What is the role of neoadjuvant therapy in the treatment of rectal cancer?

Updated: Apr 06, 2021
  • Author: Burt Cagir, MD, FACS; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Neoadjuvant long-course radiation therapy (RT) plus radiation sensitization with a fluoropyrimidine (eg, capecitabinefluorouracil), followed by a treatment break of approximately 8 weeks before surgical excision and concluding with adjuvant chemotherapy, has been a standard of care in rectal cancer. Other options for neoadjuvant treatment include short-course RT, chemotherapy (eg, with FOLFOX [leucovorin calcium (folinic acid), fluorouracil, oxaliplatin] or CAPOX [capecitabine plus oxaliplatin]) alone, or short-course RT followed by chemotherapy. [1, 42]

The randomized RAPIDO trial found that at 3 year–followup, patients receiving short-course RT (5x5 Gy), then chemotherapy with CAPOX or FOLFOX4 followed by total mesorectal excision (TME) had a disease-related treatment failure rate of 23.7%, compared with 30.4% in patients who received neoadjuvant capecitabine-based chemoradiotherapy followed by TME and optional adjuvant chemotherapy. [44]  

For locally advanced rectal cancer, a newer standard of care is total neoadjuvant therapy (TNT), which consists of induction chemotherapy (eg, with CAPOX or modified FOLFOX6 [mFOLFOX6]) followed by chemoradiation therapy and then TME. In a retrospective cohort analysis of patients with locally advanced (T3/4 or node-positive) rectal cancer, the cohort that received TNT (n = 308) had higher rates of complete response and were more likely to have temporary ileostomy reversed within 15 weeks of proctectomy, compared with the cohort that received the standard regimen of neoadjuvant chemoradiation therapy, surgery, and planned adjuvant chemotherapy (n = 320). [45]

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