高度恶性前列腺癌根治治疗加化疗非随机对照研究中期分析

doi:10.3760/cma.j.cn113030-20220909-00302

摘要
图/表
参考文献(22)
相关文章 (15)
点击分布统计
下载分布统计

全文: PDF (0 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS) 背景资料

摘要目的比较高度恶性非转移性前列腺癌患者在标准治疗基础上联合或不联合辅助化疗的疗效及安全性。方法采用前瞻性、非随机对照研究的方法,在北京大学第一医院连续入组病理确诊的Gleason评分总分9~10分或Gleason评分为包含5分的非转移性前列腺癌患者。在标准根治性治疗后增加或不增加4~6个周期多西他赛±卡铂方案化疗。主要终点为5年无事件生存（EFS）,次要终点为无远处转移生存（MFS）、总生存（OS）、治疗相关不良反应。采用Kaplan‐Meier法绘制生存曲线,log‐rank检验比较组间差异。结果 2019年11月至2022年1月连续入组患者176例患者,其中138例仅接受标准根治性治疗（对照组）,38例在根治性治疗后接受辅助化疗（化疗组）。中位随访13.4（2.0~34.0）个月,患者均存活。化疗组及对照组30个月EFS率为100%∶85.6%（P=0.064）,化疗组未出现任何事件,对照组12例出现事件,其中6例为单纯生化复发、6例为影像学进展。两组30个月MFS率为100%∶91.9%（P=0.205）。在进行1∶2倾向评分匹配后,两组的EFS率为100%∶85.7%（P=0.056）,MFS率为100%∶92.2%（P=0.209）。化疗组及对照组患者2级及以上的泌尿系统不良反应发生率分别为2.6%∶7.2%（P=0.354）,2级及以上的直肠不良反应发生率为5.3%∶5.1%（P=0.711）。化疗组患者3级及以上化疗相关不良反应为白细胞减少（31.6%）、血小板减少（2.6%）以及脱发（13.2%）。结论高度恶性前列腺癌在标准根治性治疗后增加辅助化疗有改善患者总EFS的趋势,且不良反应可耐受,期待长期随访结果证实。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	马茗微
	唐琦
	高献书
	虞巍
	李洪振
	孙明霞
	杨恺惟
	李晓颖
	亓昕
	陈佳琰
	任雪盈

关键词 ：前列腺肿瘤,高度恶性, 放射疗法, 前列腺癌根治术, 化学疗法, Gleason评分

Abstract：Objective To compare the efficacy and safety of standard treatment with or without adjuvant chemotherapy in patients with highly malignant non‐metastatic prostate cancer. Methods In this prospective non-randomized controlled study, consecutive non‐metastatic prostate cancer patients with pathologically proven Gleason score of 9‐10 or Gleason score of 5 admitted to Peking University First Hospital were enrolled. Four to six cycles of chemotherapy using docetaxel ± carboplatin regimen were added or not after standard radical therapy. The primary end point was 5‐year event‐free survival (EFS), and the secondary end points were distant metastasis‐free survival (MFS), overall survival (OS), and treatment‐related adverse events. The survival curve was drawn by Kaplan-Meier method. The differences between two groups were analyzed by log-rank test. Results A total of 176 patients were consecutively enrolled from November 2019 to January 2022 of which 138 patients received only standard radical therapy (control group), and 38 patients received adjuvant chemotherapy after standard radical therapy (chemotherapy group). The median follow‐up time was 13.4 (2.0‐34.0) months. All patients survived. The 30‐month EFS rates in the chemotherapy and control groups were 100% and 85.6%, respectively (P=0.064). There were no events in the chemotherapy group, while there were 12 cases of events in the control group, including 6 cases of biochemical recurrence and 6 cases of imaging progression. The 30‐month MFS rates in two groups were 100% and 91.9%, respectively (P=0.205). After the 1 vs. 2 propensity score matching, the EFS and MFS rates in two groups were 100% vs. 85.7% (P=0.056), and 100% vs. 92.2% (P=0.209), respectively. The incidence rates of grade 2 and above urinary toxicity in the chemotherapy and control groups were 2.6% and 7.2% (P=0.354), respectively. The incidence rates of grade 2 and above rectal toxicity were 5.3% and 5.1% (P=0.711), respectively. Grade 3 and above chemotherapy‐related toxicity in the chemotherapy group were leukopenia (31.6%), thrombocytopenia (2.6%) and alopecia (13.2%). Conclusion The addition of adjuvant chemotherapy after standard radical therapy tends to improve the overall EFS of patients with highly malignant prostate cancer, and the adverse effects are tolerable, which should be confirmed by long‐term follow‐up results.

Key words： Prostatic neoplasms,highly malignant Radiotherapy Radical prostatectomy Chemotherapy Gleason score

收稿日期: 2022-09-09

基金资助:中央高校基本科研业务费专项资金/北京大学青年科技创新培育基金（BMU2021PYB 026）; 中央高水平医院临床科研业务费资助（北京大学第一医院青年临床研究专项基金）（2022 CR109）

通讯作者: 高献书,Email：doctorgaoxs@126.com;虞巍,Email：yuweif@126.com

作者简介: 马茗微、唐琦对本文有同等贡献

引用本文:

马茗微,唐琦,高献书等. 高度恶性前列腺癌根治治疗加化疗非随机对照研究中期分析[J]. 中华放射肿瘤学杂志, 2023, 32(3): 229-234.

Ma Mingwei,Tang Qi,Gao Xianshu et al. Radical therapy with or without chemotherapy in highly malignant non‐metastatic prostate cancer: interim analysis of a prospective non-randomized controlled study[J]. Chinese Journal of Radiation Oncology, 2023, 32(3): 229-234.

链接本文:

http://journal12.magtechjournal.com/Jweb_fszlx/CN/10.3760/cma.j.cn113030-20220909-00302 或 http://journal12.magtechjournal.com/Jweb_fszlx/CN/Y2023/V32/I3/229

[1] Sweeney CJ, Chen YH, Carducci M, et al.Chemohormonal therapy in metastatic hormone-sensitive prostate cancer[J]. N Engl J Med, 2015,373(8):737-746. DOI: 10.1056/NEJMoa1503747.
[2] 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. DOI: 10.1016/S0140-6736(15)01037-5.
[3] D'Amico AV, Xie W, McMahon E, et al. Radiation and androgen deprivation therapy with or without docetaxel in the management of nonmetastatic unfavorable-risk prostate cancer: a prospective randomized trial[J]. J Clin Oncol, 2021,39(26):2938-2947. DOI: 10.1200/JCO.21.00596.
[4] Gleason DF, Mellinger GT.Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging[J]. J Urol, 1974,111(1):58-64. DOI: 10.1016/s0022-5347(17)59889-4.
[5] He J, Albertsen PC, Moore D, et al.Validation of a contemporary five-tiered Gleason grade grouping using population-based data[J]. Eur Urol, 2017,71(5):760-763. DOI: 10.1016/j.eururo.2016.11.031.
[6] Jackson W, Hamstra DA, Johnson S, et al.Gleason pattern 5 is the strongest pathologic predictor of recurrence, metastasis, and prostate cancer-specific death in patients receiving salvage radiation therapy following radical prostatectomy[J]. Cancer, 2013,119(18):3287-3294. DOI: 10.1002/cncr.28215.
[7] Koloff ZB, Hamstra DA, Wei JT, et al.Impact of tertiary Gleason pattern 5 on prostate cancer aggressiveness: lessons from a contemporary single institution radical prostatectomy series[J]. Asian J Urol, 2015,2(1):53-58. DOI: 10.1016/j.ajur.2015.04.007.
[8] Kato M, Hirakawa A, Kobayashi Y, et al.Integrating tertiary Gleason pattern 5 into the ISUP grading system improves prediction of biochemical recurrence in radical prostatectomy patients[J]. Mod Pathol, 2019,32(1):122-127. DOI: 10.1038/s41379-018-0121-8.
[9] Ma MW, Gao XS, Lyu F, et al.Development of a nomogram predicting metastatic disease and the assessment of NCCN, AUA and EAU guideline recommendations for bone imaging in prostate cancer patients[J]. World J Urol, 2021,39(6):1815-1823. DOI: 10.1007/s00345-020-03363-0.
[10] Yang DD, Mahal BA, Muralidhar V, et al.Androgen deprivation therapy and overall survival for Gleason 8 versus Gleason 9-10 prostate cancer[J]. Eur Urol, 2019,75(1):35-41. DOI: 10.1016/j.eururo.2018.08.033.
[11] Epstein JI, Amin MB, Reuter VE, et al.Contemporary Gleason grading of prostatic carcinoma: an update with discussion on practical issues to implement the 2014 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma[J]. Am J Surg Pathol, 2017,41(4):e1-e7. DOI: 10.1097/PAS.0000000000000820.
[12] Parker CC, Clarke NW, Cook AD, et al.Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial[J]. Lancet, 2020,396(10260):1413-1421. DOI: 10.1016/S0140-6736(20)31553-1.
[13] Kneebone A, Fraser-Browne C, Duchesne GM, et al.Adjuvant radiotherapy versus early salvage radiotherapy following radical prostatectomy (TROG 08.03/ANZUP RAVES): a randomised, controlled, phase 3, non-inferiority trial[J]. Lancet Oncol, 2020,21(10):1331-1340. DOI: 10.1016/S1470-2045(20)30456-3.
[14] Sargos P, Chabaud S, Latorzeff I, et al.Adjuvant radiotherapy versus early salvage radiotherapy plus short-term androgen deprivation therapy in men with localised prostate cancer after radical prostatectomy (GETUG-AFU 17): a randomised, phase 3 trial[J]. Lancet Oncol, 2020,21(10):1341-1352. DOI: 10.1016/S1470-2045(20)30454-X.
[15] Morris MJ, Mota JM, Lacuna K, et al.Phase 3 randomized controlled trial of androgen deprivation therapy with or without docetaxel in high-risk biochemically recurrent prostate cancer after surgery (TAX3503)[J]. Eur Urol Oncol, 2021,4(4):543-552. DOI: 10.1016/j.euo.2021.04.008.
[16] 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. DOI: 10.1016/S1470-2045(15)00011-X.
[17] Fizazi K, Carmel A, Joly F, et al. Updated results of GETUG-12, a phase III trial of docetaxel-based chemotherapy in high-risk localized prostate cancer, with a 12-year follow-up[J]. Ann Oncol, 2018, 29(suppl_8): VIII271. DOI: 10.1093/annonc/mdy284.
[18] Kellokumpu-Lehtinen PL, Hjälm-Eriksson M, Åström LM. A randomised phase III trial between adjuvant docetaxel and surviellance after radiacal radiotherapy for intermediate and high-risk prostate cancer: results of SPCG-13 trial[J]. J Clin Oncol, 2018(suppl): abstr 5000.
[19] Babcook MA, Akgul M, Margevicius S, et al.Ser-486/491 phosphorylation and inhibition of AMPKα activity is positively associated with Gleason score, metastasis, and castration-resistance in prostate cancer: a retrospective clinical study[J]. Prostate, 2018,78(10):714-723. DOI: 10.1002/pros.23515.
[20] 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. DOI: 10.1200/JCO.2017.75.3657.
[21] Bazan JG, Luxton G, Mok EC, et al.Normal tissue complication probability modeling of acute hematologic toxicity in patients treated with intensity-modulated radiation therapy for squamous cell carcinoma of the anal canal[J]. Int J Radiat Oncol Biol Phys, 2012,84(3):700-706. DOI: 10.1016/j.ijrobp.2011.12.072.
[22] Rosenthal SA, Hu C, Sartor O, et al.Effect of chemotherapy with docetaxel with androgen suppression and radiotherapy for localized high-risk prostate cancer: the randomized phase III NRG oncology RTOG 0521 trial[J]. J Clin Oncol, 2019,37(14):1159-1168. DOI: 10.1200/JCO.18.02158.