Organ-preserving local excision feasible for certain small rectal cancers

Last Updated: 2020-02-25

By Will Boggs MD

NEW YORK (Reuters Health) - Organ-preserving local excision is feasible for selected patients with small rectal cancers that show a good clinical response after chemotherapy, according to five-year results from a clinical trial.

"Physicians should consider organ preservation either as a new standard in small T2T3 low rectal cancer, or at least as an oncologically safe option which needs to be proposed to the patient," Dr. Eric Rullier of Haut-Leveque Hospital, in Bordeaux, France, told Reuters Health by email.

The two-year results from the GRECCAR 2 randomized trial, which compared local excision and total mesorectal excision in T2T3N0-1 low rectal cancers treated with neoadjuvant chemoradiotherapy, showed no significant differences between groups in death, disease recurrence, morbidity, or side effects.

In the new analysis, Dr. Rullier and colleagues compared local recurrence, metastatic disease and survival at five years between local excision (74 patients) and total mesorectal excision (71 patients).

In the local-excision group, 47 patients (64%) actually underwent local excision, 26 (35%) underwent local excision plus total mesorectal excision and one (1%) underwent total mesorectal excision alone. In the total-excision group, 60 patients (85%) underwent total mesorectal excision, six (8%) underwent local excision and two (3%) underwent local excision plus total mesorectal excision.

In intention-to-treat analyses, five patients in each group experienced local recurrence during five years of follow-up, with no significant difference in the five-year cumulative incidence (7% in each group), the researchers report in The Lancet Gastroenterology & Hepatology.

The number of patients with metastatic disease was also the same, with 13 in the local-excision group and 13 in the total mesorectal excision group.

Patients with poor pathological response, however, had a five-year cumulative incidence of metastatic disease nearly three times higher than did patients with good pathological response (28% vs. 10%, respectively).

The local-excision and total-excision groups did not differ significantly in five-year overall survival (84% vs. 82%, respectively), disease-free survival (70% vs. 72%), or cancer-specific mortality (7% vs. 10%).

In post hoc subgroup analyses, there were no differences in five-year oncological outcomes between the treatment groups, neither in patients with good pathological response nor in patients with bad pathological response.

"This finding will change the management of rectal cancer," Dr. Rullier said. "T2 are actually treated by surgery (rectal excision) without irradiation. In the future, T2 will be treated by chemoradiotherapy with rectal preservation (local excision can be proposed or only watch and wait)."

"Patients need to know this new opportunity, which was proposed in the past only in old patients not fit for surgery," he said. "Now, everybody can benefit."

Dr. Rullier added, "Treatment in a rectal-cancer center is now more important, because accurate tumor selection and assessment of the tumor response are becoming the key points to propose modern treatment of rectal cancer."

Dr. Fahima Dossa of St. Michael's Hospital, in Toronto, Canada, who co-authored an accompanying editorial, told Reuters Health by email, "Based on the previously published results, it was not surprising that this study reported similar outcomes for patients treated with local excision and radical surgery. On first look, this was intriguing because it suggested that select patients may be able to avoid the morbidity of radical rectal surgery. However, a closer look at the study's findings was less reassuring - when you examine the results of patients based on the treatment they actually received, there appears to be a clinically meaningful increase in cancer recurrence and decrease in survival among patients treated with local excision."

"The oncological outcomes reported in this study were not the primary outcomes of the clinical trial, so the study is underpowered to find statistically significant differences in these outcomes, but the signal we see suggests that we, at the very least, should exercise caution and question the oncological safety of local excision," she said.

"These findings demonstrate that local excision is not ready for primetime in this patient group," Dr. Dossa said. "Not only do we remain uncertain about whether local excision compromises oncological outcomes, we know from the authors' previous publication that patients who undergo local excision and subsequently require radical surgery experience very high morbidity. The current standard of care for most patients with rectal cancer remains radical surgery."

She added, "Although the standard of care remains radical surgery, there are novel approaches currently being evaluated that could spare carefully selected patients from surgery and its associated morbidity. Promising avenues include total neoadjuvant treatment (TNT) and a watch and wait (W and W) approach for patients with tumors demonstrating complete clinical response. However, the safety and efficacy of these approaches still need to be confirmed in randomized clinical trials."

SOURCE: https://bit.ly/382XkJb and https://bit.ly/2vcTFuE) Lancet Gastroenterology & Hepatology, online February 7, 2020.