730 S. Hayashi et al. The median interval from RT to postradiotherapy biochem- ical failure was 213 days (range, 31–1095 days). The median observation period was 52 months (range, 4– 108 months). The statistical analysis was performed using StatView 5.0 software (SAS Institute Inc., Cary, NC, USA). The sur- vival rates were calculated using the Kaplan–Meier method, and the survival curves were compared using the log-rank test. In univariate and multivariate analyses, the prognostic factors were evaluated using the Cox-proportional hazards model. Relationships between the prognostic factors and the treatment outcome were analyzed using logistic regres- sion models, and the models were compared using a likelihood-ratio test. A P value less than 0.05 was consid- ered statistically significant. Acute and late toxicity were graded according to the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 4.0. RESULTS Efficacy Within the first year following salvage RT, 18 patients experienced biochemical failure. During the entire observa- tion period, biochemical failure occurred in 23 patients, local recurrence occurred in 1 patient, and distant metastasis to the thoracic or lumbar spine occurred in 2 patients. None of the patients died from prostate cancer or any other cause. Fifteen patients received salvage hormonal therapy after undergoing RT. The overall 5-year clinical relapse-free sur- vival rate was 87%. The overall bDFS rate was 58% at 1 year, 38% at 3 years and 38% at 5 years (Fig. 1). Toxicity Acute Grade 1 or Grade 2 renal and urinary (RU) complications occurred in 13 cases (32%) and 4 cases (10%), respectively. Acute Grade 1 gastrointestinal (GI) Fig. 1. Biochemical disease-free survival and metastasis-free survival after salvage radiotherapy. complications occurred in 18 cases (44%). None of the patients experienced acute Grade 3/4/5 RU complications or Grade 3/4/5 GI complications. Late Grade 1 and Grade 2 RU complications occurred in 5 cases (12%) and 1 case (2%), respectively. Two patients experienced a Grade 3 RU complication consisting of a urinary tract obstruction that required operative intervention. No late GI complications were seen. Univariate and multivariate analyses Table 2 shows the univariate and multivariate analyses of possible prognostic factors for biochemical failure follow- ing salvage RT. We focused on the detailed pathological findings. Many previous reports combined LI and VI as LVI, but we distinguished LI from VI. In the multivariate analysis, the Gleason score (P = 0.030), negative surgical margin (P = 0.018), seminal vesicle invasion (P = 0.006), LI (P < 0.0001), negative VI (P = 0.011), preradiotherapy PSA level (P = 0.017), radiation dose (P = 0.010) and size of the radiation field (P = 0.047) significantly increased the risk of biochemical failure following salvage RT. The results of the univariate analyses supported the results of the multivariate analysis. The Gleason score (P = 0.013), seminal vesicle invasion (P = 0.003) and LI (P = 0.001) were significantly associated with biochemical failure. Comparison of bDFS curves Figures 2–4 show the cumulative bDFS curves according to significant prognostic factors. The differences between the survival curves were statistically significant for a Gleason score of <3 + 4 vs. greater than 4 + 3 (50% vs. 28%, 5-year bDFS, P = 0.018; Fig. 2), the LI status (52% vs. 18%, P = 0.001; Fig. 3), the status of seminal vesicle invasion (45% vs. 0%, P = 0.002; Fig. 4) and a preradiotherapy PSA level of > 0.2 ng/ml vs. < 0.2 ng/ml (59% vs. 15%, P = 0.036). The survival curves for other factors were not significantly different: surgical margin status (P = 1.00); VI status (P = 0.20); radiation dose (P = 0.80) and size of radiation field (P = 0.49). Among the patients with LI, neither the radi- ation dose (P = 0.31) nor the size of the radiation field (P = 0.13) improved the bDFS. After salvage RT, 76% patients achieved a PSA nadir of <0.2 ng/ml and 51% patients achieved a nadir of <0.05 ng/ml. A Kaplan–Meier analysis showed that the cumulative bDFS curves differed significantly between patients with a postradiotherapy PSA nadir of < 0.05 ng/ml and those with a nadir of > 0.05 ng/ml (75% vs. 10% for 5-year bDFS, P < 0.0001). In a logistic regression analysis, a negative surgical margin (P = 0.020), LI (P = 0.0001) and the preradiotherapy PSA level (P = 0.0002) were signifi- cantly associated with a postradiotherapy PSA nadir of >0.05 ng/ml.