The role of high-dose rate brachytherapy in locally advanced prostate cancer

Although the optimal management of patients with locally advanced prostate cancer remains undefined, sufficient clinical data have emerged showing that patients treated with radiation therapy (RT) have a significantly better outcome as the dose to the gland is escalated. What remains unresolved, however, is how to best deliver these higher tumoricidal doses of RT. Conformal high-dose rate brachytherapy (C-HDR BT) is an alternative means of precise dose escalation that offers similar tumoricidal effects as 3-dimensional (3D) conformal external beam radiotherapy (EBRT) with potential additional advantages. By placing HDR afterloading needles directly into the prostate gland under real-time ultrasound guidance, a steep dose gradient between the prostate and adjacent normal tissues can be generated that is unaffected by organ motion and edema or treatment setup uncertainties. The ability to control the amount of time the single radioactive source dwells at each position along the length of each brachytherapy catheter further enhances the conformity of the dose. In addition, recent radiobiologic data on prostate cancer treatment suggest that the alpha/beta ratio for tumor control is similar to (or possibly even smaller) than that for surrounding late-responding normal tissues. If true, hypofractionation (as practiced with C-HDR BT combined with EBRT) would be expected to produce tumor control and late sequelae that are at least as good as achieved with conventional fractionation, with the additional possibility that early sequelae might be reduced. Recent data from several groups performing C-HDR BT in patients with locally advanced disease have confirmed these assumptions. Combined with the physical advantages discussed earlier, C-HDR BT as a means of dose escalation should provide similar tumor control as 3D conformal EBRT with the added advantages of reduced treatment times, less acute toxicity, and no additional technological requirements to account and correct for treatment setup uncertainties and organ motion. The issues that remain unresolved with this technique (as with other methods of dose escalation) revolve around the amount of additional dose required to provide optimal tumor control, the role of androgen deprivation in the management of patients with locally advanced disease, and whether the regional lymphatics should be irradiated.