摘要:前列腺癌是男性泌尿生殖系统最常见的恶性肿瘤之一,其发病率和死亡率在我国均呈逐年上升趋势,且在 初诊患者中,局部进展和转移性患者的比例大约占 70%。临床中,对于高危或局部进展性前列腺癌单纯接受前列 腺癌根治性切除术的效果不佳,这与术后病理切缘阳性、包膜侵犯、精囊侵犯等不良病理因素相关,造成术后生 化复发率高。因此,在根治性切除手术基础上,往往需要探索多模式联合治疗策略以提高远期疗效、改善预后, 其中新辅助治疗是重要的探索方向。前列腺癌新辅助药物治疗方案包括内分泌治疗 (雄激素剥夺治疗)、化疗、 内分泌治疗联合化疗等。有研究显示,新辅助治疗能够缩小肿瘤体积并提高手术切除率、降低肿瘤分期、降低手 术切缘阳性率,但在延长疾病特异性生存和总生存方面仍存在争议,并且目前缺乏大样本、前瞻性的随机对照研 究。新辅助药物治疗依赖于有效的药物,近年来随着新型内分泌药物在转移性前列腺癌的适应证逐渐扩展,前列 腺癌新辅助治疗的探索也逐渐增多,能否得到长期生存获益有待进一步的研究。本文将对前列腺癌根治性手术前 新辅助药物治疗的相关内容进行简要概述。
暂无相关信息!
[1] Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics,2022 [J]. CA Cancer J Clin, 2022, 72(1): 7-33.
[2] 中国抗癌协会泌尿男生殖系肿瘤专业委员会. 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, 56(9):646-652.
[3] Bergstrom CP, Ruffell B, Ho CM, et al. Docetaxel andmitoxantrone before radical prostatectomy in men with high- risk prostate cancer: 10- year follow- up and immune correlates [J]. Anticancer Drugs, 2017, 28(1): 120-126.
[4] Kane CJ, Presti JJ, Amling CL, et al. Changing nature of high risk patients undergoing radical prostatectomy [J]. J Urol, 2007, 177(1): 113-117.
[5] Devos G, Devlies W, De Meerleer G, et al. Neoadjuvant hormonal therapy before radical prostatectomy in high- risk prostate cancer [J]. Nat Rev Urol, 2021, 18(12): 739-762.
[6] Liu W, Yao Y, Liu X, et al. Neoadjuvant hormone therapy for patients with high- risk prostate cancer: a systematic review and meta-analysis [J]. Asian J Androl, 2021, 23(4): 429-436.
[7] Ashrafi AN, Yip W, Aron M. Neoadjuvant therapy in high- Risk prostate cancer [J]. Indian J Urol, 2020, 36(4): 251-261.
[8] Wang X, Zhang J, Han B. Neoadjuvant hormonal therapy for prostate cancer: morphologic features and predictive parameters of therapy response [J]. Adv Anat Pathol, 2022, 29(4): 252-258.
[9] Scott WW. An evaluation of endocrine therapy plus radical perineal prostatectomy in the treatment of advanced carcinoma pf the prostate [J]. J Urol, 1964, 91: 97-102.
[10] Zhang L, Zhao H, Wu B, et al. The Impact of neoadjuvant hormone therapy on surgical and oncological outcomes for patients with prostate cancer before radical prostatectomy: a systematic review and meta- analysis [J]. Front Oncol, 2020, 10: 615801.
[11] Ravi P, Kwak L, Xie W, et al. Neoadjuvant novel hormonal therapy followed by prostatectomy versus up- front prostatectomy for high- risk prostate cancer: a comparative analysis [J]. J Urol, 2022, 208(4): 838-845.
[12] McKay RR, Xie W, Ye H, et al. Results of a randomized phase II trial of intense androgen deprivation therapy prior to radical prostatectomy in men with high- risk localized prostate cancer [J]. J Urol, 2021, 206(1): 80-87.
[13] Devos G, Tosco L, Baldewijns M, et al. ARNEO: a randomized phase II trial of neoadjuvant degarelix with or without apalutamide prior to radical prostatectomy for highrisk prostate cancer [J]. Eur Urol, 2022: S0302- 2838(22) 02638-0.
[14] Rijksen B, Pos FJ, Hulshof M, et al. Variation in the prescription of androgen deprivation therapy in intermediateand high-risk prostate cancer patients treated with radiotherapy in the Netherlands, and adherence to European Association of Urology guidelines: a population- based study [J]. Eur Urol Focus, 2021, 7(2): 332-339.
[15] Berthold DR, Pond GR, Roessner M, et al. Treatment of hormone- refractory prostate cancer with docetaxel or mitoxantrone: relationships between prostate- specific antigen, pain, and quality of life response and survival in the TAX- 327 study [J]. Clin Cancer Res, 2008, 14(9): 2763-2767.
[16] Seruga B, Tannock IF. Chemotherapy- based treatment for castration- resistant prostate cancer [J]. J Clin Oncol, 2011, 29(27): 3686-3694.
[17] James ND, Sydes MR, Clarke NW, et al. Addition of docetaxel, zoledronic acid, or both to first- line long- term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial [J]. Lancet, 2016, 387(10024): 1163-1177.
[18] Kyriakopoulos CE, Chen YH, Carducci MA, 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.
[19] Gravis G, Boher JM, Joly F, et al. Androgen deprivation therapy (ADT) plus docetaxel versus ADT alone in metastatic non castrate prostate cancer: impact of metastatic burden and long- term survival analysis of the randomized phase 3 GETUG-AFU15 trial [J]. Eur Urol, 2016, 70(2): 256-262.
[20] Dreicer R, Klein EA. Preliminary observations of singleagent docetaxel as neoadjuvant therapy for locally advanced prostate cancer [J]. Semin Oncol, 2001, 28(4 Suppl 15): 45-48.
[21] Dreicer R, Magi-Galluzzi C, Zhou M, et al. Phase II trial of neoadjuvant docetaxel before radical prostatectomy for locally advanced prostate cancer [J]. Urology, 2004, 63(6): 1138-1142.
[22] Nosov A, Reva S, Petrov S, et al. Neoadjuvant chemotherapy using reduced- dose docetaxel followed by radical prostatectomy for patients with intermediate and high- risk prostate cancer: a single- center study [J]. Prostate, 2016, 76(15): 1345-1352.
[23] Febbo PG, Richie JP, George DJ, et al. Neoadjuvant docetaxel before radical prostatectomy in patients with high- risk localized prostate cancer [J]. Clin Cancer Res, 2005, 11(14): 5233-5240.
[24] Magi-Galluzzi C, Zhou M, Reuther AM, et al. Neoadjuvant docetaxel treatment for locally advanced prostate cancer: a clinicopathologic study [J]. Cancer, 2007, 110(6): 1248- 1254.
[25] Fizazi K, Faivre L, Lesaunier F, et al. Androgen deprivation therapy plus docetaxel and estramustine versus androgen deprivation therapy alone for high- risk localised prostate cancer (GETUG 12): a phase 3 randomised controlled trial [J]. Lancet Oncol, 2015, 16(7): 787-794.
[26] Ge Q, Xu H, Yue D, et al. Neoadjuvant chemohormonal therapy in prostate cancer before radical prostatectomy: a systematic review and meta-analysis [J]. Front Oncol, 2022, 12: 906370.
洪保安,赵强,杨勇,等.新辅助药物治疗在前列腺癌根治性手术中的应用进展[J]. 泌尿外科杂志(电子版),2022,14(4):4-8.DOI:10.20020/j.CNKI.1674-7410.2022.04.02
暂无相关信息!
前列腺癌是男性泌尿生殖系统最常见的恶性肿瘤之一,也是全球男性癌症死亡的第二大原因[1]。近年来,我国前列腺癌发病率呈逐年上升趋势,占男性泌尿系统肿瘤第 1位。相较于西方前列腺癌人群,中国前列腺癌患者初诊时中晚期患者比例更高,其中高危或局部进展性患者占 20%~35%,约 54%的患者初诊时即伴有远处转移[2]。目前,对于非转移性前列腺癌,根治性前列腺切除术 (radical prostatectomy,RP) 是治疗的主要手段之一。研究报道,对于高危前列腺癌患者接受 RP 后,5 年内生化复发率大于50%[3-4]。这些研究结果提示,高危或局部进展性前列腺癌在行局部治疗后仍可能存在切缘阳性、肿瘤残余,或治疗前已出现肿瘤微转移,但由于检测技术的限制无法术前早期发现而已。同时,需要认识到前列腺癌是一种异质性很强的恶性肿瘤,不同个体间的治疗效果和临床预后存在差异。因此,在临床实践中,需要探索以局部治疗 (手术或放疗) 为基础的多模式联合治疗策略以提高远期疗效,改善患者预后。
术前实施新辅助治疗是目前研究的重要方向,近年来在多种癌症类型中开展了相关探索并取得重要进展。前列腺癌新辅助治疗指患者在进行 RP或根治性放疗前进行的治疗,主要包括新辅助内分泌治疗 (neoadjuvant hormonal therapy,NHT)、新辅助化疗(neoadjuvant chemotherapy, NCT)和新辅助内分泌治疗联合化疗 (neoadjuvant chemohormonal therapy, NCHT) 等。已有多项研究表明,前列腺癌接受局部治疗前进行新辅助治疗可以降低肿瘤分期,缩小肿瘤体积并提高手术切除率,降低前列腺包膜外侵犯及精囊侵犯和手术切缘阳性率,对淋巴结转移灶和寡转移灶具有杀伤作用,延长无生化复发时间等[5-7]。此外,新辅助治疗有利于提前控制可能存在的肿瘤微转移病灶,进一步降低肿瘤转移和术后复发的风险。而且,根据患者对新辅助治疗的反应性能够直观地提供后续辅助治疗药物疗效的个体化参考。本文针对前列腺癌根治性手术前新辅助治疗的应用进行简要介绍,旨在探讨其临床应用前景,并为制定相应临床治疗策略提供参考。
1 新辅助内分泌治疗 (NHT)
2 新辅助化疗 (NCT)
3 新辅助内分泌治疗联合化疗 (NCHT)
4 小结与展望
综上所述,单纯 NHT 或 NCT 能够降低前列腺 癌的临床分期,缩小肿瘤体积并提高手术切除率, 降低切缘阳性率,但在改善患者无进展生存期及总 生存方面未观察到显著获益。鉴于大部分前列腺癌 的发生发展具有雄激素依赖性,而且雄激素的来源 广泛,包括睾丸、肾上腺和肿瘤细胞自身分泌等, 可能单纯内分泌治疗或化疗无法完全抑制机体内雄 激素水平和强效杀伤控制肿瘤细胞,内分泌联合化 疗可能发挥协同增效的作用。现有的研究证据表 明,NCHT 可能改善患者的生存结局,具有潜在的 临床应用前景。但目前尚缺乏标准推荐的治疗方案 和合适的人群选择标准,仍需通过开展前瞻性随机 对照研究进一步明确。随着新型内分泌药物的不断发展和多药联合治疗的探索,新辅助治疗可能成为 高危和局部进展性前列腺癌的重要选择。
暂无相关信息!
暂无相关信息!