对于高危前列腺癌，与调强适形外照射放疗相比，低剂量率近距离放疗联合雄激素剥夺治疗可降低生化失败和前列腺癌死亡的风险。
The addition of low-dose-rate brachytherapy and androgen-deprivation therapy decreases biochemical failure and prostate cancer death compared with dose-escalated external-beam radiation therapy for high-risk prostate cancer.
机构信息
Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, MI 48109, USA.
出版信息
Cancer. 2013 Feb 1;119(3):681-90. doi: 10.1002/cncr.27784. Epub 2012 Aug 14.
BACKGROUND
The objective of this study was to determine whether the addition of low-dose-rate brachytherapy or androgen-deprivation therapy (ADT) improves clinical outcome in patients with high-risk prostate cancer (HiRPCa) who received dose-escalated radiotherapy (RT).
METHODS
Between 1995 and 2010, 958 patients with HiRPCa were treated at Schiffler Cancer Center (n = 484) or at the University of Michigan (n = 474) by receiving either dose-escalated external-beam RT (EBRT) (n = 510; minimum prescription dose, 75 grays [Gy]; median dose, 78 Gy) or combined-modality RT (CMRT) consisting of (103) Pd implants (n = 369) or (125) I implants (n = 79) both with pelvic irradiation (median prescription dose, 45 Gy). The cumulative incidences of biochemical failure (BF) and prostate cancer-specific mortality (PCSM) were estimated by using the Kaplan-Meier method and Fine and Gray regression analysis.
RESULTS
The median follow-up was 63.2 months (interquartile range, 35.4-99.0 months), and 250 patients were followed for >8 years. Compared with CMRT, patients who received EBRT had higher prostate-specific antigen levels, higher tumor classification, lower Gleason sum, and more frequent receipt of ADT for a longer duration. The 8-year incidence BF and PCSM among patients who received EBRT was 40% (standard error, 38%-44%) and 13% (standard error, 11%-15%) compared with 14% (standard error, 12%-16%; P < .0001) and 7% (standard error 6%-9%; P = .003) among patients who received CMRT. On multivariate analysis, the hazard ratios (HRs) for BF and PCSM were 0.35 (95% confidence interval [CI], 0.23-0.52; P < .0001) and 0.41 (95% CI, 0.23-0.75; P < .003), favoring CMRT. Increasing duration of ADT predicted decreased BF (P = .04) and PCSM (P = .001), which was greatest with long-term ADT (BF: HR, 0.33; P < .0001; 95% CI, 0.21-0.52; PCSM: HR, 0.30; P = .001; 95% CI, 0.15-0.6) even in the subgroup that received CMRT.
CONCLUSIONS
In this retrospective comparison, both low-dose-rate brachytherapy boost and ADT were associated with decreased risks of BF and PCSM compared with EBRT.
背景
本研究旨在确定在接受高剂量率近距离放射治疗（brachytherapy）或雄激素剥夺治疗（androgen-deprivation therapy，ADT）的高危前列腺癌（high-risk prostate cancer，HiRPCa）患者中，加用低剂量率近距离放射治疗或 ADT 是否能改善接受剂量递增放疗（dose-escalated radiotherapy，RT）的患者的临床结局。
方法
1995 年至 2010 年间，958 例 HiRPCa 患者在 Schiffler 癌症中心（n = 484）或密歇根大学（n = 474）接受治疗，分别接受剂量递增外照射 RT（EBRT）（n = 510；最小处方剂量 75 戈瑞[grays，Gy]；中位剂量 78 Gy）或包括盆腔照射的联合治疗（combined-modality RT，CMRT）[103Pd 植入（n = 369）或 125I 植入（n = 79）]。采用 Kaplan-Meier 法和 Fine 和 Gray 回归分析估计生化失败（biochemical failure，BF）和前列腺癌特异性死亡率（prostate cancer-specific mortality，PCSM）的累积发生率。
结果
中位随访时间为 63.2 个月（四分位间距，35.4-99.0 个月），250 例患者随访时间超过 8 年。与 CMRT 相比，接受 EBRT 的患者前列腺特异性抗原水平更高、肿瘤分级更高、Gleason 评分更低、接受 ADT 的比例更高且持续时间更长。EBRT 组的 8 年 BF 和 PCSM 发生率为 40%（标准误差，38%-44%）和 13%（标准误差，11%-15%），而 CMRT 组分别为 14%（标准误差，12%-16%；P <.0001）和 7%（标准误差，6%-9%；P =.003）。多变量分析显示，BF 和 PCSM 的风险比（hazard ratio，HR）分别为 0.35（95%置信区间，0.23-0.52；P <.0001）和 0.41（95%置信区间，0.23-0.75；P <.003），CMRT 更具优势。ADT 持续时间的增加预测 BF（P =.04）和 PCSM（P =.001）的降低，长期 ADT 的效果最大（BF：HR，0.33；P <.0001；95%CI，0.21-0.52；PCSM：HR，0.30；P =.001；95%CI，0.15-0.6），即使在接受 CMRT 的亚组中也是如此。
结论
在这项回顾性比较研究中，与 EBRT 相比，低剂量率近距离放射治疗加 ADT 均与 BF 和 PCSM 风险降低相关。
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