使用Radium-223治療轉移性去勢抗性攝護腺癌之療效預測因子

蔡仕傑¹、魏子鈞^1,2、張延驊^1,2、鍾孝仁^1,2、

黃逸修^1,2、林子平^1,2、黃志賢^{1, 2}

¹臺北榮民總醫院泌尿部；²國立陽明交通大學醫學系泌尿學科及書田泌尿科學研究中心

Predictive factors of the response for Radium-223 in treating metastatic castration resistant prostate cancer

Shi-Jie Tsai¹, Tzu-Chun Wei^{1, 2}, Yen-Hwa Chang^{1, 2}, Hsiao-Jen Chung^{1, 2},

Eric Yi-Hsiu Huang ^{1, 2}, Tzu-Ping Lin^{1, 2}, William J.S. Huang^{1, 2}

¹ Department of Urology, Taipei Veterans General Hospital,

²Department of Urology, College of Medicine and Shu-Tien Urological Science Research Center,

National Yang Ming Chiao Tung University, Taipei, Taiwan

Purpose:

Among systemic life-prolonging agents for metastatic castration-resistant prostate cancer (mCRPC), Radium-223 (Ra-223) is a radioactive isotope which emits α–particle and targets symptomatic bony metastases. Unlike other interventions of the androgen pathway, Ra-223 directly breaks down the double strand DNA, leading to the apoptosis of cells needing more calcium, particularly the osteoblastic metastatic ones. Therefore, Ra-223 inhibits the deterioration of metastatic bony structure, prevents patients from skeleton-related events (SRE), and further prolongs the overall survival. Ra-223 has been reimbursed by the National Health Insurance (NHI) for mCRPC since March 2019, but predictors for those might respond to Ra-223 have still been a clinical issue. This study was aimed to analyze it through the experience of real-word practice from a single tertiary center.

Materials and Methods:

We retrospectively reviewed patients receiving Ra-223 treatments at Taipei Veterans General Hospital from March 2019 to August 2022. Patients with treatment doses less than four were excluded. Demographic data, initial prostate specific antigen (PSA), Gleason grade group, and previous systemic treatment were collected. Progressive disease (PD) was defined as having at least two of the three criteria, including clinical, biochemical and radiological progression, while the percentage of stable disease (SD) plus partial remission (PR) were defined as clinical benefit rate (CBR), since there was no complete remission. Biochemical data focusing alkaline-phosphatase (ALK-P), lactate dehydrogenase (LDH), and PSA were analyzed by comparing the mean ratio of each value after Ra-223 treatment, with the baseline set as 100%.

Results:

Total 45 mCRPC patients were included, with 8 patients (17.7%) receiving Ra-223 as the first-line therapy, 19 (42.2%) as the second-line, and 18 (40%) as the third-line. Sixteen patients (35.5%) were defined as PD, whereas the CBR was 64.4%. The demographic data including age at diagnosis and treatment, initial Gleason group and stage, lymphadenopathy degree, previous history of chemotherapy or novel hormonal agents (NHA) were not statistically different between the CBR and PD group. Nevertheless, there was a significantly diverse trend of post-treatment ALK-P, LDH, and PSA. As demonstrated by percentage change, the mean ratio of ALK-P was 68.3% in the CBR group but 140.2% in the PD group (p=0.002). The mean ratio of post-treatment LDH was nearly unchanged (103.2%) in the CBR group while that of PD patients (140.6%) increased significantly (p=0.008). Post-treatment PSA mean ratios were both escalating in the CBR (164.3%) and PD (428.8%) group, but the latter was statistically higher (p=0.005).

Conclusions: