Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Department of Biostatistics, University of Michigan, Ann Arbor, Michigan.
Int J Radiat Oncol Biol Phys. 2023 Jan 1;115(1):132-141. doi: 10.1016/j.ijrobp.2022.07.016. Epub 2022 Jul 22.
Men with locally advanced prostate cancer who undergo radical prostatectomy (RP) often develop recurrence and require postoperative radiotherapy. We aimed to determine the safety of neoadjuvant stereotactic body radiotherapy (SBRT) before RP in this population.
A single-institution phase 1 trial (NCT02946008) of men with high-risk or node-positive prostate cancer were enrolled between March and October 2017. The primary endpoint was to determine the maximum tolerated dose of SBRT based on a composite 30-day post-RP toxicity goal of ≤28% of patients experiencing a dose-limiting toxicity (DLT). Secondary outcomes included toxicity, efficacy, and multiple quality of life (QoL) inventories. SBRT (30-35 Gy/5 fractions) was delivered to the prostate and seminal vesicles, and 25 Gy/5 fractions to the pelvic lymph nodes. RP was performed for a median of 6 weeks post-SBRT. Hormone therapy was not allowed.
Median follow-up was 40 months (range, 33-44). Twenty-five percent of the patients (n = 4) experienced a DLT within 30 days post-RP; however, the trial was stopped early (n = 16 of planned 38 patients) owing to the proportion and severity of the late adverse events. Post-RP grade 3 genitourinary and gastrointestinal toxicities occurred in 75% (n = 12) and 25% (n = 4) of patients, respectively. Two patients required cystectomy and urinary diversion ≥2 years post-RP. At 24 months post-RP, 75% (n = 12) of men used ≥1 pad/d and 0% had erections suitable for intercourse. Surgical margins were negative in all patients and 31% (n = 5) had complete or partial (pre-RP) MRI-response to SBRT. Three-year biochemical recurrence and distant metastasis were 45% (95% CI, 5%-68%) and 28% (95% CI, 0%-49%), respectively.
Neoadjuvant SBRT followed by RP resulted in unacceptably high toxicity and severe QoL declines.
接受根治性前列腺切除术（RP）的局部晚期前列腺癌男性常发生复发并需要术后放疗。我们旨在确定该人群中 RP 前新辅助立体定向体放射治疗（SBRT）的安全性。
2017 年 3 月至 10 月，单机构进行了一项高危或淋巴结阳性前列腺癌男性的 1 期试验（NCT02946008）。主要终点是根据 30 天内≤28%的患者发生剂量限制性毒性（DLT）的综合 RP 后毒性目标，确定 SBRT 的最大耐受剂量。次要结果包括毒性、疗效和多个生活质量（QoL）量表。SBRT（30-35Gy/5 个剂量）用于前列腺和精囊，25Gy/5 个剂量用于骨盆淋巴结。RP 在 SBRT 后中位 6 周进行。不允许使用激素治疗。
中位随访时间为 40 个月（范围 33-44）。25%的患者（n=4）在 RP 后 30 天内发生 DLT；然而，由于晚期不良事件的比例和严重程度，试验提前停止（n=16 of planned 38 patients）。RP 后发生 3 级泌尿生殖系统和胃肠道毒性的患者分别为 75%（n=12）和 25%（n=4）。2 例患者在 RP 后≥2 年需要行膀胱切除术和尿流改道。RP 后 24 个月时，75%（n=12）的男性每天使用≥1 个尿垫，0%的男性有适合性交的勃起。所有患者的手术切缘均为阴性，31%（n=5）的患者对 SBRT 有完全或部分（术前）MRI 反应。3 年生化复发和远处转移率分别为 45%（95%CI，5%-68%）和 28%（95%CI，0%-49%）。
RP 前新辅助 SBRT 导致不可接受的高毒性和严重的 QoL 下降。
