Exploration of the preponderant population for primary tumor resection of asymptomatic metastatic colorectal cancer

doi:10.3760/cma.j.cn371439-20220726-00143

Abstract

Abstract:

Objective To explore the population who benefit from primary tumor resection （PTR） of asymptomatic metastatic colorectal cancer （mCRC）. Methods The clinicopathological data of 121 patients with asymptomatic mCRC with unresectable liver metastases treated in the First Affiliated Hospital of Yangtze University from January 2014 to January 2019 were retrospectively analyzed. Kaplan-Meier method was used to draw the survival curve accompanied with log-rank test. Cox regression model was used to analyze the prognostic factors. Results The median overall survival （OS） of 121 mCRC patients was 20 months, and the 3- and 5-year survival rates were 34.71% and 10.74%. The median OS of PTR and non-PTR patients were 21 months and 18 months respectively, with no statistically significant difference （χ²=0.79, P=0.375）. In 65 mCRC patients received targeted therapy, the median OS of PTR and non-PTR patients were 25 months and 28 months respectively, with no statistically significant difference （χ²=1.65, P=0.199）. In 84 patients with mCRC of the left colon and rectum, the median OS of PTR and non-PTR patients were 24 months and 18 months respectively, with a statistically significant difference （χ²=4.25, P=0.039）. In 37 patients with mCRC of the right colon, the median OS of PTR and non-PTR patients were 19 months and 17 months respectively, with no statistically significant difference （χ²=0.18, P=0.675）. In 64 mCRC patients who received liver local treatment, the median OS of PTR and non-PTR patients were 36 months and 17 months respectively, with a statistically significant difference （χ²=12.60, P<0.001）. In 57 mCRC patients who did not receive liver local treatment, the median OS of PTR and non-PTR patients were 15 months and 17 months respectively, with no significant difference （χ²=0.58, P=0.445）. Univariate analysis showed that the location of the primary tumor （HR=0.51, 95%CI: 0.25-0.76, P=0.025）, the degree of differentiation （HR=1.46, 95%CI: 1.13-9.45, P=0.004）, the maximum diameter of the liver metastases （HR=1.86, 95%CI: 1.35-4.60, P=0.012）, the level of serum carcinoembryonic antigen （HR=3.55, 95%CI: 2.55-8.45, P<0.001）, local treatment of liver metastases （HR=0.35, 95%CI: 0.19-0.93, P<0.001） were influencing factors for OS of asymptomatic mCRC patients with unresectable liver metastases. Multivariate analysis showed that the primary sites of the left colon and rectum （HR=0.43, 95%CI: 0.25-0.93, P=0.039）, local treatment of liver metastases （HR=0.78, 95%CI: 0.27-0.86, P<0.001） were independent influencing factors for OS of asymptomatic mCRC patients with unresectable liver metastases. Conclusion Asymptomatic mCRC patients with unresectable liver metastases with primary sites of the left colon and rectum and local treatment of liver metastases can benefit from PTR.

Key words: Colorectal neoplasms, Surgical procedures, operative, Liver metastases, Primary tumor

Zeng Hai, Zhang Weijia, Wang Qian, Zhang Fan, Li Shuang. Exploration of the preponderant population for primary tumor resection of asymptomatic metastatic colorectal cancer[J]. Journal of International Oncology, 2022, 49(12): 729-734.

Figures/Tables 9

References 22

[1]	Li N, Lu B, Luo C, et al. Incidence, mortality, survival, risk factor and screening of colorectal cancer: a comparison among China, Europe, and Northern America[J]. Cancer Lett, 2021, 522: 255-268. DOI: 10.1016/j.canlet.2021.09.034. doi: 10.1016/j.canlet.2021.09.034 pmid: 34563640
[2]	Baldin P, van den Eynde M, Mlecnik B, et al. Prognostic assessment of resected colorectal liver metastases integrating pathological features, RAS mutation and immunoscore[J]. J Pathol Clin Res, 2021, 7(1): 27-41. DOI: 10.1002/cjp2.178. doi: 10.1002/cjp2.178
[3]	Kanemitsu Y, Shitara K, Mizusawa J, et al. Primary tumor resection plus chemotherapy versus chemotherapy alone for colorectal cancer patients with asymptomatic, synchronous unresectable metastases (JCOG1007; iPACS): a randomized clinical trial[J]. J Clin Oncol, 2021, 39(10): 1098-1107. DOI: 10.1200/JCO.20.02447. doi: 10.1200/JCO.20.02447 pmid: 33560877
[4]	Yao YC, Chen JQ, Yin L, et al. Primary tumor resection with or without metastasectomy for left- and right-sided stage Ⅳ colorectal cancer: an instrumental variable analysis[J]. BMC Gastroenterol, 2022, 22(1): 114. DOI: 10.1186/s12876-022-02184-2. doi: 10.1186/s12876-022-02184-2 pmid: 35264117
[5]	Cao G, Zhou W, Chen E, et al. A novel scoring system predicting survival benefits of palliative primary tumor resection for patients with unresectable metastatic colorectal cancer: a retrospective cohort study protocol[J]. Medicine (Baltimore), 2019, 98(37): e17178. DOI: 10.1097/MD.0000000000017178. doi: 10.1097/MD.0000000000017178
[6]	王战立, 陈勇, 徐永超, 等. 转移灶无法切除的无症状转移性结肠癌治疗方法的探讨[J]. 中国急救医学, 2015, 35(< W>12 Suppl): 303-304. DOI: 10.3969/j.issn.1002-1949.2015.z2.193. doi: 10.3969/j.issn.1002-1949.2015.z2.193
[7]	侯丁丁, 秦春和, 杨国山, 等. 腹腔镜下原发灶切除术在转移性结直肠癌中的应用[J]. 腹腔镜外科杂志, 2022, 27(5): 348-352. DOI: 10.13499/j.cnki.fqjwkzz.2022.05.348. doi: 10.13499/j.cnki.fqjwkzz.2022.05.348
[8]	Nitzkorski JR, Farma JM, Watson JC, et al. Outcome and natural history of patients with stage Ⅳ colorectal cancer receiving chemotherapy without primary tumor resection[J]. Ann Surg Oncol, 2012, 19(2): 379-383. DOI: 10.1245/s10434-011-2028-1. doi: 10.1245/s10434-011-2028-1 pmid: 21861213
[9]	Seo GJ, Park JW, Yoo SB, et al. Intestinal complications after palliative treatment for asymptomatic patients with unresectable stage Ⅳ colorectal cancer[J]. J Surg Oncol, 2010, 102(1): 94-99. DOI: 10.1002/jso.21577. doi: 10.1002/jso.21577
[10]	Park EJ, Baek JH, Choi GS, et al. The role of primary tumor rese-ction in colorectal cancer patients with asymptomatic, synchronous, unresectable metastasis: a multicenter randomized controlled trial[J]. Cancers (Basel), 2020, 12(8): 2306. DOI: 10.3390/cancers12082306. doi: 10.3390/cancers12082306
[11]	翟升永, 孙晓静, 钟晓东, 等. 手术治疗对于同时性结直肠癌肝转移预后的影响[J]. 中华普通外科杂志, 2018, 33(11): 915-919. DOI: 10.3760/cma.j.issn.1007-631X.2018.11.006. doi: 10.3760/cma.j.issn.1007-631X.2018.11.006
[12]	Chen X, Hu W, Huang C, et al. Survival outcome of palliative primary tumor resection for colorectal cancer patients with synchronous liver and/or lung metastases: a retrospective cohort study in the SEER database by propensity score matching analysis[J]. Int J Surg, 2020, 80: 135-152. DOI: 10.1016/j.ijsu.2020.06.024. doi: S1743-9191(20)30506-9 pmid: 32634480
[13]	Doah KY, Shin US, Jeon BH, et al. The impact of primary tumor resection on survival in asymptomatic colorectal cancer patients with unresectable metastases[J]. Ann Coloproctol, 2021, 37(2): 94-100. DOI: 10.3393/ac.2020.09.15.1. doi: 10.3393/ac.2020.09.15.1 pmid: 33979907
[14]	Zhang RX, Ma WJ, Gu YT, et al. Primary tumor location as a predictor of the benefit of palliative resection for colorectal cancer with unresectable metastasis[J]. World J Surg Oncol, 2017, 15(1): 138. DOI: 10.1186/s12957-017-1198-0. doi: 10.1186/s12957-017-1198-0
[15]	Arnold D, Lueza B, Douillard JY, et al. Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials[J]. Ann Oncol, 2017, 28(8): 1713-1729. DOI: 10.1093/annonc/mdx175. doi: 10.1093/annonc/mdx175 pmid: 28407110
[16]	Brouwer NPM, van der Kruijssen DEW, Hugen N, et al. The impact of primary tumor location in synchronous metastatic colorectal cancer: differences in metastatic sites and survival[J]. Ann Surg Oncol, 2020, 27(5): 1580-1588. DOI: 10.1245/s10434-019-08100-5. doi: 10.1245/s10434-019-08100-5 pmid: 31792717
[17]	van der Kruijssen DEW, Brouwer NPM, van der Kuil AJS, et al. Interaction between primary tumor resection, primary tumor location, and survival in synchronous metastatic colorectal cancer: a population-based study[J]. Am J Clin Oncol, 2021, 44(7): 315-324. DOI: 10.1097/COC.0000000000000823. doi: 10.1097/COC.0000000000000823
[18]	Nunes L, Aasebø K, Mathot L, et al. Molecular characterization of a large unselected cohort of metastatic colorectal cancers in relation to primary tumor location, rare metastatic sites and prognosis[J]. Acta Oncol, 2020, 59(4): 417-426. DOI: 10.1080/0284186X.2019.1711169. doi: 10.1080/0284186X.2019.1711169 pmid: 31924107
[19]	Stewart CL, Warner S, Ito K, et al. Cytoreduction for colorectal metastases: liver, lung, peritoneum, lymph nodes, bone, brain. When does it palliate, prolong survival, and potentially cure?[J]. Curr Probl Surg, 2018, 55(9): 330-379. DOI: 10.1067/j.cpsurg.2018.08.004. doi: 10.1067/j.cpsurg.2018.08.004
[20]	Holch JW, Ricard I, Stintzing S, et al. The relevance of primary tumour location in patients with metastatic colorectal cancer: a meta-analysis of first-line clinical trials[J]. Eur J Cancer, 2017, 70: 87-98. DOI: 10.1016/j.ejca.2016.10.007. doi: S0959-8049(16)32490-X pmid: 27907852
[21]	Ruers T, Van Coevorden F, Punt CJ, et al. Local treatment of unresectable colorectal liver metastases: results of a randomized phase Ⅱ trial[J]. J Natl Cancer Inst, 2017, 109(9): djx015. DOI: 10.1093/jnci/djx015. doi: 10.1093/jnci/djx015
[22]	Yu J, Kim DH, Lee J, et al. Radiofrequency ablation versus stere-otactic body radiation therapy in the treatment of colorectal cancer liver metastases[J]. Cancer Res Treat, 2022, 54(3): 850-859. DOI: 10.4143/crt.2021.674. doi: 10.4143/crt.2021.674

一般临床特征	例数	百分比（%）
性别
男	79	65.30
女	42	34.70
年龄（岁）
≥60	71	58.70
<60	50	41.30
原发灶部位
左半结肠、直肠	84	69.40
右半结肠	37	30.60
原发灶T分期
T_1-2	18	14.88
T_3-4	103	85.12
N分期
N₀	58	47.93
N₊	63	52.07
分化程度
低分化	46	38.02
中-高分化	75	61.98
肝转移灶最大直径（cm）
≥5	54	44.62
<5	67	55.38
血清癌胚抗原（ng/ml）
≥200	31	25.62
<200	90	74.38
靶向治疗
是	65	53.70
否	56	46.30
肝转移灶局部治疗
是	64	52.90
否	57	47.10
原发灶切除与否
是	65	53.70
否	56	46.30

因素	HR值	95%CI	P值
性别（男/女）	1.76	0.12~4.36	0.862
年龄（≥60岁/<60岁）	1.12	0.79~5.12	0.549
原发灶部位（左半结肠、直肠/右半结肠）	0.51	0.25~0.76	0.025
原发灶T分期（T_1-2/T_3-4）	0.74	0.96~8.56	0.845
N分期（N₀/N₊）	0.73	0.95~4.23	0.104
分化程度（低分化/中-高分化）	1.46	1.13~9.45	0.004
肝转移灶最大直径（≥5 cm/<5 cm）	1.86	1.35~4.60	0.012
血清癌胚抗原（≥200 ng/ml/<200 ng/ml）	3.55	2.55~8.45	<0.001
靶向治疗（是/否）	0.95	0.64~3.14	0.406
肝转移灶局部治疗（是/否）	0.35	0.19~0.93	<0.001
原发灶切除（是/否）	0.96	0.49~2.51	0.380

因素	HR值	95%CI	P值
原发灶部位（左半结直肠/右半结肠）	0.43	0.25~0.93	0.039
分化程度（低分化/中-高风化）	1.72	0.94~2.53	0.732
肝转移灶最大直径（≥5 cm/<5 cm）	1.28	0.91~8.43	0.121
血清癌胚抗原（≥200 ng/ml/<200 ng/ml）	2.12	0.76~4.21	0.824
肝转移灶局部治疗（是/否）	0.78	0.27~0.86	<0.001