局部进展期直肠癌新辅助治疗后病理完全缓解的预测因素

doi:10.16139/j.1007-9610.2025.01.09

摘要/Abstract

摘要：

目的： 分析接受新辅助放化疗（nCRT）后行腹腔镜直肠癌根治术的病人中实现病理完全缓解（pCR）的肿瘤特征以及肿瘤预后情况。方法： 回顾性收集2017年1月至2024年1月在仁济医院接受nCRT治疗的局部进展期直肠癌（LARC）病人的临床病理资料。分析影响实现pCR的因素，并比较pCR组与non-pCR组病人预后情况。结果： 单因素分析、多因素Logistic回归分析以及受试者工作特征（ROC）曲线分析显示，肿瘤长径<5 cm（截断值为5.24 cm）和基线癌胚抗原(CEA)<5 μg/L（截断值为5.33 μg/L）是nCRT后实现pCR的独立预测因素。预后生存分析表明，pCR组和non-pCR组的3年总生存（OS）率分别为92.86%和82.46%（P=0.193)，3年无病生存（DFS）率分别为85.71%和70.18%（P=0.141)，差异均无统计学意义。结论： 肿瘤长径以及基线CEA可作为LARC病人nCRT后实现pCR的独立预测因素。此外，pCR组3年OS和DFS与non-pCR组差异无统计学意义。

关键词: 局部进展期直肠癌, 新辅助放化疗, 病理完全缓解, 观察与等待, 预后

Abstract:

Objective To analyze the tumor characteristics associated with achieving pathological complete response(pCR) and tumor prognosis in the patients undergoing laparoscopic rectal cancer surgery after neoadjuvant chemoradiotherapy(nCRT). Methods A retrospective review was conducted on clinical and pathological data of locally advanced rectal cancer(LARC) patients who underwent nCRT at Renji Hospital from January 2017 to January 2024. Factors influencing the achievement of pCR were analyzed, and the patients prognosis of pCR group and non-pCR group was compared. Results Univariate analysis, multivariate Logistic regression analysis, and receiver operating characteristic (ROC) curve analysis showed that tumor length less than 5 cm(cutoff value 5.24 cm) and baseline carcinoembryonic antigen(CEA) less than 5 μg/L(cutoff value 5.33 μg/L) were independent predictors of achieving pCR after nCRT in LARC patients. Prognostic survival analysis showed that the 3-year overall survival(OS) rate for pCR group and non-pCR group were 92.86% and 82.46%, respectively (P=0.193), and the 3-year disease-free survival (DFS) rate were 85.71% and 70.18%, respectively (P=0.141), with no statistically significant differences between the two groups. Conclusions Tumor length and baseline CEA level are independent predictors for achieving pCR after nCRT in LARC patients. Additionally, there were no statistically significant differences in 3-year OS and DFS between pCR group and non-pCR group.

Key words: Locally advanced rectal cancer(LARC), Neoadjuvant chemoradiotherapy(nCRT), Pathological complete response(pCR), Watch and wait(W&W), Prognosis

中图分类号:

R735.37

李浩, 骆洋, 王廷峰, 林海萍, 贡婷月, 赵永恒, 钟鸣. 局部进展期直肠癌新辅助治疗后病理完全缓解的预测因素[J]. 外科理论与实践, 2025, 30(01): 47-53.

LI Hao, LUO Yang, WANG Tingfeng, LIN Haiping, GONG Tingyue, ZHAO Yongheng, ZHONG Ming. Predictive factors of pathological complete response after neoadjuvant therapy for locally advanced rectal cancer[J]. Journal of Surgery Concepts & Practice, 2025, 30(01): 47-53.

图/表 4

表1

表2

图1

图2

参考文献 28

[1]	ARNOLD M, SIERRA M S, LAVERSANNE M, et al. Global patterns and trends in colorectal cancer incidence and mortality[J]. Gut, 2017, 66(4):683-691. doi: 10.1136/gutjnl-2015-310912 pmid: 26818619
[2]	元玫雯, 王宏昊, 段如菲, 等. 2016年中国归因于人乳头瘤病毒感染的肿瘤发病与死亡分析[J]. 中华流行病学杂志, 2022, 43(5):702-708.
	YUAN M W, WANG H H, DUAN R F, et al. [Analysis on cancer incidence and mortality attributed to human papillomavirus infection in China, 2016][J]. Chin J Epidemiol, 2022, 43(5):702-708. doi: 10.3760/cma.j.cn112338-20211010-00777 pmid: 35589576
[3]	国家卫生健康委员会医政司, 中华医学会肿瘤学分会. 国家卫健委中国结直肠癌诊疗规范(2023版)[J]. 中国实用外科杂志, 2023, 43(6):602-630.
	Department of Medical Administration, National Health Comimission; Chinese Society of Oncology. Chinese protocol of diagnosis and treatment of colorectal cancer of the National Health Commission(2023 edition)[J]. Chin J Pract Surg, 2023, 43(6):602-630.
[4]	PARK I J, YOU Y N, AGARWAL A, et al. Neoadjuvant treatment response as an early response indicator for patients with rectal cancer[J]. J Clin Oncol, 2012, 30(15):1770-1776. doi: 10.1200/JCO.2011.39.7901 pmid: 22493423
[5]	MAAS M, NELEMANS P J, VALENTINI V, et al. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data[J]. Lancet Oncol, 2010, 11(9):835-844. doi: 10.1016/S1470-2045(10)70172-8 pmid: 20692872
[6]	ARBMAN G, NILSSON E, HALLBÖÖK O, et al. Local recurrence following total mesorectal excision for rectal cancer[J]. Br J Surg, 1996, 83(3):375-379.
[7]	PAUN B C, CASSIE S, MACLEAN A R, et al. Postoperative complications following surgery for rectal cancer[J]. Ann Surg, 2010, 251(5):807-818. doi: 10.1097/SLA.0b013e3181dae4ed pmid: 20395841
[8]	GRASS J K, PERSIANI R, TIRELLI F, et al. Robotic versus transanal total mesorectal excision in sexual, anorectal, and urinary function: a multicenter, prospective, observational study[J]. Int J Colorectal Dis, 2021, 36(12):2749-2761.
[9]	CELENTANO V, COHEN R, WARUSAVITARNE J, et al. Sexual dysfunction following rectal cancer surgery[J]. Int J Colorectal Dis, 2017, 32(11):1523-1530. doi: 10.1007/s00384-017-2826-4 pmid: 28497404
[10]	LI Y, WANG J, MA X, et al. A review of neoadjuvant chemoradiotherapy for locally advanced rectal cancer[J]. Int J Biol Sci, 2016, 12(8):1022-1031. doi: 10.7150/ijbs.15438 pmid: 27489505
[11]	HABR-GAMA A, SÃO JULIÃO G P, GAMA-RODRIGUES J, et al. Baseline T classification predicts early tumor regrowth after nonoperative management in distal rectal cancer after extended neoadjuvant chemoradiation and initial complete clinical response[J]. Dis Colon Rectum, 2017, 60(6):586-594.
[12]	SANGHERA P, WONG D W, MCCONKEY C C, et al. Chemoradiotherapy for rectal cancer: an updated analysis of factors affecting pathological response[J]. Clin Oncol (R Coll Radiol), 2008, 20(2):176-183.
[13]	SHIN J K, HUH J W, LEE W Y, et al. Clinical prediction model of pathological response following neoadjuvant chemoradiotherapy for rectal cancer[J]. Sci Rep, 2022, 12(1):7145. doi: 10.1038/s41598-022-10974-7 pmid: 35504888
[14]	李金娜, 谢凤, 王颖. 局部进展期直肠癌新辅助化疗后病理完全缓解及肿瘤降期的预测因素分析[J]. 现代肿瘤医学, 2021, 29(18):3246-3251.
	LI J N, XIE F, WANG Y. Predictive factors associated with pathologic complete response and tumor downstaging after neoadjuvant chemotherapy in locally advanced rectal cancer[J]. J Mod Oncol, 2021, 29(18):3246-3251.
[15]	MOUREAU-ZABOTTO L, FARNAULT B, DE CHAISEMARTIN C, et al. Predictive factors of tumor response after neoadjuvant chemoradiation for locally advanced rectal cancer[J]. Int J Radiat Oncol Biol Phys, 2011, 80(2):483-491.
[16]	HUANG Y, LEE D, YOUNG C. Predictors for complete pathological response for stage Ⅱ and Ⅲ rectal cancer following neoadjuvant therapy - a systematic review and meta-analysis[J]. Am J Surg, 2020, 220(2):300-308.
[17]	YAN H, WANG R, ZHU K, et al. Predictors of sensitivity to preoperative chemoradiotherapy of rectal adenocarcinoma[J]. Tumori, 2011, 97(6):717-723. doi: 10.1700/1018.11087 pmid: 22322837
[18]	DAS P, SKIBBER J M, RODRIGUEZ-BIGAS M A, et al. Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer[J]. Cancer, 2007, 109(9):1750-1755. doi: 10.1002/cncr.22625 pmid: 17387743
[19]	YANG K L, YANG S H, LIANG W Y, et al. Carcinoembryonic antigen (CEA) level, CEA ratio, and treatment outcome of rectal cancer patients receiving pre-operative chemoradiation and surgery[J]. Radiat Oncol, 2013,8:43.
[20]	YEO S G, KIM D Y, CHANG H J, et al. Reappraisal of pretreatment carcinoembryonic antigen in patients with rectal cancer receiving preoperative chemoradiotherapy[J]. Tumori, 2013, 99(1):93-99.
[21]	KANG J H, KIM Y C, KIM H, et al. Tumor volume changes assessed by three-dimensional magnetic resonance volumetry in rectal cancer patients after preoperative chemoradiation: the impact of the volume reduction ratio on the prediction of pathologic complete response[J]. Int J Radiat Oncol Biol Phys, 2010, 76(4):1018-1025.
[22]	HUH J W, KIM H R, KIM Y J. Clinical prediction of pathological complete response after preoperative chemoradiotherapy for rectal cancer[J]. Dis Colon Rectum, 2013, 56(6):698-703. doi: 10.1097/DCR.0b013e3182837e5b pmid: 23652742
[23]	HIOTIS S P, WEBER S M, COHEN A M, et al. Assessing the predictive value of clinical complete response to neoadjuvant therapy for rectal cancer: an analysis of 488 patients[J]. J Am Coll Surg, 2002, 194(2):131-135;discussion135-136.
[24]	GUILLEM J G, CHESSIN D B, SHIA J, et al. Clinical examination following preoperative chemoradiation for rectal cancer is not a reliable surrogate end point[J]. J Clin Oncol, 2005, 23(15):3475-3479. pmid: 15908656
[25]	HABR-GAMA A, SÃO JULIÃO G P, VAILATI B B, et al. Organ preservation in cT2N0 rectal cancer after neoadjuvant chemoradiation therapy: the impact of radiation therapy dose-escalation and consolidation chemotherapy[J]. Ann Surg, 2019, 269(1):102-107.
[26]	HABR-GAMA A, PEREZ R O, NADALIN W, et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results[J]. Ann Surg, 2004, 240(4):711-717;discussion717-718.
[27]	MAAS M, BEETS-TAN R G, LAMBREGTS D M, et al. Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer[J]. J Clin Oncol, 2011, 29(35):4633-4640. doi: 10.1200/JCO.2011.37.7176 pmid: 22067400
[28]	中国直肠癌新辅助治疗后等待观察数据库研究协作组, 中国医师协会外科医师分会中国医师协会肛肠医师分会, 中华医学会外科学分会结直肠外科学组, 等. 直肠癌新辅助治疗后等待观察策略专家共识(2020版)[J]. 中华胃肠外科杂志, 2020, 23(1):1-9.
	Chinese Watch & Wait Database Research Cooperation Group(CWWD); Chinese Association of Surgeons, Chinese Society of Coloproctology, Chinese Medical Doctor Association; Chinese Society of Colorectal Surgery, Chinese Medical Association, et al. [Consensus on the Watch and Wait policy in rectal cancer patients after neoadjuvant treatment (2020 version)][J]. Chin J Gastrointest Surg, 2020, 23(1):1-9.

Characteristics	Total(n=131)	pCR (n=24)	Non-pCR (n=107)	P value
Age (years)				0.154
<60	54 (41.22)	13 (54.17)	41 (38.32)
≥60	77 (58.78)	11 (45.83)	66 (61.68)
Gender				0.088
Male	104 (79.39)	16 (66.67)	88 (82.24)
Female	27 (20.61)	8 (33.33)	19 (17.76)
BMI(kg/m²)				0.303
<24	103 (78.63)	17 (70.83)	86 (80.37)
≥24	28 (21.37)	7 (29.17)	21 (19.63)
Baseline T stage				0.673
T3	55 (41.98)	11 (45.83)	44 (41.12)
T4	76 (58.02)	13 (54.17)	63 (58.88)
Baseline N stage				0.895
N0	23 (17.56)	5 (20.83)	18 (16.82)
N1	29 (22.14)	5 (20.83)	24 (22.43)
N3	79 (60.31)	14 (58.33)	65 (60.75)
Distance between tumor and anal border (cm)				0.111
<5	47 (35.88)	12 (50.00)	35 (32.71)
≥5	84 (64.12)	12 (50.00)	72 (67.29)
Tumor length (cm)				0.015
<5	58 (44.27)	16 (66.67)	42 (39.25)
≥5	73 (55.73)	8 (33.33)	65 (60.75)
Proportion of tumor in enteric cavity				0.049
≤1/2	48 (36.64)	13 (54.17)	35 (32.71)
>1/2	83 (63.36)	11 (45.83)	72 (67.29)
Baseline CEA level (μg/L)				0.024
<5	55 (41.98)	15 (62.50)	40 (37.38)
≥5	76 (58.02)	9 (37.50)	67 (62.62)
Baseline CA19-9 level (kU/L)				0.280
<27	73 (55.73)	11 (45.83)	62 (57.94)
≥27	58 (44.27)	13 (54.17)	45 (42.06)
Preoperative CEA level (μg/L)				0.077
<5	99 (75.57)	22 (91.67)	77 (71.76)
≥5	32 (24.43)	2 (8.33)	30 (28.04)
Preoperative CA19-9 level (kU/L)				0.205
<27	114 (87.02)	19 (79.17)	95 (88.79)
≥27	17 (12.98)	5 (20.83)	12 (11.21)
Operation				0.942
Low anterior resection	99 (75.57)	18 (75.00)	81 (75.70)
Abdominoperineal resection	32 (24.43)	6 (25.00)	26 (24.30)
Degree of differentiation				0.387
Poorly	19 (14.50)	4 (16.67)	15 (14.02)
Moderately	95 (72.52)	15 (62.50)	80 (74.77)
Well	17 (12.98)	5 (20.83)	12 (11.21)

	β	SE	Wald	P value	OR（95%CI）
Tumor length(cm)	0.529	0.265 9	3.955	0.047	0.347(0.122-0.985)
Proportion of tumor in enteric cavity	0.167	0.259 6	0.411	0.521	0.717(0.259-1.983)
Baseline CEA level (μg/L)	0.520	0.244 0	4.549	0.033	0.353(0.136-0.919)