What is the approach to organ preservation in rectal cancer management?

Organ Preservation in Rectal Cancer: A Paradigm Shift in Management

Organ preservation through nonoperative management (NOM) or local excision (LE) after neoadjuvant chemoradiotherapy represents an oncologically safe alternative to radical surgery for carefully selected rectal cancer patients who achieve clinical complete response (cCR), with the primary goal of maintaining anorectal function and quality of life while avoiding permanent colostomy. 1

Core Organ Preservation Strategies

Nonoperative Management (Watch-and-Wait)

The watch-and-wait approach is recommended by NCCN for patients achieving cCR after neoadjuvant therapy, demonstrating 5-year overall survival of 85% and disease-specific survival of 94%. 2

• Oncological safety: Data from the International Watch and Wait Database analyzing 880 patients shows deferral of surgery appears oncologically safe, though local recurrence occurs in 25.2% of patients, with 88% occurring within the first 2 years 1, 2, 3
• Salvage success: The majority (88%) of local regrowths can be successfully salvaged with surgery if detected early through rigorous surveillance 2
• Patient selection criteria: Requires cCR confirmed by digital rectal examination, MRI showing no residual tumor, endoscopy revealing no visible tumor or only white scar tissue, and absence of suspicious lymph nodes 2

Local Excision After Neoadjuvant Therapy

LE using transanal endoscopic microsurgery or transanal minimally invasive surgery is an alternative organ preservation approach for selected patients with small T1-T3 rectal cancers demonstrating good response after chemoradiotherapy. 1

• Trial evidence: The CARTS, TREC, and GRECCAR2 trials demonstrated feasibility of LE in patients with residual disease after neoadjuvant therapy 1
• Dual purpose: LE serves both diagnostic and therapeutic functions in patients with near-complete clinical response (ncCR), though completion total mesorectal excision (TME) may be required if adverse features are found 1

Primary Local Excision for Early-Stage Disease

LE alone without neoadjuvant therapy is the appropriate primary treatment for stage cT1N0 rectal cancers without adverse histopathological features, reducing morbidity without compromising long-term oncological outcomes. 1

• Adverse features requiring completion TME: Location in middle or lower third of submucosa (SM2), grade 3 or higher disease, venous invasion, and lymphatic invasion 1

Total Neoadjuvant Therapy: Maximizing Organ Preservation Rates

Total neoadjuvant therapy (TNT) significantly increases pathologic complete response rates and enables organ preservation in approximately 50% of appropriately selected patients. 3

Consolidation vs. Induction Chemotherapy

NCCN recommends consolidation chemotherapy after chemoradiotherapy over induction chemotherapy before chemoradiotherapy when organ preservation is the goal, based on superior TME-free survival (53% vs 41%) demonstrated in the OPRA trial. 3

• RAPIDO trial: TNT with short-course radiotherapy plus consolidation chemotherapy reduced disease-related treatment failure at 3 years (RR 0.79,95% CI 0.63-1.00) 3
• PRODIGE-23 trial: Achieved significantly improved pathologic complete response rates (OR 1.74,95% CI 1.45-2.10) and 3-year disease-free survival 3

Extended Interval to Response Assessment

Allowing adequate time between completion of neoadjuvant therapy and response assessment (typically 12-24 weeks) is critical for maximizing tumor downstaging and cCR rates. 4

Rigorous Surveillance Protocol

NCCN guidelines mandate intensive surveillance for patients managed with organ preservation: digital rectal examination, flexible sigmoidoscopy, and CEA every 4 months for the first 2 years, then every 6 months for years 3-5, plus MRI every 6 months for the first 2 years, then annually for years 3-5. 2

Follow-up Timing Consensus

• First 2 years: Endoscopy, pelvic MRI, and digital rectal examination every 3-4 months 1
• Years 3-5: Same modalities every 6 months 1
• CT chest/abdomen: Every 6-12 months during first year, then annually during years 2-5 1
• Serum CEA: Every 3 months for first 3 years, then every 6 months for years 4-5 1

Critical pitfall: Delaying surveillance beyond 4-month intervals in the first 2 years risks missing the window when 94-99% of regrowth occurs 3

Patient Selection Criteria

Baseline Tumor Characteristics

Increasing cT stage, tumor volume, tumor length, and bowel wall circumferential extent at baseline are the most important predictors of achieving cCR. 1

• Optimal candidates for planned organ preservation: Early-stage disease (cT1-T3bN0), tumors ≤5-10 cm from anal verge, maximum diameter ≤4-5 cm 1
• Location considerations: Tumors close to anal sphincter where abdominoperineal resection with permanent stoma would otherwise be required are particularly suitable candidates 1

Response Assessment Criteria

Clinical complete response requires: 2

• No palpable tumor on digital rectal examination
• No visible tumor on endoscopy (only white scar tissue acceptable)
• No residual tumor on MRI
• Lymph nodes showing regression with morphological features suggesting node negativity (diameter <5 mm, regular borders, homogeneous signal) 1

Implementation Requirements

Organ preservation should only be implemented in experienced multidisciplinary centers with expertise in rectal cancer management, including radiation oncologists, medical oncologists, surgical oncologists, pathologists, and radiologists. 1, 2

Quality of Life Outcomes

The primary rationale for organ preservation is maintaining anorectal function and avoiding permanent colostomy, thereby preserving quality of life. 1

• Functional outcomes: 85% of patients report good or excellent bowel function after organ preservation with contact X-ray brachytherapy and neoadjuvant therapy 5
• Stoma avoidance: 94-96% of patients remain stoma-free to latest follow-up 5, 6

Special Populations

Elderly and Comorbid Patients

Short-course radiotherapy (SCRT) combined with contact X-ray brachytherapy provides effective organ preservation for elderly patients (median age 81) not fit for prolonged chemoradiotherapy, achieving 70% cCR in radiotherapy-alone group and 97% in immediate-post-local-excision group. 6

Critical Pitfalls to Avoid

• Inadequate initial staging: Upstaging cT1 tumors as cT2 leads to unnecessary neoadjuvant therapy; accurate baseline staging with high-resolution MRI is essential 1
• Insufficient surveillance: Delayed detection of local regrowth compromises salvage surgery success 2
• Inappropriate patient selection: Offering watch-and-wait outside experienced centers without rigorous protocols increases risk 3
• Wrong TNT sequence: Using induction chemotherapy before chemoradiotherapy when organ preservation is the goal results in inferior TME-free survival compared to consolidation approach 3
• Premature response assessment: Evaluating response before adequate time interval (minimum 12 weeks, optimal 20-24 weeks) reduces cCR detection rates 4

Emerging Evidence

The dostarlimab trial achieved 100% clinical complete response in 12 patients with dMMR stage II-III rectal adenocarcinoma treated with anti-PD-1 immunotherapy alone, suggesting future directions for organ preservation strategies. 3