Intra-operative Electronic Brachytherapy (IOBT)

When the pathology report indicates that prostatectomy alone was insufficient to control locally advanced prostate cancer, we often turn to adjuvant radiation. However, there is a delay with adjuvant radiation of 3 to 6 months to allow tissues to heal, but that may allow the cancer to metastasize. Electronic brachytherapy is an experimental technique for killing the prostate cancer remnants during the operation.

It’s called electronic brachytherapy because it includes a miniature device that produces high dose rate but low energy X-rays electronically. It’s brachytherapy because a small bulb with the X-ray emitter is placed inside the pelvic cavity from which the prostate has just been removed. The high dose rate X-rays can kill the cancer in surrounding tissues, but their low energy means they can’t penetrate very deeply to places where it might cause toxicity. The patient is thus treated one time for 20 or 50 minutes during surgery. The clinicians need only some minimal shielding for protection.

While this is an experimental technology for prostate cancer, its efficacy and safety have been demonstrated for other cancers. For breast cancer after a lumpectomy, it’s standard care to treat the entire breast with external beam radiation. A recent large (n=1,721) randomized trial, “TARGIT-A” conducted at 33 centers in 11 countries, demonstrated that such single dose targeted intra-operative radiotherapy was not inferior in its cancer control to fractionated external beam radiotherapy, and complications like skin reactions and cardiac mortality were significantly reduced. Electronic brachytherapy has also been used for skin cancer, endometrial cancer, and spinal metastases.

There is some evidence that the intra-operative application of radiation may be safe for prostate cancer as well. Rocco et al. reported on 33 patients treated intra-operatively with a portable electron beam unit that delivered 12 Gy to the prostate area. They compared outcomes to 100 matched pairs of patients treated with adjuvant external beam radiation, and found no differences in peri-operative complications, continence, acute or late toxicity. The biochemical progression-free survival was also no different, but there were only 16 months median follow up. Krengli et al. reported similar low complications on 38 patients treated intra-operatively with electron beam therapy, and also showed that external beam radiation could be added afterwards without high toxicity.

In a proof-of-concept study, Buge et al. experimented on 9 cadavers and conducted a simulation study using the MRIs obtained from 34 patients. They looked at two IOBT models, one was the Axxent eBx™ system from Xoft, the other was the Intrabeam™ system from Zeiss. They both can be used during open prostatectomy, but the Axxent™ system with an inflatable bulb and longer stem was more amenable to laparoscopic and robotic surgery.  All were found to make good contact with the surrounding tissues where most recurrences are found, especially the anastomosis of the urethra, the neurovascular bundles, the bladder neck, and apical margins. The bulb was not able to come close enough to the seminal vesicles to provide adequate treatment, and is therefore not recommended for stage T3b. It is also unsuitable for treatment of pelvic lymph nodes. They were able to deliver 20 Gy to surfaces in direct contact, and at least 12 Gy to a depth of 5 mm. This corresponds to a very curative equivalent IMRT dose of 123 Gy to any cancer it touches. Their simulations demonstrated a very low probability of normal tissue complications for the bladder and rectum. Furthermore, the bulbs could be used to treat a wide variety of prostate sizes and shapes.

Among the possible uses are:

• ·      Guaranteed neurovascular bundle-sparing surgery (i.e., they are treated with IOBT).
• ·      Earliest possible treatment when extraprostatic extension is discovered during RP.
• ·      Planned treatment for clinically discovered extracapsular extension.
• ·      Earliest possible treatment when frozen sections reveal positive margins.
• ·      Initial single-dose adjuvant radiation that still allows for repeat treatment with fractionated external beam radiation if needed.
• ·      In conjunction with a prostate index tumor  “lumpectomy” as a kind of focal therapy.
• ·      As salvage therapy after a local radiation failure.

We must learn whether it is effective and safe in actual clinical practice on live patients. Of course this is very preliminary and, hopefully, clinical trials will be conducted.