^(68)Ga-PSMA-11 PET/CT对前列腺癌挽救性放射治疗后生化指标异常患者立体定向放射治疗的指导作用研究

Study on the guiding effect of ^(68)GA-PSMA-11-PET/CT in SBRT for patients with abnormal biochemical indicators after salvage radiotherapy for PCa

目的:探讨镓68(^(68)Ga)-前列腺特异性膜抗原(PSMA)-11正电子发射计算机断层显像(PET/CT)对前列腺癌(PCa)挽救性放射治疗后生化指标异常患者行立体定向放射治疗(SBRT)的指导作用。方法:选取在医院经手术或穿刺病理组织学检查证实为PCa,且血清前列腺特异性抗原(PSA)异常增高的46例患者,根据2014版国际泌尿病理协会(ISUP)对根治性PCa切除术后患者的病理分级,将患者分为ISUP亚群1组(27例,ISUP分级为1级和2级)和ISUP亚群2组(19例,ISUP分级为3级)。所有纳入患者治疗方案相同,均行^(68)Ga-PSMA-11 PET/CT扫描明确复发部位,随后对复发部位行SBRT,治疗后定期进行血清PSA测量和临床随访。观察并分析患者SBRT前,SBRT后3个月、6个月和9个月PSA值及SBRT前后ISUP亚群PSA值变化,评估患者的生化无复发生存期以及放射治疗相关毒性。结果:所有患者SBRT前总PSA为1.13(0.80~2.69)ng/ml,治疗后3个月和6个月PSA明显下降,分别为0.61(0.30~1.25)ng/ml和0.50(0.27~1.18)ng/ml,与SBRT前比较差异均有统计学意义(t=23.561,t=36.207;P<0.001);治疗后3个月和6个月的PSA比较差异无统计学意义。SBRT前ISUP亚群1组PSA为1.15(0.87~2.69)ng/ml,ISUP亚群2组为1.09(0.80~2.51)ng/ml;治疗后3个月和6个月,ISUP亚群1组PSA分别为0.48(0.30~0.85)ng/ml和0.46(0.24~1.01)ng/ml,ISUP亚群2组PSA分别为0.81(0.66~1.05)ng/ml和0.62(0.31~1.05)ng/ml。27例ISUP亚群1组患者治疗后3个月23例(占85.19%)患者的PSA降低,治疗后6个月16例(占59.26%)患者的PSA仍降低,治疗后9个月10例(占37.04%)患者的PSA控制在正常范围内;19例ISUP亚群2组患者治疗后3个月16例(占84.21%)患者的PSA降低,治疗后6个月12例(占63.16%)患者的PSA仍降低,治疗后9个月,7例(占36.84%)患者的PSA控制在正常范围内。所有患者总体生化无复发生存期(b-RFS)为15个月(95%CI:13~23),ISUP亚群1组b-RFS为16个月(95%CI:11~35),ISUP亚群2组b-RFS为14个月(95%CI:9~未达到),ISUP亚群1组和ISUP亚群2组之间b-RFS的差异无统计学意义。所有SBRT后PSA异常增高的患者进一步行^(68)Ga-PSMA-11 PET/CT检查,均能找到病变部位(如淋巴结转移、骨转移)。46例行SBRT的患者中,11例(占23.91%)发生1级毒性反应。结论:^(68)Ga-PSMA-11 PET/CT能够识别PCa挽救性放射治疗后生化指标异常患者的复发部位,使用SBRT对复发部位进行治疗,是一种安全有效的治疗方法。

Objective:To investigate the guiding effect of gallium 68(^(68)Ga)-prostate-specific membrane antigen(PSMA)-11 positron emission tomography/computed tomography(PET/CT)in stereotactic radiotherapy(SBRT)patients with abnormal biochemical indicators after salvage radiotherapy for prostate cancer(PCa).Methods:A total of 46 patients with abnormal increase of serum prostate specific antigen(PSA)and were confirmed as PCa by surgical or biopsy histopathological examination in hospital were selected and were divided into International Society of Urological Pathology(ISUP)subgroup 1(27 cases,grade 1and 2 as ISUP grading)and ISUP subgroup 2(19 cases,grade 3 as ISUP grading)according to the pathological grading of 2014 version of ISUP for patients who underwent PCa radical resection.The therapeutic schedules of these enrolled patients were same,and all of them underwent ^(68)Ga-PSMA-11 PET/CT scan to confirm the location of recurrence.And then,the location of recurrence underwent SBRT,and the serum PSA detection and clinical follow-up were termly performed on patients after treatment.The PSA values of patients before SBRT and 3 months,6 months and 9 months after SBRT,and the changes of PSA values of ISUP subgroup before and after SBRT were observed and analyzed.The biochemical relapse free survival(b-RFS)and the relative toxicity of radiotherapy were assessed for patients.Results:The total PSA of all patients was 1.13(0.80-2.69)ng/mL before SBRT,and it significantly decreased to 0.61(0.30-1.25)ng/mL and 0.50(0.27-1.18)ng/ml 3 and 6 months after treatment,respectively,and the differences of that between 3 months after and before treatment,and between 6 months after and before treatment were significant(t=23.561,t=36.207,P<0.001),respectively.And there was no significant difference in PSA between 3 and 6 months after treatment.PSA was 1.15(0.87-2.69)ng/mL in ISUP subgroup 1 and 1.09(0.80-2.51)ng/mL in ISUP subgroup 2 before SBRT,respectively.And the PSA of ISUP subgroup 1 was 0.48(0.30-0.85)ng/ml and 0.46(0.24-1.01)ng/mL 3 and 6 months after treatment,respectively,and the PSA of ISUP subgroup 2 was 0.81(0.66-1.05)ng/mL and 0.62(0.31-1.05)ng/mL,respectively.The PSA of 23 patients(85.19%)of ISUP subgroup 1 decreased 3 months after treatment,and that of 16 patients(59.26%)still decreased 6 months after treatment,and that of 10 cases was controlled within normal range 9 months after treatment.The PSA of 16 cases(84.21%)of ISUP subgroup 2 decreased 3 months after treatment,and that of 12 cases(63.12%)still decreased 6 months after treatment,and 7 cases(36.84%)was controlled within normal range 9 months after treatment.The overall b-RFS of all patients was 15 months(95%CI:13-23),and b-RFS of ISUP subgroup 1 was 16 months(95%CI:11-35),and b-RFS of ISUP subgroup 2 was 14 months(95%CI:9-not achieved).There was no significant difference in b-RFS between ISUP subgroup 1 and ISUP subgroup 2.All patients with PSA abnormal increase after SBRT underwent further 68GA-PMMA-11-PET/CT examination,and lesion locations(such as lymph node metastasis and bone metastasis)of all them could be found.In 46 patients who underwent SBRT,11 cases(23.91%)occurred toxic reaction with grade 1.Conclusion:68GAPSMA-11-PET/CT can identify the location of recurrence of PCa patients with abnormal biochemical indicators after salvage radiotherapy,and the used SBRT is a safe and effective treatment method in treating the location of recurrence.