Biologically Effective Dose Values for Prostate Brachytherapy: Effects on PSA Failure and Post-Treatment Biopsy Results

Abstract

Purpose/Objective: The ability to perform dose response analyses for brachytherapy with different isotopes and combined with EBRT has been difficult due to differences in doses rates, half lives and fractionation. To address this problem, we derived biologically effective dose (BED) equations for different isotopes and treatments and tested their effects on PSA failure and post-treatment biopsy. Materials/Methods: 1377 patients were treated with brachytherapy from 1990 to 2003. Disease factors were as follows: PSA ≤10 in 70%, >10–20 in 20% and >20 in 10%; Gleason score 2–6 in 69%, 7 in 20.5% and 8–10 in 10.5%; clinical stage ≤ t2a in 65% and ≥ t2b in 35%. There were three treatment groups: brachytherapy alone (571 patients) with either I–125 or Pd–103, hormonal therapy and brachytherapy (371 patients) and trimodality therapy (hormonal therapy (9 months), implant and EBRT)(435 patients). Implant dose (D90) was derived from the one month post-implant CT based dosimetry. The linear–quadratic model was used to determine the BED for EBRT using the equation BED = nd 1 + (d/α/β) where n=number of fractions, d=dose per fraction, α/β = 2. The equation for the isotopes was BED = (R0/λ)1+R0/(μ+ λ)(α/β) where R0 = initial dose rate of implant = (D90)(λ), λ=radioactive decay constant = 0.693/T1/2, T1/2 =radioactive half–life of isotope, μ=repair rate constant = 0.693/t1/2, t1/2=tissue repair half-time. BEDs from implant and EBRT were added for combined therapy. Patients were divided into 7 BED dose groups. The groups were ≤ 100 (45 patients), >100–120 (32 patients), >120–140 (51 patients), >140–160 (97 patients), >160–180 (191 patients), >180–200 (311 patients) and > 200 (594). Follow-up ranged from 2–14 years (median−4.2). PSA failure was defined by the ASTRO definition. Biopsy outcome was determined by the last biopsy result 2 or > years post-treatment. Results: The overall freedom from PSA failure (FFPF) at 10 years was 87%. BED groupings significantly affected PSA failure with demonstrated improvement in FFPF rates with increasing BED. The 10 year FFPF for the BED groups ≤100, >100–120, >120–140, >140–160, >160–180, >180–200 and >200 were 46%, 68%, 81%, 85.5%, 90%, 90% and 92%, respectively (<0.0001). Based on the above findings, patients were divided into two BED dose groups < 150 (169 patients) and ≥150 (1152 patients). 10 year FFPF rates were 69% and 91% for the two groups, respectively (p<0.0001). Cox regression found that BED and Gleason Score had the greatest effect with p values of p<0.0001. The overall last positive biopsy rate was 7% (31/446). Lower positive biopsy results were associated with increasing BED dose groups. The positive biopsy results for BED group ≤100, >100–120, >120–140, >140–160, >160–180, >180–200 and >200 were 24% (8/33), 15% (3/20), 6% (2/33), 6% (3/52), 7% (6/82), 1% (1/72), 3% (4/131), respectively (<0.0001). Dividing patients into two BED dose groups (< 150, ≥ 150) revealed positive biopsy rates of 13% (14/110) and 4%(13/312), respectively, p <0.0001. Logistic regression analysis revealed BED to be the most significant predictor of biopsy results (p=0.006). Conclusions: BED equations allow the comparison of different isotopes and combined therapies in the brachytherapy management of prostate cancer. The effects of BED on FFPF and post-treatment biopsy reveal a strong dose response relationship. These results support the recommended brachytherapy dose prescriptions but emphasize the need to achieve the stated dose goals. If current prescription doses can be achieved, excellent long-term biochemical and local control rates can be realized.