Department of Urology, Mayo Clinic, Rochester, Minnesota, USA.
Division of Nuclear Medicine, Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
Prostate. 2022 Dec;82(16):1483-1490. doi: 10.1002/pros.24413. Epub 2022 Sep 11.
Prostatic specific antigen (PSA) has well-recognized limitations as a marker for treatment response and disease progression. Post hoc analysis of the PREVAIL trial reported 24.5% of chemotherapy naïve metastatic castration-resistant prostate cancer (mCRPC) patients on enzalutamide had radiographic progression on conventional imaging with nonrising PSA. In this study, we sought to study the discordance of imaging with PSA kinetics in mCRPC patients on second generation anti-androgens (SGA) post-chemotherapy using combined conventional imaging, and new generation imaging in the form of C-11 choline positron emission tomography/computed tomography (C[11] choline PET/CT) scan.
We retrospectively reviewed the medical records of 123 patients with mCRPC treated with SGA (Abiraterone or Enzalutamide) after docetaxel between 2016 and 2019. Patients underwent PSA testing, and C[11] choline PET/CT scan at baseline level before starting treatment with SGA, then every 3-6 months as part of their follow up evaluation. Loss of response to SGA was defined by increase in corrected maximum standardized uptake value (SUVmax) of pretreatment lesions on C-11 Choline PET/CT, and/or development of new lesions. Suspicious new lesions were confirmed by biopsy and/or conventional imaging.
We identified 123 mCRPC patients who received SGA (Abiraterone, n = 106; Enzalutamide, n = 17) after docetaxel. Median duration of therapy was 13.9 months (interquartile range: 8.75-21.14). Approximately 43% (n = 53) of subjects in this study exhibited an increase in choline avidity while on SGA. Of this group, 60.4% of patients experienced a parallel rise in PSA (Group-A), whereas 39.6% displayed a paradoxical response (PR) (Group-B), defined as increased choline avidity combined with stable or down-trending PSA. Median PSA at time of increase in choline avidity was 3.1 ng/ml for Group-A, and 1.3 ng/ml for Group-B (p = 0.0176). Median SUVmax was similar in both groups (4.9 for Group-A, 4.6 for Group-B; p = 0.6072). The median time for increase in choline avidity was 9.5 versus 3.9 months for Group-A versus Group-B, respectively (Log-Rank = 0.0063).
Nearly 40% of mCRPC patients placed on SGA post docetaxel chemotherapy will exhibit paradoxical responses to therapy, therefore, warranting close follow up with imaging. C-11 choline PET/CT imaging is a useful tool that can help in early predication of disease progression or treatment failure.
前列腺特异性抗原（PSA）作为治疗反应和疾病进展的标志物存在明显的局限性。PREVAIL 试验的事后分析报告称，在接受恩扎卢胺治疗的化疗初治转移性去势抵抗性前列腺癌（mCRPC）患者中，有 24.5%的患者在常规影像学检查中出现 PSA 未升高的影像学进展。在这项研究中，我们试图研究在第二代抗雄激素（SGA）治疗后，mCRPC 患者的影像学与 PSA 动力学的不一致性，使用常规影像学和新型影像学（C-11 胆碱正电子发射断层扫描/计算机断层扫描（C[11]胆碱 PET/CT）扫描）。
我们回顾性分析了 2016 年至 2019 年期间接受多西他赛化疗后接受 SGA（阿比特龙或恩扎卢胺）治疗的 123 例 mCRPC 患者的病历。患者在开始 SGA 治疗前进行 PSA 检测和 C[11]胆碱 PET/CT 扫描，然后每 3-6 个月进行一次随访评估。SGA 治疗反应丧失的定义为 C-11 胆碱 PET/CT 扫描中预处理病灶的校正最大标准化摄取值（SUVmax）增加，和/或出现新病灶。可疑的新病灶通过活检和/或常规影像学检查证实。
我们确定了 123 例接受 SGA（阿比特龙，n=106；恩扎卢胺，n=17）治疗的 mCRPC 患者。中位治疗持续时间为 13.9 个月（四分位距：8.75-21.14）。在这项研究中，大约 43%（n=53）的患者在使用 SGA 时表现出胆碱摄取增加。在这组患者中，60.4%的患者出现 PSA 平行升高（A 组），而 39.6%的患者表现出矛盾反应（PR）（B 组），定义为胆碱摄取增加与稳定或下降的 PSA 相结合。A 组 PSA 增加时的中位 PSA 为 3.1ng/ml，B 组为 1.3ng/ml（p=0.0176）。两组 SUVmax 相似（A 组为 4.9，B 组为 4.6；p=0.6072）。A 组和 B 组的胆碱摄取增加中位时间分别为 9.5 个月和 3.9 个月（对数秩检验=0.0063）。
近 40%的接受多西他赛化疗后接受 SGA 治疗的 mCRPC 患者将出现治疗矛盾反应，因此需要密切随访影像学检查。C-11 胆碱 PET/CT 成像技术是一种有用的工具，可以帮助早期预测疾病进展或治疗失败。
