Initial management of locally advanced pMMR/MSS rectal adenocarcinoma (cT3-T4, Nx, M0 or Tx, N1-2, M0)

CAPOX: capecitabine and oxaliplatin; CRT: chemoradiation therapy; CT: computed tomography; EUS: endoscopic ultrasound; FOLFIRINOX: fluouracil, leucovorin, irinotecan, and oxaliplatin; FOLFOX: fluouracil, leucovorin, and oxaliplatin; FU: fluorouracil; M: metastasis; MRI: magnetic resonance imaging; MSS: microsatellite stable; N: node; pMMR: proficient mismatch repair; RT: radiation therapy; T: tumor; TNT: total neoadjuvant therapy.

* For TNT, chemotherapy is administered for 12 to 16 weeks with either FOLFOX, CAPOX, or FOLFIRINOX. FOLFIRINOX is typically administered prior to neoadjuvant RT, and further studies are necessary to establish its tolerability after neoadjuvant RT.

¶ Neoadjuvant chemotherapy plus response-guided use of RT allows most patients to omit RT and avoid its late toxicities.

Δ Long-course CRT is administered at 45 to 54 Gy in 25 to 30 fractions. Chemotherapy is concurrently administered with RT using either capecitabine or infusional FU. For patients with any of the following high-risk features, we suggest long-course CRT rather than short-course RT due to lower locoregional recurrence rates:

• Clinical T4a/b primary tumor
• Clinical N2 disease
• Extramural venous invasion
• Involved mesorectal fascia
• Enlarged lateral lymph nodes

◊ Short-course RT is administered at 25 Gy in 5 fractions.

§ For neoadjuvant chemotherapy followed by the response-guided use of CRT, we administer 6 cycles (3 months) of neoadjuvant FOLFOX and 6 cycles (3 months) of adjuvant FOLFOX.

¥ In most centers, all patients who undergo neoadjuvant CRT are offered adjuvant chemotherapy due to difficulty in assessing nodal status in the treated surgical specimen.

‡ A complete clinical response is scar only with no clinical evidence of residual tumor on digital rectal exam, pelvic MRI, and direct endoscopic evaluation.

† Surveillance is an option for patients with a complete clinical response^‡. Surveillance should be performed at a center of excellence in the multidisciplinary management of rectal cancer. In observational studies, although surveillance is associated with higher rates of rectal preservation, local regrowth can occur in up to one-third of patients. Randomized trials comparing surveillance with resection are necessary to accurately assess long-term rates of local and distant failure and overall survival.

** For patients who receive TNT, we omit adjuvant (postoperative) chemotherapy for those who were treated with at least 4 months of neoadjuvant chemotherapy. For patients who only receive 2 months of neoadjuvant chemotherapy, we offer 2 months of adjuvant (postoperative) chemotherapy to complete a total of 4 months of chemotherapy.