PURPOSE Focal therapy aims to provide a durable oncologic treatment option for men with prostate cancer (PCa), while preserving their quality of life. Most focal therapy modalities rely on the direct tissue effect, resulting in a possible nontargeted approach to ablation. Here, we report the results of the first human feasibility trial utilizing nanoparticle-directed focal photothermal ablation for PCa. MATERIALS AND METHODS A prospective, open-label, single-arm, multicenter study of men with localized PCa in Gleason Grade Group 1 to 3 was conducted. Men received a single infusion of gold nanoparticles (AuroShells), followed by magnetic resonance (MR)/ultrasound (US) fusion-guided laser excitation of the target tissue to induce photothermal ablation. MRI was used to assess the effectiveness of prostate tissue ablation at 48 to 96 hours, 3 months, and 12 months post treatment. At 3 months, a targeted fusion biopsy of the lesion(s) was conducted. At 12 months, a targeted fusion biopsy and standard templated biopsy were performed. Treatment success was determined based on a negative MR/US fusion biopsy outcome within the treated area. RESULTS Forty-six men were enrolled in the study, and 44 men with 45 lesions completed nanoparticle infusion and laser treatment. Baseline mean PSA levels were 9.5 ng/mL, with a statistically significant decrease of 5.9 ng/mL at 3 months and 4.7 ng/mL at 12 months (P < .0001). The oncologic success rates at 3 and 12 months resulted in 29 (66%) and 32 (73%) of 44 patients, respectively, being successfully treated, confirmed with negative MR/US fusion biopsies within the ablation zone. Among Gleason Grade Group, maximum lesion diameter on MRI, prostate volume, and Prostate Imaging Reporting and Data System scoring, the maximum lesion diameter was significantly associated with the odds of treatment failure at 12 months (P = .046). CONCLUSIONS Nanoparticle-directed focal laser ablation of neoplastic prostate tissue resulted in 73% of patients with successful treatment at 12 months post treatment, confirmed by negative MR/US fusion biopsy of the treated lesion and a systematic biopsy. CLINICAL TRIAL REGISTRATION NO. 02680535.

中文翻译：

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磁共振/超声融合引导纳米粒子定向前列腺消融局部治疗的多机构研究。


目的 局部治疗旨在为患有前列腺癌 （PCa） 的男性提供持久的肿瘤治疗选择，同时保持他们的生活质量。大多数局部治疗方式依赖于直接组织效应，导致可能的非靶向消融方法。在这里，我们报告了第一个利用纳米粒子定向聚焦光热消融治疗 PCa 的人体可行性试验的结果。材料和方法 对 Gleason 1 至 3 年级的局限性 PCa 男性进行了前瞻性、开放标签、单臂、多中心研究。男性接受单次金纳米颗粒 （AuroShells） 输注，然后对目标组织进行磁共振 （MR）/超声 （US） 融合引导激光激发以诱导光热消融。MRI 用于评估治疗后 48 至 96 小时、 3 个月和 12 个月前列腺组织消融术的有效性。3 个月时，对病灶进行靶向融合活检。12 个月时，进行靶向融合活检和标准模板化活检。根据治疗区域内的阴性 MR/US 融合活检结果确定治疗成功。结果 46 名男性参加了这项研究，44 名男性有 45 个病灶完成了纳米颗粒输注和激光治疗。基线平均 PSA 水平为 9.5 ng/mL，3 个月时下降 5.9 ng/mL，12 个月时下降 4.7 ng/mL，具有统计学意义 （P < .0001）。3 个月和 12 个月时的肿瘤学成功率导致 44 例患者中分别有 29 例 （66%） 和 32 例 （73%） 成功治疗，证实消融区内 MR/US 融合活检阴性。 在 Gleason 分级组、MRI 上的最大病灶直径、前列腺体积以及前列腺影像学报告和数据系统评分中，最大病灶直径与 12 个月时治疗失败的几率显著相关 （P = .046）。结论 纳米粒子定向肿瘤前列腺组织局部激光消融术使 73% 的患者在治疗后 12 个月成功治疗，通过治疗病灶的 MR/US 融合活检阴性和系统活检证实。临床试验注册号 02680535。