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Gastrointestinal Cancer

Locally Advanced Rectal Cancer: What Is the Evidence for Induction Chemoradiation?

Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, Middlesex, United Kingdom

Key Words. Rectal cancer • Neoadjuvant • Chemoradiation • Sphincter-sparing surgery • Circumferential resection margin • Pathological complete response

Correspondence: Rob Glynne-Jones, F.R.C.P, F.R.C.R., Mount Vernon Centre for Cancer Treatment, Northwood, Middlesex, United Kingdom, HA6 2RN. Telephone: 01923-844767; Fax: 01923-844138; e-mail: rob.glynnejones{at}nhs.net

Disclosure: R.G.-J. has received honoraria for lectures and advisory boards and has been supported in attending international meetings by Merck, Pfizer, Sanofi-Aventis, and Roche. He has also received unrestricted grants for research from Merck, Sanofi-Aventis, and Roche. M.H. has received honoraria for lectures and advisory boards and has been supported in attending international meetings by Merck, Astra-Zeneca, Pfizer, Sanofi-Aventis, and Roche.

The concept of spatial cooperation in neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer is attractive. Chemotherapy may, as a component of CRT, not only act as a radiosensitizing agent but also potentially eradicate distant micrometastases. Recent trials have demonstrated that the addition of concurrent 5-fluorouracil (5-FU)-based chemotherapy to radiation increases the pathological complete response rate, and reduces local recurrence, but as yet, a survival advantage has not been observed.

Aims. This review aims to examine the evidence for induction CRT in locally advanced rectal cancer. The endpoints of pathological complete response, a negative circumferential margin, sphincter-sparing surgery, local control, disease-free survival (DFS), and overall survival (OS) are examined, as are acute and late morbidity, surgical complications, and late functional results.

Methods. The information to produce this review was compiled by searching PubMed and MEDLINE for English language articles published until April 2007. The search term included "induction, neoadjuvant, chemotherapy, radiotherapy, chemoradiation, combined modality" in association with rectal cancer.

Conclusions. CRT in the European randomized trials of rectal cancer improves tumor downstaging, pathological complete response, and local control over radiotherapy alone, but does not translate into a benefit in terms of longer DFS or OS, or a higher chance of sphincter preservation. Metastatic disease remains a significant problem, which provides a strong rationale for the integration of a second cytotoxic drug, or biologically targeted agents.

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