Abstract：
BACKGROUND: High-dose-rate brachytherapy (HDR-BT) plays an important role in the treatment of locally recurrent prostate cancer after definitive treatment. The objective of this study is to summarize the efficacy and toxicity of HDR-BT in these patients.
METHODS: We performed a systematic review of PubMed and EMBASE from inception to July 2023. The primary endpoint was relapse-free survival (RFS) in different subgroups, and the secondary endpoint was gastrointestinal (GI) and genitourinary (GU) toxicity. A semi-automated tool (WebPlotDigitizer) and a new Shiny application combined with R software (R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria; https://www.R-project.org/ ) helped to reconstruct survival curves.
RESULTS: Twenty-six studies met the inclusion criteria for quantitative analysis, including 1447 patients. A total of 761 patients from 13 studies were included in survival reconstruction, and the median RFS time was 61.2 months (57.6-72.0 months). The estimated 2‑, 3‑, and 5‑year rates were 75.9% (95% confidence interval [CI] 72.8 ~ 79.2%), 66.7% (95% CI 63.0 ~ 70.5%), and 52.3% (95% CI 47.5 ~ 57.4%), respectively. Whole-gland irradiation with multiple fractions (≥ 2 F) resulted in better RFS compared with focal gland irradiation with fewer fractions (1 F mostly; hazard ratio [HR]: 0.60, 95% CI 0.47-0.77, p < 0.0001). According to the different median time from primary treatment to salvage therapy (TRS) and median age at recurrence, short median TRS (56-67.2 months vs. 70-120 months; HR 0.52, 95% CI 0.68-0.40; p < 0.0001) and younger median age (60-70 years vs. 71-75 years; HR 0.58, 95% CI 0.46-0.74; p < 0.0001) were positive factors for RFS. The cumulative incidences estimated for grade ≥ 3 acute and late GU toxicities were 1% (95% CI 0 ~ 1%) and 5% (95% CI 4 ~ 7%), respectively. Three patients (3/992) experienced grade ≥ 3 late GI toxicity, and no cases of grade ≥ 3 acute GI toxicity were reported.
CONCLUSIONS: HDR-BT has a high safety profile and good RFS benefit for salvage treatment of radiorecurrent prostate cancer. In terms of RFS, whole-gland irradiation with multiple fractions seems to be better than focal gland irradiation with fewer fractions, while short TRS and younger age are good prognostic factors. In view of the low level of evidence in the included studies and the large heterogeneity of each study, these conclusions still need to be confirmed by randomized controlled trials.
METHODS: We performed a systematic review of PubMed and EMBASE from inception to July 2023. The primary endpoint was relapse-free survival (RFS) in different subgroups, and the secondary endpoint was gastrointestinal (GI) and genitourinary (GU) toxicity. A semi-automated tool (WebPlotDigitizer) and a new Shiny application combined with R software (R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria; https://www.R-project.org/ ) helped to reconstruct survival curves.
RESULTS: Twenty-six studies met the inclusion criteria for quantitative analysis, including 1447 patients. A total of 761 patients from 13 studies were included in survival reconstruction, and the median RFS time was 61.2 months (57.6-72.0 months). The estimated 2‑, 3‑, and 5‑year rates were 75.9% (95% confidence interval [CI] 72.8 ~ 79.2%), 66.7% (95% CI 63.0 ~ 70.5%), and 52.3% (95% CI 47.5 ~ 57.4%), respectively. Whole-gland irradiation with multiple fractions (≥ 2 F) resulted in better RFS compared with focal gland irradiation with fewer fractions (1 F mostly; hazard ratio [HR]: 0.60, 95% CI 0.47-0.77, p < 0.0001). According to the different median time from primary treatment to salvage therapy (TRS) and median age at recurrence, short median TRS (56-67.2 months vs. 70-120 months; HR 0.52, 95% CI 0.68-0.40; p < 0.0001) and younger median age (60-70 years vs. 71-75 years; HR 0.58, 95% CI 0.46-0.74; p < 0.0001) were positive factors for RFS. The cumulative incidences estimated for grade ≥ 3 acute and late GU toxicities were 1% (95% CI 0 ~ 1%) and 5% (95% CI 4 ~ 7%), respectively. Three patients (3/992) experienced grade ≥ 3 late GI toxicity, and no cases of grade ≥ 3 acute GI toxicity were reported.
CONCLUSIONS: HDR-BT has a high safety profile and good RFS benefit for salvage treatment of radiorecurrent prostate cancer. In terms of RFS, whole-gland irradiation with multiple fractions seems to be better than focal gland irradiation with fewer fractions, while short TRS and younger age are good prognostic factors. In view of the low level of evidence in the included studies and the large heterogeneity of each study, these conclusions still need to be confirmed by randomized controlled trials.
摘要：
背景：高剂量率近距离放射治疗（HDR-BT）在确定性治疗后局部复发性前列腺癌的治疗中起着重要作用。这项研究的目的是总结HDR-BT在这些患者中的功效和毒性。
方法：我们从成立到2023年7月对PubMed和EMBASE进行了系统评价。主要终点是不同亚组的无复发生存期（RFS），次要终点是胃肠道（GI）和泌尿生殖系统（GU）毒性。一个半自动化工具（WebPlotDigitizer）和一个新的Shiny应用程序与R软件（R：一种用于统计计算的语言和环境。R统计计算基金会，维也纳,奥地利；https://www.R-project.org/)帮助重建生存曲线。
结果：26项研究符合定量分析的纳入标准，包括1447名患者。共有来自13项研究的761名患者被纳入生存重建，中位RFS时间为61.2个月（57.6-72.0个月）。估计的2-，3-,5年期利率为75.9%(95%置信区间[CI]72.8~79.2%)，66.7%（95%CI63.0~70.5%），和52.3%（95%CI47.5~57.4%），分别。与分数较少的局灶性腺体照射相比，多分数（≥2F）的全腺体照射可获得更好的RFS（主要为1F；危险比[HR]：0.60，95％CI0.47-0.77，p<0.0001）。根据从主要治疗到抢救治疗（TRS）的中位时间和复发时的中位年龄的不同，短期中位TRS（56-67.2个月与70-120个月；HR0.52，95％CI0.68-0.40；p<0.0001）和较年轻的中位年龄（60-70岁与71-75岁；HR0.58，95%CI0.46-0.74；p<0.0001）是RFS的积极因素。≥3级急性和晚期GU毒性的累积发病率分别为1%(95%CI0~1%)和5%(95%CI4~7%),分别。3例患者（3/992）出现≥3级晚期胃肠道毒性，并且没有报告≥3级急性胃肠道毒性的病例。
结论：HDR-BT在放射性复发性前列腺癌的抢救治疗中具有很高的安全性和良好的RFS益处。就RFS而言,多部分的全腺体照射似乎比少部分的局灶性腺体照射更好，而短TRS和年龄较小是良好的预后因素。鉴于纳入研究的证据水平较低，且每项研究的异质性较大，这些结论仍需要随机对照试验的证实.
方法：我们从成立到2023年7月对PubMed和EMBASE进行了系统评价。主要终点是不同亚组的无复发生存期（RFS），次要终点是胃肠道（GI）和泌尿生殖系统（GU）毒性。一个半自动化工具（WebPlotDigitizer）和一个新的Shiny应用程序与R软件（R：一种用于统计计算的语言和环境。R统计计算基金会，维也纳,奥地利；https://www.R-project.org/)帮助重建生存曲线。
结果：26项研究符合定量分析的纳入标准，包括1447名患者。共有来自13项研究的761名患者被纳入生存重建，中位RFS时间为61.2个月（57.6-72.0个月）。估计的2-，3-,5年期利率为75.9%(95%置信区间[CI]72.8~79.2%)，66.7%（95%CI63.0~70.5%），和52.3%（95%CI47.5~57.4%），分别。与分数较少的局灶性腺体照射相比，多分数（≥2F）的全腺体照射可获得更好的RFS（主要为1F；危险比[HR]：0.60，95％CI0.47-0.77，p<0.0001）。根据从主要治疗到抢救治疗（TRS）的中位时间和复发时的中位年龄的不同，短期中位TRS（56-67.2个月与70-120个月；HR0.52，95％CI0.68-0.40；p<0.0001）和较年轻的中位年龄（60-70岁与71-75岁；HR0.58，95%CI0.46-0.74；p<0.0001）是RFS的积极因素。≥3级急性和晚期GU毒性的累积发病率分别为1%(95%CI0~1%)和5%(95%CI4~7%),分别。3例患者（3/992）出现≥3级晚期胃肠道毒性，并且没有报告≥3级急性胃肠道毒性的病例。
结论：HDR-BT在放射性复发性前列腺癌的抢救治疗中具有很高的安全性和良好的RFS益处。就RFS而言,多部分的全腺体照射似乎比少部分的局灶性腺体照射更好，而短TRS和年龄较小是良好的预后因素。鉴于纳入研究的证据水平较低，且每项研究的异质性较大，这些结论仍需要随机对照试验的证实.
