1.0 BACKGROUND 1.1 Prostatic adenocarcinoma is one of the most common forms of malignancy
in men. Every year over 200000 patients are diagnosed with prostate cancer in the United
States. Treatment options for these patients include active surveillance, radical
prostectomy, external beam radiation therapy, permanent source interstitial brachytherapy
and high dose rate (HDR) brachytherapy.
1.2 Each of these treatment options vary in regards to the logistics, anticipated
outcomes, and potential side effects of therapy.
1.3 High-dose rate (HDR) brachytherapy has been used in the treatment of prostate cancer
since the 1980's with good results. Catheters are placed temporarily in the prostate, and
then loaded with a high-dose Iridium-192 source, delivering a few fractions of very
high-dose RT. Brachytherapy allows the delivery of conformal, high-dose radiotherapy to
the prostate, with a rapid dose fall-off outside of the region. It also takes advantage
of low alpha/beta ratio of prostate cancer by using a hypofractionated approach.
1.4 The TrueBeam is a noninvasive radiosurgical system, capable of treating any part of
the body from multiple targeting angles, creating a highly conformal three-dimensional
radiosurgical treatment volume, guided by orthogonal X-ray-based targeting feedback, and
delivering radiation by a highly collimated, robotically controlled linear accelerator.
The TrueBeam system targets implanted fiducial markers with sub-millimeter set-up
accuracy.
1.5 From a dosimetry standpoint, TrueBeam Stereotactic radiosurgery is capable of
producing a dose distribution comparable to that created by prostate HDR brachytherapy
treatment, without the need for invasive transperineal catheters, anesthesia, or
inpatient admission. It would therefore be possible to deliver the HDR boost portion of a
patient's treatment in a non-invasive fashion. As such, the TrueBeam prostate dose
fractionation schedule prescribed in this study is based upon prior published prostate
HDR brachytherapy experience both as a monotherapy and as a boost to external beam
radiation therapy in patients with higher risk disease. The therapeutic volume in this
study will also be made to resemble prostate HDR brachytherapy therapeutic volume, with
similar dose limitation objectives to the adjacent tissues, including the rectum, bladder
and urethra. It is theorized that such an approach should result in similar cancer
control rates while lowering overall morbidity and improving the patient's comfort and
convenience.
1.6 The feasibility of stereotactic body radiation therapy for treating localized
prostate cancer was first described by King at Stanford University. Their phase I
protocol delivered 36.25Gy in 5 fractions of 7.25Gy. In a recent report of acute and
18-month late toxicity in 26 "low-risk" patients, no patient experienced grade 3 or 4
acute or late toxicity, and only one patient experienced a grade 2 late morbidity
(urethral stricture). Toxicity was less than that reported in MD Anderson's external beam
dose escalation trial. Mean PSA 18 months after treatment was 0.22ng/ml. Naples Community
Hospital reported a series of more than 70 low and intermediate risk patients treated
with the SBRT. The prostate received 35 Gy in 5 fractions of 7 Gy each; acute toxicity
was minimal. San Diego Cyberknife, which used a virtual HDR technique, reported a series
of more than 124 low and intermediate risk patients treated. The prostate received 38Gy
in 4 fractions of 9.5Gy each; acute toxicity was minimal.
1.7 Another potential benefit of stereotactic body radiosurgery relative to HDR
brachytherapy is possibly better preservation of potency, even if the radiation
distribution is essentially identical between these modalities. This is so because needle
trauma has been identified as a potentially significant contributory factor to erectile
dysfunction with brachytherapy, including HDR-based monotherapy technique, presumably due
to direct physical injury to the neurovascular bundle and/or bulb of the penis,
particularly when greater than 13 needle insertions are performed. By comparison,
stereotactic body radiosurgery is noninvasive, and so removes this particular erectile
dysfunction risk factor.
