Dong Yanqun, Ruth Karen J, Churilla Thomas M, Viterbo Rosalia, Sobczak Mark L, Smaldone Marc C, Chen David Y T, Uzzo Robert G, Hallman Mark H, Horwitz Eric M
Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
Can J Urol. 2017 Feb;24(1):8656-8662.
To evaluate if androgen deprivation therapy (ADT) improves outcomes for patients with localized, intermediate-risk prostate cancer treated with definitive external beam radiation therapy (EBRT) in the dose-escalated era.
This is a retrospective study using a single institutional database. We included patients with localized, intermediate-risk prostate cancer treated with dose-escalated radiation therapy (RT) with 3D conformal radiotherapy or intensity-modulated radiotherapy (74-80 Gy in daily fraction of 1.8 Gy-2.0 Gy, or 70.2 Gy in daily fraction of 2.7 Gy) from 1992 to 2013. To further risk stratify the patients, PSA 10 ng/mL-20 ng/mL, Gleason 3+4, and T2b-T2c were assigned risk score (RS) of 1, while Gleason 4+3 was assigned RS of 2. Patients with prior treatment for prostate cancer, those on long term ADT (>= 23 months), or those with follow up < 1 year were excluded. We defined initial ADT as initiation within 9 months prior to the start of RT, during RT, or within 2 months after the completion of RT. Outcomes for patients who received initial ADT were compared to men treated with RT alone. Covariates included number of intermediate risk factors, age, and baseline comorbidities. Kaplan Meier estimates were compared using log rank tests. Competing risk regression and Cox proportional hazards regression were used to estimate hazard ratios adjusted for covariates.
Of 1,134 patients included in this study, 155 received initial ADT with median duration of 4.0 months (m) (range 0.5 m-22.0 m). The median follow up was 56.4 m (range 12.3 m-200.7 m). Patients on ADT had higher RS compared to those with radiation alone (RS 1: 48% versus 58%; RS 2: 35% versus 32%; RS 3: 14% versus 9%; RS 4: 3% versus 1%; p=0.01). When patients with ADT were compared to those treated with radiation alone, there were no significant differences in freedom from biochemical failure (FFBF) (84.0% versus 87.3%, p = 0.83), freedom from distant metastasis (FFDM) (94.4% versus 96.9%, p = 0.41), or overall survival (OS) (92.3% versus 90.7%, (p = 0.48) at 5 years. Among patients with RS >= 2, there were still no significant differences in FFBF, FFDM, or OS when patients treated with ADT were compared to those treated with radiation alone. In multivariable analyses adjusting for RS and age, the adjusted hazard ratio for ADT use was sHR = 0.89 (95% CI = 0.64-1.66, p = 0.64) for BCF; sHR = 1.13 (95% CI = 0.48-2.65, p = 0.77) for DM. For overall mortality, adjusted HR = 1.23 (95% CI = 0.76-2.01, p = 0.40) where comorbidities (including diabetes, cardiac disease, and hypertension) were also included as covariates.
Our study suggested that treatment of intermediate-risk prostate cancer with definitive dose-escalated EBRT alone resulted in acceptable outcomes, and it failed to show improved outcomes in patients who received short term ADT.
评估在剂量递增时代，雄激素剥夺疗法（ADT）是否能改善接受根治性外照射放疗（EBRT）的局限性、中危前列腺癌患者的预后。
这是一项使用单一机构数据库的回顾性研究。我们纳入了1992年至2013年期间接受剂量递增放疗（RT）的局限性、中危前列腺癌患者，采用三维适形放疗或调强放疗（每日分次剂量1.8 Gy - 2.0 Gy时为74 - 80 Gy，或每日分次剂量2.7 Gy时为70.2 Gy）。为进一步对患者进行风险分层，将PSA 10 ng/mL - 20 ng/mL、Gleason 3 + 4和T2b - T2c的风险评分（RS）设为1，而Gleason 4 + 3的RS设为2。排除既往接受过前列腺癌治疗的患者、长期接受ADT（≥23个月）的患者或随访时间<1年的患者。我们将初始ADT定义为在RT开始前9个月内、RT期间或RT完成后2个月内开始使用。将接受初始ADT的患者的预后与单纯接受RT治疗的男性患者进行比较。协变量包括中危因素数量、年龄和基线合并症。使用对数秩检验比较Kaplan Meier估计值。采用竞争风险回归和Cox比例风险回归来估计经协变量调整后的风险比。
本研究纳入的1134例患者中，155例接受了初始ADT，中位持续时间为4.0个月（m）（范围0.5 m - 22.0 m）。中位随访时间为56.4 m（范围12.3 m - 200.7 m）。与单纯接受放疗的患者相比，接受ADT的患者RS更高（RS 1：48%对58%；RS 2：35%对32%；RS 3：14%对9%；RS 4：3%对1%；p = 0.01）。将接受ADT的患者与单纯接受放疗的患者进行比较时，在无生化失败（FFBF）（84.零%对87.3%，p = 0.83）、无远处转移（FFDM）（94.4%对96.9%，p = 0.41）或总生存（OS）（5年时为92.3%对90.7%，（p = 0.48）方面无显著差异。在RS≥2的患者中，将接受ADT的患者与单纯接受放疗的患者进行比较时，在FFBF、FFDM或OS方面仍无显著差异。在对RS和年龄进行调整的多变量分析中，ADT使用的调整后风险比为：BCF的sHR = 0.89（95%CI = 0.64 - 1.66，p = 0.64）；DM的sHR = 1.13（95%CI = 0.48 - 2.65，p = 0.77）。对于总死亡率，调整后的HR = 1.23（95%CI = 0.76 - 2.01，p = 0.40），其中合并症（包括糖尿病、心脏病和高血压）也作为协变量纳入。
我们的研究表明，单纯使用根治性剂量递增EBRT治疗中危前列腺癌可获得可接受的预后，且未显示短期接受ADT的患者预后得到改善。
