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

Abstract

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, SanofiAventis, 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. LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Interpret the results of the relevant randomized trials of neoadjuvant induction chemoradiation from Europe and the U.S.2. Explain why induction chemoradiation is preferred over postoperative adjuvant chemoradiation.3. Discuss the rationale for using neoadjuvant induction chemoradiation in rectal cancer.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME 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. The ABSTRACT

Preoperative neo‐adjuvant therapy for curable rectal cancer – reaching a consensus 2008

“…Then a representative from each centre was asked to identify which of three neoadjuvant options (no neo-adjuvant therapy, short-course radiotherapy 25 Gy over five fractions or long-course chemoradiotherapy) he ⁄ she would use for a rectal cancer in the upper, middle or lower third of the rectum staged by MRI as being T 2 -T 4 and ⁄ or N 0 -N 2 . Representatives from all four centres agreed that preoperative staging is best achieved by using MRI scan and that the threat of local recurrence is the greatest from locally advanced cancers in the lower third of the rectum [23]. …”

“…This consensus is maintained in cases of lower third T 3a N 0 cancers. All four oncologists agreed that the histopathological finding of positive lymph nodes or -even worse -a positive circumferential margin after resection of an MRI-defined high-risk rectal cancer represents a significant lost therapeutic opportunity [23]. However, short-course radiotherapy alone or even no neo-adjuvant therapy is likely to be prescribed if the tumour is early (T 2 , N 0 ) and ⁄ or situated in the upper third of the rectum.…”

“…While enhanced local control is not seen in all comparisons of preoperative radiotherapy and chemoradiation [18], most do show a significant reduction in local recurrence rates when chemotherapy is given with preoperative radiotherapy [19][20][21][22][23]. Thus, chemotherapy adds significantly to local control [19] of preoperative radiotherapy, regardless of whether it is administered before or after surgery.…”

Inhibitory effects of oxaliplatin in experimental radiation treatment of colorectal carcinoma: does oxaliplatin improve 5-fluorouracil-dependent radiosensitivity?

“…Resectable LARC is defined more strictly as tumors with penetration through the entire rectal wall, or with evidence of involved pelvic nodes, but still a non-threatened CRM based upon preoperative MRI and without distant metastasis (3), whereas non-resectable LARC usually comprises fixed tumors for which surgery is not possible without leaving tumor tissue within the pelvis. The latter tumors may after neoadjuvant treatment become resectable (17).…”

“…It is also speculated whether NACT also induce shrinkage of primary tumor, thereby improving resectability and CRT response (202). For this reason the term "induction chemotherapy" has been proposed (17). However, NACT will delay both CRT and surgery, and in the case of cervical and head-and-nech cancer, NACT consistently failed to show any benefits in clinical trials (202).…”