Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
摘要：
背景：前列腺特异性抗原（PSA）作为治疗反应和疾病进展的标志物具有公认的局限性。PREVAIL试验的事后分析报告，使用恩杂鲁胺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上有放射学进展，PSA不升高。在这项研究中,我们试图研究mCRPC患者在第二代抗雄激素（SGA）化疗后使用联合常规成像的PSA动力学成像的不一致性，和新一代成像形式的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。
方法：我们回顾性回顾了2016年至2019年间多西他赛后接受SGA（阿比特龙或恩扎鲁他胺）治疗的123例mCRPC患者的病历。患者接受了PSA检测,和C[11]胆碱PET/CT扫描在基线水平开始用SGA治疗前，然后每3-6个月作为他们后续评估的一部分。通过C-11胆碱PET/CT上预处理病变的校正最大标准化摄取值（SUVmax）的增加来定义对SGA的反应丧失。和/或新病变的发展。通过活检和/或常规成像证实可疑的新病变。
结果：我们确定了123名接受SGA的mCRPC患者（阿比特龙，n=106；恩扎鲁胺，n=17)后多西他赛。治疗的中位持续时间为13.9个月（四分位距：8.75-21.14）。该研究中大约43%(n=53)的受试者在SGA上表现出胆碱亲和力增加。在这个群体中，60.4％的患者经历了PSA的平行升高（A组），而39.6%表现出矛盾反应(PR)(B组)，定义为胆碱亲和力增加，PSA稳定或下降。A组胆碱亲和力增加时的PSA中位数为3.1ng/ml，和1.3ng/ml的B组(p=0.0176)。两组的SUVmax中位数相似(A组为4.9，B组的4.6；p=0.6072）。A组与B组的胆碱亲和力增加的中位时间分别为9.5个月和3.9个月，分别(Log-Rank=0.0063)。
结论：在多西他赛化疗后接受SGA治疗的mCRPC患者中，近40%会表现出对治疗的矛盾反应，因此,保证密切随访成像。C-11胆碱PET/CT成像是一种有用的工具，可以帮助早期预测疾病进展或治疗失败。
方法：我们回顾性回顾了2016年至2019年间多西他赛后接受SGA（阿比特龙或恩扎鲁他胺）治疗的123例mCRPC患者的病历。患者接受了PSA检测,和C[11]胆碱PET/CT扫描在基线水平开始用SGA治疗前，然后每3-6个月作为他们后续评估的一部分。通过C-11胆碱PET/CT上预处理病变的校正最大标准化摄取值（SUVmax）的增加来定义对SGA的反应丧失。和/或新病变的发展。通过活检和/或常规成像证实可疑的新病变。
结果：我们确定了123名接受SGA的mCRPC患者（阿比特龙，n=106；恩扎鲁胺，n=17)后多西他赛。治疗的中位持续时间为13.9个月（四分位距：8.75-21.14）。该研究中大约43%(n=53)的受试者在SGA上表现出胆碱亲和力增加。在这个群体中，60.4％的患者经历了PSA的平行升高（A组），而39.6%表现出矛盾反应(PR)(B组)，定义为胆碱亲和力增加，PSA稳定或下降。A组胆碱亲和力增加时的PSA中位数为3.1ng/ml，和1.3ng/ml的B组(p=0.0176)。两组的SUVmax中位数相似(A组为4.9，B组的4.6；p=0.6072）。A组与B组的胆碱亲和力增加的中位时间分别为9.5个月和3.9个月，分别(Log-Rank=0.0063)。
结论：在多西他赛化疗后接受SGA治疗的mCRPC患者中，近40%会表现出对治疗的矛盾反应，因此,保证密切随访成像。C-11胆碱PET/CT成像是一种有用的工具，可以帮助早期预测疾病进展或治疗失败。
