Skip to main content

Advertisement

Log in

Current evidence regarding the role of adjuvant chemotherapy in rectal cancer patients with pathologic complete response after neoadjuvant chemoradiotherapy: a systematic review and meta-analysis

  • Review
  • Published:
International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

The aim of this meta-analysis was to investigate the role of adjuvant chemotherapy (AC) in rectal cancer patients with pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) and curative resection.

Methods

This study was completed in accordance to the PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The electronic scholar databases (Medline, Web of Science, Scopus) were screened for eligible articles. The level of evidence (LoE) was assessed using the GRADE methodology.

Results

Overall, 23 non-randomized studies and 17,406 patients were included in the present meta-analysis. Pooled comparisons confirmed that AC improved overall survival (HR: 0.68, p=0.0003), but not disease-free (p=0.22) and recurrence-free survival (p=0.39). However, the LoE for all outcomes was characterized as “very low,” due to the absence of RCTs.

Conclusions

Considering the study limitations and the lack of randomized studies, further high-quality RCTs are required to confirm the findings of our study.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

Data availability

Data available on request from the authors

References

  1. Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB (2019) Colorectal cancer. Lancet 394:1467–1480. https://doi.org/10.1016/S0140-6736(19)32319-0

    Article  PubMed  Google Scholar 

  2. Brouwer NPM, Bos ACRK, Lemmens VEPP, Tanis PJ, Hugen N, Nagtegaal ID, de Wilt JHW, Verhoeven RHA (2018) An overview of 25 years of incidence, treatment and outcome of colorectal cancer patients. Int J Cancer 143:2758–2766. https://doi.org/10.1002/ijc.31785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Marley AR, Nan H (2016) Epidemiology of colorectal cancer. Int J Mol Epidemiol Genet 7:105–114

    PubMed  PubMed Central  Google Scholar 

  4. Siegel RL, Miller KD, Fedewa SA, Ahnen DJ, Meester RGS, Barzi A, Jemal A (2017) Colorectal cancer statistics, 2017. CA Cancer J Clin 67:177–193. https://doi.org/10.3322/caac.21395

    Article  PubMed  Google Scholar 

  5. Benson AB, Venook AP, Al-Hawary MM et al (2020) NCCN guidelines insights: rectal cancer, version 6.2020. J Natl Compr Cancer Netw 18:806–815. https://doi.org/10.6004/jnccn.2020.0032

    Article  Google Scholar 

  6. 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. https://doi.org/10.1093/annonc/mdx224

    Article  CAS  PubMed  Google Scholar 

  7. Cercek A, Roxburgh CSD, Strombom P, Smith JJ, Temple LKF, Nash GM, Guillem JG, Paty PB, Yaeger R, Stadler ZK, Seier K, Gonen M, Segal NH, Reidy DL, Varghese A, Shia J, Vakiani E, Wu AJ, Crane CH, Gollub MJ, Garcia-Aguilar J, Saltz LB, Weiser MR (2018) Adoption of total neoadjuvant therapy for locally advanced rectal cancer. JAMA Oncol 4:e180071. https://doi.org/10.1001/jamaoncol.2018.0071

    Article  PubMed  PubMed Central  Google Scholar 

  8. Ma B, Gao P, Wang H, Xu Q, Song Y, Huang X, Sun J, Zhao J, Luo J, Sun Y, Wang Z (2017) What has preoperative radio (chemo) therapy brought to localized rectal cancer patients in terms of perioperative and long-term outcomes over the past decades? A systematic review and meta-analysis based on 41,121 patients. Int J Cancer 141:1052–1065. https://doi.org/10.1002/ijc.30805

    Article  CAS  PubMed  Google Scholar 

  9. Mohiuddin M, Winter K, Mitchell E, Hanna N, Yuen A, Nichols C, Shane R, Hayostek C, Willett C, Radiation Therapy Oncology Group Trial 0012 (2006) Randomized phase II study of neoadjuvant combined-modality chemoradiation for distal rectal cancer: Radiation Therapy Oncology Group Trial 0012. J Clin Oncol 24:650–655. https://doi.org/10.1200/JCO.2005.03.6095

    Article  CAS  PubMed  Google Scholar 

  10. Yeo S-G, Kim DY, Kim TH, Chang HJ, Oh JH, Park W, Choi DH, Nam H, Kim JS, Cho MJ, Kim JH, Park JH, Kang MK, Koom WS, Kim JS, Nam TK, Chie EK, Kim JS, Lee KJ (2010) Pathologic complete response of primary tumor following preoperative chemoradiotherapy for locally advanced rectal cancer: long-term outcomes and prognostic significance of pathologic nodal status (KROG 09-01). Ann Surg 252:998–1004. https://doi.org/10.1097/SLA.0b013e3181f3f1b1

    Article  PubMed  Google Scholar 

  11. de Campos-Lobato LF, Stocchi L, da Luz Moreira A et al (2011) Pathologic complete response after neoadjuvant treatment for rectal cancer decreases distant recurrence and could eradicate local recurrence. Ann Surg Oncol 18:1590–1598. https://doi.org/10.1245/s10434-010-1506-1

    Article  PubMed  Google Scholar 

  12. Lim YJ, Kim Y, Kong M (2019) Adjuvant chemotherapy in rectal cancer patients who achieved a pathological complete response after preoperative chemoradiotherapy: a systematic review and meta-analysis. Sci Rep 9:10008. https://doi.org/10.1038/s41598-019-46457-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ha GW, Lee MR (2020) Oncologic effects of adjuvant chemotherapy in patients with ypT0–2N0 rectal cancer after neoadjuvant chemoradiotherapy and curative surgery: a meta-analysis. Ann Surg Treat Res 99:97–109. https://doi.org/10.4174/astr.2020.99.2.97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. He F, Ju H-Q, Ding Y, Jiang Z, Li Z, Huang B, Wang X, Zhao Y, Li Y, Qi B, Luo W, Zhang Z, Pei Q, Chen H, Liu S, Pang X, Zheng J, Wang J, Ajani JA, Wan XB (2020) Association between adjuvant chemotherapy and survival in patients with rectal cancer and pathological complete response after neoadjuvant chemoradiotherapy and resection. Br J Cancer 123:1244–1252. https://doi.org/10.1038/s41416-020-0989-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Nguyen A, James DR, Dozois EJ, Kelley SR, Mathis KL (2019) The role of adjuvant chemotherapy in ypT0N0 rectal adenocarcinoma. J Gastrointest Surg 23:2263–2268. https://doi.org/10.1007/s11605-019-04129-9

    Article  PubMed  Google Scholar 

  16. Benson AB, Venook AP, Al-Hawary MM et al (2018) Rectal cancer, version 2.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Cancer Netw 16:874–901. https://doi.org/10.6004/jnccn.2018.0061

    Article  Google Scholar 

  17. Turner MC, Keenan JE, Rushing CN, Gulack BC, Nussbaum DP, Benrashid E, Hyslop T, Strickler JH, Mantyh CR, Migaly J (2019) Adjuvant chemotherapy improves survival following resection of locally advanced rectal cancer with pathologic complete response. J Gastrointest Surg 23:1614–1622. https://doi.org/10.1007/s11605-018-04079-8

    Article  PubMed  Google Scholar 

  18. Breugom AJ, van Gijn W, Muller EW, Berglund Å, van den Broek CBM, Fokstuen T, Gelderblom H, Kapiteijn E, Leer JWH, Marijnen CAM, Martijn H, Meershoek-Klein Kranenbarg E, Nagtegaal ID, Påhlman L, Punt CJA, Putter H, Roodvoets AGH, Rutten HJT, Steup WH, Glimelius B, van de Velde CJH (2015) Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo) radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial. Ann Oncol 26:696–701. https://doi.org/10.1093/annonc/mdu560

    Article  CAS  PubMed  Google Scholar 

  19. Glynne-Jones R, Counsell N, Quirke P, Mortensen N, Maraveyas A, Meadows HM, Ledermann J, Sebag-Montefiore D (2014) Chronicle: results of a randomised phase III trial in locally advanced rectal cancer after neoadjuvant chemoradiation randomising postoperative adjuvant capecitabine plus oxaliplatin (XELOX) versus control. Ann Oncol 25:1356–1362. https://doi.org/10.1093/annonc/mdu147

    Article  CAS  PubMed  Google Scholar 

  20. Collette L, Bosset J-F, den Dulk M, Nguyen F, Mineur L, Maingon P, Radosevic-Jelic L, Piérart M, Calais G, European Organisation for Research and Treatment of Cancer Radiation Oncology Group (2007) Patients with curative resection of cT3-4 rectal cancer after preoperative radiotherapy or radiochemotherapy: does anybody benefit from adjuvant fluorouracil-based chemotherapy? A Trial of the European Organisation for Research and Treatment of Cancer Rad. J Clin Oncol 25:4379–4386. https://doi.org/10.1200/JCO.2007.11.9685

    Article  CAS  PubMed  Google Scholar 

  21. Bosset J-F, Calais G, Mineur L, Maingon P, Stojanovic-Rundic S, Bensadoun RJ, Bardet E, Beny A, Ollier JC, Bolla M, Marchal D, van Laethem JL, Klein V, Giralt J, Clavère P, Glanzmann C, Cellier P, Collette L (2014) Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol 15:184–190. https://doi.org/10.1016/S1470-2045(13)70599-0

    Article  CAS  PubMed  Google Scholar 

  22. Morris MC, Winer LK, Lee TC, Shah SA, Rafferty JF, Paquette IM (2020) Omission of adjuvant chemotherapy in rectal cancer patients with pathologic complete response: a national analysis. J Gastrointest Surg. https://doi.org/10.1007/s11605-020-04749-6

  23. Hu X, Li Y-Q, Ma X-J, Zhang L, Cai SJ, Peng JJ (2019) Adjuvant chemotherapy for rectal cancer with complete pathological response (pCR) may not be necessary: a pooled analysis of 5491 patients. Cancer Cell Int 19:127. https://doi.org/10.1186/s12935-019-0851-9

    Article  PubMed  PubMed Central  Google Scholar 

  24. Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement. PLoS Med 6:e1000097. https://doi.org/10.1371/journal.pmed.1000097

    Article  PubMed  PubMed Central  Google Scholar 

  25. Higgins JPT, Cochrane Collaboration (2019) Cochrane handbook for systematic reviews of interventions, 2nd edition. Wiley-Blackwell Publishing Ltd

  26. Sterne JA, Hernán MA, Reeves BC et al (2016) ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ 355:i4919. https://doi.org/10.1136/bmj.i4919

    Article  PubMed  PubMed Central  Google Scholar 

  27. Parmar MK, Torri V, Stewart L (1998) Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 17:2815–2834

    Article  CAS  PubMed  Google Scholar 

  28. Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR (2007) Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 8:16. https://doi.org/10.1186/1745-6215-8-16

    Article  PubMed  PubMed Central  Google Scholar 

  29. Hozo SP, Djulbegovic B, Hozo I (2005) Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 5:13. https://doi.org/10.1186/1471-2288-5-13

    Article  PubMed  PubMed Central  Google Scholar 

  30. Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, Guyatt GH, Harbour RT, Haugh MC, Henry D, Hill S, Jaeschke R, Leng G, Liberati A, Magrini N, Mason J, Middleton P, Mrukowicz J, O'Connell D, Oxman AD, Phillips B, Schünemann HJ, Edejer T, Varonen H, Vist GE, Williams JW Jr, Zaza S, GRADE Working Group (2004) Grading quality of evidence and strength of recommendations. BMJ 328:1490. https://doi.org/10.1136/bmj.328.7454.1490

    Article  PubMed  Google Scholar 

  31. Capirci C, Valentini V, Cionini L et al (2008) Prognostic value of pathologic complete response after neoadjuvant therapy in locally advanced rectal cancer: long-term analysis of 566 ypCR patients. Int J Radiat Oncol 72:99–107. https://doi.org/10.1016/j.ijrobp.2007.12.019

    Article  Google Scholar 

  32. Huh JW, Kim HR (2009) Postoperative chemotherapy after neoadjuvant chemoradiation and surgery for rectal cancer: is it essential for patients with ypT0-2N0? J Surg Oncol 100:387–391. https://doi.org/10.1002/jso.21342

    Article  CAS  PubMed  Google Scholar 

  33. Lee KH, Kim JC, Kim JY, Kim JS (2015) Oncologic results and prognostic predictors of patients with locally advanced rectal cancer showing ypN0 after radical surgery following neoadjuvant chemoradiotherapy. Int J Color Dis 30:1041–1050. https://doi.org/10.1007/s00384-015-2261-3

    Article  Google Scholar 

  34. Galata C, Merx K, Mai S, Gaiser T, Wenz F, Post S, Kienle P, Hofheinz RD, Horisberger K (2018) Impact of adjuvant chemotherapy on patients with ypT0-2 ypN0 rectal cancer after neoadjuvant chemoradiation: a cohort study from a tertiary referral hospital. World J Surg Oncol 16:156. https://doi.org/10.1186/s12957-018-1455-x

    Article  PubMed  PubMed Central  Google Scholar 

  35. Xu Z, Mohile SG, Tejani MA, Becerra AZ, Probst CP, Aquina CT, Hensley BJ, Arsalanizadeh R, Noyes K, Monson JRT, Fleming FJ (2017) Poor compliance with adjuvant chemotherapy use associated with poorer survival in patients with rectal cancer: an NCDB analysis. Cancer 123:52–61. https://doi.org/10.1002/cncr.30261

    Article  CAS  PubMed  Google Scholar 

  36. Kim CG, Ahn JB, Shin SJ, Beom SH, Heo SJ, Park HS, Kim JH, Choe EA, Koom WS, Hur H, Min BS, Kim NK, Kim H, Kim C, Jung I, Jung M (2017) Role of adjuvant chemotherapy in locally advanced rectal cancer with ypT0-3N0 after preoperative chemoradiation therapy and surgery. BMC Cancer 17:615. https://doi.org/10.1186/s12885-017-3624-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Lu Z, Cheng P, Zhang MG, Wang XS, Zheng ZX (2018) Is adjuvant chemotherapy necessary for patients with ypT0–2N0 rectal cancer treated with neoadjuvant chemoradiotherapy and curative surgery? Gastroenterol Rep 6:277–283. https://doi.org/10.1093/gastro/goy029

    Article  Google Scholar 

  38. Gamaleldin M, Church JM, Stocchi L, Kalady M, Liska D, Gorgun E (2017) Is routine use of adjuvant chemotherapy for rectal cancer with complete pathological response justified? Am J Surg 213:478–483. https://doi.org/10.1016/j.amjsurg.2016.11.028

    Article  PubMed  Google Scholar 

  39. Tay RY, Jamnagerwalla M, Steel M et al (2017) Survival Impact of adjuvant chemotherapy for resected locally advanced rectal adenocarcinoma. Clin Colorectal Cancer 16:e45–e54. https://doi.org/10.1016/j.clcc.2016.09.011

    Article  PubMed  Google Scholar 

  40. Peng JH, Lin JZ, Rong YM, Zhu Y, Deng YX, Zhao YJ, Lu ZH, Wu XJ, Pan ZZ (2018) Oxaliplatin-containing adjuvant chemotherapy improves the survival of locally advanced rectal cancer patients with pathological complete response after pre-operative chemoradiotherapy. Gastroenterol Rep 6:195–201. https://doi.org/10.1093/gastro/goy009

    Article  Google Scholar 

  41. Kuan F-C, Lai C-H, Ku H-Y, Wu CF, Hsieh MC, Liu TW, Yeh CY, Lee KD (2017) The survival impact of delayed surgery and adjuvant chemotherapy on stage II/III rectal cancer with pathological complete response after neoadjuvant chemoradiation. Int J Cancer 140:1662–1669. https://doi.org/10.1002/ijc.30562

    Article  CAS  PubMed  Google Scholar 

  42. Lorenzon L, Parini D, Rega D, Mellano A, Vigorita V, Biondi A, Jaminez-Rosellon R, Scheiterle M, Giannini I, Gallo G, Marino G, Turati L, Marsanic P, de Franco L, Marano L, de Luca R, Delrio P, D'Ugo D, Balducci G, Montesi G, Muratore A, Poblador AR, Persiani R, Frasson M, Roviello F, Vincenti L, Trompetto M, la Torre G, Sgroi G, Patriti A, Simone M, de Luca R (2017) Long-term outcomes in ypT0 rectal cancers: an international multi-centric investigation on behalf of Italian Society of Surgical Oncology Young Board (YSICO). Eur J Surg Oncol 43:1472–1480. https://doi.org/10.1016/j.ejso.2017.04.017

    Article  CAS  PubMed  Google Scholar 

  43. Polanco PM, Mokdad AA, Zhu H, Choti MA, Huerta S (2018) Association of adjuvant chemotherapy with overall survival in patients with rectal cancer and pathologic complete response following neoadjuvant chemotherapy and resection. JAMA Oncol 4:938–943. https://doi.org/10.1001/jamaoncol.2018.0231

    Article  PubMed  PubMed Central  Google Scholar 

  44. Shahab D, Gabriel E, Attwood K, Ma WW, Francescutti V, Nurkin S, Boland PM (2017) Adjuvant chemotherapy is associated with improved overall survival in locally advanced rectal cancer after achievement of a pathologic complete response to chemoradiation. Clin Colorectal Cancer 16:300–307. https://doi.org/10.1016/j.clcc.2017.03.005

    Article  PubMed  Google Scholar 

  45. Lichthardt S, Zenorini L, Wagner J, Baur J, Kerscher A, Matthes N, Kastner C, Pelz J, Kunzmann V, Germer CT, Wiegering A (2017) Impact of adjuvant chemotherapy after neoadjuvant radio- or radiochemotherapy for patients with locally advanced rectal cancer. J Cancer Res Clin Oncol 143:2363–2373. https://doi.org/10.1007/s00432-017-2483-6

    Article  CAS  PubMed  Google Scholar 

  46. Zhou J, Qiu H, Lin G, Xiao Y, Wu B, Wu W, Sun X, Lu J, Zhang G, Xu L, Liu Y (2016) Is adjuvant chemotherapy necessary for patients with pathological complete response after neoadjuvant chemoradiotherapy and radical surgery in locally advanced rectal cancer? Long-term analysis of 40 ypCR patients at a single center. Int J Color Dis 31:1163–1168. https://doi.org/10.1007/s00384-016-2579-5

    Article  Google Scholar 

  47. Geva R, Itzkovich E, Shamai S, Shacham-Shmueli E, Soyfer V, Klausner JM, Tulchinsky H (2014) Is there a role for adjuvant chemotherapy in pathological complete response rectal cancer tumors following neoadjuvant chemoradiotherapy? J Cancer Res Clin Oncol 140:1489–1494. https://doi.org/10.1007/s00432-014-1712-5

    Article  CAS  PubMed  Google Scholar 

  48. Kiran RP, Kirat HT, Burgess AN, Nisar PJ, Kalady MF, Lavery IC (2012) Is adjuvant chemotherapy really needed after curative surgery for rectal cancer patients who are node-negative after neoadjuvant chemoradiotherapy? Ann Surg Oncol 19:1206–1212. https://doi.org/10.1245/s10434-011-2044-1

    Article  PubMed  Google Scholar 

  49. Dossa F, Acuna SA, Rickles AS, Berho M, Wexner SD, Quereshy FA, Baxter NN, Chadi SA (2018) Association between adjuvant chemotherapy and overall survival in patients with rectal cancer and pathological complete response after neoadjuvant chemotherapy and resection. JAMA Oncol 4:930–937. https://doi.org/10.1001/jamaoncol.2017.5597

    Article  PubMed  PubMed Central  Google Scholar 

  50. Govindarajan A, Reidy D, Weiser MR, Paty PB, Temple LK, Guillem JG, Saltz LB, Wong WD, Nash GM (2011) Recurrence rates and prognostic factors in ypN0 rectal cancer after neoadjuvant chemoradiation and total mesorectal excision. Ann Surg Oncol 18:3666–3672. https://doi.org/10.1245/s10434-011-1788-y

    Article  PubMed  Google Scholar 

  51. Maas M, Nelemans PJ, Valentini V, Crane CH, Capirci C, Rödel C, Nash GM, Kuo LJ, Glynne-Jones R, García-Aguilar J, Suárez J, Calvo FA, Pucciarelli S, Biondo S, Theodoropoulos G, Lambregts DMJ, Beets-Tan RGH, Beets GL (2015) Adjuvant chemotherapy in rectal cancer: defining subgroups who may benefit after neoadjuvant chemoradiation and resection A pooled analysis of 3,313 patients. Int J Cancer 137:212–220. https://doi.org/10.1002/ijc.29355

    Article  CAS  PubMed  Google Scholar 

  52. Song C, Chung J-H, Kang S-B, Kim D-W, Oh H-K, Lee HS, Kim JW, Lee K-W, Kim JH, Kim J-S (2018) Impact of tumor regression grade as a major prognostic factor in locally advanced rectal cancer after neoadjuvant chemoradiotherapy: a proposal for a modified staging system. Cancers 10(9):319. https://doi.org/10.3390/cancers10090319

  53. Manfredi S, Lepage C, Hatem C et al (2006) Epidemiology and management of liver metastases from colorectal cancer. Ann Surg 244:254–259. https://doi.org/10.1097/01.sla.0000217629.94941.cf

    Article  PubMed  PubMed Central  Google Scholar 

  54. Valentini V, van Stiphout RGPM, Lammering G, Gambacorta MA, Barba MC, Bebenek M, Bonnetain F, Bosset JF, Bujko K, Cionini L, Gerard JP, Rödel C, Sainato A, Sauer R, Minsky BD, Collette L, Lambin P (2011) Nomograms for predicting local recurrence, distant metastases, and overall survival for patients with locally advanced rectal cancer on the basis of European randomized clinical trials. J Clin Oncol 29:3163–3172. https://doi.org/10.1200/JCO.2010.33.1595

    Article  PubMed  Google Scholar 

  55. Aldo S, Valentina CLN, Vincenzo V et al (2014) No benefit of adjuvant Fluorouracil Leucovorin chemotherapy after neoadjuvant chemoradiotherapy in locally advanced cancer of the rectum (LARC): long term results of a randomized trial (I-CNR-RT). Radiother Oncol 113:223–229. https://doi.org/10.1016/j.radonc.2014.10.006

    Article  Google Scholar 

  56. Hong YS, Kim SY, Lee JS, Nam BH, Kim KP, Kim JE, Park YS, Park JO, Baek JY, Kim TY, Lee KW, Ahn JB, Lim SB, Yu CS, Kim JC, Yun SH, Kim JH, Park JH, Park HC, Jung KH, Kim TW (2019) Oxaliplatin-Based Adjuvant Chemotherapy for Rectal Cancer After Preoperative Chemoradiotherapy (ADORE): long-term results of a randomized controlled trial. J Clin Oncol 37:3111–3123. https://doi.org/10.1200/JCO.19.00016

    Article  CAS  PubMed  Google Scholar 

  57. Rödel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, Hofheinz RD, Ghadimi M, Wolff HA, Lang-Welzenbach M, Raab HR, Wittekind C, Ströbel P, Staib L, Wilhelm M, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, Liersch T, German Rectal Cancer Study Group (2015) Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 16:979–989. https://doi.org/10.1016/S1470-2045(15)00159-X

    Article  CAS  PubMed  Google Scholar 

  58. Grothey A, Sobrero AF, Shields AF, Yoshino T, Paul J, Taieb J, Souglakos J, Shi Q, Kerr R, Labianca R, Meyerhardt JA, Vernerey D, Yamanaka T, Boukovinas I, Meyers JP, Renfro LA, Niedzwiecki D, Watanabe T, Torri V, Saunders M, Sargent DJ, Andre T, Iveson T (2018) Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med 378:1177–1188. https://doi.org/10.1056/NEJMoa1713709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Milinis K, Thornton M, Montazeri A, Rooney PS (2015) Adjuvant chemotherapy for rectal cancer: is it needed? World J Clin Oncol 6:225–236. https://doi.org/10.5306/wjco.v6.i6.225

    Article  PubMed  PubMed Central  Google Scholar 

  60. Chun LJ, Haigh PI, Tam MS, Abbas MA (2012) Defunctioning loop ileostomy for pelvic anastomoses: predictors of morbidity and nonclosure. Dis Colon Rectum 55:167–174. https://doi.org/10.1097/DCR.0b013e31823a9761

    Article  PubMed  Google Scholar 

  61. Menahem B, Lubrano J, Vallois A, Alves A (2018) Early closure of defunctioning loop ileostomy: is it beneficial for the patient? A meta-analysis. World J Surg 42:3171–3178. https://doi.org/10.1007/s00268-018-4603-0

    Article  PubMed  Google Scholar 

  62. Hanna MH, Vinci A, Pigazzi A (2015) Diverting ileostomy in colorectal surgery: when is it necessary? Langenbeck's Arch Surg 400:145–152. https://doi.org/10.1007/s00423-015-1275-1

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Conception and design of the study: TZOVARAS, BALOYIANNIS

Acquisition of data: PERIVOLIOTIS, VEDERAKI

Drafting the article: PERIVOLIOTIS, BALOYIANNIS

Critical revision: KOUKOULIS, SYMEONIDIS

Final approval: TZOVARAS, BALOYIANNIS

Corresponding author

Correspondence to Konstantinos Perivoliotis.

Ethics declarations

Ethics approval and consent to participate

Not applicable

Consent for publication

Not applicable

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note

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

Supplementary Information

ESM 1

(DOCX 787 kb)

ESM 2

(DOCX 47 kb)

Appendix

Appendix

Fig. 1
figure 1

Study flow diagram

Fig. 2
figure 2

Hazard ratio of overall survival

Fig. 3
figure 3

Sensitivity analysis of the primary outcome

Table 1 Study characteristics
Table 2 Summary of findings table

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Baloyiannis, I., Perivoliotis, K., Vederaki, S. et al. Current evidence regarding the role of adjuvant chemotherapy in rectal cancer patients with pathologic complete response after neoadjuvant chemoradiotherapy: a systematic review and meta-analysis. Int J Colorectal Dis 36, 1395–1406 (2021). https://doi.org/10.1007/s00384-021-03915-9

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00384-021-03915-9

Keywords

Navigation