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Neoadjuvant chemotherapy in locally advanced colon cancer: a systematic review

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Abstract

Background

Preoperative or neoadjuvant chemotherapy (NAC) has emerged as a novel alternative to treat locally advanced colon cancer (LACC), as in other gastrointestinal malignancies. However, evidence of its efficacy and safety has not yet been gathered in the literature. The aim of the present study was to perform an extensive review of the scientific evidence for NAC in patients with LACC.

Methods

PubMed, EMBASE, MEDLINE and Cochrane Library were searched for a systematic review of the literature from 2010 to 2019. Six eligible studies were included, with a total of 27,937 patients, 1232 of them (4.4%) treated with NAC. There were only one randomized controlled trial, three phase II non-randomized single arm studies and two retrospective studies.

Results

The baseline computed tomography scan showed that most of patients had a T3 tumor. The completion rate of the planned neoadjuvant treatment ranged from 52.5 to 93.8%. Between 97.2 and 100% of patients had the scheduled surgery. The median tumor volume reduction after NAC ranged from 62.5 to 63.7%. The anastomotic leak rate in the NAC group ranged from 0 to 7%, with no cases of postoperative mortality. There was major pathological tumor regression in 4–34.7% of cases. Between 84 and 100% of NAC patients had R0-surgery. Survival after NAC seems to be encouraging although significant improvement has only been proven in T4b tumours.

Conclusions

According to our systematic review, the NAC may be a safe and effective emerging therapeutic alternative for treating LACC. This approach, which is still being tested, increases the reliance on accurate radiological staging.

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References

  1. Ferlay J, Shin HR, Bray F, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893–2917. https://doi.org/10.1002/ijc.25516

    Article  CAS  PubMed  Google Scholar 

  2. Benson AB 3rd, Venook AP, Cederquist L et al (2017) Colon cancer, version 1.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 15:370–398

    Article  CAS  Google Scholar 

  3. Maupoey J, Pàmies J, Frasson M, Boscà A, Giner F, García-Granero E (2019) Accuracy of CT colonography in the preoperative staging of colon cancer: a prospective study of 227 patients. Colorectal Dis 21:1151–1163. https://doi.org/10.1111/codi.14724

    Article  Google Scholar 

  4. Benson AB 3rd, Schrag D, Somerfield MR et al (2004) American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol 22:3408–3419

    Article  Google Scholar 

  5. Foxtrot Collaborative G (2012) Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: the pilot phase of a randomised controlled trial. Lancet Oncol 13:1152–1160. https://doi.org/10.1016/S1470-2045(12)70348-0

    Article  CAS  Google Scholar 

  6. Arredondo J, Baixauli J, Pastor C et al (2017) Mid-term oncologic outcome of a novel approach for locally advanced colon cancer with neoadjuvant chemotherapy and surgery. Clin Transl Oncol 19:379–385. https://doi.org/10.1007/s12094-016-1539-4

    Article  CAS  PubMed  Google Scholar 

  7. Karoui M, Rullier A, Luciani A et al (2015) Neoadjuvant FOLFOX 4 versus FOLFOX 4 with Cetuximab versus immediate surgery for high-risk stage II and III colon cancers: a multicentre randomised controlled phase II trial–the PRODIGE 22–ECKINOXE trial. BMC Cancer 15:511. https://doi.org/10.1186/s12885-015-1507-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Edge SB, Byrd DR, Compton CC et al (2010) AJCC cancer staging manual, 7th edn. Springer, New York

    Google Scholar 

  9. Sauer R, Becker H, Hohenberger W et al (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731–1740

    Article  CAS  Google Scholar 

  10. Cunningham D, Allum WH, Stenning SP, for the MAGIC Trial Participants et al (2006) Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355:11–20

    Article  CAS  Google Scholar 

  11. Medical Research Council Oesophageal Cancer Working Party (2002) Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial. Lancet 359:1727–1733

    Article  Google Scholar 

  12. Moehler M, Lyros O, Gockel I, Galle PR, Lang H (2008) Multidisciplinary management of gastric and gastroesophageal cancers. World J Gastroenterol 14:3773–3780

    Article  Google Scholar 

  13. Zhou Z, Nimeiri HS, Benson AB 3rd (2013) Preoperative chemotherapy for locally advanced resectable colon cancer - a new treatment paradigm in colon cancer? Ann Transl Med 1:11. https://doi.org/10.3978/j.issn.2305-5839.2013.01.01

    Article  PubMed  PubMed Central  Google Scholar 

  14. Jakobsen A, Andersen F, Fischer A et al (2015) Neoadjuvant chemotherapy in locally advanced colon cancer. A phase II trial. Acta Oncol 29:1–7. https://doi.org/10.3109/0284186X.2015.1037007

    Article  CAS  Google Scholar 

  15. Liu F, Yang L, Wu Y et al (2016) CapOX as neoadjuvant chemotherapy for locally advanced operable colon cancer patients: a prospective single-arm phase II trial. Chin J Cancer Res 28:589–597. https://doi.org/10.21147/j.issn.1000-9604.2016.06.05

    Article  PubMed  PubMed Central  Google Scholar 

  16. Zhou H, Song Y, Jiang J et al (2016) A pilot phase II study of neoadjuvant triplet chemotherapy regimen in patients with locally advanced resectable colon cancer. Chin J Cancer Res 28:598–605. https://doi.org/10.21147/j.issn.1000-9604.2016.06.06

    Article  PubMed  PubMed Central  Google Scholar 

  17. Dehal AN, Graff-Baker AN, Vuong B et al (2018) Neoadjuvant chemotherapy improves survival in patients with clinical T4b colon cancer. J Gastrointest Surg 22:242–249. https://doi.org/10.1007/s11605-017-3566-z

    Article  PubMed  Google Scholar 

  18. Moher D, Liberati A, Tezlaff J, Altman DG, PRISMA group (2010) Preferred reporting items for systematic review and meta-analysis: the PRISMA statement. Int J Surg 8:336–341. https://doi.org/10.1016/j.ijsu.2010.02.007

    Article  PubMed  Google Scholar 

  19. Arredondo J, Pastor C, Baixauli J et al (2013) Preliminary outcome of a treatment strategy based on perioperative chemotherapy and surgery in patients with locally advanced colon cancer. Colorectal Dis 15:552–557. https://doi.org/10.1111/codi.12119

    Article  CAS  PubMed  Google Scholar 

  20. Arredondo J, González I, Baixauli J et al (2014) Tumor response assessment in locally advanced colon cancer after neoadjuvant chemotherapy. J Gastrointest Oncol 5:104–111. https://doi.org/10.3978/j.issn.2078-6891.2014.006

    Article  PubMed  PubMed Central  Google Scholar 

  21. Arredondo J, Simó V, Castañón C, Suarez MJ, Alvarez MC (2019) Complete pathologic response after neoadjuvant chemotherapy in locally advanced colon cancer. Cir Esp. https://doi.org/10.1016/j.ciresp.2019.06.003

    Article  PubMed  Google Scholar 

  22. Liu F, Tong T, Huang D et al (2019) CapeOX perioperative chemotherapy versus postoperative chemotherapy for locally advanced resectable colon cancer: protocol for a two-period randomised controlled phase III trial. BMJ Open. https://doi.org/10.1136/bmjopen-2017-017637

    Article  PubMed  PubMed Central  Google Scholar 

  23. Huh JW, Jeong YY, Kim HR, Kim YJ (2012) Prognostic value of preoperative radiological staging assessed by computed tomography in patients with nonmetastatic colon cancer. Ann Oncol 23:1198–1206. https://doi.org/10.1093/annonc/mdr404

    Article  CAS  PubMed  Google Scholar 

  24. Smith NJ, Bees N, Barbachano Y, Norman AR, Swift RI, Brown G (2007) Preoperative computed tomography staging of nonmetastatic colon cancer predicts outcome: implications for clinical trials. Br J Cancer 96:1030–1036

    Article  CAS  Google Scholar 

  25. Dighe S, Swift I, Magill L et al (2011) Accuracy of radiological staging in identifying high-risk colon cancer patients suitable for neoadjuvant chemotherapy: a multicentre experience. Colorectal Dis 14:438–444. https://doi.org/10.1111/j.1463-1318.2011.02638.x

    Article  Google Scholar 

  26. Dighe S, Purkayastha S, Swift I, Tekkis PP, Darzi A, A´Hern R, Brown G (2010) Diagnostic precision of CT in local staging of colon cancers: a meta-analysis. Clin Radiol 65:708–719. https://doi.org/10.1016/j.crad.2010.01.024

    Article  CAS  PubMed  Google Scholar 

  27. Dighe S, Swift I, Brown G (2008) CT staging of colon cancer. Clin Radiol 63:1372–1379. https://doi.org/10.1016/j.crad.2008.04.021

    Article  CAS  PubMed  Google Scholar 

  28. Karantanas AH, Yarmenitis S, Papanikolaou N, Gourtsoyiannis N (2007) Preoperative imaging staging of rectal cancer. Dig Dis 25:20–32

    Article  CAS  Google Scholar 

  29. Filippone A, Ambrosini R, Fuschi M, Arinelly T, Genovesi D, Bonomo L (2004) Preoperative T and N staging of colorectal cancer: accuracy of contrast-enhanced multi-detector row CT colonography–initial experience. Radiology 231:83–90

    Article  Google Scholar 

  30. McCollough CH (2002) Optimization of multidetector array CT acquisition parameters for CT colonography. Abdom Imaging 27:253–259

    Article  CAS  Google Scholar 

  31. Kanamoto T, Matsuki M, Okuda J et al (2007) Preoperative evaluation of local invasion and metastatic lymph nodes of colorectal cancer and mesenteric vascular variations using multidetector-row computed tomography before laparoscopic surgery. J Comput Assist Tomogr 31:831–839

    Article  Google Scholar 

  32. Duman M, Tas S, Mecit EA et al (2012) Preoperative local staging of colorectal cancer patients with MDCT. Hepatogastroenterology 59:1108–1112. https://doi.org/10.5754/hge11869

    Article  PubMed  Google Scholar 

  33. Dehal AN, Graff-Baker AN, Vuong B et al (2018) Correlation between clinical and pathologic staging in colon cancer: implications for neoadjuvant treatment. J Gastrointest Surg 22:1764. https://doi.org/10.1007/s11605-018-3777-y

    Article  PubMed  Google Scholar 

  34. Park H, Cho SH, Kim JE et al (2019) Potential image-based criteria of neoadjuvant chemotherapy for colon cancer: multireaders' diagnostic performance. Abdom Radiol. https://doi.org/10.1007/s00261-019-02243-5

    Article  Google Scholar 

  35. Horvat N, Raj A, Liu S et al (2019) CT colonography in preoperative staging of colon cancer: evaluation of FOxTROT inclusion criteria for neoadjuvant therapy. AJR Am J Roentgenol. https://doi.org/10.2214/AJR.18.19928

    Article  PubMed  Google Scholar 

  36. Burton S, Brown G, Bees N et al (2008) Accuracy of CT prediction of poor prognostic features in colonic cancer. Br J Radiol 81:10–19

    Article  CAS  Google Scholar 

  37. Nørgaard A, Dam C, Jakobsen A, Pløen J, Lindebjerg J, Rafaelsen SR (2012) Selection of colon cancer patients for neoadjuvant chemotherapy by preoperative CT scan. Scand J Gastroenterol 49:202–208. https://doi.org/10.3109/00365521.2013.862294

    Article  CAS  Google Scholar 

  38. Iachetta F, ReggianiBonetti L, Marcheselli L et al (2013) Lymph node evaluation in stage IIA colorectal cancer and its impact on patient prognosis: a population-based study. Acta Oncol 52:1682–1690. https://doi.org/10.3109/0284186X.2013.808376

    Article  CAS  PubMed  Google Scholar 

  39. Maas M, Nelemans PJ, Valentini V et al (2010) Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol 11:835–844. https://doi.org/10.1016/S1470-2045(10)70172-8

    Article  PubMed  Google Scholar 

  40. Garcia-Aguilar J, Hernandez de Anda E, Sirivongs P, Lee SH, Madoff RD, Rothenberger DA (2003) A pathologic complete response to preoperative chemoradiation is associated with lower local recurrence and improved survival in rectal cancer patients treated by mesorectal excision. Dis Colon Rectum 46:298–304

    Article  Google Scholar 

  41. Huang C, Huang M, Ma C et al (2017) Neoadjuvant FOLFOX chemotherapy combined with radiotherapy followed by radical resection in patients with locally advanced colon cancer. Radiat Oncol 12:48. https://doi.org/10.1186/s13014-017-0790-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Qui B, Ding PR, Cai L et al (2016) Outcomes of preoperative chemoradiotherapy followed by surgery in patients with unresectable locally advanced sigmoid colon cancer. Chin J Cancer 35:65. https://doi.org/10.1186/s40880-016-0126-y

    Article  Google Scholar 

  43. Cukier M, Smith AJ, Milot L et al (2012) Neoadjuvant chemoradiotherapy and multivisceral resection for primary locally advanced adherent colon cancer: a single institution experience. Eur J Surg Oncol. https://doi.org/10.1016/j.ejso.2012.05.001

    Article  PubMed  Google Scholar 

  44. Martel G, Al-Suhaibani Y, Moloo H et al (2008) Neoadjuvant therapy and anastomotic leak after tumor-specific mesorectal excision for rectal cancer. Dis Colon Rectum 51:1195–1201. https://doi.org/10.1007/s10350-008-9368-3

    Article  PubMed  Google Scholar 

  45. Arredondo J, Martínez P, Baixauli J et al (2014) Analysis of surgical complications of primary tumor resection after neoadjuvant treatment in stage IV colon cancer. J Gastrointest Oncol 5:148–153. https://doi.org/10.3978/j.issn.2078-6891.2014.015

    Article  PubMed  PubMed Central  Google Scholar 

  46. Navarro GV, Mompean JA, Agüera QH et al (2007) Influence of the neo-adjuvant radiochemotherapy as a factor in the surgical treatment of rectal cancer by expert surgeon. A comparative study. Int J Colorectal Dis 22:1233–1238

    Article  Google Scholar 

  47. Seymour M, Morton D, on behalf of the International FOxTROT Trial Investigators (2019) FOxTROT: an international randomized controlled trial in 1052 patients evaluating neoadjuvant chemotherapy for colon cancer. J Clin Oncol 37(15 Suppl):3504–3504

    Article  Google Scholar 

  48. NCCN, BNCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Colon Cancer,^ Version 1.2017 (2016)

  49. Takenami T, Tsu**aka S, Takahashi J et al (2019) Efficacy of neoadjuvant chemotherapy with capecitabine plus oxaliplatin in the treatment of locally advanced sigmoid colon cancer invading the urinary bladder: a report of three cases. Case Rep Surg 2019:8129358. https://doi.org/10.1155/2019/8129358

    Article  PubMed  PubMed Central  Google Scholar 

  50. Bayraktar UD, Chen E, Bayraktar S et al (2010) Does delay of adjuvant chemotherapy impact survival in patients with resected stage II and III colon adenocarcinoma? Cancer 117:2364–2370. https://doi.org/10.1002/cncr.25720

    Article  PubMed  Google Scholar 

  51. Hendren S, Birkmeyer JD, Yin H, Banerjee M, Sonnenday C, Morris AM (2010) Surgical complications are associated with omission of chemotherapy for stage III colorectal cancer. Dis Colon Rectum 53:1587–1593. https://doi.org/10.1007/DCR.0b013e3181f2f202

    Article  PubMed  Google Scholar 

  52. Alberts SR, Sargent DJ, Nair S et al (2012) Effect of oxaliplatin, fluorouracil, and leucovorin with or without cetuximab on survival among patients with resected stage III colon cancer: a randomized trial. JAMA 307:1383–1393. https://doi.org/10.1001/jama.2012.385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Mols F, Beijers T, Lemmens V, van den Hurk CJ, Vreughdenhil G, van de Poll-Franse LV (2013) Chemotherapy-induced neuropathy and its association with quality of life among 2- to 11-year colorectal cancer survivors: results from the population based PROFILES registry. J Clin Oncol 31:2699–2707. https://doi.org/10.1200/JCO.2013.49.1514

    Article  PubMed  Google Scholar 

  54. Sargent DJ, Marsoni S, Monges G et al (2010) Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol 28:3219–3226. https://doi.org/10.1200/JCO.2009.27.1825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kato M, Murata A, Nishikawa S et al (2017) A case of effective neoadjuvant chemotherapy for transverse colon cancer with extensive abdominal wall invasion. Gan To Kagaku Ryoho 44:1692–1694

    PubMed  Google Scholar 

  56. Aomatsu N, Uchima Y, Nobori C et al (2017) A case of curatively resected ascending colon cancer after long-term chemotherapy found in abdominal trauma. Gan To Kagaku Ryoho 44:1766–1768

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Unit of Coloproctology, Service of General Surgery, University Hospital of Leon, 24071, C/Altos de Nava s/n León, Spain

    J. Arredondo, E. Pastor, V. Simó, M. Beltrán & B. Ielpo

  2. Service of Oncology, University Hospital of León, León, Spain

    C. Castañón

  3. Service of Radiology, University Hospital of León, León, Spain

    M. C. Magdaleno

  4. Service of Pathology, University Hospital of León, León, Spain

    I. Matanza

  5. Service of General Surgery, Università Degli Studi Di Bari, Bari, Italy

    M. Notarnicola

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  1. J. Arredondo
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Contributions

JA, EP and CC had the idea for the article. VS, MB, MCM, IM, MN, BI and JA performed the literature search and data analysis. All authors critically revised the work and approved the final manuscript.

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Correspondence to J. Arredondo.

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Arredondo is the principal investigator of the ELECLA trial. The other authors declare that they have no conflict of interest.

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Arredondo, J., Pastor, E., Simó, V. et al. Neoadjuvant chemotherapy in locally advanced colon cancer: a systematic review. Tech Coloproctol 24, 1001–1015 (2020). https://doi.org/10.1007/s10151-020-02289-4

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