What is the best next step for a patient with rectal adenocarcinoma, 5 cm from the anal verge, with no lymph nodes (LNs) involved?

From the Guidelines

For rectal cancer located 5 cm from the anal verge with no lymph node involvement, the best next step is option B: Neoadjuvant chemoradiation (Nigro protocol) with concurrent chemoradiotherapy using 5-FU, radiation, and mitomycin C. This approach is recommended because tumors in the mid to low rectum (within 5-8 cm from the anal verge) benefit from downstaging prior to surgery, as stated in the guidelines by the Chinese Society of Clinical Oncology (CSCO) 1. Neoadjuvant therapy can reduce tumor size, potentially convert an unresectable tumor to resectable, increase the likelihood of sphincter preservation, and reduce local recurrence rates.

Key Considerations

• The standard regimen typically includes 5-FU as a radiosensitizer along with external beam radiation therapy over 5-6 weeks, followed by surgery after 6-10 weeks to allow for maximal tumor response.
• This approach is appropriate regardless of whether the tumor is adenocarcinoma (most common in rectum) or squamous cell carcinoma.
• After neoadjuvant therapy and appropriate waiting period, surgical options would be reassessed based on response, with LAR (Low Anterior Resection) preferred when possible to preserve sphincter function, while APER (Abdominoperineal Resection) would be considered if the tumor remains too close to the sphincter complex for safe resection with adequate margins, as recommended by the NCCN guidelines 1.

Additional Recommendations

• The CSCO guidelines also recommend that patients with difficulties in anal sphincter preservation should undergo radical surgery of rectal cancer, with options for preoperative concurrent chemoradiotherapy for patients with a strong desire for sphincter preservation 1.
• The NCCN guidelines suggest that transanal local excision may be an option for selected T1,N0 early-stage cancers, but careful patient selection and examination of the resection specimen are crucial to ensure optimal outcomes 1.

From the Research

Treatment Options for Rectal Cancer

• The treatment for rectal cancer 5 cm from the anal verge with no lymph nodes (LNs) involves several options, including:
  • Abdominoperineal resection (APER) for rectal cancer when the cancer is located close to the anus
  • Neoadjuvant chemoradiation (Nigro) concurrent CRT (5-FU, Radio, mitomycine)
  • Low anterior resection (LAR) when the cancer is located well above the anus

Considerations for Treatment

• According to the study by 2, the distance of the tumor from the anal verge is correlated with 3-year disease-free survival, and patients with tumor at 4-5 cm from the anal verge may not benefit from survival when they undergo sphincter-preserving operations.
• The study by 3 found that the distance of rectal cancer from the anal verge influences the use of neo-adjuvant treatment and ultimate R0 resection rate, but does not influence loco-regional or systemic recurrence rates.
• The study by 4 evaluated preoperative infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/bevacizumab with selective rather than consistent use of chemoradiotherapy, and found that for selected patients with clinical stages II to III rectal cancer, neoadjuvant chemotherapy and selective radiation does not seem to compromise outcomes.
• The study by 5 proposed that an initial node size of ≥8 mm with an anal verge-to-tumor distance of >5 cm and ≥6 mm with an anal verge-to-tumor distance of ≤5 cm are optimal indications for lateral pelvic lymph node dissection in rectal cancer.
• The study by 6 compared induction chemotherapy and long-course chemoradiation versus short-course radiation and consolidative chemotherapy, and found that total neoadjuvant therapy with either approach was associated with similar perioperative morbidity and complete response rates.

Tumor Type and Location

• The type of tumor (adenocarcinoma or squamous cell carcinoma) and its location (distance from the anal verge) are important factors in determining the best course of treatment for rectal cancer.
• According to the study by 2, the survival rate for patients with sphincter-preserving at 6-7 cm from the anal verge was significantly higher than that at 4-5 cm.
• The study by 5 found that tumors located within 5 cm distance from the anal verge were significant predictors of lateral pelvic lymph node metastasis.