• TNT is an evolving approach for rectal cancers and can be considered as one of the standards of care.  Several clinical trials have studied different approaches for rectal cancer and a consensus statement from the Western GI Consensus has been produced.
• All patients should be discussed at multidisciplinary rounds. A staging MRI should be performed and reported in a synoptic standard.  It can be used for patients with good performance status with T4, N2 disease, EMVI, involved mesorectal fascia and/or enlarged lateral lymph nodes and patients with low rectal cancers at risk for APR. It can be used in select cases for patients with less bulky disease.
• Fluoropyrimidine and oxaliplatin based chemotherapy is the favoured systemic therapy approach in TNT and in select cases the addition of irinotecan can be considered. Both long course and short course radiation are reasonable options in the TNT approach and may be tailored based on tumour and patient factors.  Four months of chemotherapy is recommended.
• The optimal sequencing can be short course or long course chemoradiation prior to consolidative chemotherapy as this leads to improved pathologic complete response (CR).

Summary:

• Long course chemoradiation with capecitabine or short course radiation followed by 4 months of chemotherapy approximately 2 weeks after completion of radiation.
• Patients should undergo standard oncologic surgery for rectal cancer with the standard surveillance strategy. In the cases of a CR, non-operative management with a surveillance strategy can be considered in the context of a clinical trial. See table 1.
• Long term data is still pending and a final approach is still to be determined.

Non Operative Management (Active Surveillance

Table 1 Active Surveillance Schedule

Assessment for Local Re-growth

Regular assessments for local re-growth will be performed by the treating surgeon and will consist of DRE, endoscopy and MRI as per the schedule in Table 1. If any of these investigations do not meet criteria for cCR or if there is any uncertainty about these findings, this will be considered a local re-growth. Biopsies of the local re-growth will be required, however, surgery will be recommended for both positive and negative biopsy results (due to concerns about false negative results).

Assessment for Metastatic Disease

Regular assessments for metastatic disease will be performed by the treating medical oncologist and will consist of CEA and CT CAP as per the schedule in Table 1. If at any time point the CEA is elevated, this will prompt a CT CAP if this has not already been done.

Local Excision for Early Rectal Cancer

In select patients with early stage rectal cancer, a reasonable alternative to radical resection is combination neoadjuvant therapy followed by transanal endoscopic surgery (TES).

Patients considered for this approach should be discussed at multidisciplinary conference. Surgery for these patients should be provided at a high volume centre where >20 TES procedures are performed per year.

Patients should be counselled about the increased risk (10-15%) of local recurrence but similar 5 year disease free survival. These patients should be followed by an intensive surveillance program if medically fit for early salvage surgery.

POST TES (Active Surveillance)

Table 2 Active Surveillance Schedule

• Endoscopy after 36 months would be at the discretion of the endoscopist

Patients should be considered for a clinical trial.

Assessment for Local Re-growth

Regular assessments for local re-growth will be performed by the treating surgeon and will consist of DRE, endoscopy and MRI as per the schedule in Table 2. If any of these investigations do not meet criteria for cCR or if there is any uncertainty about these findings, this will be considered a local re-growth. Biopsies of the local re-growth will be required, however, surgery will be recommended for both positive and negative biopsy results (due to concerns about false negative results).

Assessment for Metastatic Disease

Regular assessments for metastatic disease will be performed by the treating medical oncologist and will consist of CEA and CT CAP as per the schedule in Table 2. If at any time point the CEA is elevated, this will prompt a CT CAP if this has not already been done.

Stage IV: any T, any N, M1

• In spite of the presence of metastases, excision of the primary tumour may provide the best form of local palliation. In appropriate circumstances, operation may be facilitated by preoperative chemotherapy and radiation.
• Locoregional/organ specific directed therapy may be considered for patients with isolated liver or lung metastasis. Referral to BC Cancer for multi-disciplinary assessment is recommended.
• Palliative radiation therapy or stereotactic body radiation therapy (SBRT) in selected patients; referral of SBRT patients to BC Cancer for multi-disciplinary assessment is recommended.
• Palliative chemotherapy has been shown to significantly improve survival in patients with unresectable metastatic colorectal cancer achieving an estimated median overall survival of 24 to 28 months as compared to 6 to 12 months with supportive care alone. Currently approved chemotherapeutic agents for metastatic colon cancer include: capecitabine, 5-fluorouracil (5-FU), irinotecan and oxaliplatin.
  • The most commonly used regimens are:
    • oxaliplatin with 5-FU (FOLFOX) or capecitabine (CAPOX)
    • irinotecan with 5-FU (FOLFIRI) or capecitabine (CAPIRI)
    • capecitabine monotherapy
  • The choice and sequence of chemotherapy is determined by disease-related factors, patient factors and patient preferences as assessed by the medical oncologist.
• Currently approved targeted therapies include: bevacizumab, cetuximab, and panitumumab.
  • Bevacizumab is recommended for use in combination with first-line FOLFIRI chemotherapy (FOLFOX may be considered in selected circumstances). It may also be considered for use in combination with second-line doublet chemotherapy for those patients who did not receive it in first-line.
  • Cetuximab or panitumumab is indicated in patients with previously treated metastatic colorectal cancer with wild-type K-ras gene (i.e. tumour K-ras gene is not mutated).
• Please refer to current treatment protocols for indications, dosing and eligibility criteria.
• Consider treatment on a clinical trial, if available.
• Symptom management, best supportive care, and involvement of palliative care services as indicated by patient’s clinical status.