732 S. Hayashi et al. Fig. 4. biochemical disease-free survival after salvage radiotherapy following a radical prostatectomy, stratified according to seminal vesicle invasion (sv). PSA-DT (<10 months), a high Gleason score (8), a short interval between prostatectomy and biochemical failure (1– 2 years), lymph node metastasis and seminal vesicle inva- sion are more likely to develop distant metastasis than local recurrence [3, 11, 12]. In addition, previously reported prognostic factors for biochemical failure following salvage RT include the preprostatectomy PSA level, the prera- diotherapy PSA level, the disease stage and grade, the Gleason score, the surgical margin status and the presence of seminal vesicle invasion, LVI, and perineural invasion as well as the radiation dose [5, 7, 8–10, 16]. The results of our study are almost identical to those of previous studies. The Gleason score, seminal vesicle inva- sion and LI were considered to be reliable predictors of biochemical failure following salvage RT, since the results of the univariate analysis, multivariate analysis and Kaplan–Meier analysis were consistent. In addition, a prera- diotherapy PSA level and a negative surgical margin were independent predictors of biochemical failure following salvage RT in the multivariate analysis. The previous study already reported that negative surgical margin increase the risk of biochemical failure [8], because it suggested high risk of distant micrometastasis at the beginning of the period of salvage RT. On the other hand, PSA-DT and the interval from RP to postoperative biochemical failure were not predictors of the treatment outcome in the present series. The reason for this discrepancy may be related to the population that was used in the present study. Previous studies have reported that a shorter PSA-DT (<10 months) and the interval from RP to postoperative biochemical failure (1–2 years) were associated with the failure of salvage RT [3, 11, 12]. From this perspective, most of the patients in the present study had a high risk of biochemical failure, since the median PSA-DT was 4.8 months and the median interval from RP to postprostatectomy biochemical failure was 370 days. Furthermore, the characteristics of the enrolled patients were thought to be one of the reasons why the 5-year bDFS rate was 38% in our study, which was somewhat lower than in previous reports [5–7]. Some previous reports have examined the frequency of LVI and the association between LVI and the outcome of salvage RT. The reported frequency of LVI ranged widely from 5 to 53% [13, 17, 18]. Some authors reported that LVI was associated with disease progression and distant metastasis after RP [13, 16], whereas others did not [18]. However, these reports combined LI and VI as LVI. We distinguished between LI and VI and found that LI was an independently significant predictive factor of a poor outcome of salvage RT, while VI was not significantly asso- ciated with an inferior outcome of treatment. This finding might resolve the discrepancies among previous reports regarding the association between LVI and the outcome of salvage RT. The reason why negative VI increases the risk of biochemical failure is abstruse. Although the statistical problem of significance caused by small group setting was undeniable, the velocity of vascular metastasis might be more gradual than LI especially in case of vein invasion. The radiation dose of salvage RT for local recurrence or biochemical failure following RP has been recommended to be greater than 64 Gy [5, 6]; however, an optimal dose has not yet been defined. In our study, the multivariate ana- lysis suggested that dose escalation may slightly decrease the risk of biological failure. However, no significant differ- ence was observed between bDFS curves constructed according to the radiation dose using a Kaplan–Meier ana- lysis; thus, other confounding factors were thought to be present. The radiation dose also did not cause a significant difference in the bDFS among the patients with LI. Nevertheless, the efficacy of dose escalation among patients with LI may become evident if the number of cases is increased and if a multivariate method is used. Regarding the widening of the radiation field, the results of the univariate analysis differed from those of the multi- variate analysis, and the P values of the analyses were too large to prove a relation between the size of the radiation field and the treatment outcome. The reason was assumed to be that because the radiation field was directed at the prostate bed, the size of the radiation field largely depended on the patient’s preoperative prostate volume. Therefore, the efficacy of extended irradiation to the pelvic region was not investigated in this study. Since cancer cells are thought to migrate from lymphatic vessels in the prostate to regional lymph nodes, the early initiation of RT before the cancer cells migrate to a distant area or additional radiation beyond the prostate bed might offer some benefit to patients with LI and no lymph node metastasis. A prospective study is needed to resolve this problem. Though the diagnosis of biochemical failure is import- ant for the initiation of secondary therapy, such as salvage