International Journal of Colorectal Disease

, Volume 33, Issue 11, pp 1533–1541 | Cite as

Repeating of local therapy of distant metastases increases overall survival in patients with synchronous metastasized rectal cancer—a monocentric analysis

  • Marlen HaderleinEmail author
  • Sebastian Lettmaier
  • Melanie Langheinrich
  • Axel Schmid
  • Sabine Semrau
  • Markus Hecht
  • Michael Beck
  • Daniela Schmidt
  • Robert Grützmann
  • Rainer Fietkau
  • Axel Denz
Original Article



The aim was to evaluate the outcome of treatment-naive patients with synchronous metastatic rectal cancer after chemotherapy with FOLFOXIRI followed by local therapeutic procedures of all tumor lesions as complete as possible.


We reviewed data of 30 patients with synchronous distant metastatic rectal cancer who underwent chemotherapy with FOLFOXIRI and subsequent local therapy in our institution.


Median follow-up was 28 months (range: 8; 74). Cumulative overall survival (OS) and progression-free survival (PFS) was 93.3, 76.9, 55.6% and 46.2, 29.7, 29.7% after 1, 2, 4 years. Non-response to chemotherapy with FOLFOXIRI was associated with a highly significant decreased OS (p < 0.0001). The consistent use of local ablative procedures led to a statistically significant increase in OS (p < 0.0001), but not in PFS (p = 0.635). Patients with ≤ 4 distant metastases showed a better OS (p = 0.033).


Response to intensified first-line chemotherapy with FOLFOXIRI, treatment of the primary rectal tumor, and repeated thorough local ablative procedures in patients with synchronous metastasized rectal cancer may lead to long-term survival, even in a subset of patients with unresectable disease at initial diagnosis.


Rectal cancer Synchronous distant metastases FOLFOXIRI Local ablative procedures 


Compliance with ethical standards

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Statement of informed consent

For this retrospective type of study, formal consent is not required.

Supplementary material

384_2018_3113_MOESM1_ESM.docx (25 kb)
ESM 1 (DOCX 24 kb)


  1. 1.
    Butte JM, Gonen M, Ding P et al (2012) Patterns of failure in patients with early onset (synchronous) resectable liver metastases from rectal cancer. Cancer 118:5414–5423CrossRefGoogle Scholar
  2. 2.
    Sauer R, Liersch T, Merkel S et al (2012) Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol 30:1926–1933CrossRefGoogle Scholar
  3. 3.
    Kogler P, DeVries AF, Eisterer W et al (2018) Intensified preoperative chemoradiation by adding oxaliplatin in locally advanced, primary operable (cT3NxM0) rectal cancer: impact on long-term outcome. Results of the phase II TAKO 05/ABCSG R02 trial. Strahlenther Onkol 194:41–49CrossRefGoogle Scholar
  4. 4.
    Hodek M, Sirak I, Ferko A et al (2016) Neoadjuvant chemoradiotherapy of rectal carcinoma: baseline hematologic parameters influencing outcomes. Strahlenther Onkol 192:632–640CrossRefGoogle Scholar
  5. 5.
    Van Cutsem E, Cervantes A, Nordlinger B, Arnold D, Group EGW (2014) Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 25(Suppl 3):iii1-9PubMedGoogle Scholar
  6. 6.
    AWMF (2017) AWMF S3-Leitlinie kolorektales Karzinom S3 guideline colorectal cancer; AWMF Registernummer:021/007OL; version november 2017Google Scholar
  7. 7.
    Slesser AA, Georgiou P, Brown G, Mudan S, Goldin R, Tekkis P (2013) The tumour biology of synchronous and metachronous colorectal liver metastases: a systematic review. Clin Exp Metastasis 30:457–470CrossRefGoogle Scholar
  8. 8.
    Souglakos J, Androulakis N, Syrigos K et al (2006) FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicentre randomised phase III trial from the Hellenic Oncology Research Group (HORG). Br J Cancer 94:798–805CrossRefGoogle Scholar
  9. 9.
    Montagnani F, Chiriatti A, Turrisi G, Francini G, Fiorentini G (2011) A systematic review of FOLFOXIRI chemotherapy for the first-line treatment of metastatic colorectal cancer: improved efficacy at the cost of increased toxicity. Color Dis 13:846–852CrossRefGoogle Scholar
  10. 10.
    Gruenberger T, Bridgewater J, Chau I et al (2015) Bevacizumab plus mFOLFOX-6 or FOLFOXIRI in patients with initially unresectable liver metastases from colorectal cancer: the OLIVIA multinational randomised phase II trial. Ann Oncol 26:702–708CrossRefGoogle Scholar
  11. 11.
    Cheng Y, Zhang L, Li H et al (2017) Laparoscopic versus open liver resection for colorectal liver metastases: a systematic review. J Surg Res 220:234–246CrossRefGoogle Scholar
  12. 12.
    Gillams AR, Lees WR (2009) Five-year survival in 309 patients with colorectal liver metastases treated with radiofrequency ablation. Eur Radiol 19:1206–1213CrossRefGoogle Scholar
  13. 13.
    Van Tilborg AA, Meijerink MR, Sietses C et al (2011) Long-term results of radiofrequency ablation for unresectable colorectal liver metastases: a potentially curative intervention. Br J Radiol 84:556–565CrossRefGoogle Scholar
  14. 14.
    Otto G, Duber C, Hoppe-Lotichius M, Konig J, Heise M, Pitton MB (2010) Radiofrequency ablation as first-line treatment in patients with early colorectal liver metastases amenable to surgery. Ann Surg 251:796–803CrossRefGoogle Scholar
  15. 15.
    Solbiati L, Ahmed M, Cova L, Ierace T, Brioschi M, Goldberg SN (2012) Small liver colorectal metastases treated with percutaneous radiofrequency ablation: local response rate and long-term survival with up to 10-year follow-up. Radiology 265:958–968CrossRefGoogle Scholar
  16. 16.
    Herfarth KK, Debus J, Wannenmacher M (2004) Stereotactic radiation therapy of liver metastases: update of the initial phase-I/II trial. Front Radiat Ther Oncol 38:100–105CrossRefGoogle Scholar
  17. 17.
    van der Pool AE, Mendez Romero A, Wunderink W et al (2010) Stereotactic body radiation therapy for colorectal liver metastases. Br J Surg 97:377–382CrossRefGoogle Scholar
  18. 18.
    Ricke J, Mohnike K, Pech M et al (2010) Local response and impact on survival after local ablation of liver metastases from colorectal carcinoma by computed tomography-guided high-dose-rate brachytherapy. Int J Radiat Oncol Biol Phys 78:479–485CrossRefGoogle Scholar
  19. 19.
    Mohnike K, Wolf S, Damm R et al (2016) Radioablation of liver malignancies with interstitial high-dose-rate brachytherapy: complications and risk factors. Strahlenther Onkol 192:288–296CrossRefGoogle Scholar
  20. 20.
    Agcaoglu O, Aliyev S, Karabulut K et al (2013) Complementary use of resection and radiofrequency ablation for the treatment of colorectal liver metastases: an analysis of 395 patients. World J Surg 37:1333–1339CrossRefGoogle Scholar
  21. 21.
    Sasaki K, Margonis GA, Andreatos N et al (2016) Combined resection and RFA in colorectal liver metastases: stratification of long-term outcomes. J Surg Res 206:182–189CrossRefGoogle Scholar
  22. 22.
    van Amerongen MJ, van der Stok EP, Futterer JJ et al (2016) Short term and long term results of patients with colorectal liver metastases undergoing surgery with or without radiofrequency ablation. Eur J Surg Oncol 42:523–530CrossRefGoogle Scholar
  23. 23.
    Modest DP, Denecke T, Pratschke J et al (2018) Surgical treatment options following chemotherapy plus cetuximab or bevacizumab in metastatic colorectal cancer-central evaluation of FIRE-3. Eur J Cancer 88:77–86CrossRefGoogle Scholar
  24. 24.
    Falcone A, Ricci S, Brunetti I et al (2007) Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol 25:1670–1676CrossRefGoogle Scholar
  25. 25.
    Ruers T, Punt C, Van Coevorden F et al (2012) Radiofrequency ablation combined with systemic treatment versus systemic treatment alone in patients with non-resectable colorectal liver metastases: a randomized EORTC Intergroup phase II study (EORTC 40004). Ann Oncol 23:2619–2626CrossRefGoogle Scholar
  26. 26.
    Ruers T, Van Coevorden F, Punt CJ, et al (2017) Local treatment of unresectable colorectal liver metastases: results of a randomized phase II trial. J Natl Cancer Inst 109(9).
  27. 27.
    Nanji S, Karim S, Tang E, et al (2018) Pulmonary metastasectomy for colorectal cancer: predictors of survival in routine surgical practice. Ann Thorac Surg 105(6):1605–1612. CrossRefGoogle Scholar
  28. 28.
    Fanucchi O, Ambrogi MC, Aprile V et al (2016) Long-term results of percutaneous radiofrequency ablation of pulmonary metastases: a single institution experience. Interact Cardiovasc Thorac Surg 23:57–64CrossRefGoogle Scholar
  29. 29.
    Wild AT, Yamada Y (2017) Treatment options in oligometastatic disease: stereotactic body radiation therapy-focus on colorectal cancer. Visc Med 33:54–61CrossRefGoogle Scholar
  30. 30.
    Neal CP, Nana GR, Jones M et al (2017) Repeat hepatectomy is independently associated with favorable long-term outcome in patients with colorectal liver metastases. Cancer Med 6:331–338CrossRefGoogle Scholar
  31. 31.
    Sponholz S, Schirren M, Baldes N, Oguzhan S, Schirren J (2017) Repeat resection for recurrent pulmonary metastasis of colorectal cancer. Langenbeck’s Arch Surg 402:77–85CrossRefGoogle Scholar
  32. 32.
    Bellier J, De Wolf J, Hebbar M et al (2018) Repeated resections of hepatic and pulmonary metastases from colorectal cancer provide long-term survival. World J Surg 42:1171–1179CrossRefGoogle Scholar
  33. 33.
    Nitsche U, Stoss C, Stecher L, Wilhelm D, Friess H, Ceyhan GO (2017) Meta-analysis of outcomes following resection of the primary tumour in patients presenting with metastatic colorectal cancer. Br J Surg 105(7):784–796. CrossRefGoogle Scholar
  34. 34.
    Poskus E, Kryzauskas M, Poskus T et al (2018) Improved perioperative care is associated with improved long-term survival in colorectal cancer. Int J Color Dis 33(6):779–785CrossRefGoogle Scholar
  35. 35.
    Curtis NJ, Taylor M, Fraser L et al (2018) Can the combination of laparoscopy and enhanced recovery improve long-term survival after elective colorectal cancer surgery? Int J Color Dis 33:231–234CrossRefGoogle Scholar
  36. 36.
    Manfredi S, Jooste V, Gay C, Faivre J, Drouillard A, Bouvier AM (2017) Time trends in colorectal cancer early postoperative mortality. A French 25-year population-based study. Int J Color Dis 32:1725–1731CrossRefGoogle Scholar
  37. 37.
    Fossum CC, Alabbad JY, Romak LB et al (2017) The role of neoadjuvant radiotherapy for locally-advanced rectal cancer with resectable synchronous metastasis. J Gastrointest Oncol 8:650–658CrossRefGoogle Scholar
  38. 38.
    Salvador-Roses H, Lopez-Ben S, Casellas-Robert M, et al (2017) Oncological strategies for locally advanced rectal cancer with synchronous liver metastases, interval strategy versus rectum first strategy: a comparison of short-term outcomes. Clin Transl Oncol. CrossRefGoogle Scholar
  39. 39.
    Liu KT, Wan JF, Zhu J et al (2016) Role of pelvic radiotherapy for locally advanced rectal cancer and synchronous unresectable distant metastases. Cancer Radiother 20:805–810CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Marlen Haderlein
    • 1
    Email author
  • Sebastian Lettmaier
    • 1
  • Melanie Langheinrich
    • 2
  • Axel Schmid
    • 3
  • Sabine Semrau
    • 1
  • Markus Hecht
    • 1
  • Michael Beck
    • 4
  • Daniela Schmidt
    • 4
  • Robert Grützmann
    • 2
  • Rainer Fietkau
    • 1
  • Axel Denz
    • 2
  1. 1.Department of Radiation OncologyUniversity Hospital of ErlangenErlangenGermany
  2. 2.Department of SurgeryUniversity Hospital of ErlangenErlangenGermany
  3. 3.Department of RadiologyUniversity Hospital of ErlangenErlangenGermany
  4. 4.Department of Nuclear MedicineUniversity Hospital of ErlangenErlangenGermany

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