Nonoperative Management After Total Neoadjuvant Therapy in Rectal Cancer
A recent Italian phase II clinical trial (NO-CUT), published in The Lancet Oncology, evaluated whether some patients with stage II–III rectal cancer can safely avoid surgery after responding completely to upfront treatment. The study focused on patients with a common tumor subtype known as pMMR/MSS.
pMMR/MSS: proficient mismatch repair / microsatellite stable, describes a “normal” state in cancer cells, especially colorectal cancer, where the DNA repair system know as “mismatch repair” (MMR) works correctly, leading to stable DNA (“microsatellite stable”) and fewer mutations compared to dMMR/MSI-High tumors, often resulting in poor response to immunotherapy but a different prognosis and treatment approach.
The study
All 179 participants received chemotherapy and radiation before any surgery (called total neoadjuvant therapy). After treatment:
- Patients whose cancer appeared to be completely gone were closely monitored without surgery (“watch-and-wait” approach).
- Patients with remaining cancer proceeded to surgery.
Researchers wanted to know whether avoiding surgery increased the risk of cancer spreading elsewhere in the body.
Key Findings
- 26% of patients had a complete response and were able to avoid surgery.
- After about 3 years of follow-up, 95% of patients who avoided surgery had no distant cancer spread.
- 83% of patients in the non-surgical group remained surgery-free at 2 years.
- Overall cancer control was comparable to patients who underwent surgery.
Safety
- About 31% of patients experienced serious side effects, most commonly bowel-related or blood count issues.
- 17% had serious complications, and 7% stopped treatment early due to side effects.
- There were no treatment-related deaths.
Take-home message
This study supports a growing body of evidence that some patients with rectal cancer may safely avoid surgery if they respond completely to initial treatment. This approach may:
- Preserve normal bowel function
- Reduce long-term side effects
- Maintain strong cancer outcomes with careful monitoring
For selected patients with stage II–III rectal cancer, chemotherapy and radiation first, followed by close monitoring instead of immediate surgery, may be a safe and effective treatment option, offering the chance to preserve quality of life without compromising cancer control.
