In the U.S., it is common for patients with rectal cancer to undergo neoadjuvant long-course chemoradiotherapy over six weeks using a single chemotherapeutic drug as a radiosensitizer, which is not particularly effective against micrometastatic disease. Then patients undergo surgery six to 10 weeks after the completion of chemoradiotherapy. Only after they have recovered from their operation, typically four to six weeks in the absence of complications, do they receive triple-drug cytotoxic chemotherapy.

“When you add up all those delays, it could be many months before a patient with rectal cancer ever receives effective chemotherapy,” says Thomas E. Read, M.D., a professor and chief of the division of gastrointestinal surgery at UF Health. “It has never made sense to many of us that full-dose chemotherapy was being administered so remote from diagnosis. As surgeons, we have gotten better at controlling local disease. We need to get patients effective chemotherapy to control micrometastatic distant disease sooner.”

To target micrometastasis earlier in the course of treatment, the team at UF Health has instituted a relatively novel protocol for patients with clinical stage II or III rectal cancer:

• Newly diagnosed patients are staged with a CT, MRI, serum measurement of carcinoembryonic antigen, endoscopy with biopsy, clearing colonoscopy to the cecum and tumor molecular profiling to check for deficient DNA mismatch repair, or MMR, and next-generation sequencing, or NGS, status. Each patient’s case is reviewed by a multidisciplinary gastrointestinal tumor board.
• Once a patient is confirmed to have clinical Stage II or III rectal cancer, they begin total neoadjuvant therapy, or TNT, which is a short-course radiotherapy (5 Gy x 5 fractions over one week), followed by eight cycles of FOLFOX chemotherapy for four months. They are then restaged before undergoing surgery, generally two to four weeks after the last chemotherapy dose.

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