What is the recommended treatment for rectal adenocarcinoma?

Treatment of Rectal Adenocarcinoma

Treatment of rectal adenocarcinoma requires a stage-based, multidisciplinary approach with surgery as the cornerstone for localized disease, combined with neoadjuvant chemoradiotherapy for locally advanced tumors (T3/T4 or node-positive), and systemic chemotherapy for metastatic disease.

Risk Stratification and Treatment Selection

Treatment decisions depend on clinical staging using endorectal ultrasound for early tumors (cT1-T2) or rectal MRI for all others to assess depth of invasion, nodal status, and relationship to the mesorectal fascia 1.

Early/Favorable Disease (T1-T2, N0)

For T1 sm1-2 tumors (Haggitt 1-3) without vessel invasion or poor differentiation, local excision using transanal endoscopic microsurgery (TEM) is appropriate 1.

• The resection must be complete with safe margins (R0) and no signs of vessel invasion or poor differentiation 1
• If deeper submucosal invasion (T1 sm3, Haggitt 4) or T2 tumors are present, the recurrence risk exceeds 10% and immediate radical surgery with total mesorectal excision (TME) is required 1
• For early favorable cases (cT1-2, early cT3a-b with clear mesorectal fascia) above the levators, surgery alone with TME is appropriate since local failure risk is very low 1

Intermediate/Locally Advanced Disease (Most T3, T4a, N+)

Preoperative therapy is strongly preferred over postoperative treatment because it is more effective and less toxic [1, 1.

Two preoperative approaches are acceptable:

1. Short-course radiotherapy: 25 Gy in 5 fractions over 1 week followed by immediate surgery (<10 days) 1

   • This is a convenient, simple, and low-toxicity option 1

2. Long-course chemoradiotherapy: 45-50.4 Gy in 1.8-2 Gy fractions with concurrent 5-FU (bolus, continuous infusion, or oral) 1

   • Surgery should be performed 6-8 weeks after completion 1

All patients with T3/T4 or node-positive disease should receive adjuvant radiotherapy and chemotherapy (Category 1 recommendation) 1.

Surgical Approach

Total mesorectal excision (TME) with sharp dissection is mandatory for all rectal lesions not amenable to local excision 1.

• For mid-to-upper rectal lesions: low anterior resection is the treatment of choice 1
• For low rectal lesions: abdominoperineal resection or coloanal anastomosis is required 1
• The mesorectum distal to the tumor must be removed as an intact unit to reduce local recurrence risk 1
• For upper third tumors, partial mesorectal excision with ≥5 cm mesorectal margin is acceptable 1
• At least 12 lymph nodes should be examined pathologically 1

Most Locally Advanced/Non-Resectable Disease (T3 crm+, T4b)

For tumors with threatened or involved circumferential resection margin or overgrowth to non-readily resectable organs, preoperative chemoradiotherapy with 50-50.4 Gy in 1.8 Gy fractions plus concurrent 5-FU-based therapy is required 1.

• Surgery should be performed 6-8 weeks after completion of chemoradiotherapy 1
• A major goal is to decrease tumor volume and enhance sphincter preservation 1

Postoperative Therapy

Postoperative chemoradiotherapy (50 Gy with concurrent 5-FU) is no longer routinely recommended but should be used only in patients with positive circumferential margins, tumor perforation, or high local recurrence risk if preoperative radiotherapy was not given 1.

Adjuvant chemotherapy can be provided for node-positive or high-risk stage II disease, similar to colon cancer, though evidence is less robust 1.

• Continuous infusion 5-FU plus radiotherapy is more effective than bolus 5-FU 1

Metastatic Disease (Stage IV)

Resectable Metastases

For patients with resectable liver or lung metastases, surgical resection should be considered as part of curative-intent treatment 1.

• Simultaneous rectal and hepatic surgery is appropriate if hepatectomy involves ≤3 segments 1
• Alternatively, metastasectomy can be performed 3 months after rectal surgery depending on progression 1

Unresectable/Symptomatic Metastases

First-line palliative chemotherapy should be initiated early and consists of 5-FU/leucovorin combined with either oxaliplatin or irinotecan, with or without bevacizumab 1, 2.

• For patients with good performance status able to tolerate intensive therapy: irinotecan alone or 5-FU/leucovorin/irinotecan or 5-FU/leucovorin/oxaliplatin 1
• For patients unable to tolerate intensive therapy: capecitabine, protracted IV 5-FU, or bolus/infusional 5-FU/leucovorin 1
• Weekly bolus 5-FU/leucovorin/irinotecan may cause severe gastrointestinal toxicity and requires careful monitoring during the first 60 days 1

Second-line chemotherapy should be considered for patients with maintained good performance status 1.

For symptomatic primary tumors, palliative resection, fulguration, or radiotherapy followed by systemic therapy are options 1.

Recurrent Disease

Patients with local recurrence who did not receive prior radiotherapy should receive preoperative radiotherapy with concurrent chemotherapy 1.

• Surgery should be attempted 6-8 weeks after radiotherapy 1
• In previously irradiated patients, additional external beam or intraoperative radiotherapy can be attempted, though evidence is limited 1

Critical Pitfalls to Avoid

• Do not perform local excision alone for T1 sm3 or T2 tumors—the recurrence risk is too high (≥10%) and salvage surgery yields poor survival 1
• Do not use postoperative chemoradiotherapy routinely—preoperative treatment is more effective and less toxic 1
• Do not perform inadequate mesorectal excision—TME with sharp dissection is essential to achieve local recurrence rates <10% 1
• For patients not candidates for radical resection, adjuvant chemoradiotherapy after local excision is required to reduce local recurrence 1