From the Guidelines
Neoadjuvant treatment is the standard of care for stage 3 rectal cancer, and the most recent guidelines recommend a combination of chemotherapy and radiation therapy given before surgery. The typical approach involves chemoradiation, with the standard regimen including 5-fluorouracil (5-FU) or capecitabine (Xeloda) along with radiation therapy, typically delivered over 5-6 weeks 1. According to the most recent NCCN guidelines, capecitabine is usually given at 825 mg/m² twice daily on radiation days, while 5-FU is administered as a continuous infusion at 225 mg/m²/day throughout radiation. Some centers may use more intensive regimens that add oxaliplatin (FOLFOX or CAPOX) either before or after chemoradiation.
Key Considerations
- The goal of neoadjuvant therapy is to reduce local recurrence rates, increase the likelihood of achieving negative surgical margins, and in some cases, allow for sphincter-preserving surgery rather than permanent colostomy 1.
- Approximately 15-20% of patients may achieve a complete pathological response, which has been associated with improved long-term outcomes.
- The total duration of perioperative therapy, including chemoradiation and chemotherapy, should not exceed 6 months 1.
- Recent updates to the NCCN Guidelines for Rectal Cancer include the addition of endoscopic submucosal dissection as an option for early-stage rectal cancer, updates to the total neoadjuvant therapy approach, and the addition of a “watch-and-wait” nonoperative management approach for clinical complete responders to neoadjuvant therapy 1.
Treatment Approach
- Patients typically wait 8-12 weeks after completing neoadjuvant therapy before undergoing surgery to allow for maximum tumor response.
- The use of sequenced multimodality therapy following a multidisciplinary approach is recommended to balance curative-intent therapy with minimal impact on quality of life, particularly for patients with distal rectal cancer 1.
From the Research
Neoadjuvant Treatment for Stage 3 Rectal Cancer
- Neoadjuvant chemoradiation is considered the standard of care in the management of stage II/III rectal cancer, as it results in a decrease in local relapse rates and a favorable toxicity profile 2.
- The combination of fluorouracil (5-FU) plus radiation is a common neoadjuvant treatment, but recent studies have shown that capecitabine (Xeloda) plus radiation can be an acceptable alternative 2.
- The addition of oxaliplatin (Eloxatin) or irinotecan (Camptosar) to 5-FU or capecitabine concurrently with radiation therapy may result in more favorable pathologic responses, but further investigation is needed 2.
- Combined chemoradiotherapy offers the lowest rates of local and distant relapse for stage II and III rectal cancers, and is typically delivered neoadjuvantly to improve tolerability and optimize surgical outcomes 3.
Recent Developments in Neoadjuvant Treatment
- A phase I study of lenvatinib and capecitabine with external radiation therapy in locally advanced rectal adenocarcinoma showed promising results, with a downstaging rate of 84.2% and a pathologic complete response rate of 37.8% 4.
- Neoadjuvant chemoradiation has become a standard of care in stage II and III rectal cancer, and has impacted the way pathological evaluation of resection specimens is conducted 5.
- A clinical practice guideline focused update provides evidence-based recommendations for the indications and dose-fractionation regimens for neoadjuvant radiation therapy, optimal sequencing of RT and systemic therapy, and considerations for selective omission of RT and surgery for rectal cancer 6.
Key Considerations
- Neoadjuvant radiation therapy is strongly recommended for patients with stage II-III rectal cancer, but consideration of omission of neoadjuvant RT may be conditionally recommended in favor of neoadjuvant chemotherapy with a favorable treatment response or upfront surgery 6.
- A total neoadjuvant therapy (TNT) approach is strongly recommended for patients with T3-T4 and node-positive rectal cancer undergoing neoadjuvant RT 6.
- Selection of RT dose-fractionation regimen, sequencing of therapies, and consideration of nonoperative management should be determined by multidisciplinary consensus and based on disease extent, disease location, patient preferences, and quality of life considerations 6.