Photons or Protons? You Choose

BY RALPH BLUM


Following in the footsteps of robotic surgeons, prostate cancer continues to go high-tech. Radiation, for instance, is no longer just radiation. There are now numerous different ways to deliver it. But the two methods I want to write about here are Intensity Modulated Radiation Therapy (IMRT), and Proton Beam Therapy (PBT).


The predominant method in the U.S. for the past decade is IMRT, a complex procedure that precisely targets the prostate gland with multiple beams of high energy light (photons) at different angles and intensities while significantly lowering the risk of damage to the surrounding tissues and organs.  This greater accuracy in targeting also allows the therapist to maximize the radiation dose to the tumor.  IMRT has at least as effective a cure rate as surgery, and without the risks and side effects of a major surgical procedure.


Having said that, I have recently been checking out Proton Beam Therapy, a form of radiation that targets the tumor with charged particles called protons. Several decades ago, Loma Linda University in California was the first to begin administering PBT. At that time, I had a friend who, at 55, developed prostate cancer and was one of the first patients at Loma Linda when proton therapy was at a very early stage.  Bill has been free of cancer for over twenty years, and only recently had a rise in PSA and is discussing further treatment.


Since then, thanks in part to marketing hype, PBT is becoming increasingly popular.  Now, M.D. Anderson, Harvard, and the University of Florida in Jacksonville, are among the major medical centers that have made PBT available. And The Mayo Clinic is building two proton therapy centers (one in Rochester, one in Arizona) at a cost of $380 million. Naturally PBT costs considerably more than IMRT.


When weighing treatment options, patients generally consider two main factors: potential side-effects, and successful outcome. So how do these two therapies measure up? Well, there is considerable controversy in the urologic community. The good news is both therapies have a high cure rate. Studies that have tried to compare IMRT with Proton therapy indicate that the outcomes are quite similar and that the side effects are comparable.  No large randomized trials have been published that directly compare patient outcomes with the different techniques.  So in the end, a treatment decision usually depends on such variables as patient preference and doctor preference.


It is reasonable, therefore, to keep in mind that any medical center that has invested an astronomical amount of money on equipment will end up wanting to use it.

Provenge in 2012

BY MARK SCHOLZ, MD

Doctors finally seem to be comfortable with starting Provenge, a recently FDA approved immune therapy for prostate cancer.  Dendreon, the manufacturer of Provenge, just reported a sharp uptick in their quarterly financials, indicating that the use of Provenge is increasing as doctors increase the amount of the drug they order.

Although, Provenge has been on the market for 18 months but the medical community was slower to embrace this new treatment than was expected.  It seems that it has taken time for doctors to make peace with the fact that Provenge extends life, even though there is no lowering of PSA and very few side effects.

At Prostate Oncology Specialists, we recently completed an in-house review of the first 50 men treated with Provenge, I’ll jump right to the simple and somewhat mundane conclusion or our analysis: Provenge is relatively easy to give and side effects are uncommon.

Historically, the effectiveness of cancer treatments—like chemotherapy for example—has been closely associated with notable side effects. Side effects were often equated with effectiveness.  Even some of the new immune treatments, like Ipilimumab for example, usually have side effects. It’s ironic that patients receiving Ipilimumab on investigational trials are actually comforted when they get side effects—it confirms that they are not getting a placebo.

It’s also ironic that while doctors look for PSA decline as a measure of success, PSA has been rejected by the FDA as a method for measuring the effectiveness of drugs. The FDA demands a survival endpoint rather than changes in PSA.  (Personally, I think the FDA is crazy. I think that both PSA and survival endpoints are valid.)

Nevertheless, doctors and patients alike are confused. Their seemingly logical question is, “How can someone’s life be extended without PSA dropping?”  My explanation is as follows: When Provenge strengthens the immune system, is slows the rate of cancer growth.  Using the rise in PSA as analogous for cancer growth, Provenge slows the rate of PSA rise.

I am very comfortable with the idea that effective immune therapy slows cancer growth rather than reversing it.  This phenomenon of slowing the rate of PSA rise is exactly what we reported to the American Society of Clinical Oncology in 2010 when we presented our results with three medicines with immune activity, Leukine, Low-dose cytoxan and Celebrex.  The combination of these three agents caused substantial slowing in the rate of PSA rise.

Since Provenge is so well tolerated, the next logical step is to evaluate Provenge in combination with other immunologically active treatments.  MD Anderson is ramping up to do a trial of Provenge with full-dose Ipilimumab.  At Prostate Oncology Specialists we look forward to working with treatment options such as Provenge and Ipilimumab for our patients. Hopefully the net result will be greater than the sum of the parts.