Zhang Tian, Howard Lauren, Koontz Bridget F, Tagawa Scott T, Nagar Himanshu, Bitting Rhonda L, Frizzell Bart A, Nordquist Luke, Rasmussen Julia, Riggan Colleen, Reyes Marco, Davies Catrin, Gray Steven R, Newman Carly R, Fernandez Escarleth, Ramalingam Sundhar, Harrison Michael R, George Daniel J, Wu Yuan, Armstrong Andrew J
Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC, USA; Division of Hematology and Oncology, Department of Internal Medicine, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA.
Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC, USA.
Eur Urol Oncol. 2025 Apr;8(2):287-295. doi: 10.1016/j.euo.2024.06.013. Epub 2024 Jul 5.
Androgen deprivation therapy (ADT) with salvage radiation therapy (RT) improves survival for patients with prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP) for prostate cancer (PC), but many patients suffer further relapse. This study aims to determine the benefit of the combination of ADT, apalutamide, salvage RT, and docetaxel for high-risk PSA recurrent PC.
STARTAR is a multicenter, investigator-initiated phase 2 trial of men with PSA recurrent PC after RP. The key inclusion criteria included M0 by computed tomography/bone scan, Gleason 7 with either T3/positive margin/N1 disease or Gleason 8-10 prostate adenocarcinoma, PSA relapse (0.2-4 ng/ml) <4 yr after RP, and fewer than four positive resected lymph nodes. Patients received ADT with apalutamide for 9 mo, RT starting week 8, and then six cycles of docetaxel. The primary endpoint was 36-mo progression-free survival (PFS) with testosterone recovery and compared against the prior STREAM trial.
We enrolled 39 men, including those with Gleason 8-10 (46%), pN1 (23%); the median PSA was 0.58 ng/ml. The median follow-up was 37 mo. All patients achieved undetectable PSA nadir. At 24 and 36 mo, PFS rates were 84% and 71%, respectively, which improved significantly over 3-yr 47% historic PFS and 54% enzalutamide/ADT/RT (STREAM) PFS rates (p = 0.004 and p = 0.039, respectively). Common any-grade adverse events included 98% hot flashes, 88% fatigue, 77% alopecia, 53% rash (10% G3), and 5% febrile neutropenia.
In this phase 2 trial of ADT, apalutamide, salvage RT, and six cycles of docetaxel for high-risk PSA recurrence, the 3-yr PFS rate improved to 71%, indicating feasible and efficacious treatment intensification, with durable remissions beyond historic data.
Prostate cancer recurrence after surgical removal of the tumor occurs often, and current treatment options to limit recurrence after surgery are only partially effective. In this study, we found that the addition of an androgen receptor inhibitor and docetaxel chemotherapy to standard postsurgery radiation therapy and androgen deprivation therapy significantly improved progression-free survival at 3 yr after treatment. These results suggest that intensification of treatment after surgery can provide long-term benefit to a subset of patients with high-risk prostate cancer.
雄激素剥夺疗法（ADT）联合挽救性放射治疗（RT）可提高前列腺癌（PC）根治性前列腺切除术（RP）后前列腺特异性抗原（PSA）复发患者的生存率，但许多患者仍会进一步复发。本研究旨在确定ADT、阿帕他胺、挽救性RT和多西他赛联合应用于高危PSA复发PC的益处。
STARTAR是一项由研究者发起的多中心2期试验，针对RP后PSA复发的男性患者。关键纳入标准包括计算机断层扫描/骨扫描显示M0、Gleason评分7分伴T3/切缘阳性/N1疾病或Gleason评分8 - 10分的前列腺腺癌、RP后<4年PSA复发（0.2 - 4 ng/ml）以及切除的阳性淋巴结少于4个。患者接受ADT联合阿帕他胺治疗9个月，第8周开始RT，然后进行6个周期的多西他赛治疗。主要终点是睾酮恢复后的36个月无进展生存期（PFS），并与之前的STREAM试验进行比较。
我们纳入了39名男性患者，其中Gleason评分8 - 10分的患者占46%，pN1患者占23%；PSA中位数为0.58 ng/ml。中位随访时间为37个月。所有患者的PSA最低点均不可检测。在24个月和36个月时，PFS率分别为84%和71%，显著高于3年47%的历史PFS率和54%的恩杂鲁胺/ADT/RT（STREAM）PFS率（分别为p = 0.004和p = 0.039）。常见的任何级别的不良事件包括98%的潮热、88%的疲劳、77%的脱发、53%的皮疹（10%为3级）和5%的发热性中性粒细胞减少。
在这项针对高危PSA复发的ADT、阿帕他胺、挽救性RT和6个周期多西他赛的2期试验中，3年PFS率提高到71%，表明强化治疗可行且有效，缓解持续时间超过历史数据。
肿瘤手术切除后前列腺癌复发很常见，目前限制术后复发的治疗选择仅部分有效。在本研究中，我们发现，在标准的术后放射治疗和雄激素剥夺治疗中添加雄激素受体抑制剂和多西他赛化疗，可显著提高治疗后3年的无进展生存期。这些结果表明，术后强化治疗可为一部分高危前列腺癌患者带来长期益处。
