Salvage low-dose-rate permanent seed brachytherapy for locally recurrent prostate cancer: Association between dose and late toxicity - Beyond the Abstract

This report highlights several important features of salvage low dose rate (LDR) brachytherapy after local recurrence following definitive external beam radiotherapy (EBRT). Most importantly, patient selection is essential for optimal outcomes.

In terms of biochemical disease control, 8 out of 8 patients who had a high likelihood of organ confined disease had no evidence of disease after a mean of 4.6 years follow-up. Conversely, the success rate amongst patients with high risk features was 6/10. Likewise, the only instance of grade 4 toxicity occurred in a patient with poor baseline voiding function.

RTOG 0526 is a phase II trial of transperineal ultrasound-based brachytherapy for locally recurrent prostate cancer after EBRT (currently closed to accrual). From this trial, favorable features for salvage LDR brachytherapy after definitive EBRT include original T1-2, Gleason < 7 and PSA < 10 ng/ml, and at salvage a PSA doubling time >12 months (or > 6 months if other features favorable) and PSA < 6 ng/ml. Other important features include a positive prostate biopsy with little or no radiation effect (for accurate Gleason grading), negative systemic staging and no residual toxicity > grade 1, as specified in the RTOG 0526 eligibility criteria. Dose recommendations from RTOG 0526 include a prescription dose of 140 Gy, V150 < 45%, and V200 < 10% (Vx – volume of target receiving dose of x Gy).

These recommendations as well as our results apply to patients treated with standard dose radiotherapy (ie < 74 Gy) and may represent a moving target in the future. Indeed, 14/18 of our patients received < 74 Gy initially. With the advent of intensity-modulated radiotherapy (IMRT) and stereotactic ablative radiotherapy (SABR), there is a current trend towards escalation of dose, larger fraction sizes and shorter treatment schedules. The impact of these modalities on options for salvage is unknown. In our series, the 5 patients with late toxicity received an initial median EBRT dose of 70 Gy (range 66-78) and there was no clear relationship with late toxicity.

Toxicity is expected to be higher in the salvage setting and this report suggests the treatment approach should be adjusted accordingly. In the primary brachytherapy (I¬¬125) setting it is well established that a D90 < 130 Gy is associated with increased risk of recurrence. The optimal dose in the salvage setting, however, is not established. Three patients in this report received partial gland implants where the goal of planning was to cover the regions of the gland that were positive on biopsy which allowed relative sparing of the contralateral gland and urethra. Multiparametric MRI is an emerging modality that may help locate recurrent disease and facilitate partial gland implants. High dose rate brachytherapy is an attractive modality for salvage as it has the advantage of precise control over dose placement and may be more effective at delivering adequate dose to the known sites of disease while sparing organs at risk. A single fraction high dose rate brachytherapy approach would eliminate inter-fraction needle movement. Further study in these areas is needed to optimize salvage brachytherapy.

Written by:
Rose JN, Crook JM
Department of Radiation Oncology, British Columbia Cancer Agency, Center for the Southern Interior, Kelowna, British Columbia, Canada; British Columbia Cancer Agency, Provincial Brachytherapy Program, British Columbia, Canada;

Abstract:Salvage low-dose-rate permanent seed brachytherapy for locally recurrent prostate cancer: Association between dose and late toxicity