Harvard Medical School, Boston, MA, USA; Harvard Radiation Oncology Program, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA; Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA.
Eur Urol. 2019 Jan;75(1):35-41. doi: 10.1016/j.eururo.2018.08.033. Epub 2018 Oct 24.
While the addition of androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) is known to improve overall survival (OS) in Gleason 8-10 (Grade Group 4-5) prostate cancer (PCa), it has been hypothesized that Gleason 9-10 disease, which is less differentiated than Gleason 8 disease, may be less sensitive to ADT.
To examine the association between ADT and OS for Gleason 8 versus Gleason 9-10 PCa.
DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study of 20 139 men from the National Cancer Database with localized or locally advanced, Gleason 8-10 PCa who received EBRT. Data were collected from 2004 to 2012.
ADT.
Cox proportional hazards regression was used to examine the association between ADT and OS.
Overall, 9509 (78%) of the 12 160 men with Gleason 8 disease and 6908 (87%) of the 7979 men with Gleason 9-10 disease received ADT. On multivariable analysis, ADT was associated with a significant improvement in OS for Gleason 8 patients (adjusted hazard ratio 0.78, 95% confidence interval 0.70-0.87, p<0.001) but not for Gleason 9-10 patients (adjusted hazard ratio 0.96, 95% confidence interval 0.84-1.11, p=0.6), with a significant interaction (p=0.020). A higher Gleason score (8, 9, 10) correlated with an increased adjusted hazard ratio for the association between ADT and OS (p=0.042). Our study may be limited by the relatively short follow-up (median of 4.0 yr).
In contrast to the significant survival advantage of ADT for Gleason 8 disease, our results suggest that Gleason 9-10 disease derives less survival benefit from ADT and that a higher Gleason score predicts lesser benefit. Consideration should be given to treatment intensification for Gleason 9-10 patients through enrollment in clinical trials or potentially adding novel antiandrogens or docetaxel, which have shown efficacy in both castration-resistant and castration-sensitive settings.
In this study, we examined the effect of androgen deprivation therapy (ADT) for Gleason 8 (Grade Group 4) versus Gleason 9-10 (Grade Group 5) prostate cancer. We found that Gleason 9-10 disease may derive a smaller survival benefit from ADT than Gleason 8 disease.
雄激素剥夺疗法（ADT）联合外照射放疗（EBRT）已被证实可改善 Gleason 8-10（G 分级 4-5）前列腺癌（PCa）患者的总生存期（OS），但有假说认为，Gleason 9-10 级（G 分级 4-5）肿瘤分化程度低于 Gleason 8 级肿瘤，可能对 ADT 不敏感。
研究 ADT 对 Gleason 8 级和 Gleason 9-10 级 PCa 患者 OS 的影响。
设计、地点和参与者：本研究为回顾性队列研究，纳入了 2004 年至 2012 年期间在国家癌症数据库中接受 EBRT 治疗的 20139 例局限性或局部进展性 Gleason 8-10 PCa 患者。数据收集自全国癌症数据库。
ADT。
采用 Cox 比例风险回归分析评估 ADT 与 OS 的相关性。
总体而言，12160 例 Gleason 8 级患者中有 9509 例（78%）和 7979 例 Gleason 9-10 级患者中有 6908 例（87%）接受了 ADT。多变量分析显示，ADT 可显著改善 Gleason 8 级患者的 OS（调整后危险比 0.78，95%置信区间 0.70-0.87，p<0.001），但对 Gleason 9-10 级患者无显著影响（调整后危险比 0.96，95%置信区间 0.84-1.11，p=0.6），且存在显著的交互作用（p=0.020）。Gleason 评分越高（8、9、10），ADT 与 OS 之间的相关性的调整后危险比越高（p=0.042）。本研究可能受到随访时间（中位数 4.0 年）较短的限制。
与 ADT 对 Gleason 8 级疾病的显著生存优势形成鲜明对比的是，我们的研究结果表明，Gleason 9-10 级疾病从 ADT 中获得的生存获益较少，且 Gleason 评分越高，获益越少。对于 Gleason 9-10 级患者，考虑通过参加临床试验或潜在添加新型抗雄激素药物或多西他赛进行治疗强化，这些药物在去势抵抗性和去势敏感性环境中均显示出疗效。
在这项研究中，我们研究了雄激素剥夺疗法（ADT）对 Gleason 8（G 分级 4）和 Gleason 9-10（G 分级 5）前列腺癌的疗效。我们发现，Gleason 9-10 级疾病从 ADT 中获得的生存获益可能低于 Gleason 8 级疾病。
