Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Int J Radiat Oncol Biol Phys. 2022 Nov 15;114(4):693-704. doi: 10.1016/j.ijrobp.2022.06.080. Epub 2022 Aug 27.
The role of metastasis-directed therapy (MDT) in molecularly defined oligorecurrent prostate cancer (PCa) remains irresolute. We present extended follow-up and an independent validation cohort of a prospective trial.
This study consists of 2 sequential single-arm phase-2 trials of patients with biochemical recurrence (prostate specific antigen [PSA] 0.4-3.0 ng/mL) and negative conventional imaging after radical prostatectomy and postoperative radiation therapy. All patients underwent [F]DCFPyL positron emission tomography/computed tomography. Patients with molecularly defined oligorecurrent prostate cancer underwent MDT with stereotactic body radiation therapy or surgery, without androgen deprivation therapy (ADT). The primary end point was biochemical response (≥50% PSA decline from baseline). Secondary end points included PSA progression-free survival and ADT-free survival. The sample size of 37 MDT patients was determined based on a Simon's 2-stage design with biochemical response rate >20%, and this design was also applied for the subsequent independent validation cohort.
Seventy-four patients underwent MDT: 37 each in the initial and validation cohorts. Both cohorts met the prespecified biochemical response rate and completed the planned 2-stages of accrual. For the pooled cohort, the median number of prostate specific membrane antigen positron emission tomography avid lesions was 2 and most (87%) recurrences were nodal. Sixty-four (87%) had stereotactic body radiation therapy and 10 (13%) had surgery. Median follow-up (interquartile range [IQR]) for the initial, validation and combined cohorts were 41 (35-46) months, 14 months (7-21), and 24 months (14-41), respectively. The biochemical response rates for the initial, validation and combined cohorts were 59%, 43%, and 51%, respectively. For the combined cohort, median biochemical progression-free survival was 21 months (95% confidence interval, 13-not reached), and median ADT-free survival was 45 months (95% confidence interval, 31-not reached).
Half of patients treated with MDT for molecularly defined-only oligorecurrent prostate cancer exhibited a biochemical response. This study provides necessary and validated evidence to support randomized trials aiming to determine whether MDT (alone or with systemic therapy) can affect clinically meaningful end points.
转移性治疗（MDT）在分子定义的寡复发前列腺癌（PCa）中的作用仍不确定。我们展示了一项前瞻性试验的扩展随访和独立验证队列。
本研究由 2 项连续的单臂 2 期试验组成，纳入了根治性前列腺切除术和术后放疗后生化复发（前列腺特异性抗原[PSA]0.4-3.0ng/mL）且常规影像学检查阴性的患者。所有患者均行[F]DCFPyL 正电子发射断层扫描/计算机断层扫描。分子定义的寡复发前列腺癌患者接受 MDT 治疗，包括立体定向体部放射治疗或手术，不包括雄激素剥夺治疗（ADT）。主要终点是生化反应（PSA 较基线下降≥50%）。次要终点包括 PSA 无进展生存期和 ADT 无进展生存期。根据 Simon 的 2 期设计，37 例 MDT 患者的样本量确定为生化反应率>20%，该设计也应用于随后的独立验证队列。
74 例患者接受了 MDT：初始队列和验证队列各 37 例。两个队列均达到了预设的生化反应率，并完成了计划的 2 期入组。对于汇总队列，中位前列腺膜抗原正电子发射断层扫描阳性病变数为 2，大多数（87%）复发为淋巴结。64 例（87%）接受了立体定向体部放射治疗，10 例（13%）接受了手术。初始队列、验证队列和联合队列的中位随访时间（四分位间距[IQR]）分别为 41（35-46）个月、14 个月（7-21）和 24 个月（14-41）。初始、验证和联合队列的生化反应率分别为 59%、43%和 51%。对于联合队列，中位生化无进展生存期为 21 个月（95%置信区间，13-未达到），中位 ADT 无进展生存期为 45 个月（95%置信区间，31-未达到）。
接受 MDT 治疗的分子定义寡复发前列腺癌患者中有一半表现出生化反应。本研究提供了必要的验证证据，支持旨在确定 MDT（单独或联合系统治疗）是否能影响有临床意义的终点的随机试验。
