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.
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