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Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Colorectal Cancer | Research

Combining perineural invasion with staging improve the prognostic accuracy in colorectal cancer: a retrospective cohort study

Authors: Bin Zhang, Yanyun Lin, Chao Wang, Zexian Chen, Tianze Huang, Hao Chen, Guannan Wang, Ping Lan, Xiaowen He, Xiaosheng He

Published in: BMC Cancer | Issue 1/2023

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Abstract

Background

Current guidelines only propose the importance of perineural invasion(PNI) on prognosis in stage II colon cancer. However, the prognostic value of PNI in other stages of colorectal cancer (CRC) is ambiguous.

Methods

This single-center retrospective cohort study included 3485 CRC patients who underwent primary colorectal resection between January 2013 and December 2016 at the Sixth Affiliated Hospital of Sun Yat-sen University. Associations of PNI with overall survival (OS) and disease-free survival (DFS) were evaluated using multivariable Cox proportional hazards regression models. In addition, interaction analyses were performed to explore the prognostic effects of PNI in different clinical subgroups.

Results

After median follow-up of 61.9 months, we found PNI was associated with poorer OS (adjusted hazard ratio [aHR], 1.290; 95% CI, 1.087–1.531) and DFS (aHR, 1.397; 95% CI, 1.207–1.617), irrespective of tumor stage. Interestingly, the weight of PNI was found second only to incomplete resection in the nomogram for risk factors of OS and DFS in stage II CRC patients. Moreover, OS and DFS were insignificantly different between stage II patients with PNI and stage III patients (both P > 0.05). PNI was found to be an independent prognostic factor of DFS in stage III CRC (aHR: 1.514; 95% CI, 1.211–1.892) as well. Finally, the adverse effect of PNI on OS was more significant in female, early-onset, and diabetes-negative patients than in their counterparts (interaction P = 0.0213, 0.0280, and 0.0186, respectively).

Conclusion

PNI was an important prognostic factor in CRC, more than in stage II. The survival of patients with stage II combined with perineural invasion is similar with those with stage III. PNI in stage III CRC also suggests a worse survival.
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Literature
1.
go back to reference Siegel RL, Miller KD, Fuchs HE, et al. Cancer Statistics, 2021. CA: Cancer J Clin. 2021;71(1):7–33. Siegel RL, Miller KD, Fuchs HE, et al. Cancer Statistics, 2021. CA: Cancer J Clin. 2021;71(1):7–33.
2.
go back to reference Xie Y, Shi L, He X, et al. Gastrointestinal cancers in China, the USA, and Europe. Gastroenterol Rep (Oxf). 2021;9(2):91–104.CrossRefPubMed Xie Y, Shi L, He X, et al. Gastrointestinal cancers in China, the USA, and Europe. Gastroenterol Rep (Oxf). 2021;9(2):91–104.CrossRefPubMed
3.
go back to reference Diagnosis, Treatment Guidelines For Colorectal Cancer Working Group C. Chinese Society of Clinical Oncology (CSCO) diagnosis and treatment guidelines for colorectal cancer 2018 (English version). Chin J Cancer Res. 2019;31(1):117–34. Diagnosis, Treatment Guidelines For Colorectal Cancer Working Group C. Chinese Society of Clinical Oncology (CSCO) diagnosis and treatment guidelines for colorectal cancer 2018 (English version). Chin J Cancer Res. 2019;31(1):117–34.
4.
go back to reference Gradishar WJ, Anderson BO, Balassanian R, et al. Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2021;19(3):329–59. Gradishar WJ, Anderson BO, Balassanian R, et al. Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2021;19(3):329–59.
5.
go back to reference Hu G, Li L, Hu K. Clinical implications of perineural invasion in patients with colorectal cancer. Medicine (Baltimore). 2020;99(17): e19860.CrossRefPubMed Hu G, Li L, Hu K. Clinical implications of perineural invasion in patients with colorectal cancer. Medicine (Baltimore). 2020;99(17): e19860.CrossRefPubMed
6.
go back to reference Liebig C, Ayala G, Wilks J, et al. Perineural invasion is an independent predictor of outcome in colorectal cancer. J Clin Oncol. 2009;27(31):5131–7.CrossRefPubMedPubMedCentral Liebig C, Ayala G, Wilks J, et al. Perineural invasion is an independent predictor of outcome in colorectal cancer. J Clin Oncol. 2009;27(31):5131–7.CrossRefPubMedPubMedCentral
7.
go back to reference Leijssen LGJ, Dinaux AM, Taylor MS, et al. Perineural invasion is a prognostic but not a predictive factor in nonmetastatic colon cancer. Dis Colon Rectum. 2019;62(10):1212–21.CrossRefPubMed Leijssen LGJ, Dinaux AM, Taylor MS, et al. Perineural invasion is a prognostic but not a predictive factor in nonmetastatic colon cancer. Dis Colon Rectum. 2019;62(10):1212–21.CrossRefPubMed
8.
go back to reference Guo JA, Hoffman HI, Shroff S, et al. Pan-cancer transcriptomic predictors of perineural invasion improve occult histopathological detection. Clin Cancer Res. 2021;27(10):2807–15. Guo JA, Hoffman HI, Shroff S, et al. Pan-cancer transcriptomic predictors of perineural invasion improve occult histopathological detection. Clin Cancer Res. 2021;27(10):2807–15.
10.
11.
go back to reference Amit M, Na’Ara S, Gil Z. Mechanisms of cancer dissemination along nerves. Nat Rev Cancer. 2016;16(6):399–408.CrossRefPubMed Amit M, Na’Ara S, Gil Z. Mechanisms of cancer dissemination along nerves. Nat Rev Cancer. 2016;16(6):399–408.CrossRefPubMed
12.
go back to reference van Wyk HC, Going J, Horgan P, et al. The role of perineural invasion in predicting survival in patients with primary operable colorectal cancer: a systematic review. Crit Rev Oncol Hematol. 2017;112:11–20.CrossRefPubMed van Wyk HC, Going J, Horgan P, et al. The role of perineural invasion in predicting survival in patients with primary operable colorectal cancer: a systematic review. Crit Rev Oncol Hematol. 2017;112:11–20.CrossRefPubMed
13.
go back to reference Cienfuegos JA, Martínez P, Baixauli J, et al. Perineural invasion is a major prognostic and predictive factor of response to adjuvant chemotherapy in stage I-II colon cancer. Ann Surg Oncol. 2017;24(4):1077–84.CrossRefPubMed Cienfuegos JA, Martínez P, Baixauli J, et al. Perineural invasion is a major prognostic and predictive factor of response to adjuvant chemotherapy in stage I-II colon cancer. Ann Surg Oncol. 2017;24(4):1077–84.CrossRefPubMed
14.
go back to reference Figueredo A, Charette ML, Maroun J, et al. Adjuvant therapy for stage II colon cancer: a systematic review from the Cancer Care Ontario Program in evidence-based care’s gastrointestinal cancer disease site group. J Clin Oncol. 2004;22(16):3395–407.CrossRefPubMed Figueredo A, Charette ML, Maroun J, et al. Adjuvant therapy for stage II colon cancer: a systematic review from the Cancer Care Ontario Program in evidence-based care’s gastrointestinal cancer disease site group. J Clin Oncol. 2004;22(16):3395–407.CrossRefPubMed
15.
go back to reference Al BBI, Schrag D, Somerfield MR, et al. American society of clinical oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 2004;22(16):3408–19.CrossRef Al BBI, Schrag D, Somerfield MR, et al. American society of clinical oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 2004;22(16):3408–19.CrossRef
16.
go back to reference Huang Y, He L, Dong D, et al. Individualized prediction of perineural invasion in colorectal cancer: development and validation of a radiomics prediction model. Chin J Cancer Res. 2018;30(1):40–50.CrossRefPubMedPubMedCentral Huang Y, He L, Dong D, et al. Individualized prediction of perineural invasion in colorectal cancer: development and validation of a radiomics prediction model. Chin J Cancer Res. 2018;30(1):40–50.CrossRefPubMedPubMedCentral
17.
go back to reference Alotaibi AM, Lee JL, Kim J, et al. Prognostic and oncologic significance of perineural invasion in sporadic colorectal cancer. Ann Surg Oncol. 2017;24(6):1626–34.CrossRefPubMed Alotaibi AM, Lee JL, Kim J, et al. Prognostic and oncologic significance of perineural invasion in sporadic colorectal cancer. Ann Surg Oncol. 2017;24(6):1626–34.CrossRefPubMed
18.
go back to reference Kinugasa T, Mizobe T, Shiraiwa S, et al. Perineural invasion is a prognostic factor and treatment indicator in patients with rectal cancer undergoing curative surgery: 2000–2011 data from a single-center study. Anticancer Res. 2017;37(7):3961–8.PubMed Kinugasa T, Mizobe T, Shiraiwa S, et al. Perineural invasion is a prognostic factor and treatment indicator in patients with rectal cancer undergoing curative surgery: 2000–2011 data from a single-center study. Anticancer Res. 2017;37(7):3961–8.PubMed
19.
go back to reference Kim YI, Kim CW, Kim JH, et al. Clinical implication of perineural and lymphovascular invasion in rectal cancer patients who underwent surgery after preoperative chemoradiotherapy. Dis Colon Rectum. 2022;65(11):1325–34.CrossRefPubMed Kim YI, Kim CW, Kim JH, et al. Clinical implication of perineural and lymphovascular invasion in rectal cancer patients who underwent surgery after preoperative chemoradiotherapy. Dis Colon Rectum. 2022;65(11):1325–34.CrossRefPubMed
20.
go back to reference Kang JH, Son IT, Kim BC, et al. Recurrence-free survival outcomes based on novel classification combining lymphovascular invasion, perineural invasion, and T4 status in stage II-III colon cancer. Cancer Manag Res. 2022;14:2031–40.CrossRefPubMedPubMedCentral Kang JH, Son IT, Kim BC, et al. Recurrence-free survival outcomes based on novel classification combining lymphovascular invasion, perineural invasion, and T4 status in stage II-III colon cancer. Cancer Manag Res. 2022;14:2031–40.CrossRefPubMedPubMedCentral
21.
go back to reference Fujisawa T, Shimamura T, Goto K, et al. A novel role of interleukin 13 receptor alpha2 in perineural invasion and its association with poor prognosis of patients with pancreatic ductal adenocarcinoma. Cancers. 2020;12(5):1294.CrossRefPubMedPubMedCentral Fujisawa T, Shimamura T, Goto K, et al. A novel role of interleukin 13 receptor alpha2 in perineural invasion and its association with poor prognosis of patients with pancreatic ductal adenocarcinoma. Cancers. 2020;12(5):1294.CrossRefPubMedPubMedCentral
22.
go back to reference Crippa S, Pergolini I, Javed AA, et al. Implications of perineural invasion on disease recurrence and survival after pancreatectomy for pancreatic head ductal adenocarcinoma. Ann Surg. 2020;276(2):378–85. Crippa S, Pergolini I, Javed AA, et al. Implications of perineural invasion on disease recurrence and survival after pancreatectomy for pancreatic head ductal adenocarcinoma. Ann Surg. 2020;276(2):378–85.
23.
go back to reference Brouwer N, Nagtegaal ID. Tumor deposits improve staging in colon cancer: what are the next steps? Ann Oncol. 2021;32(10):1209–11.CrossRefPubMed Brouwer N, Nagtegaal ID. Tumor deposits improve staging in colon cancer: what are the next steps? Ann Oncol. 2021;32(10):1209–11.CrossRefPubMed
24.
go back to reference Cohen R, Shi Q, Meyers J, et al. Combining tumor deposits with the number of lymph node metastases to improve the prognostic accuracy in stage III colon cancer: a post hoc analysis of the CALGB/SWOG 80702 phase III study (Alliance)(). Ann Oncol. 2021;32(10):1267–75.CrossRefPubMed Cohen R, Shi Q, Meyers J, et al. Combining tumor deposits with the number of lymph node metastases to improve the prognostic accuracy in stage III colon cancer: a post hoc analysis of the CALGB/SWOG 80702 phase III study (Alliance)(). Ann Oncol. 2021;32(10):1267–75.CrossRefPubMed
25.
go back to reference Liebig C, Ayala G, Wilks JA, et al. Perineural invasion in cancer: a review of the literature. Cancer. 2009;115(15):3379–91.CrossRefPubMed Liebig C, Ayala G, Wilks JA, et al. Perineural invasion in cancer: a review of the literature. Cancer. 2009;115(15):3379–91.CrossRefPubMed
26.
go back to reference Huang X, Liu J, Wu G, et al. Development and validation of a nomogram for preoperative prediction of perineural invasion in colorectal cancer. Med Sci Monit. 2019;25:1709–17.CrossRefPubMedPubMedCentral Huang X, Liu J, Wu G, et al. Development and validation of a nomogram for preoperative prediction of perineural invasion in colorectal cancer. Med Sci Monit. 2019;25:1709–17.CrossRefPubMedPubMedCentral
27.
go back to reference Cao Y, Deng S, Yan L, et al. Perineural invasion is associated with poor prognosis of colorectal cancer: a retrospective cohort study. Int J Colorectal Dis. 2020;35(6):1067–75.CrossRefPubMed Cao Y, Deng S, Yan L, et al. Perineural invasion is associated with poor prognosis of colorectal cancer: a retrospective cohort study. Int J Colorectal Dis. 2020;35(6):1067–75.CrossRefPubMed
28.
go back to reference Spencer NJ, Hu H. Enteric nervous system: sensory transduction, neural circuits and gastrointestinal motility. Nat Rev Gastroenterol Hepatol. 2020;17(6):338–51.CrossRefPubMedPubMedCentral Spencer NJ, Hu H. Enteric nervous system: sensory transduction, neural circuits and gastrointestinal motility. Nat Rev Gastroenterol Hepatol. 2020;17(6):338–51.CrossRefPubMedPubMedCentral
29.
go back to reference Silverman DA, Martinez VK, Dougherty PM, et al. Cancer-associated neurogenesis and nerve-cancer cross-talk. Cancer Res. 2021;81(6):1431–40.CrossRefPubMed Silverman DA, Martinez VK, Dougherty PM, et al. Cancer-associated neurogenesis and nerve-cancer cross-talk. Cancer Res. 2021;81(6):1431–40.CrossRefPubMed
30.
go back to reference Jin Z, Sinicrope FA. Mismatch repair-deficient colorectal cancer: building on checkpoint blockade. J Clin Oncol. 2022;40(24):2735–50.CrossRefPubMed Jin Z, Sinicrope FA. Mismatch repair-deficient colorectal cancer: building on checkpoint blockade. J Clin Oncol. 2022;40(24):2735–50.CrossRefPubMed
31.
go back to reference Baxter NN, Kennedy EB, Bergsland E, et al. Adjuvant therapy for stage II colon cancer: ASCO Guideline Update. J Clin Oncol. 2021;40(8):892–910. Baxter NN, Kennedy EB, Bergsland E, et al. Adjuvant therapy for stage II colon cancer: ASCO Guideline Update. J Clin Oncol. 2021;40(8):892–910.
33.
go back to reference Liu Q, Ma Z, Cao Q, et al. Perineural invasion-associated biomarkers for tumor development. Biomed Pharmacother. 2022;155: 113691.CrossRefPubMed Liu Q, Ma Z, Cao Q, et al. Perineural invasion-associated biomarkers for tumor development. Biomed Pharmacother. 2022;155: 113691.CrossRefPubMed
35.
go back to reference Bjornstad P, Drews KL, Caprio S, et al. Long-term complications in youth-onset type 2 diabetes. N Engl J Med. 2021;385(5):416–26.CrossRefPubMed Bjornstad P, Drews KL, Caprio S, et al. Long-term complications in youth-onset type 2 diabetes. N Engl J Med. 2021;385(5):416–26.CrossRefPubMed
Metadata
Title
Combining perineural invasion with staging improve the prognostic accuracy in colorectal cancer: a retrospective cohort study
Authors
Bin Zhang
Yanyun Lin
Chao Wang
Zexian Chen
Tianze Huang
Hao Chen
Guannan Wang
Ping Lan
Xiaowen He
Xiaosheng He
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-11114-8

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