Guidelines recommend chemoradiation (CRT) before surgery for patients with clinical stage II-III rectal cancer in order to lower the risk of locoregional recurrence, but there is a growing concern among oncologists that the approach leads to overtreatment.
But the issue has been how best to identify patients who would do well with less intensive treatment.
A German team reported a promising approach to this issue, describing the use of preoperative MRI to assess the mesorectal fascia (MRF) for the presence of a tumor. The paper was published on June 19 in the Journal of Clinical Oncology.
The thinking is that with uninvolved MRF, the tumor is removed by total mesorectal excision (TME) alone, while patients with involved MRF need neoadjuvant chemoradiation therapy to shrink the tumor before resection.
The team put the idea to the test in 884 patients with cT2-4 rectal cancer.
There were 530 patients (60%) with clear MRFs, and they proceeded directly to total mesorectal excision. The 5-year locoregional recurrence rate was just 2.9% in this group.
In comparison, almost 6% of the 354 patients who received neoadjuvant CRT in this study had a locoregional recurrence within 5 years of TME.
Neoadjuvant chemoradiation offers “no advantage over optimized surgery” for such patients “if a 5-year [locoregional recurrence] rate of approximately 5% is acceptable,” said investigators, led by Reinhard Ruppert, MD, of the Department of General and Visceral Surgery, Endocrine Surgery, and Coloproctology at the Municipal Hospital of Munich-Neuperlach, Munich, Germany.
If so, neoadjuvant chemoradiation “and its adverse effects can be avoided in 60% of the total population and in 45% of patients with clinical stage II and III cancer” as found in the study, they said.
“The risk of undertreatment because of the omission of” neoadjuvant chemoradiation is low, they commented. Of the 10 patients who had a negative MRF but turned out to have positive resection margins at surgery, only one had a recurrence, the team noted.
Overall, the study suggests that neoadjuvant chemoradiation therapy can be restricted to patients at high risk of locoregional recurrence. “These findings may be used for guiding clinical surgical practice and the administration of neoadjuvant radiotherapy or neoadjuvant chemoradiotherapy,” the investigators said.
Concern About Reproducibility
Approached for comment, Alan Venook, MD, a gastrointestinal oncologist at the University of California, San Francisco, said, “This is another paper that pretty much confirms the assumption that we overtreat many patients with rectal cancer.”
These “data support the principle that many, if not most, patients with localized rectal cancer do not require trimodality therapy (chemotherapy, radiation, surgery) to achieve cure. That said, it remains a real challenge to figure out which of the modalities can or should be omitted in the average patient,” Venook told Medscape Medical News.
Overall, the German results “are excellent” but it’s unknown if the results can be replicated in community settings, given the expertise needed to discern MRF involvement on MRI and the fact that not every patient gets TME, the gold-standard surgery used in the trial, he said.
Venook said that at his university, given the rapidly evolving literature on de-escalating treatment, every rectal cancer case is discussed at a multidisciplinary tumor board to decide the best course of action.
Patients in the trial were treated at 14 centers in Germany from 2007 to 2016; nodal involvement was allowed, but subjects had no distant metastases. The call on whether or not they had MRF involvement was based on the distance between the MRF on preoperative MRI and their tumor, suspicious lymph nodes, and tumor deposits.
Patients with a distance greater than 1 mm were considered low risk for recurrence and underwent upfront total mesorectal excision. Those with a distance of 1 mm or fewer as well as patients with cT4 tumors and cT3 tumors in the lower rectal third — a location that makes it difficult to assess the MRF involvement — received up to 50.4 Gy radiation plus fluorouracil before surgery.
The 5-year rate of distant metastases was 15.9% in the upfront surgery group vs 30.5% in the nCRT arm; 11% of the upfront surgery group died of rectal cancer during follow-up vs 21.8% of the nCRT arm.
The work was funded by Johannes Gutenberg University Mainz. Venook and Ruppert report no relevant financial relationships. Three investigators reported honoraria and/or travel expenses from Intuitive Surgical, AbbVie, Johnson & Johnson, and other companies.
Journal of Clinical Oncology. Published online June 19, 2023. Abstract.
M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: [email protected]
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