激素敏感性前列腺癌患者中PSMA PET/CT衍生参数与循环肿瘤DNA特征之间的相关性分析

doi:10.19401/j.cnki.1007-3639.2024.07.007

摘要/Abstract

摘要：

背景与目的：前列腺特异性膜抗原（prostate-specific membrane antigen，PSMA）正电子发射计算机体层显像（positron emission tomography/computed tomography，PET/CT）和循环肿瘤DNA（circulating tumor DNA，ctDNA）的检测结果都是激素敏感性前列腺癌（hormone-sensitive prostate cancer，HSPC）治疗决策的参考依据。本研究旨在分析HSPC患者中PSMA PET/CT衍生参数与ctDNA特征之间的相关性。方法：回顾性纳入于复旦大学附属肿瘤医院就诊且接受PSMA PET/CT和ctDNA测序的间隔≤2周、有完整病历记录的HSPC患者。排除存在除前列腺癌外的活动性恶性肿瘤，以及组织学特征支持纯神经内分泌癌或小细胞癌诊断的患者。本研究经复旦大学附属肿瘤医院伦理委员会批注（伦理编号：1909207-12）。采用Spearman相关系数评价PSMA PET/CT衍生参数最大标准摄取值（maximum standardized uptake value，SUV_max）、总肿瘤体积（total tumor volume，TTV）、病灶摄取总量（total lesion uptake，TLU）与ctDNA分数（ctDNA%）之间的相关性。结果：共纳入60例HSPC患者，TP53（3.3%）、BRCA2（3.3%）和ATM（3.3%）是最常见的突变基因。在相关性分析中，ctDNA%与SUV_max有显著相关性（Spearman’s rho=0.272，P=0.036）；ctDNA%与TLU（Spearman’s rho=0.160，P=0.222）和TTV（Spearman’s rho=0.162，P=0.215）无显著相关性。结论：SUV_max与ctDNA%之间有显著相关性，提示与无PSMA阳性病灶和低PSMA摄取病灶的患者相比，存在高PSMA摄取病灶的患者接受联合靶向治疗的概率增加，本研究结果有望作为制订个体化治疗方案的参考。

关键词: 激素敏感性前列腺癌, 前列腺特异性膜抗原, 正电子发射计算机体层显像, 循环肿瘤DNA, 相关性分析

Abstract:

Background and purpose: Both prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and circulating tumor DNA (ctDNA) sequencing outcomes serve as references for therapeutic decision-making in hormone-sensitive prostate cancer (HSPC) treatment. This study aimed to analyze the association between PSMA PET/CT-derived parameters and ctDNA characteristics in patients with HSPC. Methods: HSPC patients who received PSMA PET/CT and ctDNA sequencing at an interval of less than 2 weeks and with complete medical records were retrospectively included in Fudan University Shanghai Cancer Center. Patients with active malignancies other than prostate cancer and those with histological features supporting a diagnosis of pure neuroendocrine carcinoma or small cell carcinoma were excluded. This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center (Ethics number: 1909207-12). The correlation between PSMA PET/CT-derived parameters, including the maximum standardized uptake value (SUVmax), total tumor volume (TTV), total lesion uptake (TLU) and ctDNA fraction (ctDNA%) was evaluated using the Spearman correlation coefficient. Results: A total of 60 HSPC patients were included, with TP53 (3.3%), BRCA2 (3.3%) and ATM (3.3%) being the most common mutated genes. In the correlation analysis, a significant correlation was observed between ctDNA% and SUVmax levels (Spearman’s rho=0.272, P=0.036); however, no significant correlation was found between ctDNA% and TLU (Spearman’s rho=0.160, P=0.222) or TTV (Spearman’s rho=0.162, P=0.215). Conclusion: There was a significant correlation between SUVmax and ctDNA%, suggesting that patients with high PSMA uptake lesions were more likely to receive combined targeted therapy than patients with no PSMA positive lesions and patients with low PSMA uptake lesions, which provided a certain reference for the formulation of individualized treatment plans.

Key words: Hormone-sensitive prostate cancer, Prostate-specific membrane antigen, Positron emission tomography/computed tomography, Circulating tumor DNA, Correlation analysis

中图分类号:

R737.25

潘剑, 叶定伟, 朱耀, 王备合. 激素敏感性前列腺癌患者中PSMA PET/CT衍生参数与循环肿瘤DNA特征之间的相关性分析[J]. 中国癌症杂志, 2024, 34(7): 680-685.

PAN Jian, YE Dingwei, ZHU Yao, WANG Beihe. Correlation analysis of PSMA PET/CT-derived parameters and circulating tumor DNA features in patients with hormone-sensitive prostate cancer[J]. China Oncology, 2024, 34(7): 680-685.

图/表 3

参考文献 27

[1]	DÖRR M, HÖLZEL D, SCHUBERT-FRITSCHLE G, et al. Changes in prognostic and therapeutic parameters in prostate cancer from an epidemiological view over 20 years[J]. Oncol Res Treat, 2015, 38(1/2): 8-14.
[2]	潘剑, 朱耀, 戴波, 等. 2022年度前列腺癌基础研究及临床诊疗新进展[J]. 中国癌症杂志, 2023, 33(3): 210-217. doi: 10.19401/j.cnki.1007-3639.2023.03.003
	PAN J, ZHU Y, DAI B, et al. Advances in basic research, clinical diagnosis and treatment of prostate cancer in 2022[J]. China Oncol, 2023, 33(3): 210-217.
[3]	WU J N, FISH K M, EVANS C P, et al. No improvement noted in overall or cause-specific survival for men presenting with metastatic prostate cancer over a 20-year period[J]. Cancer, 2014, 120(6): 818-823. doi: 10.1002/cncr.28485 pmid: 24258693
[4]	CRAWFORD E D, PETRYLAK D, SARTOR O. Navigating the evolving therapeutic landscape in advanced prostate cancer[J]. Urol Oncol, 2017, 35S: S1-S13. doi: 10.1016/j.urolonc.2017.01.020 pmid: 28283376
[5]	PAN J, YE D W, ZHU Y. Olaparib outcomes in metastatic castration-resistant prostate cancer: first real-world experience in safety and efficacy from the Chinese mainland[J]. Prostate Int, 2022, 10(3): 142-147. doi: 10.1016/j.prnil.2022.04.005 pmid: 36225282
[6]	EMMETT L, METSER U, BAUMAN G, et al. Prospective, multisite, international comparison of ¹⁸F-fluoromethylcholine PET/CT, multiparametric MRI, and ⁶⁸Ga-HBED-CC PSMA-11 PET/CT in men with high-risk features and biochemical failure after radical prostatectomy: clinical performance and patient outcomes[J]. J Nucl Med, 2019, 60(6): 794-800.
[7]	CALAIS J, CECI F, EIBER M, et al. ¹⁸F-fluciclovine PET-CT and ⁶⁸Ga-PSMA-11 PET-CT in patients with early biochemical recurrence after prostatectomy: a prospective, single-centre, single-arm, comparative imaging trial[J]. Lancet Oncol, 2019, 20(9): 1286-1294.
[8]	HOFMAN M S, LAWRENTSCHUK N, FRANCIS R J, et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study[J]. Lancet, 2020, 395(10231): 1208-1216. doi: S0140-6736(20)30314-7 pmid: 32209449
[9]	CALAIS J, FENDLER W P, EIBER M, et al. Impact of ⁶⁸Ga-PSMA-11 PET/CT on the management of prostate cancer patients with biochemical recurrence[J]. J Nucl Med, 2018, 59(3): 434-441.
[10]	PIENTA K J, GORIN M A, ROWE S P, et al. A phase 2/3 prospective multicenter study of the diagnostic accuracy of prostate specific membrane antigen PET/CT with ¹⁸F-DCFPyL in prostate cancer patients (OSPREY)[J]. J Urol, 2021, 206(1): 52-61.
[11]	HADASCHIK B, OST P. Re: assessment of ⁶⁸Ga-PSMA-11 PET accuracy in localizing recurrent prostate cancer: a prospective single-arm clinical trial[J]. Eur Urol, 2019, 76(4): 538-539.
[12]	PASCUAL J, ATTARD G, BIDARD F C, et al. ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group[J]. Ann Oncol, 2022, 33(8): 750-768. doi: 10.1016/j.annonc.2022.05.520 pmid: 35809752
[13]	SHEN H R, LIU J L, CHEN K X, et al. Language model enables end-to-end accurate detection of cancer from cell-free DNA[J]. Brief Bioinform, 2024, 25(2): bbae053.
[14]	PAN J, WEI Y, ZHANG T W, et al. Stereotactic radiotherapy for lesions detected via ⁶⁸Ga-prostate-specific membrane antigen and ¹⁸F-fluorodexyglucose positron emission tomography/computed tomography in patients with nonmetastatic prostate cancer with early prostate-specific antigen progression on androgen deprivation therapy: a prospective single-center study[J]. Eur Urol Oncol, 2022, 5(4): 420-427.
[15]	PAN J, ZHAO J O, NI X D, et al. The prevalence and prognosis of next-generation therapeutic targets in metastatic castration-resistant prostate cancer[J]. Mol Oncol, 2022, 16(22): 4011-4022. doi: 10.1002/1878-0261.13320 pmid: 36209367
[16]	PAN J, ZHAO J O, NI X D, et al. Heterogeneity of[⁶⁸Ga]Ga-PSMA-11 PET/CT in metastatic castration-resistant prostate cancer: genomic characteristics and association with abiraterone response[J]. Eur J Nucl Med Mol Imaging, 2023, 50(6): 1822-1832.
[17]	SCHER H I, MORRIS M J, STADLER W M, et al. Trial design and objectives for castration-resistant prostate cancer: updated recommendations from the prostate cancer clinical trials working group 3[J]. J Clin Oncol, 2016, 34(12): 1402-1418. doi: 10.1200/JCO.2015.64.2702 pmid: 26903579
[18]	PAN J, ZHANG T W, CHEN S Z, et al. Nomogram to predict the presence of PSMA-negative but FDG-positive lesion in castration-resistant prostate cancer: a multicenter cohort study[J]. Ther Adv Med Oncol, 2024, 16: 17588359231220506.
[19]	PAN J, WANG J, WEI Y, et al. Combination of body mass index and albumin predicts the survival in metastatic castration-resistant prostate cancer patients treated with abiraterone: a post hoc analysis of two randomized trials[J]. Cancer Med, 2021, 10(19): 6697-6704.
[20]	SARTOR O, BONO J D, CHI K N, et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer[J]. N Engl J Med, 2021, 385(12): 1091-1103.
[21]	HOFMAN M S, EMMETT L, SANDHU S, et al. [¹⁷⁷Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial[J]. Lancet, 2021, 397(10276): 797-804.
[22]	EAPEN R S, BUTEAU J P, JACKSON P, et al. Administering[¹⁷⁷Lu]Lu-PSMA-617 prior to radical prostatectomy in men with high-risk localised prostate cancer (LuTectomy): a single-centre, single-arm, phase 1/2 study[J]. Eur Urol, 2024, 85(3): 217-226.
[23]	COHEN S A, LIU M C, ALESHIN A. Practical recommendations for using ctDNA in clinical decision making[J]. Nature, 2023, 619(7969): 259-268.
[24]	JAHR S, HENTZE H, ENGLISCH S, et al. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells[J]. Cancer Res, 2001, 61(4): 1659-1665. pmid: 11245480
[25]	VANDEKERKHOVE G, STRUSS W J, ANNALA M, et al. Circulating tumor DNA abundance and potential utility in de novo metastatic prostate cancer[J]. Eur Urol, 2019, 75(4): 667-675. doi: S0302-2838(18)31050-9 pmid: 30638634
[26]	CORCORAN R B, CHABNER B A. Application of cell-free DNA analysis to cancer treatment[J]. N Engl J Med, 2018, 379(18): 1754-1765.
[27]	VOLIK S, ALCAIDE M, MORIN R D, et al. Cell-free DNA (cfDNA): clinical significance and utility in cancer shaped by emerging technologies[J]. Mol Cancer Res, 2016, 14(10): 898-908. pmid: 27422709

Pathway	Gene
DDR pathway	ABRAXAS1, ATM, ATR, BAP1, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CDKN1B, CDKN2A, CHEK1, CHEK2, EMSY, EPCAM, ERCC2, ERCC3, ERCC4, FANCA, FANCD2, FANCI, FANCL, FANCM, GEN1, MLH1, MLH3, MRE11A, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, POLE, PPP2R2A, RAD50, RAD51, RAD51B, RAD51C, RAD51D, RAD52, RAD54L, XRCC2
AR-associated pathway	AR, FOXA1, NCOR1, NCOR2, SPOP, ZBTB16
Cell cycle pathway	CCND1, CDKN2B, MYC, RB1, TP53
PI3K pathway	AKT1, PIK3CA, PIK3CB, PIK3R1, PTEN, STK11
WNT pathway	APC, CTNNB1, RNF43, RSPO2, ZNRF3
Chromatin modifiers pathway	BRAF, CHD1, ESR1, HDAC2, HOXB13, RAF1, TMPRSS2