What is the recommended treatment approach for rectal cancer?

From the Guidelines

The recommended treatment approach for rectal cancer involves a multidisciplinary strategy tailored to the stage of disease, with a focus on minimizing impact on quality of life while achieving optimal outcomes in terms of morbidity, mortality, and quality of life. For early-stage rectal cancer (Stage I), surgery alone, such as a local excision or total mesorectal excision (TME), may be sufficient, as noted in the NCCN Guidelines Insights: Rectal Cancer, version 3.2024 1.

Key Considerations for Treatment

• For more advanced disease (Stages II-III), neoadjuvant (pre-surgical) therapy is usually recommended, consisting of chemoradiation with 5-fluorouracil (5-FU) or capecitabine combined with radiation therapy for 5-6 weeks, followed by surgery 6-10 weeks later, as supported by recent clinical trials and guidelines 1.
• After surgery, adjuvant chemotherapy with FOLFOX (5-FU, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) for 3-6 months is often recommended, particularly for patients with high-risk features, to reduce the risk of recurrence and improve survival rates.
• For metastatic rectal cancer (Stage IV), systemic chemotherapy regimens like FOLFOX, FOLFIRI (5-FU, leucovorin, and irinotecan), or targeted therapies based on molecular testing are used, aiming to control the disease, alleviate symptoms, and improve quality of life.

Recent Updates and Recommendations

• The NCCN Guidelines Insights: Rectal Cancer, version 3.2024, highlights the importance of a multidisciplinary approach, including the consideration of endoscopic submucosal dissection for early-stage rectal cancer, updates to total neoadjuvant therapy, and the option of a "watch-and-wait" nonoperative management approach for clinical complete responders to neoadjuvant therapy 1.
• The ASCO guideline on the management of locally advanced rectal cancer also emphasizes the role of total neoadjuvant therapy and discusses the potential for omitting radiation therapy in certain scenarios, as well as the use of immunotherapy for patients with microsatellite instability-high (MSI-H) or mismatch repair–deficient (dMMR) tumors 1.

Individualized Treatment Decisions

• Treatment decisions should always be individualized based on patient factors, including age, comorbidities, tumor location, and molecular characteristics of the cancer, to ensure the best possible outcomes in terms of morbidity, mortality, and quality of life.
• The choice of treatment according to risk category for primary rectal cancer without distant metastases, as outlined in guidelines such as those from ESMO 1, should be carefully considered, taking into account the latest evidence and guidelines to inform treatment planning.

From the FDA Drug Label

OPDIVO may be used alone or in combination with ipilimumab when your colon or rectal cancer: ▪ has spread, is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), and ▪ you have received treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, and it did not work or is no longer working.

The recommended treatment approach for metastatic rectal cancer is nivolumab (OPDIVO) alone or in combination with ipilimumab for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors who have received prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan 2.

For early rectal cancer, there is no direct information in the provided drug labels.

Key points:

• Nivolumab (OPDIVO) is used for metastatic rectal cancer with MSI-H or dMMR tumors.
• Irinotecan is used in combination with 5-fluorouracil (5-FU) and leucovorin (LV) for metastatic colorectal cancer 3.

From the Research

Treatment Approaches for Rectal Cancer

The treatment of rectal cancer involves a multidisciplinary approach, with various options available depending on the stage and severity of the disease. Some of the key treatment approaches include:

• Surgery: Total mesorectal excision (TME) is the standard surgical approach for rectal cancer, which has been shown to improve oncological outcomes 4, 5.
• Radiotherapy: Radiotherapy before or after radical surgery is used to control local recurrence of advanced rectal cancer 5.
• Chemotherapy: Neoadjuvant concurrent chemotherapy and radiotherapy is considered the standard therapy for rectal cancer, with 5-FU-based concurrent chemoradiotherapy being the only standard treatment option 5.
• Multidisciplinary approach: A multidisciplinary team approach is essential for the management of rectal cancer, involving surgeons, gastroenterologists, medical and radiation oncologists, radiologists, and pathologists 6, 4, 7.

Early Rectal Cancer Treatment

For early rectal cancer, the following treatment options are available:

• Local excision (LE): Endoscopic submucosal dissection and transanal endoscopic microsurgery are established approaches for LE of selected early rectal cancer 7.
• Organ-sparing approaches: Neoadjuvant therapies followed by LE may be considered, but their role should be formally assessed by randomized controlled trials 7.
• Rectal resection and TME: Indicated in the presence of unfavorable features at the pathological evaluation of the LE specimen 7.

Metastatic Rectal Cancer Treatment

For metastatic rectal cancer, the treatment approach may involve:

• Intensification of chemotherapy: The integration of newer generation chemotherapeutics and target agents into fluoropyrimidines-based chemoradiotherapy (CRT) has been explored to improve distant control and survival in rectal cancer 8.
• Multidisciplinary approach: A risk-adapted strategy should be pursued in the postoperative setting, with the selection of patients for different multidisciplinary treatment strategies based on clinico-pathological features 8.