PSA bounce, which is frequently observed after LDR-brachytherapy, is a curious phenomenon caused by an unknown mechanism. Reportedly, 17% to 62% of patients are diagnosed with PSA bounce using several definitions [1–10]. The median time to PSA bounce varied from 15 months to 26 months [1, 2, 4, 6, 7, 9, 10]. The median height of PSA bounce was 0.4 ng/mL to 0.8 ng/mL [1, 2, 4, 6–9]. The median duration of PSA bounce was 6.8 months to 22.5 months [2, 3, 6, 7]. In daily practice, doctors and patients are annoyed when PSA elevation shows biochemical recurrence or PSA bounce due to the comparatively high incidence and long duration of PSA bounce. In the present study, the incidence of PSA bounce, the median time to PSA bounce, the median height of PSA bounce, and the median duration of PSA bounce were 25%, 17 months, 0.29 ng/mL, and 7.0 months, respectively. The median height in our series was lower than that in previous studies. Presumably, it was caused by the definition of PSA bounce (cut-off value of 0.1 ng/mL).
In the subgroup analysis, the incidence of PSA elevation of ≥0.1 ng/mL was significantly higher in the monotherapy with neoadjuvant ADT group than the combination therapy without neoadjuvant ADT (p = 0.006) group. However, the incidence of PSA bounce was not significantly different in these four groups. This result was comparable to that of previous reports [5, 6, 10]. Moreover, the estimated 3-year bounce-free rates in these four groups showed no significant differences in this study.
The present study showed that %UD90, UD90, and BED were significantly different between patients with PSA bounce and those without PSA bounce, whereas age and prostate volume showed no significant difference among all patients. To avoid the influence of neoadjuvat/adjuvant ADT and EBRT, we evaluated the predictive parameters of PSA bounce in patients treated with LDR-brachytherapy alone without neoadjuvant/adjuvant ADT. In this group, %UD90, UD90 and %UD30 showed a significant difference between patients with PSA bounce and those without PSA bounce, while age showed a marginal difference (p = 0.06). Previous studies have reported that age, D90, isotope, and prostate volume were the significant predictive factors of PSA bounce [3–9]. On the other hand, age, %UD90 and %UD30 were significant predictive parameters of PSA bounce by univariate analysis using a Cox proportional regression hazard model in this study. Multivariate analysis indicated %UD90 as predictive parameters. The pathological reason why %UD90 affects the incidence of PSA bounce is unknown. It is most probable that a higher dose to the urethra causes a higher incidence of radiation-induced urethritis and prostatitis.
Various factors including age, radiation-induced proctitis, prostatitis (radiation-induced or infection), ejaculation, laboratory error, urinary retention, testosterone recovery after ADT, and instrumentation, are considered as etiologies of PSA bounce. Assessment strongly suggests that sexual activity, inflammatory stimulation and androgen manipulation are associated with PSA bounce. It is necessary to investigate the correlation between PSA bounce and the data of urine analysis, urodynamics study, and serum androgen level in the future.
Our present study has some limitations such as a small number of patients and a short follow-up period. Indeed, there were only 50 patients who showed PSA bounce out of the 82 patients with PSA elevation of ≥ 0.1 ng/mL after LDR-brachytherapy without PSA failure. The other 32 patients with PSA elevation did not reach the PSA nadir level during the follow-up period. Longer follow-up is necessary to confirm PSA bounce in this patient group. The difference in the prescribed monotherapy dose (145 Gy vs. 160 Gy) may also influence the incidence of PSA bounce. In this study, we did not evaluate this matter because the follow-up period of the patients who received a prescribed dose of 160 Gy was significantly shorter than that of the patients who received 145 Gy (data not shown). The definition of PSA bounce is also controversial. In this study, we adopted a cut-off value of 0.1 ng/mL. The results of studies with a longer follow-up period and a different cut-off value of PSA bounce are expected in the near future.