Okada Takuya, Takayama Kenji, Kokubo Masaki, Kono Yuka, Matsumoto Keiyu, Sumiyoshi Takayuki, Masuda Norihiko, Shiraishi Yusuke, Negoro Hiromitsu, Utsunomiya Noriaki, Tsunemori Hiroyuki, Okubo Kazutoshi, Segawa Takehiko, Moroi Seiji, Muguruma Koei, Kawakita Mutsushi
Department of Urology, Kobe City Medical Center General Hospital.
Department of Radiation Oncology, Kobe City Medical Center General Hospital.
Nihon Hinyokika Gakkai Zasshi. 2016;107(3):162-169. doi: 10.5980/jpnjurol.107.162.
(Purpose) We investigated the outcome of external-beam radiotherapy (EBRT) with neoadjuvant androgen deprivation therapy (NeoADT) for high-risk prostate cancer defined by National Comprehensive Cancer Network (NCCN) guideline. (Patients and method) From 2002 to 2013, 70 patients with high-risk prostate cancer (PSA ≥20 ng/ml or clinical T stage ≥T3a, Gleason score ≥8) were treated with NeoADT and EBRT. EBRT consisted of three-dimensional conformal or intensity modulated radiotherapy with or without whole-pelvic radiation. Biochemical failure was defined according to the Phoenix definition. Biochemical progression-free survival (bPFS) and overall survival (OS) were calculated by Kaplan-Meier method, and prognostic factors for bPFS were analyzed by using the Cox proportional hazard model. (Result) The median age and initial prostate-specific antigen (PSA) level were 72 years old and 25.2 ng/ml, respectively. 43 patients had PSA level ≥20 ng/ml, 51 patients had clinical stage ≥T3a, 27 patients had Gleason score ≥8. The number of risk factors patients possessed was 1 (RiskN-1) in 31 patients, 2 (RiskN-2) in 27 patients and 3 (RiskN-3) in 12 patients. Median EBRT dose and duration of Neo ADT were 74 Gy and13.0 months, respectively. Whole-pelvic radiation was administered in 7 patients. After median follow-up of 4.8 years, biochemical and clinical failure occurred in 23 and 2 patients, respectively. No patients died of cancer. Five-year/8-year bPFS and OS were 63%/54% and 100%/91%, respectively. In multivariate analysis, three high-risk factor of NCCN guideline (PSA, clinical stage, Gleason score) did not predict outcome after EBRT independently, but RiskN (-1 vs -2, 3, HR 35.35, 95%CI 2.51-498.05, p<0.01) and pre-EBRT PSA (continuous, hazard ratio 1.31, 95%CI 1.01-1.71, p<0.05) were the significant predictors of bPFS. Five-year/8-year bPFS in RiskN-1 group and RiskN-2 or -3 group were 89%/79% and 47%/39%, respectively. Grade 3/4 adverse events (CTCAE ver4.0-JCOG) occurred in 2 patients. (Conclusion) Median dose of 74 Gy EBRT with intermediate-term NeoADT was safe and beneficial for high-risk prostate cancer. The number of risk factors and pre-EBRT PSA level were the independent prognostic factors for biochemical progression-free survival.
（目的）我们研究了根据美国国立综合癌症网络（NCCN）指南定义的高危前列腺癌患者，接受新辅助雄激素剥夺治疗（NeoADT）联合外照射放疗（EBRT）的疗效。（患者与方法）2002年至2013年期间，70例高危前列腺癌患者（前列腺特异性抗原[PSA]≥20 ng/ml或临床T分期≥T3a， Gleason评分≥8）接受了NeoADT和EBRT治疗。EBRT包括三维适形放疗或调强放疗，有或无全盆腔照射。生化失败根据Phoenix定义确定。采用Kaplan-Meier法计算生化无进展生存期（bPFS）和总生存期（OS），并使用Cox比例风险模型分析bPFS的预后因素。（结果）患者的中位年龄和初始PSA水平分别为72岁和25.2 ng/ml。43例患者PSA水平≥20 ng/ml，51例患者临床分期≥T3a，27例患者Gleason评分≥8。具有1个风险因素（RiskN-1）的患者有31例，具有2个风险因素（RiskN-2）的患者有27例，具有3个风险因素（RiskN-3）的患者有12例。EBRT的中位剂量和NeoADT的持续时间分别为74 Gy和13.0个月。7例患者接受了全盆腔照射。中位随访4.8年后，分别有23例和2例患者发生生化和临床失败。无患者死于癌症。5年/8年bPFS和OS分别为63%/54%和100%/91%。多因素分析显示，NCCN指南的三个高危因素（PSA、临床分期、Gleason评分）并不能独立预测EBRT后的结局，但RiskN（-1与-2、3相比，风险比35.35，95%置信区间2.51-498.05，p<0.01）和放疗前PSA（连续变量，风险比1.31，95%置信区间1.01-1.71，p<0.05）是bPFS的显著预测因素。RiskN-1组和RiskN-2或-3组的5年/8年bPFS分别为89%/79%和47%/39%。2例患者发生3/4级不良事件（CTCAE ver4.0-JCOG）。（结论）74 Gy的EBRT联合中期NeoADT对高危前列腺癌患者是安全且有益的。风险因素数量和放疗前PSA水平是生化无进展生存期的独立预后因素。
