The NO-CUT trial at ESMO 2024: can more aggressive treatment prevent the need for surgery?
September 2024
Findings from the NO-CUT trial were presented at the European Society for Medical Oncology (ESMO) Congress 2024 this September in Barcelona, Spain. The study explored the efficacy of more aggressive initial treatment known as total neoadjuvant therapy followed by non-operative management in patients with mismatch repair proficient (pMMR) locally advanced rectal cancer.
Total neoadjuvant therapy: a treatment approach that involves radiation and chemotherapy given prior to surgery. It is a new strategy in managing locally advanced rectal cancer, and has been shown to have the capacity to reduce the risk of distant metastasis and increase survival outcomes (Boublikova, 2023)
Non-operative management: also referred to as non-surgical management or watch and wait. This is a novel treatment approach that can be used for patients with rectal cancer who achieve a clinical complete response (the disappearance of all signs of cancer in response to treatment) after neoadjuvant therapy. Instead of immediately undergoing surgery, they undergo close surveillance and monitoring of the disease with the option to convert to surgery if the cancer recurs. (Konishi, 2022)
Mismatch repair proficient (pMMR): microsatellite stable (MSS) or mismatch repair proficient is the “normal” state our cells are in when the mismatch repair (MMR) pathway is active and normal. (Colontown University)
Surgery has been the gold standard treatment for non-metastatic rectal cancer. However, rectal surgery requires removing at least a portion of the rectum, which can affect bowel functioning and sometimes require a colostomy. Furthermore, the surgery carries the risk of damage to surrounding pelvic organs such as the bladder and reproductive organs. Together, this has spurred growing interest in organ preservation strategies over the past years.
The study
The NO-CUT trial assessed whether non-operative management negatively impacted the risk for distant metastasis (spread of the cancer to distant organs such as the liver or lungs).
180 patients with mismatch repair proficient locally advanced rectal cancer received total neoadjuvant treatment, which included capecitabine plus oxaliplatin chemotherapy followed by long-course chemoradiotherapy. Patients underwent an interval of 12 weeks of no treatment and were restaged. Patients who had reached a complete clinical response were assigned to the non-operative management study group which involved intensive follow-up. Patients who did not reach a complete response after neoadjuvant treatment underwent surgery and standard follow-up.
In the group of patients that received no surgery after neoadjuvant therapy, the 30-month distant relapse-free survival rate (patients who did not develop any distant metastasis in the specified timeframe) was 96.9%. The researchers noted that the distant relapse-free survival rate was higher than that which was observed in the group of patients that did receive surgery – 74%.
Conclusion
The NO-CUT trial findings add to the growing body of evidence to support organ preservation approaches for select patients with locally advanced rectal cancer. The researchers emphasized that there is still a need for further research to better understand which patient population is most likely to benefit from this treatment approach. Additionally, more research is needed to understand the best radiation and chemotherapy sequencing in total neoadjuvant therapy, and to explore strategies to improve complete clinical response rates and validate the findings of the NO-CUT trial in larger patient populations.
Ludmila Boublikova, Alena Novakova, Jaromir Simsa, Radka Lohynska, Total neoadjuvant therapy in rectal cancer: the evidence and expectations. Critical Reviews in Oncology/Hematology, Volume 192, 2023, 104196. ISSN 1040-8428. https://doi.org/10.1016/j.critrevonc.2023.104196.
Konishi T. A Clinical Calculator in the Era of Nonoperative Management for Rectal Cancer—How Should We Intensify or Deescalate Surveillance? JAMA Netw Open. 2022;5(9):e2233868. doi:10.1001/jamanetworkopen.2022.33868
Colontown University. Is my tumour MSS (pMMR) or MSI-H (dMMR)? https://learn.colontown.org/topic/is-my-tumor-mss-pmmr-or-msi-h-dmmr/ Accessed September 18, 2024.
