PURPOSE The purpose of this study was to assess safety and feasibility of percutaneous MR-guided placement of an implantable microdevice (IMD) to evaluate in situ intratumor response to multiple pharmacologic agents in men with intermediate-risk and high-risk localized prostate cancer. MATERIALS AND METHODS Biocompatible IMDs measuring 750 µm in diameter and 5 mm in length were prepared with 20 reservoirs containing candidate drug and drug combinations including second-generation androgen inhibitors, PARP inhibitors, PD-1 inhibitors, and conventional chemotherapy. Men with intermediate-risk or high-risk localized prostate cancer and MRI-visible lesions were enrolled. Up to 4 IMDs were placed using a transperineal approach into MRI-visible tumors 2 days before planned radical prostatectomy. After radical prostatectomy, the IMDs and a small segment of surrounding tumor tissue were removed and sectioned, stained, and analyzed for tissue drug response by a variety of pharmacodynamic markers. RESULTS Fourteen patients were enrolled: 7 (50%) with intermediate-risk and 7 (50%) with high-risk localized prostate cancer. A total of 53 IMDs were implanted (mean 3.8 per patient), and 49 IMDs (92%) were successfully retrieved. All men underwent uncomplicated robotic-assisted radical prostatectomy and bilateral pelvic lymph node dissection 2 days after IMD placement. There were no severe adverse events. Pathological examination of the tissues adjacent to the IMDs demonstrated differential drug response within patients and between patients. Limitations include small sample size. CONCLUSIONS A multidrug IMD can be safely placed percutaneously into MRI-visible lesions before radical prostatectomy, enabling assessment of tumor-specific local response to multiple agents simultaneously within the tumor's normal stromal environment to guide targeted systemic therapy.

中文翻译：

---

用于原位测试全身治疗药物的新型前列腺内 MR 引导的多药物洗脱微装置植入：中危和高危前列腺癌的概念验证。


目的 本研究的目的是评估经皮 MR 引导下植入植入式微型装置 （IMD） 的安全性和可行性，以评估中危和高危局限性前列腺癌男性对多种药物的原位肿瘤内反应。材料和方法 用 20 个储液器制备了直径为 750 μm、长度为 5 mm 的生物相容性 IMD，其中包含候选药物和药物组合，包括第二代雄激素抑制剂、PARP 抑制剂、PD-1 抑制剂和常规化疗。纳入患有中危或高危局限性前列腺癌和 MRI 可见病变的男性。在计划根治性前列腺切除术前 2 天，使用经会阴入路将多达 4 个 IMD 放置在 MRI 可见肿瘤中。根治性前列腺切除术后，去除 IMD 和一小段周围肿瘤组织并进行切片、染色，并通过各种药效学标志物分析组织药物反应。结果 共纳入 14 例患者： 7 例 （50%） 中危前列腺癌和 7 例 （50%） 高危局限性前列腺癌。共植入 53 个 IMD （平均每个患者 3.8 个），成功取出 49 个 IMD （92%）。所有男性在 IMD 放置后 2 天接受了无并发症的机器人辅助根治性前列腺切除术和双侧盆腔淋巴结清扫术。没有严重的不良事件。对 IMD 附近组织的病理检查显示患者内部和患者之间的药物反应不同。限制包括样本量小。 结论 在根治性前列腺切除术前，多药 IMD 可以安全地经皮置于 MRI 可见病灶中，从而能够在肿瘤的正常基质环境中同时评估肿瘤对多种药物的肿瘤特异性局部反应，以指导靶向全身治疗。