Morbidity effect of the time gap between supplemental beam radiation and Pd-103 prostate brachytherapy

To determine if gap time variations between prostate brachytherapy and supplemental beam radiation (EBRT) affect postimplant morbidity.

Ninety-one patients with 1997 AJC clinical stage T1c-T2a prostatic carcinoma, Gleason grade 7-9, or PSA 10-20 ng/ml, were randomized to implantation with 90 Gy Pd-103 versus 115 Gy (NIST-1999) with 44 Gy versus 20 Gy preimplant supplemental beam radiation, respectively. Pd-103 implantation was performed by standard techniques, using a modified peripheral loading pattern. Beam radiation was delivered with a four-field arrangement, designed to cover the prostate and seminal vesicles with a 2-cm margin, reduced to 1.0 cm posteriorly. A post-implant computed tomography (CT) scan was obtained on the same day. Dosimetric parameters analyzed included the V100 - the percent of the postimplant prostate or rectal volume covered by the prescription dose, and the D90 - the dose that covers 90% of the post-implant prostate or rectal volume. For EBRT rectal D90s, the rectal volume included slices 0.9 cm above and below the seminal vesicles and apex, respectively. Treatment-related morbidity was monitored by mailed questionnaires, using standard American Urologic Association (AUA) and Radiation Therapy Oncology Group (RTOG) criteria at 1, 3, 6, 12, 18, and 24 months. Use of alpha-blockers to relieve obstructive symptoms was not controlled for, but was noted at each follow-up point. Median follow-up at the time of this analysis was 21 months, with a range of 18-26 months.

Variability in the total radiation delivery time within each treatment arm was due almost exclusively to gap time variability. Patients receiving 20 Gy EBRT completed their beam radiation over an average of 12 days (+/-1 day). Patients receiving 44 Gy did so over an average of 31 days (+/- 2 days). The median gap interval for patients receiving 20 Gy EBRT was 5 days (range: 1-40 days) versus 9 days (range: 0-15 days) for patients receiving 44 Gy EBRT. Urinary morbidity, measured by a change in the AUA score from baseline (DeltaAUA) was greater at 1-month postimplant in patients who had shorter gap intervals. The effect of gap time on AUA score changes was lost by 6 months. When looking at the treatment arms separately, the dependence on gap interval was limited to those patients receiving 44 Gy beam radiation. No patient has developed RTOG grade 3 rectal morbidity, and no patient has required invasive therapy for rectal bleeding. There was no relationship between gap interval and rectal morbidity at any time point. There was no relationship between beam doses and RTOG rectal morbidity scores.

The findings reported here are suggestive that short gap times are safe.