What are the options for non-operative management of rectal cancer?

Non-Operative Management of Rectal Cancer

Non-operative management (NOM) may be offered as an alternative to total mesorectal excision for patients with locally advanced rectal cancer who achieve a clinical complete response (cCR) after total neoadjuvant therapy, particularly when abdominoperineal resection would otherwise be required. 1

Patient Selection Criteria

NOM should only be considered for patients meeting strict criteria for clinical complete response after neoadjuvant therapy 1:

• Digital rectal examination: No palpable tumor material present 1
• Rectoscopy findings: No residual tumor material and no erythematous ulcer (only a scar may be present) 1
• MRI criteria: Substantial tumor downsizing with no observable residual tumor material, or residual fibrosis only with limited signal on diffusion-weighted imaging, sometimes with residual wall thickening from edema, and no suspicious lymph nodes 1
• Endoscopic biopsy: Not mandatory to define cCR and should not be performed if DRE, rectoscopy, and MRI criteria are all fulfilled 1

Optimal Neoadjuvant Regimen to Achieve cCR

Total neoadjuvant therapy (TNT) with long-course chemoradiotherapy followed by consolidation chemotherapy is the preferred approach to maximize the likelihood of achieving cCR suitable for NOM. 1, 2

The specific TNT regimen should include 1, 2:

• Long-course chemoradiation (50 Gy in 1.8 Gy fractions with concurrent 5-FU-based chemotherapy) 1
• Followed by consolidation chemotherapy (FOLFOX or similar regimen) 1, 2
• Surgery delayed 6-8 weeks after completion of neoadjuvant therapy to allow maximal tumor response 1

Avoid short-course radiotherapy-based TNT for patients being considered for NOM, as the RAPIDO trial demonstrated higher locoregional recurrence rates (10% vs 6%) with this approach. 2

Special Population: MSI-H/dMMR Tumors

For patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) locally advanced rectal cancer, immunotherapy is the recommended treatment and may result in exceptionally high rates of complete response. 1, 2

Patients with contraindications to immunotherapy may consider standard TNT options, though dMMR tumors are sensitive to chemoradiation and historically fluorouracil-based chemotherapy has been less effective in this population. 1

Patient Counseling and Shared Decision-Making

The discussion of NOM versus surgery should address 1:

• Improved functional outcomes with NOM, including preserved anorectal function and quality of life 1
• Surgical risk factors including patient age, comorbidities, and performance status 1
• Likelihood of identifying complete response based on clinical assessment accuracy 1
• Intensive surveillance requirements necessary with NOM approach 1
• Reduced risk of permanent ostomy if NOM is successful, particularly relevant for low rectal cancers requiring abdominoperineal resection 1

Surveillance Protocol for NOM

Patients selecting NOM require intensive, standardized follow-up 1, 3:

• Regular digital rectal examinations 1
• Serial endoscopic assessments 1, 3
• Interval MRI imaging with diffusion-weighted sequences 1
• CEA monitoring 4

The optimal timing and frequency of surveillance assessments remains an area requiring standardization, though more frequent monitoring is necessary in the first 2 years when most local regrowth occurs. 1

Salvage Surgery for Local Regrowth

Patients who develop local tumor regrowth during NOM surveillance should undergo immediate salvage surgery with total mesorectal excision. 3, 5

Data from retrospective studies demonstrate that salvage surgery after local regrowth can still achieve acceptable oncologic outcomes, though this requires early detection through rigorous surveillance. 3, 5

Critical Pitfalls to Avoid

Do not offer NOM outside of clinical trials or highly experienced centers with established surveillance protocols. 3 The accurate assessment of cCR without pathologic verification requires expertise in multimodal clinical assessment. 3, 5

Do not use PET/CT as the sole determinant of cCR, though post-treatment SUVmax <4.3 or >66% SUV decrease may provide supportive evidence. 6 However, MRI with DWI, endoscopy, and digital rectal examination remain the primary assessment modalities. 1

Ensure patients understand that NOM is not equivalent to "refusing surgery" - these are distinct patient populations with different outcomes and motivations. 7 Planned NOM after documented cCR differs fundamentally from declining recommended surgery. 7

Do not apply NOM to patients without high-risk features who would otherwise be candidates for surgery alone - these patients should proceed directly to total mesorectal excision without neoadjuvant therapy. 4

Current Evidence Level

While retrospective and prospective cohort studies demonstrate high rates of local control and disease-free survival with NOM comparable to surgery-based therapy 3, 5, total mesorectal excision after neoadjuvant therapy remains the standard of care for locally advanced rectal cancer. 3 Multiple ongoing prospective trials are comparing NOM versus standard surgical management. 1, 3