtandi as Primary Therapy


The largest oncology market in the world is the early-stage prostate cancer market. Every year, 80,000 men undergo surgery. Even greater numbers are treated with IMRT, seed implants, cyberknife and proton therapy.

What about Hormones?
Hormone therapy is another popular treatment approach, especially for older men. For example, the Capsure database indicates that hormone blockade is used more commonly than radioactive seeds.  Randomized clinical trials also indicate that intermittent hormone therapy is feasible:  Men who stop hormone therapy and take “treatment holidays” have identical survival rates to men who stay on continuous treatment.

Standard Treatment is Deplorable
Since PSA screening started in the early 1990s, surgery and radiation have been all the rage.  Aggressive treatment has succeeded in reducing annual prostate cancer mortality by half a percent. Now “only” 2.5% of men die of prostate cancer. Previously, prior to the advent of PSA screening, 3% of men died from prostate cancer. The “cost” of achieving this mortality reduction, however, should be measured in terms of diminished quality-of-life. The frequency of serious side effects is typically under-appreciated. For example, at the highest quality treatment centers only 5% of men recover sexual function similar to what they enjoyed prior to treatment. 7% of men are grossly incontinent; 50% have stress incontinence and 20% chronically ejaculate urine.

The reason for such a minuscule impact of local treatment on survival is obvious: Surgery and radiation are only effective when implemented prior to metastases. Ironically, until metastases occur, local treatment is unnecessary. After metastases, local treatment is ineffective.  Logically, early therapy with an anticancer agent with both local and systemic effects will result in better cancer control.

Active Surveillance is Now Mainstream
It is now known that Low-Risk disease (Gleason 6, PSA < 10, Stage T1c or T2a) can safely be monitored with active surveillance. At worst, active surveillance has the positive effect of delaying treatment and postponing treatment-related side effects like impotence and incontinence. With delayed local treatment, men benefit from the fact that medical technology is continually improving.  The best case scenario of active surveillance is when cancer never progresses and men are able to avoid treatment indefinitely.

Widely-accepted active surveillance methodology relies on periodic random 12-core needle biopsies.  Now encouraging studies are reporting that 3T multiparametric MRI detects high-grade disease more accurately than biopsy.  Also, new computerized imaging technology enables doctors to record the exact location of the cancer within the prostate gland so that areas of known disease can accurately be resampled with targeted biopsies.

Hormone Therapy Causes Remission of Localized High-Risk Disease with Reversible Side-Effects
A study using a six-month induction course of abiraterone (Zytiga) shows complete pathologic remission or close to complete remission in a third of men with High-Risk disease. Logic predicts that complete response rates will be substantially better in men with Intermediate-Risk prostate cancer.

For the most part, side effects of hormone therapy are reversible or preventable—hot flashes, breast enlargement, osteoporosis, and erectile dysfunction respond to DepoProvera, Femara, Prolia and Viagra respectively. Muscle atrophy can be counteracted with strength training. Low libido dissipates after therapy is stopped. Careful diet averts weight gain.

However, the reversibility of hormone therapy depends on the resumption of normal testosterone production after treatment is stopped. Unfortunately, LHRH agonists, the traditional hormone medications employed, often induce lingering low testosterone levels. Some men, particularly those over 70, are saddled with permanently low testosterone.

Xtandi is Well-Suited to Intermittent Administration
Xtandi has several potential advantages over LHRH agonists.   First, it is more potent.  Studies show that Xtandi has notable activity even after cancer had developed resistance to LHRH agonists. Second, Xtandi blocks testosterone activity rather than suppressing testicular production. Therefore the risk of delayed testosterone recovery or long-term testicular atrophy is circumvented.  Third, though perhaps this is a relatively small issue, most men would rather take a pill than a shot.

An Observational Trial of Intermittent Xtandi Could Revolutionize Intermediate-Risk
Laurence Klotz, M.D. prospectively accrued men with Low-Risk (and some Intermediate-Risk) prostate cancer to a simple observational trial starting in the mid-1990s.  By simply reporting a very favorable ten-year mortality rate he brought about a total change in clinical practice patterns in the United States and throughout the world.

Intermittent hormone therapy as primary treatment is certainly feasible for localized prostate cancer.  Active surveillance methodology has been refined with improved imaging.  New genetic tests can estimate cancer aggressiveness with more accuracy. The animus to delay treatment, even for a few years, is increasing as the pace of technological innovation accelerates and the hope for the discovery of less toxic treatment increases. Now, with the recent FDA approval of this more potent, more convenient oral agent that is free of lingering effects, the impetus for men to embark on a six-month induction course of Xtandi followed by active surveillance will be even greater.

Selecting a Meaningful Endpoint for an Observational Clinical Trial
Published studies already document excellent survival with primary hormone therapy (see attached). Hence, the most meaningful clinical outcome measure of Xtandi efficacy would be its capacity to forestall or delay local treatment. The objective endpoint, therefore, should measure the number of months or years before local therapy is required, starting from the date of initiating Xtandi and ending when (and if) local therapy is ultimately implemented.

While complete avoidance of local treatment may be a frequent occurrence (in the men who show durable responses to a single cycle of Xtandi) it can be anticipated that men who have locally recurrent disease and whose initial experience with Xtandi was tolerable, may elect to use repeated cycles of Xtandi at the time of recurrence rather than risking the potentially irreversible side effects of local therapy. Conversely, the men most likely to select local therapy are those who experience a particularly short treatment holiday or suffer more severe hormone-related side effects.

A six-month course of Xtandi can also function as a “disease-related stress test.” Men in the subgroup manifesting either high PSA nadir or rapid disease recrudescence after treatment are those most likely to harbor an aggressive prostate cancer variant. Thus, this initial “test” using Xtandi will help ensure that men referred for radical local therapy are those who actually need it.

Tuesday, August 20, 2013

Vasek Polak, The Benefactor: From Porsches to Prostates


My IMRT sessions are two-thirds done, and I’m feeling hopeful. After 30 sessions, with only two weeks to go, I got my second PSA reading. To my profound relief, it registered another downward shift—this time from 24 to 17.5. Yeah team!

Yet before I get any further, I need to express my gratitude. In particular, to Vasek Polak, (Pronounced “Vachek”) who funded the state-of-the-art Accelerator with RapidArc technology at St. John’s, in the unit named for him, my every weekday Monday through Friday IMRT destination.

To get from the Emergency Entrance to the IMRT unit, I have to traverse an entire block from Arizona Avenue to Santa Monica Boulevard, take an elevator to the lower level “Garden” level (No basements in this Bel Air crossed with Easthampton part of West LA), then down another long corridor to the electronic doors that close off the Radiation unit.

It is cool and quiet down here: twenty-foot high white and teal colored walls. The lighting is benign (round, inset ceiling bulbs - the kind used to illuminate single paintings) and the only sound a distant faint humming, like you might hear late at night on a giant cruise ship.

Around the last curve and you can see the legend. High on the outside wall, in silver letters—the size of letters I’d seen used to spell Eisenhower’s name on monuments; letters tall enough to cast shadows on the teal blue wall—are listed the Benefactors of this vast medical complex. And there’s my man, albeit given a supporting player credit under John Wayne’s star billing (“The John Wayne Cancer Center”), but there it is and I’d passed under it mindlessly every time I came for IMRT: Vasek Polak Radiation Treatment Center

I’d never heard of Polak, so I started by checking him out with “Dr. Google.” Turns out, he was a Czech immigrant, a genius Porsche mechanic and racing driver with a hair-trigger temper and a knack for making money, a muscular, wavy haired, roughneck wizard who liked to have a flask of Pilzner Czech beer at his side when he worked.

Polak opened the first exclusively Porsche dealership in the United States and built it into a South Bay-based auto empire. From all reports, Polak was overbearing and dictatorial, “A man of strong opinions, which he did not keep to himself,” as one of his mechanic friends told me. “He was an S.O.B. who could also be kind and very generous.” And he used his fortune to fight cancer.

Reading about this cantankerous genius, and interviewing several of his friends and co-workers, I was struck with the fact that Polak was fearless. The size of the challenge didn’t seem to faze him: a faulty ring or piston, an entire transmission to be replaced just hours before a race, grappling with a drunken mechanic—whatever the situation, like a bull-rider, Polak took it by the horns, and dealt with it. All his energy went into problem solving, winning races, and building a Porsche empire. And underwriting state-of-the-art healing facilities.

Polak built major treatment centers in this country as well as in his native Czech Republic. In the Los Angeles area alone, thanks to his generosity, we have the Long Beach Children’s Clinic, the Vasek Polak Health Clinic in Hawthorne (“No appointment or insurance needed.”), Polak’s Breast Diagnostic Center in Torrance, and the St. John’s installation where, thanks to Polak’s over 6 million dollar funding, I am receiving IMRT, each $3,000 session paid for by Medicare and AARP.

IMRT RapidArc technology enables the linear accelerator to deliver precise forms of radiation up to eight times faster than other systems. This allows St. John's patients to receive higher dose radiation precisely targeted to their particular tumor in shorter sessions. As a result, healthy tissue is spared, side effects are held to a minimum, and outcomes are improved.

However, as I pointed out in my last IMRT blog, the continuing availability of IMRT is under siege. Which is why I’m checking in—starting with my gratitude to this amazing dude who thought it was “a hoot” that the slang word for syphilis in the Czech language was “music” (musika). And who is probably saving my life.

I’d like to have gotten to know Vasek Polak, thanked him personally, and had a chance to buy him the best Czech Pilsner.

Tuesday, August 13, 2013

The PCRI Conference: Standing in the Gap in a Woeful Medical Situation


September is prostate cancer awareness month. Every year the PCRI hosts a three-day educational symposium for patients.  “For patients?”  But people always ask, “What about doctors?”

In the cancer world, prostate cancer is the last bastion of surgeons (urologists).  Surgeons, as it happens, are the primary supervisors of this, the most common type of cancer in men.  Thirty years ago all cancers were managed by surgeons because back then surgery was the only available treatment. While the true cancer specialists of today—medical oncologists—have assumed primary responsibility for every other type of cancer, urologists continue to take primary responsibility of caring for men with prostate cancer.

Therefore surgeons tenaciously hang on to the “way it has always been done,” even though surgery is usually the least effective way to treat prostate cancer. In fact, despite tremendous improvement in other methods of treatment, the reliance on traditional surgery has been on the rise.  The excitement surrounding robotic surgery is probably the reason for the increase. Sadly, numerous scientific studies showing that older surgical techniques work just as well have not changed urologists’ minds.

The theme of this year’s PCRI conference—Quality of Life—naturally emphasizes alternatives to surgery.  Active surveillance, seed implants, IMRT and focal therapy all have survival rates at least as good as surgery, but with far fewer side effects.

This year the conference will feature its very first celebrity—actor Ryan O’Neal.  Mr. O’Neal had such excellent results from his focal therapy that he has volunteered to attend the conference and share his experience.  His story will be featured in the next issue of PCRI Insights which should hit the stands next week.  PCRI Insights is a free quarterly newsletter published by the PCRI.  You can sign up at the PCRI website and have it emailed to you.

Back to the question, “Why patients?”  Basically, Dr. Stephen Strum and I founded the PCRI to educate patients because unlike the surgeons, patients are highly motivated to learn and embrace new options in therapy, especially when the new therapy can convincingly be shown to be equally effective and less toxic.  A patient-orientated approach has proven successful, and the popularity of the conference continues unabated.

So far I have only been commenting on treatment issues related to the newly-diagnosed men with early stage disease. What about men with advanced disease?  Believe it or not urologists are still managing the majority of men with advanced disease, even when metastases are present, and despite the fact that in the last few years  five new products—all of which are proven to prolong life—have been approved for use by the FDA to treat advanced prostate cancer.
Do urologists know how to administer these new treatments?  Are they even aware of them? The complexity of managing advanced prostate cancer has increased exponentially due to the availability of these new treatment options.  The question is: How can urologists, who typically manage prostate cancer in their spare time, keep up with all these new developments when they also have to treat so many other serious issues—kidney stones, urinary incontinence, erectile dysfunction, kidney cancer, bladder cancer, testicular problems, urinary infections—in addition to the time they spend in the operating room  performing various types of surgery?
I would suggest that it is not safe to abdicate your health choices to a urologist. To inform yourself about your options, plan to attend the PCRI Conference on September 6th, 7th & 8th at the LAX Marriott.  Tickets can be purchased on line at

Tuesday, August 6, 2013

Three Days and Counting


The result of my first PSA test—after 15 IMRT sessions—was encouraging.  Given I was warned that the PSA during treatment can be artificially elevated, the drop from 34 to 24 was a huge relief to me. There’s no way of knowing, during the IMRT sessions, what effect the radiation is having, whether or not it is killing the cancer. So PSA is the only clue you get.
The staff at St. John’s--especially James, the oncology tech, and oncology nurses, Jan and Janet--have been very patient with me, going over the details, helping me understand why IMRT trumps conformal beam radiation.
IMRT is an advanced form of 3D radiation using a huge computer-driven machine that actually moves around the patient as it delivers radiation. In addition to shaping the beams and aiming them at the prostate from multiple, laser guided angles, the intensity (strength) of the beams can be adjusted to minimize the dose reaching the most sensitive normal tissues, while permitting delivery of a higher dose to the cancerous areas. As of 2013, most major hospitals and cancer centers now include IMRT in the protocols they offer. But that may soon stop.
The St. John’s machine is a state-of-the-art Varian Trilogy, and costs several million dollars. The machine. called RapidArc, provides access to a variety of small fields that allow the beam to be shaped, and the dose to be modified to get better distribution with a minimum of side effects.
The maximum total safe dose, measured in “rads”—units of energy produced by photons, and/or light particles—is eighty-one hundred “rads.” So I must receive no more than 180 rads a day for the 45 days of treatment. That is a therapeutic dose given only to a small area, in my case, the prostate gland plus lymph nodes. You wouldn’t give that dose to the entire body. When I asked James about the effective limit with rads, he told me, “We know that the prostate has what’s known as ‘a dose response curve,’ meaning simply that the higher the dose the better response.
In the St. John’s unit, I lie in my form-fitted nest while the ion chamber passes overhead like a planetary formation from another universe. I confess, I love it! It’s a piece of major magic working for my benefit: pain free, and to date, free of all negative side effects.
One day, after my treatment when James allowed me to peer into the ion chamber through a metal flap, it was like finding myself in the contemporary version of Stanley Kubrick’s 1968 space age chronicle, “2001.” I was looking at “multileaf collimators”—computer controlled mechanical devices that use up to 120 moveable tungsten “leaves” that conform the shape of the radiation beam to the shape of the tumor from any angle. and can move independently in and out of the path of a particle beam in order to block it. There is now software for calculating the number of beam angles, beam shapes, exposure times, and the treatment schedule needed to deliver the prescribed dose to the targeted area while minimizing exposure to surrounding healthy tissue.
Concerns over IMRT include a higher risk of error due to the extreme complexity of planning and delivery, as well as difficulties in quality assurance, radiation safety, and portal verification. IMRT is expensive, complex, and time-consuming, and will not—for some patients-- necessarily offer an advantage over more conventional techniques such as conformal beam radiation. Long-term follow-up of patients treated with IMRT is necessary to resolve these issues. That lack, plus the astonishing cost, are responsible for a trend to reduce IMRT usage.
Meanwhile I consider myself fortunate to be getting this advanced image-guided radiation treatment, and Dr. Chaiken’s team is undoubtedly among the best.
After 30 sessions, I got my second PSA reading. To my profound relief, it registered another downward shift—this time from 24 to 16.5—with only one more cycle to go!