International Journal of Radiation Oncology*Biology*Physics
Clinical investigationProstateBiologically effective dose values for prostate brachytherapy: Effects on PSA failure and posttreatment biopsy results
Introduction
Recent advances in the radiotherapeutic management of prostate cancer have focused on the relationship of radiation dose and tumor control. Although new technology such as three-dimensional conformal and intensity-modulated external beam radiation therapy (EBRT) has brought attention to this relationship, it is not a new area of study. Hanks et al., through the patterns of care studies, helped demonstrate that increasing dose in the external beam management of prostate cancer could translate into improved local control (1). Fuks et al. explored the relationship between implant quality and local control in a cohort of patients treated with retropubic I-125 prostate implants and found a similar improvement in outcome with higher dose distributions (2). These early studies used the digital rectal examination to assess local control and as an endpoint for the dose–response analysis. In recent years, investigators have shifted the emphasis toward examining the relationship between dose and biochemical control. Retrospective studies have demonstrated that increasing dose over the standard 70 Gy of EBRT has resulted in improved biochemical control rates. These findings were confirmed in a randomized trial reported by Pollack et al. (3). In 1998, our institution established the first dose–response relationship for ultrasound-guided I-125 implants (4). Subsequent studies confirmed these findings with longer follow-up and greater numbers of patients (5, 6). In addition, brachytherapy dose–response relationships were found using posttreatment biopsy as an endpoint (6, 7). A dose–response for prostate permanent seed implantation has also been supported using other data sets (8, 9). These reports sought to explore these relationships by comparing isotope and treatment regimens. This was accomplished by looking at the implant dose derived from the postimplant dosimetric analysis as a percentage of the prescription dose. This method is problematic because prescription doses have been empirically chosen and the same percentage of a prescription dose for one isotope or treatment does not necessarily equate biologically to another.
To overcome these problems, we analyzed the dose–response relationship by developing biologically effective dose (BED) values for all brachytherapy treatments. In this way, different isotopes and treatment regimens (i.e., combined implant and EBRT) could be compared on a valid basis to test a dose–response relationship. In addition, the connection between local control and biochemical control was explored by testing the effect of BED on both prostate-specific antigen (PSA) failure and posttreatment biopsy results.
Section snippets
Methods and materials
A total of 1377 patients with T1 to T3 prostate cancer were treated with brachytherapy at Mount Sinai Hospital in New York from June 1990 to January 2003. No patient had radiologic or pathologic evidence of metastatic disease. All patients were staged using the 1992 American Joint Committee on Cancer staging system (10). The clinical stage, presenting Gleason score, and presenting PSA for all patients can be found in Table 1.
Seminal vesicle biopsy was performed in 609 patients (44%).
Biochemical control
The overall freedom from PSA failure (FFPF) for the whole cohort at 10 years was 87% (Fig. 1). Patient age had a significant effect on PSA failure. Ten-year FFPF rates for patients <60 (305), >60–70 (659), and >70 (413) were 91%, 87%, and 85%, respectively (p = 0.03). The FFPF rates broken out by presenting disease characteristics can be found in Table 2. All of the disease characteristics significantly affected FFPF in univariate analysis. The choice of treatment did not significantly affect
Discussion
In 1998, we published our first report on the effect of implant dose on biochemical outcome using I-125 implants (4). The decision made at that time was to perform the dose–response analysis only on one isotope to avoid having to compare doses between two isotopes with different half-lives and dose rates. In addition, patients treated with combined implant and EBRT were also excluded for similar reasons. In 2000, we analyzed the effect of dose on posttreatment biopsy outcomes. Because of our
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