CPCC晚期前列腺癌中国专家共识——转移性激素敏感性前列腺癌起始应用新型内分泌治疗的全程管理（2022年版）

doi:10.19401/j.cnki.1007-3639.2022.12.013

摘要/Abstract

摘要：

转移性激素敏感性前列腺癌（metastatic hormone-sensitive prostate cancer，mHSPC）是需要持续关注的男性健康问题。2021年国内外各大指南关于mHSPC初始系统治疗推荐进行了重要更新，新型内分泌治疗（novel hormone therapy，NHT）联合雄激素剥夺治疗（androgen deprivation therapy，ADT）成为最重要的系统治疗方案。同时转移性前列腺癌原发灶局部治疗、转移灶定向治疗（metastasis-directed therapy，MDT）、基因检测、新型影像学（next-generation imaging，NGI）等新技术、新理念快速发展，推动mHSPC全程诊疗格局进一步改变。中国与欧美地区前列腺癌在遗传背景、早筛开展、初诊疾病分布及临床表现等方面均存在明显差异，为解答中国mHSPC临床管理相关的热点及争议问题，由中国前列腺癌研究协作组（Chinese Prostate Cancer Consortium，CPCC）组织多学科专家筛选关键决策问题，结合最新发表数据，经过多轮投票及讨论，最终形成《CPCC晚期前列腺癌中国专家共识——转移性激素敏感性前列腺癌起始应用新型内分泌治疗的全程管理（2022年版）》，以期为mHSPC真实世界临床管理提供决策参考。

关键词: 转移性激素敏感性前列腺癌, 新型内分泌治疗, 全程管理, 精准诊断, 多模式治疗

Abstract:

Metastatic hormone-sensitive prostate cancer (mHSPC) is a male health concern requiring continuous attention. In 2021, an important update was included in domestic and international guidelines regarding the recommendations of initial systemic therapy for mHSPC, in which androgen deprivation therapy (ADT) combined with novel hormone therapy (NHT) has became the most important systemic treatment strategy. Meanwhile, emerging technologies and concepts, such as local therapy for the primary tumor in mHSPC, metastasis-directed therapy (MDT), genetic testing, and next generation imaging (NGI), have developed rapidly to promote further changes in the pattern of diagnosis and treatment of mHSPC. There are significant differences observed between China and western countries including genetics, screening policy, disease stage distribution and clinical characteristics at diagnosis. Focus on the controversial issues related to the clinical management of mHSPC in China, Chinese Prostate Cancer Consortium (CPCC) organized multidisciplinary experts to screen key decision-making questions based on the latest evidence. After multiple rounds of voting and discussion, the “Chinese Prostate Cancer Consortium (CPCC) Chinese expert consensus on advanced prostate cancer: clinical management of patients with metastatic hormone-sensitive prostate cancer treated by initial novel hormone therapy (2022 edition)” is finally formed, aiming to provide a decision-making reference for clinical management of mHSPC in the real-world.

Key words: Metastatic hormone-sensitive prostate cancer, Novel hormone therapy, Clinical management, Precise diagnosis, Multi-model therapy

中图分类号:

R737.25

中国前列腺癌研究协作组（CPCC）, 叶定伟, 黄健. CPCC晚期前列腺癌中国专家共识——转移性激素敏感性前列腺癌起始应用新型内分泌治疗的全程管理（2022年版）[J]. 中国癌症杂志, 2022, 32(12): 1242-1258.

Chinese Prostate Cancer Consortium (CPCC), YE Dingwei, HUANG Jian. Chinese Prostate Cancer Consortium (CPCC) Chinese expert consensus on advanced prostate cancer: clinical management of patients with metastatic hormone-sensitive prostate cancer treated by initial novel hormone therapy (2022 edition)[J]. China Oncology, 2022, 32(12): 1242-1258.

图/表 2

表1

强烈共识*"

编号	题干及达成共识选项
6	对初诊为局限性前列腺癌经治疗后出现PSA复发/PSA持续的患者，是否推荐使用PSMA PET CT进行远处转移灶判定? ◆ 是的，大部分患者（87%）
10	若您认为有必要在mHSPC诊断时进行基因检测，您会优先选择何种检测方式 ◆ NGS-胚系检测+体系检测（80%）
13	您是否推荐mHSPC患者进行精准病理学分型（筛状结构、导管内癌等） ◆ 是（97%）
19	NHT+ADT已经成为无论高瘤、低瘤mHSPC的标准治疗方案，2022年更新了NHT+多西他赛+ADT三联系统治疗对比多西他赛+ADT的数据（PEACE-1、ARASENS、ENZAMET），而目前尚缺乏三联系统治疗对比NHT+ADT的数据，您是否认可对大多数患者推荐三联系统治疗? ◆ 否（92%^**）
20	您认为哪些患者可推荐局部治疗联合NHT+ADT的标准系统治疗? ◆ 仅mHSPC诊断时低瘤/寡转移患者（82%）
23	您认为哪些患者适合推荐局部治疗联合NHT+ADT再联合MDT? ◆ 仅低瘤或寡转移或M1a等转移负荷较低的患者（85%）
24	您更倾向选择哪种MDT ◆ SBRT（92%）
26	您优先选择的治疗应答判定指标是 ◆ PSA应答，如PSA50/PSA90/PSA≤0.2 ng/mL等（92%）
27	您如何看待治疗应答? ◆ 评估患者的疾病固有特性对当下治疗的敏感性以决策是否进行治疗调整/强化等（85%）
28	SWOG9346提出的7个月后PSA达到0.2 ng/mL及以下是更好的预后组，CHAARTED研究事后分析同样可见接受多西他赛+ADT患者群体也可将PSA降低至0.2 ng/mL及以下作为预后分析组；2021年则更新了TITAN在3个月的PSA达到0.2 ng/mL以下生存获益显著，您是否认可3个月的PSA应答可作为预后评估分层因素? ◆ 是（83%）
32	您认为mHSPC初始应用NHT后如何判定进展? ◆ PSA进展、影像学进展、临床症状进展中至少出现两项者（85%）
33	若初诊时已经进行基因检测，进展至mCRPC后您会推荐再次进行基因检测吗? ◆ 会（82%）
35	您推荐的影像学进展判定标准为 ◆ PCWG3指标：RECIST标准；对于骨转移灶“2+2”原则，至少发现2处新增转移灶，且需要再进行一次确认检查，再发现2处新增转移灶（85%）
36	您推荐NHT治疗进展后的停止目前治疗的指征是? ◆ 参考PCWG3标准：PSA进展，临床症状进展，影像学进展三者中有两项出现后进行决策，不推荐单纯PSA进展作为立刻停止目前治疗的指征（87%）

表1

表2

参考文献 103

[1]	SUNG H, FERLAY J, SIEGEL R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. doi: 10.3322/caac.21660
[2]	International Agency for Research on Cancer. Estimated age-standardized incidence rates (World) in 2020, World, both sexes, all ages[EB/OL]. https://gco.iarc.fr/today. [2022-09-29].
[3]	ZHU Y, MO M, WEI Y, et al. Epidemiology and genomics of prostate cancer in Asian men[J]. Nat Rev Urol, 2021, 18(5): 282-301. doi: 10.1038/s41585-021-00442-8 pmid: 33692499
[4]	CHEN W Q, ZHENG R S, BAADE P D, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132. doi: 10.3322/caac.21338
[5]	WANG Y C, LU D S, CHUNG Y J, et al. Genetic structure, divergence and admixture of Han Chinese, Japanese and Korean populations[J]. Hereditas, 2018, 155: 19. doi: 10.1186/s41065-018-0057-5 pmid: 29636655
[6]	YOSHINO T, ARGILÉS G, OKI E, et al. Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis treatment and follow-up of patients with localised colon cancer[J]. Ann Oncol, 2021, 32(12): 1496-1510. doi: 10.1016/j.annonc.2021.08.1752 pmid: 34411693
[7]	KITAGAWA Y, NAMIKI M. Prostate-specific antigen-based population screening for prostate cancer: current status in Japan and future perspective in Asia[J]. Asian J Androl, 2015, 17(3): 475-480. doi: 10.4103/1008-682X.143756 pmid: 25578935
[8]	LI J, XU C L, LEE H J, et al. A genomic and epigenomic atlas of prostate cancer in Asian populations[J]. Nature, 2020, 580(7801): 93-99. doi: 10.1038/s41586-020-2135-x
[9]	DESAI M M, CACCIAMANI G E, GILL K, et al. Trends in incidence of metastatic prostate cancer in the US[J]. JAMA Netw Open, 2022, 5(3): e222246.
[10]	BURGESS L, ALDRIGHETTI C M, GHOSH A, et al. Association of the USPSTF grade D recommendation against prostate-specific antigen screening with prostate cancer-specific mortality[J]. JAMA Netw Open, 2022, 5(5): e2211869.
[11]	US PREVENTIVE SERVICES TASK FORCE, GROSSMAN D C, CURRY S J, et al. Screening for prostate cancer: US preventive services task force recommendation statement[J]. JAMA, 2018, 319(18): 1901-1913. doi: 10.1001/jama.2018.3710 pmid: 29801017
[12]	VAN POPPEL H, ALBREHT T, BASU P, et al. Serum PSA-based early detection of prostate cancer in Europe and globally: past, present and future[J]. Nat Rev Urol, 2022, 19(9): 562-572. doi: 10.1038/s41585-022-00638-6 pmid: 35974245
[13]	CHEN R, REN S C, CHINESE PROSTATE CANCER CONSORTIUM, et al. Prostate cancer in Asia: a collaborative report[J]. Asian J Urol, 2014, 1(1): 15-29. doi: 10.1016/j.ajur.2014.08.007 pmid: 29511634
[14]	马春光, 叶定伟, 李长岭, 等. 前列腺癌的流行病学特征及晚期一线内分泌治疗分析[J]. 中华外科杂志, 2008, 46(12): 921-925.
	MA C G, YE D W, LI C L, et al. Epidemiology of prostate cancer from three centers and analysis of the first-fine hormonal therapy for the advanced disease[J]. Chin J Surg, 2008, 46(12): 921-925.
[15]	UEMURA H, YE D W, KANESVARAN R, et al. United in Fight against prOstate cancer (UFO) registry: first results from a large, multi-centre, prospective, longitudinal cohort study of advanced prostate cancer in Asia[J]. BJU Int, 2020, 125(4): 541-552. doi: 10.1111/bju.14980 pmid: 31868997
[16]	中国临床肿瘤学会指南工作委员会组织. 中国临床肿瘤学会(CSCO)前列腺癌诊疗指南-2021[M]. 北京: 人民卫生出版社, 2021.
	Organization of Guidelines Working Committee of Chinese Society of Clinical Oncology. Chinese Society of Clinical Oncology (CSCO) guidelines for diagnosis and treatment of prostate cancer-2021[M]. Beijing: People's Health Publishing House, 2021.
[17]	KANESVARAN R, CASTRO E, WONG A, et al. Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with prostate cancer[J]. ESMO Open, 2022, 7(4): 100518.
[18]	EAU guidelines presented at the EAU Annual Congress Milan 2021[EB/OL]. http://uroweb.org/guidelines/compilations-of-all-guidelines2021/ [2022-09-28].
[19]	中国抗癌协会泌尿男生殖系肿瘤专业委员会, 朱耀. 2018版转移性前列腺癌诊治中国专家共识[J]. 中华外科杂志, 2018(9): 646-652.
	Chinese Anticancer Association Genitourinary Oncology Committee, ZHU Y. Chinese experts consensus on the treatment of metastatic prostate cancer 2018 edition[J]. Chin J Surg, 2018(9): 646-652.
[20]	Hormone therapy for prostate cancer[EB/OL]. https://www.cancer.org/cancer/prostate-cancer/treating/hormone-therapy.html [2022-09-30].
[21]	VIRGO K S, RUMBLE R B, DE WIT R, et al. Initial management of noncastrate advanced, recurrent, or metastatic prostate cancer: ASCO guideline update[J]. J Clin Oncol, 2021, 39(11): 1274-1305. doi: 10.1200/JCO.20.03256
[22]	DAI B, ZHANG S, WAN F N, et al. Combination of androgen deprivation therapy with radical local therapy versus androgen deprivation therapy alone for newly diagnosed oligometastatic prostate cancer: a phase Ⅱ randomized controlled trial[J]. Eur Urol Oncol, 2022, 5(5): 519-525.
[23]	HELLMAN S, WEICHSELBAUM R R. Oligometastases[J]. J Clin Oncol, 1995, 13(1): 8-10. doi: 10.1200/JCO.1995.13.1.8 pmid: 7799047
[24]	KATIPALLY R R, PITRODA S P, JULOORI A, et al. The oligometastatic spectrum in the era of improved detection and modern systemic therapy[J]. Nat Rev Clin Oncol, 2022, 19(9): 585-599. doi: 10.1038/s41571-022-00655-9 pmid: 35831494
[25]	CONNOR M J, SMITH A, MIAH S, et al. Targeting oligometastasis with stereotactic ablative radiation therapy or surgery in metastatic hormone-sensitive prostate cancer: a systematic review of prospective clinical trials[J]. Eur Urol Oncol, 2020, 3(5): 582-593. doi: 10.1016/j.euo.2020.07.004 pmid: 32891600
[26]	ASHRAM S, BAHIG H, BARRY A, et al. Planning trade-offs for SABR in patients with 4 to 10 metastases: a substudy of the SABR-COMET-10 randomized trial[J]. Int J Radiat Oncol Biol Phys, 2022, 114(5): 1011-1015. doi: 10.1016/j.ijrobp.2022.05.035
[27]	FAROLFI A, HADASCHIK B, HAMDY F C, et al. Positron emission tomography and whole-body magnetic resonance imaging for metastasis-directed therapy in hormone-sensitive oligometastatic prostate cancer after primary radical treatment: a systematic review[J]. Eur Urol Oncol, 2021, 4(5): 714-730. doi: 10.1016/j.euo.2021.02.003 pmid: 33750684
[28]	STEUBER T, JILG C, TENNSTEDT P, et al. Standard of care versus metastases-directed therapy for PET-detected nodal oligorecurrent prostate cancer following multimodality treatment: a multi-institutional case-control study[J]. Eur Urol Focus, 2019, 5(6): 1007-1013. doi: S2405-4569(18)30077-4 pmid: 29530632
[29]	DE BLESER E, JERECZEK-FOSSA B A, PASQUIER D, et al. Metastasis-directed therapy in treating nodal oligorecurrent prostate cancer: a multi-institutional analysis comparing the outcome and toxicity of stereotactic body radiotherapy and elective nodal radiotherapy[J]. Eur Urol, 2019, 76(6): 732-739. doi: S0302-2838(19)30533-0 pmid: 31331782
[30]	GLICKSMAN R M, METSER U, VINES D, et al. Curative-intent metastasis-directed therapies for molecularly-defined oligorecurrent prostate cancer: a prospective phase II trial testing the oligometastasis hypothesis[J]. Eur Urol, 2021, 80(3): 374-382. doi: 10.1016/j.eururo.2021.02.031 pmid: 33685838
[31]	PHILLIPS R, SHI W Y, DEEK M, et al. Outcomes of observation vs stereotactic ablative radiation for oligometastatic prostate cancer: the ORIOLE phase 2 randomized clinical trial[J]. JAMA Oncol, 2020, 6(5): 650-659. doi: 10.1001/jamaoncol.2020.0147
[32]	OST P, REYNDERS D, DECAESTECKER K, et al. Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence: a prospective, randomized, multicenter phase Ⅱ trial[J]. J Clin Oncol, 2018, 36(5): 446-453.
[33]	EAU guidelines presented at the EAU Annual Congress Amsterdam 2022[EB/OL]. http://uroweb.org/guidelines/compilations-of-all-guidelines2022/[2022-09-28].
[34]	中国临床肿瘤学会指南工作委员会组织. 中国临床肿瘤学会(CSCO)乳腺癌诊疗指南-2022[M]. 北京: 人民卫生出版社, 2022.
	Organization of Guidelines Working Committee of Chinese Society of Clinical Oncology. Chinese Society of Clinical Oncology (CSCO) breast cancer diagnosis and treatment guideline-2022 [M] Beijing: People’s Health Publishing House, 2022.
[35]	GILLESSEN S, ARMSTRONG A, ATTARD G, et al. Management of patients with advanced prostate cancer: report from the advanced prostate cancer consensus conference 2021[J]. Eur Urol, 2022, 82(1): 115-141. doi: 10.1016/j.eururo.2022.04.002 pmid: 35450732
[36]	CECI F, OPREA-LAGER D E, EMMETT L, et al. E-PSMA: The EANM standardized reporting guidelines v1.0 for PSMA-PET[J]. Eur J Nucl Med Mol Imaging, 2021, 48(5): 1626-1638. doi: 10.1007/s00259-021-05245-y
[37]	EIBER M, HERRMANN K, CALAIS J, et al. Prostate cancer molecular imaging standardized evaluation (PROMISE): proposed miTNM classification for the interpretation of PSMA-ligand PET/CT[J]. J Nucl Med, 2018, 59(3): 469-478. doi: 10.2967/jnumed.117.198119
[38]	EAU guidelines presented at the EAU Annual Congress Amsterdam 2020[EB/OL]. http://uroweb.org/guidelines/compilations-of-all-guidelines2020/ [2022-09-28].
[39]	Preliminary results in APCCC 2022EB/OL. www.apccc.org. [2022-09-30].
[40]	SUNDAHL N, GILLESSEN S, SWEENEY C, et al. When what you see is not always what you get: raising the bar of evidence for new diagnostic imaging modalities[J]. Eur Urol, 2021, 79(5): 565-567. doi: 10.1016/j.eururo.2020.07.029 pmid: 32847699
[41]	BARBATO F, FENDLER W P, RAUSCHER I, et al. PSMA-PET for the assessment of metastatic hormone-sensitive prostate cancer volume of disease[J]. J Nucl Med, 2021, 62(12): 1747-1750. doi: 10.2967/jnumed.121.262120
[42]	FIZAZI K, TRAN N, FEIN L, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer[J]. N Engl J Med, 2017, 377(4): 352-360. doi: 10.1056/NEJMoa1704174
[43]	KYRIAKOPOULOS C E, CHEN Y H, CARDUCCI M A, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase Ⅲ E3805 CHAARTED trial[J]. J Clin Oncol, 2018, 36(11): 1080-1087. doi: 10.1200/JCO.2017.75.3657
[44]	ABIDA W, ARMENIA J, GOPALAN A, et al. Prospective genomic profiling of prostate cancer across disease states reveals germline and somatic alterations that may affect clinical decision making[J]. JCO Precis Oncol, 2017, 2017: PO.17.00029.
[45]	SANDHU S, MOORE CM, CHIONG E, et al. Prostate cancer[J]. Lancet, 2021, 398(10305): 1075-1090. doi: 10.1016/S0140-6736(21)00950-8 pmid: 34370973
[46]	DEEK M P, VAN DER EECKEN K, PHILLIPS R, et al. The mutational landscape of metastatic castration-sensitive prostate cancer: the spectrum theory revisited[J]. Eur Urol, 2021, 80(5): 632-640. doi: 10.1016/j.eururo.2020.12.040 pmid: 33419682
[47]	ZHU Y, WEI Y, ZENG H, et al. Inherited mutations in Chinese men with prostate cancer[J]. J Natl Compr Canc Netw, 2021, 20(1): 54-62. doi: 10.6004/jnccn.2021.7010
[48]	GIRI V N, KNUDSEN K E, KELLY W K, et al. Implementation of germline testing for prostate cancer: Philadelphia prostate cancer consensus conference 2019[J]. J Clin Oncol, 2020, 38(24): 2798-2811. doi: 10.1200/JCO.20.00046 pmid: 32516092
[49]	中国抗癌协会泌尿男生殖系肿瘤专业委员会, 中国临床肿瘤学会前列腺癌专家委员会. 中国前列腺癌患者基因检测专家共识(2020年版)[J]. 中国癌症杂志, 2022, 30(7): 551-560.
	China Anti-Cancer Association Genitourinary Cancer Committee, Chinese Society of Clinical Oncology Committee on Prostate Cancer. Chinese expert consensus on genomic testing of prostate cancer patients (the 2020 edition)[J]. China Oncol, 2022, 30(7): 551-560.
[50]	KENCH J G, AMIN M B, BERNEY D M, et al. WHO Classification of tumours fifth edition: evolving issues in the classification, diagnosis, and prognostication of prostate cancer[J]. Histopathology, 2022, 81(4): 447-458. doi: 10.1111/his.14711
[51]	ZAFFUTO E, POMPE R, ZANATY M, et al. Contemporary incidence and cancer control outcomes of primary neuroendocrine prostate cancer: a SEER database analysis[J]. Clin Genitourin Cancer, 2017, 15(5): e793-e800. doi: 10.1016/j.clgc.2017.04.006
[52]	NETTO G J, AMIN M B, BERNEY D M, et al. The 2022 World Health Organization classification of tumors of the urinary system and male genital organs-part B: prostate and urinary tract tumors[J]. Eur Urol, 2022, 82(5): 469-482. doi: 10.1016/j.eururo.2022.07.002 pmid: 35965208
[53]	ZHAO J G, LIU J D, SUN G X, et al. The prognostic value of the proportion and architectural patterns of intraductal carcinoma of the prostate in patients with de novo metastatic prostate cancer[J]. J Urol, 2019, 201(4): 759-768. doi: 10.1016/j.juro.2018.10.016 pmid: 30652989
[54]	DINERMAN B F, KHANI F, GOLAN R, et al. Population-based study of the incidence and survival for intraductal carcinoma of the prostate[J]. Urol Oncol, 2017, 35(12): 673. e9-673673.e14.
[55]	PORTER L H, LAWRENCE M G, ILIC D, et al. Systematic review links the prevalence of intraductal carcinoma of the prostate to prostate cancer risk categories[J]. Eur Urol, 2017, 72(4): 492-495. doi: S0302-2838(17)30178-1 pmid: 28342640
[56]	ZHAO T, LIAO B H, YAO J, et al. Is there any prognostic impact of intraductal carcinoma of prostate in initial diagnosed aggressively metastatic prostate cancer?[J]. Prostate, 2015, 75(3): 225-232. doi: 10.1002/pros.22906 pmid: 25307858
[57]	WANG Z P, ZHU S, ZHAO J G, et al. The heterogeneity of intraductal carcinoma of the prostate is associated with different efficacy of standard first-line therapy for patients with metastatic castration-resistant prostate cancer[J]. Prostate, 2021, 81(15): 1191-1201. doi: 10.1002/pros.24215 pmid: 34435696
[58]	ANTONARAKIS E S, SHAUKAT F, ISAACSSON VELHO P, et al. Clinical features and therapeutic outcomes in men with advanced prostate cancer and DNA mismatch repair gene mutations[J]. Eur Urol, 2019, 75(3): 378-382. doi: S0302-2838(18)30750-4 pmid: 30337059
[59]	BÖTTCHER R, KWELDAM C F, LIVINGSTONE J, et al. Cribriform and intraductal prostate cancer are associated with increased genomic instability and distinct genomic alterations[J]. BMC Cancer, 2018, 18(1): 8. doi: 10.1186/s12885-017-3976-z pmid: 29295717
[60]	SCHWEIZER M T, ANTONARAKIS E S, BISMAR T A, et al. Genomic characterization of prostatic ductal adenocarcinoma identifies a high prevalence of DNA repair gene mutations[J]. JCO Precis Oncol, 2019, 3: 1-9.
[61]	CHUA M L K, LO W, PINTILIE M, et al. A prostate cancer “nimbosus”: genomic instability and SChLAP1 dysregulation underpin aggression of intraductal and cribriform subpathologies[J]. Eur Urol, 2017, 72(5): 665-674. doi: 10.1016/j.eururo.2017.04.034
[62]	ZHAO J G, SUN G X, ZHU S, et al. Circulating tumour DNA reveals genetic traits of patients with intraductal carcinoma of the prostate[J]. BJU Int, 2022, 129(3): 345-355. doi: 10.1111/bju.15530
[63]	TAYLOR R A, FRASER M, LIVINGSTONE J, et al. Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories[J]. Nat Commun, 2017, 8: 13671. doi: 10.1038/ncomms13671
[64]	ISAACSSON VELHO P, SILBERSTEIN J L, MARKOWSKI M C, et al. Intraductal/ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer[J]. Prostate, 2018, 78(5): 401-407. doi: 10.1002/pros.23484 pmid: 29368341
[65]	FIZAZI K, FOULON S, CARLES J, et al. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design[J]. Lancet, 2022, 399(10336): 1695-1707. doi: 10.1016/S0140-6736(22)00367-1
[66]	SMITH M R, HUSSAIN M, SAAD F, et al. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer[J]. N Engl J Med, 2022, 386(12): 1132-1142. doi: 10.1056/NEJMoa2119115
[67]	DAVIS I D, MARTIN A J, ZIELINSKI R R, et al. Updated overall survival outcomes in ENZAMET (ANZUP 1304), an international, cooperative group trial of enzalutamide in metastatic hormone-sensitive prostate cancer (mHSPC)[J]. J Clin Oncol, 2022, 40(17_suppl): LBA5004. doi: 10.1200/JCO.2022.40.17_suppl.LBA5004
[68]	MAIORANO B A, DE GIORGI U, ROVIELLO G, et al. Addition of androgen receptor-targeted agents to androgen-deprivation therapy and docetaxel in metastatic hormone-sensitive prostate cancer: a systematic review and meta-analysis[J]. ESMO Open, 2022, 7(5): 100575.
[69]	ROY S, SAYYID R, SAAD F, et al. Addition of docetaxel to androgen receptor axis-targeted therapy and androgen deprivation therapy in metastatic hormone-sensitive prostate cancer: a network meta-analysis[J]. Eur Urol Oncol, 2022, 5(5): 494-502. doi: 10.1016/j.euo.2022.06.003 pmid: 35811293
[70]	FALLARA G, ROBESTI D, NOCERA L, et al. Chemotherapy and advanced androgen blockage, alone or combined, for metastatic hormone-sensitive prostate cancer a systematic review and meta-analysis[J]. Cancer Treat Rev, 2022, 110: 102441.
[71]	YANAGISAWA T, RAJWA P, THIBAULT C, et al. Androgen receptor signaling inhibitors in addition to docetaxel with androgen deprivation therapy for metastatic hormone-sensitive prostate cancer: a systematic review and meta-analysis[J]. Eur Urol, 2022, 82(6): 584-598. doi: 10.1016/j.eururo.2022.08.002 pmid: 35995644
[72]	CICCARESE C, IACOVELLI R, STERNBERG C N, et al. Triplet therapy with androgen deprivation, docetaxel, and androgen receptor signalling inhibitors in metastatic castration-sensitive prostate cancer: a meta-analysis[J]. Eur J Cancer, 2022, 173: 276-284. doi: 10.1016/j.ejca.2022.07.011 pmid: 35964470
[73]	PARKER C C, JAMES N D, BRAWLEY C D, et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial[J]. Lancet, 2018, 392(10162): 2353-2366. doi: S0140-6736(18)32486-3 pmid: 30355464
[74]	ALI A, HOYLE A, HARAN Á M, et al. Association of bone metastatic burden with survival benefit from prostate radiotherapy in patients with newly diagnosed metastatic prostate cancer: a secondary analysis of a randomized clinical trial[J]. JAMA Oncol, 2021, 7(4): 555-563. doi: 10.1001/jamaoncol.2020.7857 pmid: 33599706
[75]	PARKER C C, JAMES N D, BRAWLEY C D, et al. Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: long-term results from the STAMPEDE randomised controlled trial[J]. PLoS Med, 2022, 19(6): e1003998.
[76]	REYES D K, TROCK B J, TRAN P T, et al. Interim analysis of companion, prospective, phase Ⅱ, clinical trials assessing the efficacy and safety of multi-modal total eradication therapy in men with synchronous oligometastatic prostate cancer[J]. Med Oncol, 2022, 39(5): 63. doi: 10.1007/s12032-022-01662-7
[77]	REYES D K, ROWE S P, SCHAEFFER E M, et al. Multidisciplinary total eradication therapy (TET) in men with newly diagnosed oligometastatic prostate cancer[J]. Med Oncol, 2020, 37(7): 60. doi: 10.1007/s12032-020-01385-7 pmid: 32524295
[78]	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
[79]	BEER T M, ARMSTRONG A J, RATHKOPF D E, et al. Enzalutamide in metastatic prostate cancer before chemotherapy[J]. N Engl J Med, 2014, 371(5): 424-433. doi: 10.1056/NEJMoa1405095
[80]	RYAN C J, SMITH M R, DE BONO J S, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy[J]. N Engl J Med, 2013, 368(2): 138-148. doi: 10.1056/NEJMoa1209096
[81]	FIZAZI K, JONES R, OUDARD S, et al. Phase Ⅲ, randomized, double-blind, multicenter trial comparing orteronel (TAK-700) plus prednisone with placebo plus prednisone in patients with metastatic castration-resistant prostate cancer that has progressed during or after docetaxel-based therapy: ELM-PC 5[J]. J Clin Oncol, 2015, 33(7): 723-731. doi: 10.1200/JCO.2014.56.5119
[82]	NATIONAL COMPREHENSIVE CANCER NETWORK (NCCN). NCCN Guidelines Version 4.2022 Prostate Cancer[EB/OL]. https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf [2022-09-29].
[83]	HUSSAIN M, TANGEN C M, HIGANO C, et al. Absolute prostate-specific antigen value after androgen deprivation is a strong independent predictor of survival in new metastatic prostate cancer: data from Southwest Oncology Group Trial 9346 (INT-0162)[J]. J Clin Oncol, 2006, 24(24): 3984-3990. doi: 10.1200/JCO.2006.06.4246 pmid: 16921051
[84]	HARSHMAN L C, CHEN Y H, LIU G, et al. Seven-month prostate-specific antigen is prognostic in metastatic hormone-sensitive prostate cancer treated with androgen deprivation with or without docetaxel[J]. J Clin Oncol, 2018, 36(4): 376-382. doi: 10.1200/JCO.2017.75.3921 pmid: 29261442
[85]	MATSUBARA N, CHI K N, ÖZGÜROĞLU M, et al. Correlation of prostate-specific antigen kinetics with overall survival and radiological progression-free survival in metastatic castration-sensitive prostate cancer treated with abiraterone acetate plus prednisone or placebos added to androgen deprivation therapy: post hoc analysis of phase 3 LATITUDE study[J]. Eur Urol, 2020, 77(4): 494-500. doi: S0302-2838(19)30894-2 pmid: 31843335
[86]	SAAD F, HUSSAIN M H A, TOMBAL B F, et al. Association of prostate-specific antigen (PSA) response and overall survival (OS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) from the phase 3 ARASENS trial[J]. J Clin Oncol, 2022, 40(16_suppl): 5078. doi: 10.1200/JCO.2022.40.16_suppl.5078
[87]	GRAVIS X, MALDONANDO G, RPUBAUD R S, et al. 8-month PSA predicts outcomes of men with metastatic castration-sensitive prostate cancer in the PEACE-1 phase 3 trial[C]. Oral presentation at ESMO congress. Paris, France. 2022, September 9-13.
[88]	CHOWDHURY S, BJARTELL A, AGARWAL N, et al. Apalutamide for metastatic castration-sensitive prostate cancer in TITAN: prognostic importance of prostate-specific-antigen response[C]. Oral presentation at AUA Annual Meeting (Virtual). Abstract PD10. Washington, USA. 2022, May 15-18.
[89]	SMALL E J, CHI K N, CHOWDHURY S, et al. Association between patient-reported outcomes (PROs) and changes in prostate-specific antigen (PSA) in patients (pts) with advanced prostate cancer treated with apalutamide (APA) in the SPARTAN and TITAN studies[C]. Poster presentation at ASCO GU. San Francisco, USA. 2022, February 17-19.
[90]	CHI K N, SAAD F, CHOWDHURY S, et al. PD34-prostate-specific antigen kinetics in patients with advanced prostate cancer treated with apalutamide: results from the TITAN and SPARTAN studies[J]. J Urol, 2021. 206(Suppl3): e587-e587.
[91]	SANTIS D, GILLESSEN S, GRUMMET J, et al. Eau-eanm-estro esur isup siog-guidelines-on-prostate-cancer-2021[EB/OL]. http://uroweb.org/guidelines/prostate-cancer/chapter/followup2021 [2022-09-28].
[92]	BRYCE A H, CHEN Y H, LIU G, et al. Patterns of cancer progression of metastatic hormone-sensitive prostate cancer in the ECOG3805 CHAARTED trial[J]. Eur Urol Oncol, 2020, 3(6): 717-724. doi: 10.1016/j.euo.2020.07.001 pmid: 32807727
[93]	ARMSTRONG A J, MOTTET N, IGUCHI T, et al. Radiographic progression in the absence of prostate-specific antigen (PSA) progression in patients with metastatic hormone-sensitive prostate cancer (mHSPC): post hoc analysis of ARCHES[J]. J Clin Oncol, 2022, 40(16_suppl): 5072. doi: 10.1200/JCO.2022.40.16_suppl.5072
[94]	European Association of Urology. EAU-EANM-ESTRO-ESUR-ISUP-SIOG guidelines on prostate cancer 2022[EB/OL]. https://uroweb.org/guidelines/prostate-cancer/chapter/followup2022/ [2022-09-28].
[95]	JUNG J H, HONG C M, JO I, et al. Reliability of alkaline phosphatase for differentiating flare phenomenon from disease progression with bone scintigraphy[J]. Cancers (Basel), 2022, 14(1): 254. doi: 10.3390/cancers14010254
[96]	SCHER HI, MORRIS MJ, STADLER WM, et al. The Prostate Cancer Working Group 3 (PCWG3) consensus for trials in castration-resistant prostate cancer (CRPC)[J]. 2015, 33(15_suppl): 5000-5000.
[97]	SWAMI U, SINNOTT J A, HAALAND B, et al. Treatment pattern and outcomes with systemic therapy in men with metastatic prostate cancer in the real-world patients in the United States[J]. Cancers (Basel), 2021, 13(19): 4951. doi: 10.3390/cancers13194951
[98]	CHI K N, CHOWDHURY S, BJARTELL A, et al. Apalutamide in patients with metastatic castration-sensitive prostate cancer: final survival analysis of the randomized, double-blind, phase Ⅲ TITAN study[J]. J Clin Oncol, 2021, 39(20): 2294-2303. doi: 10.1200/JCO.20.03488
[99]	ARMSTRONG A J, AZAD A A, IGUCHI T, et al. Improved survival with enzalutamide in patients with metastatic hormone-sensitive prostate cancer[J]. J Clin Oncol, 2022, 40(15): 1616-1622. doi: 10.1200/JCO.22.00193
[100]	EAU guidelines presented at the EAU Annual Congress Copenhagen 2018[EB/OL]. http://uroweb.org/guidelines/compilations-of-all-guidelines2018/ [2022-09-28].
[101]	SWAMI U, HONG A, EL-CHAAR N N, et al. Underutilization of standard of care (SOC) treatment intensification in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) by specialty[J]. J Clin Oncol, 2022, 40(6_suppl): 183.
[102]	TEWARI A K, GILLESSEN S, SWEENEY C J. Metastatic prostate cancer: in search of more granularity[J]. J Clin Oncol, 2021, 39(26): 2968-2969. doi: 10.1200/JCO.21.00643
[103]	VOGL U M, BEER T M, DAVIS I D, et al. Lack of consensus identifies important areas for future clinical research: advanced Prostate Cancer Consensus Conference (APCCC) 2019 findings[J]. Eur J Cancer, 2022, 160: 24-60. doi: 10.1016/j.ejca.2021.09.036