Department of Radiation Oncology, Duke Cancer Institute, Durham, North Carolina, USA.
Int J Radiat Oncol Biol Phys. 2013 Sep 1;87(1):88-93. doi: 10.1016/j.ijrobp.2013.05.014. Epub 2013 Jun 19.
To evaluate, in a phase 1 study, the safety of neoadjuvant whole-pelvis radiation therapy (RT) administered immediately before radical prostatectomy in men with high-risk prostate cancer.
Twelve men enrolled and completed a phase 1 single-institution trial between 2006 and 2010. Eligibility required a previously untreated diagnosis of localized but high-risk prostate cancer. Median follow-up was 46 months (range, 14-74 months). Radiation therapy was dose-escalated in a 3 × 3 design with dose levels of 39.6, 45, 50.4, and 54 Gy. The pelvic lymph nodes were treated up to 45 Gy with any additional dose given to the prostate and seminal vesicles. Radical prostatectomy was performed 4-8 weeks after RT completion. Primary outcome measure was intraoperative and postoperative day-30 morbidity. Secondary measures included late morbidity and oncologic outcomes.
No intraoperative morbidity was seen. Chronic urinary grade 2+ toxicity occurred in 42%; 2 patients (17%) developed a symptomatic urethral stricture requiring dilation. Two-year actuarial biochemical recurrence-free survival was 67% (95% confidence interval 34%-86%). Patients with pT3 or positive surgical margin treated with neoadjuvant RT had a trend for improved biochemical recurrence-free survival compared with a historical cohort with similar adverse factors.
Neoadjuvant RT is feasible with moderate urinary morbidity. However, oncologic outcomes do not seem to be substantially different from those with selective postoperative RT. If this multimodal approach is further evaluated in a phase 2 setting, 54 Gy should be used in combination with neoadjuvant androgen deprivation therapy to improve biochemical outcomes.
在一项 1 期研究中评估高风险前列腺癌患者在根治性前列腺切除术前即刻接受新辅助全骨盆放疗的安全性。
2006 年至 2010 年间，12 名男性入组并完成了一项单机构 1 期试验。入选标准要求患者患有先前未经治疗的局限性但高风险前列腺癌。中位随访时间为 46 个月（范围，14-74 个月）。放疗采用 3×3 剂量递增设计，剂量水平分别为 39.6、45、50.4 和 54 Gy。盆腔淋巴结接受 45 Gy 治疗，其余剂量给予前列腺和精囊。放疗完成后 4-8 周行根治性前列腺切除术。主要观察指标为术中及术后 30 天的发病率。次要观察指标包括迟发性发病率和肿瘤学结果。
术中无并发症。慢性尿毒性 2+级发生率为 42%；2 例（17%）发生有症状的尿道狭窄，需要扩张。2 年生化无复发生存率为 67%（95%置信区间 34%-86%）。接受新辅助放疗的 pT3 或阳性切缘患者与具有相似不良因素的历史队列相比，生化无复发生存率有改善趋势。
新辅助放疗是可行的，具有中度尿毒性。然而，肿瘤学结果似乎与选择性术后放疗没有显著差异。如果这种多模式方法在 2 期研究中进一步评估，应结合新辅助雄激素剥夺治疗使用 54 Gy，以改善生化结果。
