Prostate-specific antigen spikes after permanent prostate brachytherapy.

PURPOSE: To evaluate whether any clinical, treatment, or dosimetric parameters correlated with the development of a prostate-specific antigen (PSA) spike after permanent prostate brachytherapy. METHODS AND MATERIALS: The evaluated population consisted of 218 hormone-naive patients free of biochemical or clinical failure who underwent permanent prostate brachytherapy with or without supplemental external beam radiotherapy for clinical Stage T1b-T3a adenocarcinoma of the prostate gland (1997 AJCC) between August 1995 and November 1999. No patient underwent pre- or postimplant hormonal manipulation, pretreatment seminal vesicle biopsy, or pathologic lymph node staging. In addition, none of the 218 patients possessed equivocal biochemical results (one or two consecutive PSA rises or a declining PSA >1.0 ng/mL). The median patient follow-up was 46.2 months. A PSA spike was defined as a rise of >or=0.2 ng/mL, followed by a durable decline. The clinical parameters evaluated included patient age, clinical T stage, Gleason score, pretreatment PSA level, prostate volume, brachytherapy planning volume, and patient follow-up in months. The evaluated treatment parameters included isotope and use of supplemental external beam radiotherapy. The dosimetric parameters evaluated included the minimal dose received by 90% of the prostate gland (D(90)), the percentage of the prostate volume receiving 100% (V(100)), 150%, and 200% (V(200)) of the prescribed minimal peripheral dose, and the mean, median, maximal, and minimal urethral doses. Biochemical disease-free survival was defined by the American Society for Therapeutic Radiology and Oncology consensus definition with the additional constraint that the most recent PSA level was <or=1.0 ng/mL.
RESULTS: Fifty-two patients (23.9%) developed a PSA spike at a mean and median of 19.5 +/- 9.4 months and 16.3 months (range 6.5-59.9), respectively. The median serum PSA before the PSA spike was 0.50 ng/mL, and the median PSA at the time of the spike was 0.90 ng/mL (range 0.3-3.0). On average, patients experiencing a PSA spike were 3.4 years younger (63.9 vs. 67.3 years, p = 0.002) than patients not experiencing a spike and were more likely to have been implanted with 125I than with 103Pd (32.7% vs. 16.7%, p = 0.006). In addition, the mean first postimplant PSA level was significantly higher in the spike than in the nonspike patients (1.2 vs. 0.7 ng/mL, p <0.001). By 66 months, the mean and median serum PSA levels for the spike and nonspike patients were all <or=0.1 ng/mL. Stratified into three nadir PSA groups, patients with a nadir PSA <or=0.2 ng/mL were significantly less likely to develop a PSA spike than those patients with a PSA nadir >0.2 to <or=0.5 ng/mL or >0.5 to 1.0 ng/mL (20%, 50%, and 80%, respectively, p <0.001). In Cox multivariate regression analysis, patient age, clinical stage, first postimplant PSA level, and V(150) were predictive for the development of a PSA spike. A postimplant dosimetric threshold of either <115% of the minimal peripheral dose for D(90) or <55% of the prostate volume for V(150) was strongly predictive of a spike. When the variables only determinable after the occurrence of the PSA spike were included in the multivariate analysis, V(150), preimplant PSA level, and nadir PSA were the significant predictors.
CONCLUSION: Of the patients, 23.9% developed a PSA spike with a median time to development of 16.3 months and a median prespike and median postspike PSA of 0.50 ng/mL and 0.90 ng/mL, respectively. In multivariate analysis, patient age, clinical stage, first postimplant PSA level, and V(150) were predictive for the development of a PSA spike. At approximately 66 months after implantation, the PSA curves converged for spike and nonspike patients, with a median PSA level <0.1 ng/mL.