Skip to main content

Advertisement

SpringerLink
Log in

Pretreatment MRI-detected extramural venous invasion as a prognostic and predictive biomarker for neoadjuvant chemoradiotherapy in non-metastatic rectal cancer: a propensity score matched analysis

  • Oncology
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

This study evaluated pretreatment magnetic resonance imaging (MRI)–detected extramural venous invasion (pmrEMVI) as a predictor of survival after neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC).

Materials and methods

Medical records of 1184 patients with rectal adenocarcinoma who underwent TME between January 2011 and December 2016 were reviewed. MRI data were collected from a computerized radiologic database. Cox proportional hazards analysis was used to assess local, systemic recurrence, and disease-free survival risk based on pretreatment MRI-assessed tumor characteristics. After propensity score matching (PSM) for pretreatment MRI features, nCRT therapeutic outcomes according to pmrEMVI status were evaluated. Cox proportional hazards analysis was used to identify risk factors for early recurrence in patients receiving nCRT.

Results

Median follow-up was 62.8 months. Among all patients, the presence of pmrEMVI was significantly associated with worse disease-free survival (DFS; HR 1.827, 95% CI 1.285–2.597, p = 0.001) and systemic recurrence (HR 2.080, 95% CI 1.400–3.090, p < 0.001) but not local recurrence. Among patients with pmrEMVI, nCRT provided no benefit for oncological outcomes before or after PSM. Furthermore, pmrEMVI( +) was the only factor associated with early recurrence on multivariate analysis in patients receiving nCRT.

Conclusions

pmrEMVI is a poor prognostic factor for DFS and SR in patients with non-metastatic rectal cancer and also serves as a predictive biomarker of poor DFS and SR following nCRT in LARC. Therefore, for patients who are positive for pmrEMVI, consideration of alternative treatment strategies may be warranted.

Clinical relevance statement

This study demonstrated the usefulness of pmrEMVI as a predictive biomarker for nCRT, which may assist in initial treatment decision-making in patients with non-metastatic rectal cancer.

Key Points

• Pretreatment MRI-detected extramural venous invasion (pmrEMVI) was significantly associated with worse disease-free survival and systemic recurrence in patients with non-metastatic rectal cancer.

• pmrEMVI is a predictive biomarker of poor DFS following nCRT in patients with LARC.

• The presence of pmrEMVI was the only factor associated with early recurrence on multivariate analysis in patients receiving nCRT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

CRM:

Circumferential resection margin

DFS:

Disease-free survival

LARC:

Locally advanced rectal cancer

LN:

Lymph node

LRR:

Local recurrence rate

nCRT:

Neoadjuvant chemoradiotherapy

pmrEMVI:

Pretreatment magnetic resonance imaging (MRI)–detected extramural venous invasion

PSM:

Propensity score matching

TME:

Total mesorectal excision

References

  1. Smith JJ, Garcia-Aguilar J (2015) Advances and challenges in treatment of locally advanced rectal cancer. J Clin Oncol 33:1797–1808

    Article  PubMed  PubMed Central  Google Scholar 

  2. Nougaret S, Reinhold C, Mikhael HW, Rouanet P, Bibeau F, Brown G (2013) The use of MR imaging in treatment planning for patients with rectal carcinoma: have you checked the “DISTANCE”? Radiology 268:330–344

    Article  PubMed  Google Scholar 

  3. Heald RJ, Ryall RD (1986) Recurrence and survival after total mesorectal excision for rectal cancer. Lancet 1:1479–1482

    Article  CAS  PubMed  Google Scholar 

  4. Kapiteijn E, Marijnen CA, Nagtegaal ID et al (2001) Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 345:638–646

    Article  CAS  PubMed  Google Scholar 

  5. Taylor FG, Quirke P, Heald RJ et al (2011) Preoperative high-resolution magnetic resonance imaging can identify good prognosis stage I, II, and III rectal cancer best managed by surgery alone: a prospective, multicenter, European study. Ann Surg 253:711–719

    Article  PubMed  Google Scholar 

  6. Braendengen M, Tveit KM, Berglund A et al (2008) Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer. J Clin Oncol 26:3687–3694

    Article  CAS  PubMed  Google Scholar 

  7. Hong YS, Nam BH, Kim KP et al (2014) Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (ADORE): an open-label, multicentre, phase 2, randomised controlled trial. Lancet Oncol 15:1245–1253

    Article  CAS  PubMed  Google Scholar 

  8. Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Kryj M (2006) Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg 93:1215–1223

    Article  CAS  PubMed  Google Scholar 

  9. Peeters KC, Marijnen CA, Nagtegaal ID et al (2007) The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma. Ann Surg 246:693–701

    Article  PubMed  Google Scholar 

  10. Dayde D, Tanaka I, Jain R, Tai MC, Taguchi A (2017) Predictive and prognostic molecular biomarkers for response to neoadjuvant chemoradiation in rectal cancer. Int J Mol Sci 18(3):573

    Article  PubMed  PubMed Central  Google Scholar 

  11. Dienstmann R, Vermeulen L, Guinney J, Kopetz S, Tejpar S, Tabernero J (2017) Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer. Nat Rev Cancer 17:79–92

    Article  CAS  PubMed  Google Scholar 

  12. Guinney J, Dienstmann R, Wang X et al (2015) The consensus molecular subtypes of colorectal cancer. Nat Med 21:1350–1356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Chand M, Swift RI, Tekkis PP, Chau I, Brown G (2014) Extramural venous invasion is a potential imaging predictive biomarker of neoadjuvant treatment in rectal cancer. Br J Cancer 110:19–25

    Article  CAS  PubMed  Google Scholar 

  14. Hunter C, Brown G (2016) Pre-operative staging of rectal cancer: a review of imaging techniques. Expert Rev Gastroenterol Hepatol 10:1011–1025

    Article  CAS  PubMed  Google Scholar 

  15. Talbot IC, Ritchie S, Leighton MH, Hughes AO, Bussey HJ, Morson BC (1980) The clinical significance of invasion of veins by rectal cancer. Br J Surg 67:439–442

    Article  CAS  PubMed  Google Scholar 

  16. Gibson KM, Chan C, Chapuis PH, Dent OF, Bokey L (2014) Mural and extramural venous invasion and prognosis in colorectal cancer. Dis Colon Rectum 57:916–926

    Article  PubMed  Google Scholar 

  17. Brown G, Radcliffe AG, Newcombe RG, Dallimore NS, Bourne MW, Williams GT (2003) Preoperative assessment of prognostic factors in rectal cancer using high-resolution magnetic resonance imaging. Br J Surg 90:355–364

    Article  CAS  PubMed  Google Scholar 

  18. Smith NJ, Shihab O, Arnaout A, Swift RI, Brown G (2008) MRI for detection of extramural vascular invasion in rectal cancer. AJR Am J Roentgenol 191:1517–1522

    Article  PubMed  Google Scholar 

  19. Fang J, Sun W, Wu D et al (2022) Value of texture analysis based on dynamic contrast-enhanced magnetic resonance imaging in preoperative assessment of extramural venous invasion in rectal cancer. Insights Imaging 13:179

    Article  PubMed  PubMed Central  Google Scholar 

  20. Siddiqui MRS, Simillis C, Hunter C et al (2017) A meta-analysis comparing the risk of metastases in patients with rectal cancer and MRI-detected extramural vascular invasion (mrEMVI) vs mrEMVI-negative cases. Br J Cancer 116:1513–1519

    Article  PubMed  PubMed Central  Google Scholar 

  21. Smith NJ, Barbachano Y, Norman AR, Swift RI, Abulafi AM, Brown G (2008) Prognostic significance of magnetic resonance imaging-detected extramural vascular invasion in rectal cancer. Br J Surg 95:229–236

    Article  CAS  PubMed  Google Scholar 

  22. Sohn B, Lim JS, Kim H et al (2015) MRI-detected extramural vascular invasion is an independent prognostic factor for synchronous metastasis in patients with rectal cancer. Eur Radiol 25:1347–1355

    Article  PubMed  Google Scholar 

  23. Zhang XY, Wang S, Li XT et al (2018) MRI of extramural venous invasion in locally advanced rectal cancer: relationship to tumor recurrence and overall survival. Radiology 289:677–685

    Article  PubMed  Google Scholar 

  24. Chen S, Li N, Tang Y et al (2021) The prognostic value of MRI-detected extramural vascular invasion (mrEMVI) for rectal cancer patients treated with neoadjuvant therapy: a meta-analysis. Eur Radiol 31:8827–8837

    Article  PubMed  Google Scholar 

  25. Kim KH, Park MJ, Lim JS et al (2016) Circumferential resection margin positivity after preoperative chemoradiotherapy based on magnetic resonance imaging for locally advanced rectal cancer: implication of boost radiotherapy to the involved mesorectal fascia. Jpn J Clin Oncol 46:316–322

    Article  PubMed  PubMed Central  Google Scholar 

  26. Brown G, Richards CJ, Bourne MW et al (2003) Morphologic predictors of lymph node status in rectal cancer with use of high-spatial-resolution MR imaging with histopathologic comparison. Radiology 227:371–377

    Article  PubMed  Google Scholar 

  27. Chang JS, Yoon HI, Cha HJ et al (2013) Bladder filling variations during concurrent chemotherapy and pelvic radiotherapy in rectal cancer patients: early experience of bladder volume assessment using ultrasound scanner. Radiat Oncol J 31:41–47

    Article  PubMed  PubMed Central  Google Scholar 

  28. Shin SJ, Kim NK, Keum KC et al (2010) Phase II study of preoperative chemoradiotherapy (CRT) with irinotecan plus S-1 in locally advanced rectal cancer. Radiother Oncol 95:303–307

    Article  CAS  PubMed  Google Scholar 

  29. Park YA, Kim JM, Kim SA et al (2010) Totally robotic surgery for rectal cancer: from splenic flexure to pelvic floor in one setup. Surg Endosc 24:715–720

    Article  PubMed  Google Scholar 

  30. Kim NK, Kim YW, Cho MS (2015) Total mesorectal excision for rectal cancer with emphasis on pelvic autonomic nerve preservation: expert technical tips for robotic surgery. Surg Oncol 24:172–180

    Article  CAS  PubMed  Google Scholar 

  31. Benson AB 3rd, Venook AP, Al-Hawary MM et al (2018) Rectal cancer, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 16:874–901

    Article  PubMed  PubMed Central  Google Scholar 

  32. Ryuk JP, Choi GS, Park JS et al (2014) Predictive factors and the prognosis of recurrence of colorectal cancer within 2 years after curative resection. Ann Surg Treat Res 86:143–151

    Article  PubMed  PubMed Central  Google Scholar 

  33. Wald A (1943) Tests of statistical hypotheses concerning several parameters when the number of observations is large. Trans Am Math Soc 54:426–482

    Article  Google Scholar 

  34. Ballman KV (2015) Biomarker: predictive or prognostic? J Clin Oncol 33:3968–3971

    Article  CAS  PubMed  Google Scholar 

  35. Garcia-Aguilar J, Patil S, Gollub MJ et al (2022) Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy. J Clin Oncol 40:2546–2556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. van der Valk MJM, Hilling DE, Bastiaannet E et al (2018) Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch & Wait Database (IWWD): an international multicentre registry study. Lancet 391:2537–2545

    Article  PubMed  Google Scholar 

  37. Cho YB, Chun HK, Yun HR, Lee WS, Yun SH, Lee WY (2007) Clinical and pathologic evaluation of patients with recurrence of colorectal cancer five or more years after curative resection. Dis Colon Rectum 50:1204–1210

    Article  PubMed  Google Scholar 

  38. Salem ME, Hartley M, Unger K, Marshall JL (2016) Neoadjuvant combined-modality therapy for locally advanced rectal cancer and its future direction. Oncology (Williston Park) 30:546–562

    PubMed  Google Scholar 

  39. Talbot IC, Ritchie S, Leighton MH, Hughes AO, Bussey HJ, Morson BC (1981) Spread of rectal cancer within veins. Histologic features and clinical significance. Am J Surg 141:15–17

    Article  CAS  PubMed  Google Scholar 

  40. Aghili M, Izadi S, Madani H, Mortazavi H (2010) Clinical and pathological evaluation of patients with early and late recurrence of colorectal cancer. Asia Pac J Clin Oncol 6:35–41

    Article  PubMed  Google Scholar 

  41. Cercek A, Goodman KA, Hajj C et al (2014) Neoadjuvant chemotherapy first, followed by chemoradiation and then surgery, in the management of locally advanced rectal cancer. J Natl Compr Canc Netw 12:513–519

    Article  PubMed  PubMed Central  Google Scholar 

  42. Chau I, Brown G, Cunningham D et al (2006) Neoadjuvant capecitabine and oxaliplatin followed by synchronous chemoradiation and total mesorectal excision in magnetic resonance imaging-defined poor-risk rectal cancer. J Clin Oncol 24:668–674

    Article  CAS  PubMed  Google Scholar 

  43. Glynne-Jones R, Anyamene N, Moran B, Harrison M (2012) Neoadjuvant chemotherapy in MRI-staged high-risk rectal cancer in addition to or as an alternative to preoperative chemoradiation? Ann Oncol 23:2517–2526

    Article  CAS  PubMed  Google Scholar 

  44. Petrelli F, Trevisan F, Cabiddu M et al (2019) Total neoadjuvant therapy in rectal cancer: a systematic review and meta-analysis of treatment outcomes. Ann Surg. https://doi.org/10.1097/sla.0000000000003471

    Article  Google Scholar 

  45. Rouanet P, Rullier E, Lelong B et al (2017) Tailored treatment strategy for locally advanced rectal carcinoma based on the tumor response to induction chemotherapy: preliminary results of the French Phase II Multicenter GRECCAR4 trial. Dis Colon Rectum 60:653–663

    Article  PubMed  Google Scholar 

  46. Chand M, Evans J, Swift RI et al (2015) The prognostic significance of postchemoradiotherapy high-resolution MRI and histopathology detected extramural venous invasion in rectal cancer. Ann Surg 261:473–479

    Article  PubMed  Google Scholar 

  47. Bahadoer RR, Dijkstra EA, van Etten B et al (2021) Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol 22:29–42

    Article  CAS  PubMed  Google Scholar 

  48. Conroy T, Bosset JF, Etienne PL et al (2021) Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 22:702–715

    Article  CAS  PubMed  Google Scholar 

  49. Chand M, Moran BJ, Jones RG, Heald RJ, Brown G (2014) Lymph node status does not predict local recurrence in the total mesorectal excision era. Dis Colon Rectum 57:127–129

    Article  PubMed  Google Scholar 

  50. Engelen SM, Maas M, Lahaye MJ et al (2013) Modern multidisciplinary treatment of rectal cancer based on staging with magnetic resonance imaging leads to excellent local control, but distant control remains a challenge. Eur J Cancer 49:2311–2320

    Article  CAS  PubMed  Google Scholar 

  51. Glynne-Jones R, Wyrwicz L, Tiret E et al (2017) Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 28:iv22-iv40

Download references

Funding

The authors state that this work has not received any funding.

Author information

Authors and Affiliations

  1. Department of Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-Gu, Seoul, 03722, Korea

    Seung Yoon Yang, Yoon Dae Han, Min Soo Cho, Hyuk Hur, Byung Soh Min, Nam Kyu Kim & Kang Young Lee

  2. Department of Radiology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-Gu, Seoul, 03722, Korea

    Heejin Bae, Nieun Seo, Kyunghwa Han & Joon Seok Lim

Authors
  1. Seung Yoon Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Heejin Bae
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nieun Seo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kyunghwa Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yoon Dae Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Min Soo Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hyuk Hur
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Byung Soh Min
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Nam Kyu Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kang Young Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Joon Seok Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Kang Young Lee or Joon Seok Lim.

Ethics declarations

Guarantor

The scientific guarantor of this publication is Kang Young Lee.

Conflict of interest

The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and biometry

One of the authors (Kyunghwa Han) has significant statistical expertise.

Informed consent

Written informed consent was waived by the Institutional Review Board.

Ethical approval

Institutional Review Board approval was obtained.

Study subjects or cohorts overlap

No study subjects or cohorts have been previously reported.

Methodology

  • retrospective

  • case–control study

  • performed at one institution

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, S.Y., Bae, H., Seo, N. et al. Pretreatment MRI-detected extramural venous invasion as a prognostic and predictive biomarker for neoadjuvant chemoradiotherapy in non-metastatic rectal cancer: a propensity score matched analysis. Eur Radiol (2023). https://doi.org/10.1007/s00330-023-10300-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00330-023-10300-3

Keywords

Search

Navigation