Treatment margins predict biochemical outcomes after prostate brachytherapy

PURPOSE: Due to the theoretical role of treatment margins (TMs) in cancer, we have correlated biochemical outcomes with post-implant TMs in patients treated with brachytherapy for early stage prostate cancer. METHODS: From November 1998 through September 2003, 492 of a planned total of 600 patients with 1997 AJC clinical stage T1c-T2a prostatic carcinoma (Gleason score 5 or 6, PSA 4 to 10 ng/mL) have been randomized to implantation with ¹²⁵I (144 Gy, TG-43) versus ¹⁰³Pd (125 Gy, NIST-99). This preliminary analysis included only the first 122 analyzable patients, while accrual to the trial finishes. Isotope implantation was performed by standard techniques, using a modified peripheral loading pattern. Axial CT images at 3 mm intervals were acquired within four hours postoperatively for post-implant dosimetry. The contoured images and sources were entered into Varian Variseed™ system 7.1 (Charlottesville, VA). After completion of standard dosimetric calculations, the 100% prescription dose TMs were measured and tabulated around the prostate periphery at the 0.0, 1.0, 2.0 and 3.0 cm planes, going distal from the bladder-prostate interface. Measurements were limited to the transverse planes. Freedom from biochemical failure was defined as a serum PSA ≤ 0.5 ng/mL at last follow-up. Patients were censored at last follow-up if their serum PSA was still decreasing. Patients whose serum PSA nadired at a value >0.5 ng/mL were scored as failures at the time at which their PSA nadired. The follow-up period for non-failing patients ranged from 2.1-5.0 years (median: 3.3 years). RESULTS: The average 100% prescription dose treatment margin (for individual patients) ranged from -5.0 to 8.7 mm, with an overall average of 2.6 mm (±3.1). In univariate analysis, the D90 was the best predictor of biochemical control for ¹²⁵I, while the average TM was the best predictor for ¹⁰³Pd. Similarly, in multivariate analysis using the D₉₀, V₁₀₀. and average TM as the independent variables and biochemical control as the dependent variable, the D₉₀ was most closely related to biochemical control for ¹²⁵I patients, while average TM was most closely related for ¹⁰³Pd patients. In separate analysis of TM by site, the anterior TMs were the best predictors of biochemical outcomes CONCLUSION: V₁₀₀. D₉₀, and TMs all appear to have a bearing on biochemical freedom from relapse after prostate brachytherapy. Efforts to better identify and test geographic dosimetric parameters are theoretically appealing, and supported by the clinical data summarized here.