Selecting Patients With Locally Advanced Rectal Cancer for Neoadjuvant Treatment Strategies

Abstract

Rectal cancer remains a significant problem worldwide. Outcomes vary significantly according to the stage of disease and prognostic factors, including the distance of the tumor from the circumferential resection margin. Accurate staging, including high-resolution magnetic resonance imaging, allows stratification of patients into low-, moderate-, and high-risk disease; this information can be used to inform multidisciplinary team decisions regarding the role of neoadjuvant therapy. Both neoadjuvant short-course radiotherapy and long-course chemoradiation reduce the risk of local recurrence compared with surgery alone, but they have little impact on survival. Although there remains a need to reduce overtreatment of those patients at moderate risk, evaluation of intensified regimens for those with high-risk disease is still required to reduce distant failure rates and improve survival in these patients with an otherwise poor prognosis. The Oncologist 2013;18:833-842Implications for Practice: The use of preoperative therapy in rectal cancer should be made in a multidisciplinary team setting based on accurate staging in combination with magnetic resonance imaging findings and patient characteristics. Circumferential resection margin involvement, extent of extramural spread, lymph node burden, extramural venous invasion and low-lying position of primary rectal cancer are all established pathological risk factors and can be identified by MRI preoperatively. This would allow stratification of patients to receive neoadjuvant therapy. Those patients with low risk rectal cancer can undergo surgery alone with favorable long-term outcomes sparing them from radiation-induced long-term toxicities. Those patients with high risk disease will need to be evaluated for intensified preoperative regimens to reduce distant failures and improve survival. Continuous research efforts are essential to identify both tissue and imaging biomarkers to predict efficacy to preoperative therapy which are lacking currently in order to optimize long-term outcome and minimize toxicities.

Neoadjuvant therapy in rectal cancer: how are we choosing?

“…These include tumour height, extramural vascular invasion, levator involvement and distance from the MRF . While our institution's radiotherapy protocol is consistent with the understanding that LCR may be required to facilitate shrinkage of the tumour mass in order to achieve an R0 resection, it lacks the above radiological factors which are incorporated into international guidelines. Our protocol is therefore pragmatic, but overly simple, lacking precision in differentiating between LCR and SCR.…”

A perspective on the current treatment strategies for locally advanced rectal cancer

“…Rectal cancer comprises a heterogeneous group of tumours in which outcomes vary significantly depending on different prognostic factors. In addition to T and N stage, the involvement of the circumferential resection margin (CRM), the location in the lower portion of the rectum, the extent of extramural spread and extramural venous invasion, are also relevant risk factors for local and systemic recurrence (Dewdney et al, 2013;Glimelius et al, 2013). High-resolution magnetic resonance imaging (MRI) allows preoperative identification of such risk factors and helps defining three different prognostic groups: "the Good, the Bad and the Ugly", quoting the epic 1966 Western directed by Sergio Leone (Smith and Brown, 2008).…”

“…The low risk subgroup (the "good"), includes T1-2 rectal cancer (so-called "very early"), T3 extending ≤5 mm into perirectal fat and with a clear margin at MRI >1 mm from the mesorectal fascia (MRF), T3 lesion located in the mid/upper third of the rectum without extramural venous invasion and negative lymph nodes (N0) (Dewdney et al, 2013;Glimelius et al, 2013;Smith and Brown, 2008). In this category of patients, standard TME surgery alone with sharp radical dissection of the mesorectal fat including all lymph nodes is appropriate because the risk of local failure is very low.…”

“…EMS, extramural spread; MRF±, radial margin at MRI ≤1/>1 mm from the mesorectal fascia; EMVI±, presence/absence of extramural venous invasion; CRT, Chemoradiotherapy; CT, chemotherapy; SCRT, short-course radiotherapy; TME, total mesorectal excision; TEM, transanal excision microsurgery; cCR, clinical complete response. >1 mm from the MRF, T3 located in the mid/upper third of the rectum and with presence of extramural venous invasion or T1-3/N1 cancers (Dewdney et al, 2013;Glimelius et al, 2013;Smith and Brown, 2008). In this population, preoperative fluoropyrimidebased CRT or hypofractionated SCRT are valid treatment options (Bosset et al, 2006;Gerard et al, 2006;Kapiteijn et al, 2001;SebagMontefiore et al, 2009).…”

“…The "ugly" subgroup, usually referred as locally advanced disease, includes T4 rectal cancer, T3 with a margin at MRI ≤1 mm from MRF, T3 low-lying at or below the elevator muscles of the pelvis, T3 extending >5 mm into perirectal fat and with presence of extramural venous invasion or any T-N2 (Dewdney et al, 2013;Glimelius et al, 2013;Smith and Brown, 2008). For such patients the challenge is to implement an intensified therapeutic strategy that improves both distant and local control of disease.…”