Skip to main content
SpringerLink
Log in

Neoadjuvant Radiotherapy (5 × 5 Gy): Immediate Versus Delayed Surgery

  • Chapter
  • First Online:
Early Gastrointestinal Cancers II: Rectal Cancer

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 203))

Abstract

Goals: To evaluate the role of length of the interval between 5 × 5 Gy and surgery. Methods: PubMed was searched to perform a systematic review. Results: There were 10 studies on 5 × 5 Gy with delayed surgery (no of patients (n) = 1343), and six studies on 5 × 5 Gy with consolidation chemotherapy delivered over a long interval prior to surgery in a tight sequence (n = 244). In total, there were four randomized studies, five phase II studies, and seven retrospective studies. Trials that compared immediate with delayed surgery after 5 × 5 Gy showed a benefit in terms of lower rate of severe acute post-radiation toxicity (4.2 % absolute difference) in the immediate-surgery group. However, this benefit was counterbalanced by the increase in minor postoperative complications (13 % of absolute difference) in the group with immediate surgery compared with that with the delayed surgery. The pathological complete response (pCR) rate was about 10 % higher in the delayed-surgery group. There were no differences in sphincter preservation and R0 resection rate between the two groups. Small studies suggest no differences in the oncological outcomes. Regarding elderly patients who were unfit for chemotherapy, short-course radiotherapy with delayed surgery produced favourable outcomes for “unresectable” cancer or for small cancer after full-thickness local excision. A watch-and-wait policy in complete responders after short-course radiotherapy is feasible. A pCR of over 20 % was recorded after short-course radiotherapy and consolidation chemotherapy compared with about 10 % after 5 × 5 Gy and delayed surgery. Favourable outcomes after short-course radiotherapy and consolidation chemotherapy were observed in patients with potentially resectable stage IV disease. Conclusions: Evidence showed that 5 × 5 Gy with delayed surgery can be used routinely for the management of elderly patients who are unfit for chemotherapy in case of “unresectable” cancer or early cancer prior to local excision. Short-course radiotherapy with consolidation chemotherapy is a promising treatment that can be used routinely for potentially resectable stage IV disease.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Bujko K, Michalski W, Kepka L et al (2007) Association between pathologic response in metastatic lymph nodes after preoperative radiochemotherapy and the risk for distant metastases in rectal cancer: an analysis of outcomes in a randomized trial. Int J Rad Oncol Biol Phys 67:369–377

    Article  Google Scholar 

  • Benzen SM (2009) Dose-response relationship in radiotherapy. In: Joiner M, van der Kogel A (eds) Basic clinical radiobiology, 4th edn. Edward Arnold, London, pp 56–67

    Google Scholar 

  • Bujko K, Nowacki MP, Nasierowska-Guttmejer A et al (2004) Sphincter preservation following preoperative radiotherapy for rectal cancer: report of a randomized trial comparing short-term radiotherapy vs. conventionally fractionated radiochemotherapy. Radiother Oncol 72:15–24

    Article  CAS  PubMed  Google Scholar 

  • Bujko K, Richter P, Smith FM et al (2013a) Preoperative radiotherapy and local excision of rectal cancer with immediate radical re-operation for poor responders: a prospective multicentre study. Radiother Oncol 106:198–205

    Google Scholar 

  • Bujko K, Nasierowska-Guttmejer A, Wyrwicz L et al (2013b) Neoadjuvant treatment for unresectable rectal cancer: an interim analysis of a multicentre randomized study. Radiother Oncol 107:171–177

    Google Scholar 

  • Bujko K, Nowacki MP, Nasierowska-Guttmejer A et al (2006) Long-term results of 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 

  • 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 

  • Bosset JF, Collette L, Calais G et al (2006) Chemoradiotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 355:1114–1123

    Article  CAS  PubMed  Google Scholar 

  • Faria S, Kopek N, Hijal T et al (2014) Phase II trial of short-course radiotherapy followed by delayed surgery for locoregionally advanced rectal cancer. Colorectal Dis 16:66–70

    Article  Google Scholar 

  • Francois Y, Nemoz CJ, Bauliex J et al (1999) Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90-01 randomized trial. J Clin Oncol 17:2396–2402

    CAS  PubMed  Google Scholar 

  • Foster JD, Jones EL, Falk S et al (2013) Timing of surgery after long-course neoadjuvant chemoradiotherapy for rectal cancer: a systematic review of the literature. Dis Colon Rectum 56:921–930

    Article  PubMed  Google Scholar 

  • Fokstuen T, Holm T, Glimelius B (2009) Postoperative morbidity and mortality in relation to leukocyte counts and time to surgery after short-course preoperative radiotherapy for rectal cancer. Radiother Oncol 93:293–297

    Article  PubMed  Google Scholar 

  • Frykholm GJ, Glimelius B, Pahlman L et al (1993) Preoperative or postoperative irradiation in adenocarcinoma of the rectum: final treatment results of a randomized trial and evaluation of late secondary effects. Dis Colon Rectum 36:564–572

    Article  CAS  PubMed  Google Scholar 

  • Folkesson J, Birgisson H, Pahlman L et al (2005) Swedish rectal cancer trial: long lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol 23:5644–5650

    Article  PubMed  Google Scholar 

  • Gasinska A, Skolyszewski J, Popiela T et al (2007) Bromodeoxyuridine labeling index as an indicator of early tumor response to preoperative radiotherapy in patients with rectal cancer. J Gastrointest Surg 11:520–528

    Article  PubMed Central  PubMed  Google Scholar 

  • Glimelius B (2013) Neo-adjuvant radiotherapy in rectal cancer. World J Gastroenterol 19:8489–8501

    Article  PubMed Central  PubMed  Google Scholar 

  • Graf W, Dahlberg M, Osman MM et al (1997) Short-term preoperative radiotherapy results in down-staging of rectal cancer: a study of 1316 patients. Radiother Oncol 43:133–137

    Article  CAS  PubMed  Google Scholar 

  • Habr-Gama A, Gama-Rodrigues J et al (2014) Local recurrence after complete clinical response and watch and wait in rectal cancer after neoadjuvant chemoradiation: impact of salvage therapy on local disease control. Int J Radiat Oncol Biol Phys 88:822–828

    Google Scholar 

  • Hatfield P, Hingorani M, Radhakrishna G et al (2009) Short-course radiotherapy, with elective delay prior to surgery, in patients with unresectable rectal cancer who have poor performance status or significant co-morbidity. Radiother Oncol 92:210–214

    Article  PubMed  Google Scholar 

  • Hartley A, Giridharan S, Gray L et al (2002) Retrospective study of acute toxicity following short-course preoperative radiotherapy. Br J Surg 89:889–895

    Article  CAS  PubMed  Google Scholar 

  • Latkauskas T, Pauzas H, Gineikiene I et al (2012) Initial results of a randomised controlled trial comparing clinical and pathological downstaging of rectal cancer after preoperative short-course radiotherapy or long term chemoradiotherapy both with delayed surgery. Colorectal Dis 14:294–298

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Marijnen CA, Nagtegaal ID, Klein Kranenbarg E et al (2001) No downstaging after short-term preoperative radiotherapy in rectal cancer patients. J Clin Oncol 19:1976–1984

    Google Scholar 

  • Martling AL, Holm T, Johansson H et al (2001) The Stockholm II trial on preoperative radiotherapy in rectal carcinoma: long-term follow-up of a population-based study. Cancer 92:896–902

    Article  CAS  PubMed  Google Scholar 

  • Marijnen CA, Kapiteijn E, van de Velde CJ et al (2002) Acute side effects and complications after short-term preoperative radiotherapy combined with total mesorectal excision in primary rectal cancer: report of a multicenter randomized trial. J Clin Oncol 20:817–825

    Article  CAS  PubMed  Google Scholar 

  • Myerson RJ, Tan B, Hunt S et al (2014) Five fractions of radiation therapy followed by 4 cycles of FOLFOX chemotherapy as preoperative treatment for rectal cancer. Int J Radiat Oncol Biol Phys 88:829–836

    Article  PubMed  Google Scholar 

  • Ngan SY, Burmeister B, Fisher RJ et al (2012) Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: trans-Tasman radiation oncology group trial 01.04. J Clin Oncol 30:3827–3833

    Google Scholar 

  • Nilsson PJ, van Etten B, Hospers GA et al (2013) Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer–the RAPIDO trial. BMC Cancer 13:279

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pach R, Kulig J, Richter P et al (2012) Randomized clinical trial on preoperative radiotherapy 25 Gy in rectal cancer: treatment results at 5-year follow-up. Langenbecks Arch Surg 397:801–807

    Article  PubMed Central  PubMed  Google Scholar 

  • 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 

  • Pettersson D, Cedermark B, Holm T et al (2010) Interim analysis of the Stockholm III trial of preoperative radiotherapy regimens for rectal cancer. Br J Surg 97:580–587

    Article  CAS  PubMed  Google Scholar 

  • Pettersson D, Glimelius B, Iversen H et al (2013) Impaired postoperative leucocyte counts after preoperative radiotherapy for rectal cancer in the Stockholm III Trial. Br J Surg 100:969–975

    Article  CAS  PubMed  Google Scholar 

  • Pettersson D, Lorinc E, Holm T et al (2012) Tumour regression and pathological outcomes in the randomized Stockholm III trial of different radiotherapy regiments in rectal cancer. Preoperative radiotherapy in rectal cancer: aspects of different regimens. Thesis, Karolinska Institutet, Stockholm

    Google Scholar 

  • Pettersson D, Holm T, Iversen H et al (2012b) Preoperative short-course radiotherapy with delayed surgery in primary rectal cancer. Br J Surg 99:577–583

    Article  CAS  PubMed  Google Scholar 

  • Perez RO, Habr-Gama A, São Julião GP et al (2012) Optimal timing for assessment of tumor response to neoadjuvant chemoradiation in patients with rectal cancer: do all patients benefit from waiting longer than 6 weeks? Int J Radiat Oncol Biol Phys 84:1159–1165

    Google Scholar 

  • Petrelli F, Sgroi G, Sarti E et al (2013) Increasing the interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer: a meta-analysis of published studies. Ann Surg (Epub ahead of print)

    Google Scholar 

  • Pucciarelli S, De Paoli A, Guerrieri M et al (2013) Local excision after preoperative chemoradiotherapy for rectal cancer: results of a multicenter phase II clinical trial. Dis Colon Rectum 56:1349–1356

    Article  PubMed  Google Scholar 

  • Radu C, Berglund A, Pahlman L et al (2008) Short course preoperative radiotherapy with delayed surgery in rectal cancer: a retrospective study. Radiother Oncol 87:343–349

    Article  PubMed  Google Scholar 

  • Rutten H, den Dulk M, Lemmens V et al (2007) Survival of elderly rectal cancer patients not improved: analysis of population based data on the impact of TME surgery. Eur J Cancer 3:2295–2300

    Article  Google Scholar 

  • 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  PubMed  Google Scholar 

  • Sebag-Montefiore D, Stephens RJ, Steele R et al (2009) Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet 373:811–820

    Article  PubMed Central  PubMed  Google Scholar 

  • Shin SJ, Yoon HI, Kim NK et al (2011) Upfront systemic chemotherapy and preoperative short-course radiotherapy with delayed surgery for locally advanced rectal cancer with distant metastases. Radiat Oncol 6:99–106

    Article  PubMed Central  PubMed  Google Scholar 

  • Stockholm Colorectal Cancer Study Group (1990) Preoperative short-term radiation therapy in operable rectal carcinoma: a prospective randomized trial. Cancer 66:49–55

    Article  Google Scholar 

  • Saglam S, Bugra D, Saglam EK et al (2014) Fourth versus eighth week surgery after neoadjuvant radiochemotherapy in T3-4/N0 + rectal cancer: Istanbul R-01 study. J Gastrointest Oncol 5:9–17

    PubMed Central  PubMed  Google Scholar 

  • Sloothaak DA, Geijsen DE, van Leersum NJ et al (2013) Dutch surgical colorectal audit: optimal time interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer. Br J Surg 100:933–993

    Google Scholar 

  • Suit HD, Gallager HS (1964) Intact tumor cells in irradiated tissue. Arch Pathol 78:648–651

    CAS  PubMed  Google Scholar 

  • Tyc-Szczepaniak D, Wyrwicz L, Kepka et al (2013) Palliative radiotherapy and chemotherapy instead of surgery in symptomatic rectal cancer with synchronous unresectable metastases: a phase II study. Ann Oncol 24:2829–2834

    Google Scholar 

  • van den Broek CB, Vermeer TA, Bastiaannet E et al (2013) Impact of the interval between short-course radiotherapy and surgery on outcomes of rectal cancer patients. Eur J Cancer 49:3131–3139

    Article  PubMed  Google Scholar 

  • van Dijk TH, Tamas K, Beukema JC et al (2013) Evaluation of short-course radiotherapy followed by neoadjuvant bevacizumab, capecitabine, and oxaliplatin and subsequent radical surgical treatment in primary stage IV rectal cancer. Ann Oncol 24:1762–1769

    Article  PubMed  Google Scholar 

  • Veenhof AA, Kropman RH, Engel AF et al (2007) Preoperative radiation therapy for locally advanced rectal cancer: a comparison between two different time intervals to surgery. Int J Colorectal Dis 22:507–513

    Article  CAS  PubMed  Google Scholar 

  • Widder J, Herbst F, Scheithauer W (2005) Preoperative sequential short-term radiotherapy plus chemotherapy can induce complete remission in T3N2 rectal cancer. Acta Oncol 44:921–923

    Article  CAS  PubMed  Google Scholar 

  • Yeo SG, Oh JH, Kim DY et al (2013) Preoperative short-course concurrent chemoradiation therapy followed by delayed surgery for locally advanced rectal cancer: a phase 2 multicenter study (KROG 10-01). Int J Radiat Oncol Biol Phys 86:34–39

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The study was supported by grant No. N N403 580538 from the Polish Ministry of Science and Higher Education. The study sponsor had no role in the study design, in the collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication.

Author information

Authors and Affiliations

  1. The Maria Sklodowska-Curie Memorial Cancer Centre, 5, W. K. Roentgena, 02-781, Warsaw, Poland

    Krzysztof Bujko, Maciej Partycki & Lucyna Pietrzak

Authors
  1. Krzysztof Bujko
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maciej Partycki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lucyna Pietrzak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Krzysztof Bujko .

Editor information

Editors and Affiliations

  1. Department of Medical Oncology, Tumor- und Brustzentrum ZeTuP, St. Gallen, Switzerland

    Florian Otto

  2. Caritasklinik St. Theresia, Saarbrücken, Germany

    Manfred P. Lutz

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Bujko, K., Partycki, M., Pietrzak, L. (2014). Neoadjuvant Radiotherapy (5 × 5 Gy): Immediate Versus Delayed Surgery. In: Otto, F., Lutz, M. (eds) Early Gastrointestinal Cancers II: Rectal Cancer. Recent Results in Cancer Research, vol 203. Springer, Cham. https://doi.org/10.1007/978-3-319-08060-4_12

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-08060-4_12

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-08059-8

  • Online ISBN: 978-3-319-08060-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation