Category: General Patient Information

Two  recent reviews have been published in Oncology describing the history, developmental clinical study results, treatment optimization and future directions for radium-223 chloride in prostate and other cancers.  It should be noted that these articles are primarily written for physicians and health care providers.  See the accompanying links.

Radium-223 chloride (alpha-radin) is an alpha-particle- emitting radiopharmaceutical which is specifically taken up by bone cells (osteoblasts).  These high energy alpha particles with short tissue penetration range allow for targeted prostate cancer cell killing with low toxicity.  Improvement in overall survival and relief of skeletal symptoms have been demonstrated in prostate cancer patients who are hormone resistant and have multi-focal symptomatic bone metastases.

The May 2015 issue of the Prostate Cancer Research Institute (PCRI) Prostate Insights contained an excellent summary article describing the potential side effects of both radical prostatectomy and radiation treatment for prostate cancer.  The entire article is linked.  It is noted that the author went into more detail about the negative side effects of surgery compared to radiation.  Therefore, the reader is urged to consult his health provider for further information and clarification regarding side effects of both treatment options and their potential severity.

 A blue heron poses in Charlotte Harbor, FL; Photo: BJ Gabrielsen

A updated review of brachytherapy by Dr. John Blasko of the Seattle Prostate Institute recently appeared in the May 2015 issue of the Prostate Cancer Research Institute (PCRI) Insights.  Low dose rate brachytherapy for prostate cancer involves the insertion of small radioactive pellets (seed implants) into the prostate by transrectal ultrasound guidance in order to deliver a focused dose of radiation to the prostate.  The seeds contain one of three possible radioactive isotopes, namely palladium-103, iodine-125 or cesium-137.  While they have slightly different characteristics, they all emit a low energy radiation dose for a period of a few months and then become inert.  This radiation dose is delivered to the prostate with very little reaching the sensitive surrounding organs such as the bladder and rectum.  The seed implants have proven to be safe and effective for over 25 years. But how does brachytherapy compare with some of the other types of prostate cancer treatment?

Canadian researchers have recently completed analysis of a trial called ASCENDE-RT, a multi-center randomized trial of dose-escalated external beam radiation therapy (EBRT) versus brachytherapy for men with unfavorable-risk prostate cancer.  A total of 276 men with high-risk disease and 122 with intermediate-risk disease all received twelve (12) months of androgen deprivation (hormonal) therapy (ADT) plus 46 Gy of whole pelvis external beam radiation (EBRT).  Then half of the men (200) were randomly assigned to a conformal external beam boost of 32 Gy while 198 men were randomly assigned a brachytherapy boost of 155 Gy with iodine-125 seeds.  Historically, seed implants have been used in one of two ways; as a stand-alone treatment for low-risk cancer or as part of a combination with modest doses of external beam radiation for intermediate and high-risk prostate cancer patients.  In high risk cases, hormonal therapy (ADT) has also often been administered.  Many radiation experts have contended that while seed implant boost is effective, the combination of hormones with intensity-modulated radiation therapy (IMRT) is just as effective and simpler to administer.  The median observation time after radiation for the 398 men in the trial was 6.5 years enabling statistical projections to be made for 9 years.  Using PSA measurements as success indicators, at 5 years, 77% of the men treated with hormone + IMRT alone were relapse-free compared to 89% of the hormone + IMRT + seed boost patients.  At 9 years, the relapse free rates were more dramatic at 63% versus 83%, respectively.  The researchers conclude that after 9 years of treatment, the PSA-based cure rate of the seed boost patients was improved by 20%!  The rationale cited for this improvement is that brachytherapy delivers a higher and more effective dose of radiation to the prostate which is unachievable with external radiation alone.  If prostate cancer survival were used as a study endpoint, no difference was seen between the seed boost and the EBRT alone groups.  However this may be the case because not enough follow-up time has elapsed for PSA failures to manifest mortalities.  An additional 6-7 years of follow up for the PSA failures would be required to translate into survival statistics.

Other innovations have occurred in the application of brachytherapy.  Quality of life studies have demonstrated the favorable side effect profile of brachytherapy compared to surgery or IMRT.  In addition, transrectal ultrasound imaging has made tremendous strides in clarity of images.  There is now also the capability of merging and coordinating MRI imaging with transrectal ultrasound thus increasing the fine control of seed placement.  The control of radiation doses to the urethra, bladder and rectum is also greatly improved.  Comparative cost and effectiveness analyses by the Institute for Clinical and Economic Review at Harvard University concluded that brachytherapy for low-risk disease is the most effective and least expensive initial treatment compared to IMRT, proton beam or surgery.   While the use of brachytherapy has decreased from 2002-2010, use of surgical and other treatments have increased primarily due to the introduction of new expensive technologies such as robotics, IMRT and proton beam.  While these new approaches may generate more revenue for hospitals and physicians, the popularity of brachytherapy is growing rapidly in many countries where medical reimbursement costs are fixed.  The author of this review concludes that “multiple studies over the past 25 years have demonstrated that brachytherapy either alone or in combination with external beam radiation is as effective and, – particularly in intermediate and high-risk disease -, superior to prostatectomy or IMRT alone for cure and potential quality-of-life.  The  ASCENDE-RT prospective, randomized trial proves the superior cure rates attainable with seed implantation.”  It is also cost-effective.

The content of this post is for informational purposes only.  Please discuss it with your personal health-care provider as needed.

The following was written by a prostate cancer survivor on the website “Prostatesnatchers” to which I highly suggest you subscribe.

“Back in 1990, when a suspicious lump was discovered on my prostate, my ignorance of the prostate gland and the possibility of prostate cancer was monumental. No one in my family or even among my close friends had ever had prostate cancer, and it never occurred to me that I might one day have the disease.

Now, 25 years later, I am still alive, the average man over 50 is more aware of prostate cancer, and also many less toxic and more effective treatment options are available. And yet one thing has not changed: just hearing the doctor say, “I’m afraid it’s cancer,” can leave even the most pragmatic man planning the music for his funeral.

Truth is there is still a lot of misinformation and misunderstanding out there about this disease. So here are some facts that I hope will alleviate some of your fears, and also clarify why I still contend that if you have to have cancer, prostate cancer is the best deal in town.

Prostate cancer is unique among cancers because the mortality rate is so low. According to the American Cancer Society, more than 2 million men who have been diagnosed at some point are living with the disease in the U.S. It’s difficult to determine actual prostate cancer survival rates because most men are around 70 years old when diagnosed, and many of them will die from medical problems unrelated to the disease. But if you check out the “relative” 5-year survival rate of all stages of prostate cancer, you will find it is almost 100%. And that almost 100% of men with low-risk or  intermediate-risk disease live more than 10 years after diagnosis.

Why is it that the statistics for prostate cancer are so much less frightening than for other cancers?

1)    The PSA test is an early warning system that other cancers don’t have.
2)    It can easily be diagnosed at an early stage.
3)    In most cases it has an exceptionally slow growth rate.
4)    Extremely effective monitoring and treatment is now available.
5)    It has a pattern of spread that spares critical organs like the brain, lungs and liver.
6)    There is a safety net like no other called “hormone blockade” that induces remissions lasting more than 10 years in men with relapsed disease after surgery or radiation.

So instead of thinking about your funeral, what you really want to be focusing on is not rushing into some form of radical treatment that will virtually guarantee  some degree of impotence or incontinence.

It appears that patients and doctors alike struggle with the idea of “watching” anything called cancer. But unless you have the less common high-risk form of the disease, my advice to you is to consider ‘Active Surveillance’ really carefully, especially if you are over 70. Because bottom line—and it bears repeating—out of over 200,000 men in the U.S. diagnosed annually with prostate cancer, the overwhelming majority will die with the disease, and not from it.”

In the January 23rd, 2015 issue [290(4):2024-33] of the Journal of Biological Chemistry, researchers published the finding of potential benefit for a combination of metformin and the gene inhibitor B12536 in late-stage prostate cancer.  Late-stage prostate cancer is commonly treated with androgen (hormone) deprivation therapy (ADT); however, the disease eventually becomes resistant to treatment.  Androgen deprivation can disturb the body’s metabolism, leading to insulin resistance that can stimulate unwanted androgen production.  Metformin, a drug commonly used to treat diabetes, helps reduce insulin resistance and has been associated with protection against specific cancers.  It is known that the gene poly-like kinase 1 (PLK1) can become over-expressed (overactive) during ADT and that its over-expression can also stimulate androgen synthesis, researchers tested the effects of administering the PLK1-inhibitor B12536 with low-dose metformin in prostate cancer cells.  The team found that the drugs worked synergistically to inhibit prostate cancer cell proliferation. The findings were confirmed in mice that received human prostate cell grafts. Further animal studies are underway with the eventual goal of initial human trials.