Prostate-specific antigen spikes after permanent prostate brachytherapy

Abstract

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 ≥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 (D90), the percentage of the prostate volume receiving 100% (V100), 150%, and 200% (V200) 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 ≤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 ≤0.1 ng/mL. Stratified into three nadir PSA groups, patients with a nadir PSA ≤0.2 ng/mL were significantly less likely to develop a PSA spike than those patients with a PSA nadir >0.2 to ≤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 V150 were predictive for the development of a PSA spike. A postimplant dosimetric threshold of either <115% of the minimal peripheral dose for D90 or <55% of the prostate volume for V150 was strongly predictive of a spike. When the variables only determinable after the occurrence of the PSA spike were included in the multivariate analysis, V150, 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 V150 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.