1. FREEDOM FROM PROGRESSION FOR PATIENTS RECEIVING I 125 VERSUS Pd 103 FOR PROSTATE BRACHYTHERAPY Jane Cho, Carol Morgenstern, Barbara Napolitano, Lee Richstone, Louis Potters The Arthur Smith Institute for Urology, North Shore-Long Island Jewish Health System Department of Radiation Medicine, North Shore-Long Island Jewish Health System INTRODUCTION & OBJECTIVES There are no reports of outcome differences between I 125 and Pd 103, the standard isotopes used for PPB. Preliminary data from a prospective randomized multicenter trial have failed to identify any difference in biochemical failure between the two isotopes. However, theoretical radiobiological models suggest a therapeutic advantage for Pd 103 over I 125 in the treatment of high Gleason score tumors. The purpose of this study was to present an update on long term biochemical outcomes of our large cohort PPB database. Preliminary analysis of the data revealed an advantage for Pd 103, which prompted a more detailed evaluation of this finding. METHODS 2369 consecutive patients with T1-T2NXM0 adenocarcinoma Isotope selection was generally based on prostate volume >45 cm 3 treated with I 125 (144Gy – 145Gy) <45 cm 3 were treated with Pd 103 (136Gy – 125Gy) Primary analysis endpoint was “disease progression” Biochemical recurrence (Phoenix definition: ≥2 ng/mL above nadir) initiation of adjuvant hormone treatment clinical recurrence radiologic evidence of metastasis cancer related death RESULTS Overall Kaplan-Meier time until progression for this cohort was 103.3 months, with a mean time until death from prostate cancer (disease- specific) of 112.8 months. Overall 10-year FFP was 85.6% Pd 103 : 89.5% vs. I 125 : 76.2% (log-rank test, p<0.0001) Multivariate analysis showed a statistical difference in outcome for Gleason sum, iPSA, year of treatment, % core positive and isotope Isotope selection had the highest hazard ratio of the variables D90% values were available for 1668 patients The same variables of Gleason sum, iPSA, year of treatment, % core positive and isotope were found to be significant along with D90% and the addition of hormone treatment. CONCLUSIONS These results from a retrospective study with a large cohort, identified a significant difference in FFP for men undergoing PPB favoring Pd 103 over I 125. Patient selection for the isotopes was based on volume instead of Gleason score. This allowed an extensive analysis of both isotopes for both low and high Gleason scores. This is the first study to demonstrate a therapeutic advantage for Pd 103 in the PPB treatment of prostate cancer, an advantage that was not limited to high Gleason score tumors. Additional studies are needed to validate these results. Table 1. Multivariable Cox Regression Model for all Patients (n=2119) Multivariate Analyses Variable Hazard Ratio 95% CIP-value Age (continuous)0.9990.976 – 1.0220.925 Gleason sum1.451.240 – 1.696<0.0001 Clinical Stage1.2050.963 – 1.5060.1023 iPSA1.0261.016 – 1.035<0.0001 Year of Rx0.8190.769 – 0.872<0.0001 % Positive Cores1.0091.003 – 1.0140.0022 Isotope2.261.701 – 3.003<0.0001 Table 2. Multivariable Cox Regression Model for Patients with Post-Implant Dosimetry (n=1668) Multivariate Analyses Variable Hazard Ratio 95% CIP-value Gleason sum1.5421.297 – 1.834<0.0001 Clinical Stage1.2010.955 – 1.5110.1174 iPSA1.0301.019 – 1.040<0.0001 Year of Rx0.8480.796 – 0.903<0.0001 % Positive Cores1.0091.003 – 1.0150.0016 D900.9910.985 – 0.9980.0122 Treatment (vs. PPB alone) Hormone0.5830.355 – 0.9570.0330 EBRT1.0680.696 – 1.6390.7636 Trimodality0.7550.417 – 1.3670.3533 Isotope2.5521.896 – 3.434<0.0001 ABSTRACT Objectives: To evaluate and compare disease progression between I 125 and Pd 103 for prostate cancer patients who underwent permanent prostate brachytherapy (PPB). Methods: Between 1992 and 2005, 2119 consecutive patients (pts), with T1-T2NXM0 prostate cancer underwent PPB. 607 (28.7%) pts received I 125 and 1512 (71.4%) pts received Pd 103. Isotope selection was based on prostate volume. Treatment modalities included PPB only, PPB with hormone, PPB with external beam radiotherapy (EBRT) and PPB with both hormone and EBRT. Disease progression was defined using the Phoenix definition. Freedom from progression (FFP) of the two isotope groups was calculated using the Kaplan-Meier product-limit method and compared using the log-rank test. Multivariate Cox regression analysis was also performed. Results: The mean follow up time was 58.2 months with an overall 10-year FFP of 85.6%. The 10-year FFP for I 125 was 76.2% and 89.5% for Pd 103 (p<0.0001). The 10-year FFP among only pts with Gleason sum 6 (n=1199) was 93.0% for Pd 103 and 89.9% for I 125 (p=0.08). Multivariate analysis identified isotope (p<0.0001), Gleason score (p<0.0001), year of treatment (p<0.0001), D90% (p=0.012), and % positive cores (p<0.002) independent risk factors for FFP, while stage (p=0.97) was not predictive of FFP. The hazard ratio for isotope was 2.26 favoring Pd 103. Conclusion: These results from a retrospective study with a large cohort, identified a significant difference in FFP for men undergoing PPB favoring Pd 103 over I 125. Additional studies are needed to validate these results. FIGURE 1. Overall Freedom From Progression Rates FIGURE 2. Freedom From Progression Rates Stratified by Isotope