What are the indications for adjuvant (additional) chemotherapy in patients with rectal cancer?

From the Guidelines

Postoperative chemotherapy is recommended for all patients with stage II/III rectal cancer after neoadjuvant chemoRT and surgery, regardless of the surgical pathology results, as stated in the NCCN guidelines 1. The indications for postoperative chemotherapy in rectal cancer are based on the stage of the disease and the patient's response to neoadjuvant therapy.

• For patients with stage II/III rectal cancer, adjuvant chemotherapy is recommended, even if they received neoadjuvant chemoradiation therapy, as it may improve disease-free survival (DFS) and overall survival (OS) 1.
• High-risk stage II patients, such as those with obstruction, perforation, inadequate lymph node sampling, poorly differentiated histology, lymphovascular invasion, or perineural invasion, should receive adjuvant chemotherapy similar to stage III patients.
• The choice of adjuvant chemotherapy regimen depends on the initial clinical staging and predicted CRM status, with FOLFOX or CAPEOX as preferred options for higher-risk patients and 5-FU/LV or capecitabine as additional options in some cases 1.
• The timing of adjuvant chemotherapy is important, with optimal outcomes when started within 8 weeks of surgery.
• Treatment decisions should be individualized based on patient factors, including age, comorbidities, and performance status, with dose modifications made for patients with renal impairment, neuropathy, or other conditions that may affect tolerance to specific agents. Some studies have shown that the addition of oxaliplatin to 5-FU may improve DFS, but results are not consistent and there is no effect on OS 1. However, a systematic review published in 2017 identified 8 phase III trials and 1 randomized phase II trial comparing adjuvant chemotherapy with observation in patients with nonmetastatic rectal cancer treated with neoadjuvant chemoRT, and the authors reported that the data are not robust enough to warrant routine use of adjuvant therapy in this population 1. The most recent and highest quality study, the NCCN guidelines 1, recommends the use of adjuvant chemotherapy in patients with stage II/III rectal cancer, and this recommendation should be followed in clinical practice.

From the Research

Indications for Postoperative Chemotherapy in Rectal Cancer

• The decision to administer postoperative chemotherapy in rectal cancer is based on various factors, including the stage of the disease and the presence of high-risk features 2.
• For patients with resected stage II or III rectal cancer who have not received preoperative radiotherapy, postoperative therapy with concurrent chemoradiotherapy plus fluoropyrimidine-based chemotherapy is recommended 3.
• Adjuvant chemotherapy has been shown to improve overall survival, disease-specific survival, and disease-free survival in patients with high-risk stage II colorectal cancer 2.
• However, the benefit of postoperative chemoradiotherapy versus chemotherapy alone in stage II and III upper rectal cancer is still debated, with some studies suggesting that omission of radiotherapy may not jeopardize oncologic outcomes 4.

High-Risk Features

• High-risk features that may indicate the need for postoperative chemotherapy in rectal cancer include T4 tumor, less than 12 lymph nodes harvested, poor differentiation, lymphovascular or perineural invasion, and emergency surgery 2.
• The presence of these features can increase the risk of recurrence and mortality, and adjuvant chemotherapy may help to improve outcomes in these patients.

Chemotherapy Regimens

• Various chemotherapy regimens have been studied in the context of postoperative rectal cancer treatment, including fluorouracil, leucovorin, and oxaliplatin 5, 6.
• The choice of chemotherapy regimen depends on various factors, including the stage of the disease, the presence of high-risk features, and the patient's overall health and performance status.

Timing of Chemoradiotherapy

• The optimal timing of chemoradiotherapy in rectal cancer is still a topic of debate, with some studies suggesting that early postoperative chemoradiotherapy may be beneficial in certain patient populations 5.
• However, other studies have found that the timing of chemoradiotherapy does not significantly impact outcomes, and that other factors such as the presence of high-risk features and the use of adjuvant chemotherapy are more important determinants of recurrence and survival 4.