BACKGROUND In the PURE-01 study, pembrolizumab was given preoperatively before radical cystectomy in clinical T2-4aN0M0 patients. An accurate clinical response assessment may be useful for developing new perioperative strategies in these patients. OBJECTIVE To evaluate the association between bladder multiparametric magnetic resonance imaging (mpMRI) findings after pembrolizumab and the pathological complete response (CR; pT0). DESIGN, SETTING, AND PARTICIPANTS Patients were staged using bladder mpMRI whereby radiologists were asked to characterize the following parameters: residual disease at T1- and T2-weighted images (step 1: yes/no), presence of hyperintense spots within the bladder wall on diffusion-weighted imaging (step 2: yes/no), and presence of pathological contrast enhancement (step 3: yes/no), before and after three cycles of pembrolizumab. Examinations were internally assessed by two senior radiologists and externally evaluated by a third senior radiologist. INTERVENTION To evaluate bladder tumor response after neoadjuvant pembrolizumab, mpMRI was used. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary objective was to predict the pT0 after neoadjuvant pembrolizumab by relying on the mpMRI findings. Cohen's kappa statistics was used to assess interobserver variability. Univariable analyses for pT0 were performed including internal and external post-therapy mpMRI steps. RESULTS AND LIMITATIONS From February 2017 to October 2018, 82 patients (164 total mpMRI assessments) were analyzed. The agreement between the internal and external mpMRI assessments after therapy was acceptable (κ values ranging from 0.5 to 0.76). Each mpMRI step was significantly associated with pT0 in both internal and external assessments. In patients with CR/no evidence of residual disease (NED) in all internally evaluated mpMRI steps (N = 37), the pT0 was seen in 23 (62%), compared with 19 of 26 externally evaluated NED patients (73%). CONCLUSIONS In post-pembrolizumab muscle-invasive bladder cancer, mpMRI sequence assessment had acceptable interobserver variability and represented the basis for the proposal of a radiological CR/NED status definition predicting the pT0 response to pembrolizumab. After validation of these findings with external datasets, we propose this tool for developing bladder-sparing immunotherapy maintenance therapies. PATIENT SUMMARY Assessment of the extent of disease in patients with muscle-invasive bladder cancer using conventional imaging yields serious limitations. In the PURE-01 study, we evaluated the potential of bladder multiparametric magnetic resonance imaging (MRI) to predict the pathological complete response to neoadjuvant pembrolizumab. After validation with larger datasets, the proposed stepwise assessment incorporating multiparametric MRI sequences will be used at our center to develop bladder-sparing approaches in future studies.

中文翻译：

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多参数磁共振成像作为对新辅助帕博利珠单抗在肌肉浸润性膀胱癌中肿瘤反应的无创评估：PURE-01 研究的初步结果。

背景 在 PURE-01 研究中，临床 T2-4aN0M0 患者在根治性膀胱切除术前术前给予派姆单抗。准确的临床反应评估可能有助于为这些患者制定新的围手术期策略。目的 评估派姆单抗后膀胱多参数磁共振成像 (mpMRI) 发现与病理完全缓解 (CR; pT0) 之间的关联。设扩散加权成像（第 2 步：是/否），以及是否存在病理对比增强（第 3 步：是/否），在三个周期的派姆单抗之前和之后。检查由两名高级放射科医师进行内部评估，并由第三名高级放射科医师进行外部评估。干预 为了评估新辅助派姆单抗后膀胱肿瘤的反应，使用了 mpMRI。结果测量和统计分析 主要目标是依靠 mpMRI 结果预测新辅助派姆单抗后的 pT0。Cohen 的 kappa 统计数据用于评估观察者间的变异性。对 pT0 进行了单变量分析，包括治疗后的内部和外部 mpMRI 步骤。结果和局限性从 2017 年 2 月到 2018 年 10 月，对 82 名患者（总共 164 次 mpMRI 评估）进行了分析。治疗后内部和外部 mpMRI 评估之间的一致性是可以接受的（κ 值范围从 0.5 到 0.76）。在内部和外部评估中，每个 mpMRI 步骤都与 pT0 显着相关。在所有内部评估的 mpMRI 步骤 (N = 37) 中，CR/无残留疾病 (NED) 证据的患者中，23 人 (62%) 观察到 pT0，而外部评估的 26 名 NED 患者中有 19 人 (73%) 观察到 pT0。结论 在 pembrolizumab 后肌肉浸润性膀胱癌中，mpMRI 序列评估具有可接受的观察者间变异性，并代表了提出放射学 CR/NED 状态定义的基础，该定义预测 pT0 对 pembrolizumab 的反应。在使用外部数据集验证了这些发现后，我们提出了这个工具来开发保留膀胱的免疫治疗维持疗法。患者总结 使用常规成像评估肌肉浸润性膀胱癌患者的疾病程度会产生严重的局限性。在 PURE-01 研究中，我们评估了膀胱多参数磁共振成像 (MRI) 预测对新辅助派姆单抗的病理完全反应的潜力。在使用更大的数据集进行验证后，我们中心将使用所提出的包含多参数 MRI 序列的逐步评估，以在未来的研究中开发保留膀胱的方法。