Adjuvant systemic chemotherapy in rectal cancer

Neoadjuvant/adjuvant therapy of clinical stage II (T3-4, node-negative disease with tumour penetration through the muscle wall) or stage III (node positive disease without distant metastasis) rectal cancer often includes locoregional treatment due to the relatively high risk of locoregional recurrence. A total of approximately 6 months of 5-FU-based perioperative treatment is preferred. Preoperative chemoradiotherapy showed fewer local recurrences (relative risk, 0.46; 95% CI 0.26-0.82; from 6% to 13%) and less acute and late toxicities.

Patients, with resected stage II or III rectal cancer, who have not received preoperative radiotherapy should be offered postoperative therapy with concurrent chemoradiotherapy in addition to fluoropyrimidine-based chemotherapy. It is recommended that the total duration for perioperative therapy be approximately 6 months.

Although acknowledging that few studies have evaluated the effect of adjuvant chemotherapy in patients with rectal cancer, and that its role is not well defined, NCCN recommends adjuvant chemotherapy for all patients with stage II/III rectal cancer following neoadjuvant chemoRT/surgery regardless of the surgical pathology results (e.g. NCCN recommends that most patients should receive postoperative chemotherapy even following an apparent complete response (CR)).

The role and optimal duration of treatment with adjuvant oxaliplatin in addition to 5-FU in rectal cancer is still unclear. Oxaliplatin may be added to 5-FU as adjuvant therapy. Most of the support for addition of oxaliplatin to 5-FU as adjuvant chemotherapy in rectal cancer is an extrapolation from the data available for colon cancer. The use of a shorter course of adjuvant oxaliplatin in addition to 5-FU in rectal cancer (i.e. ~ 4 months) is justified when preoperative chemoRT is administered.

The panel recommends against the use of bevacizumab, cetuximab, panitumumab, or irinotecan in adjuvant therapy for non-metastatic disease.

The workgroup members unanimously support the general adoption of the NCCN guidelines.

The workgroup members unanimously support the following statements as modifications to the NCCN guidelines:

Evidence for the role of adjuvant 5-FU and oxaliplatin in rectal cancer is limited and at times conflicting, nevertheless till more definitive data emerges, adoption of the NCCN guidelines is prudent.

The role of adjuvant therapy in patients with pT3N0 rectal cancer following upfront surgery remains contentious.