GRECCAR 2: Local Excision After Chemoradiotherapy Feasible For T2T3 Low Rectal Cancer

Author: By Lynda Williams, Senior medwireNews Reporter

medwireNews: Low rectal cancer patients with a good response to neoadjuvant treatment may be able to avoid the need for total mesorectal excision, suggest the GRECCAR 2 investigators. 

“Local excision can be proposed in selected patients having a small T2T3 low rectal cancer with a good clinical response after chemoradiotherapy”, say Eric Rullier, from Haut-Lévèque Hospital in Pessac, France, and co-authors in The Lancet Gastroenterology & Hepatology.

The 5-year findings for the phase III trial did not reveal any significant differences in the oncological outcomes for the 74 patients who were randomly assigned to undergo local excision after achieving a residual tumour of 2 cm or smaller with fluorouracil-based chemotherapy plus 50 Gy radiation over 5 weeks, and the 71 patients who instead underwent total mesorectal excision after chemoradiotherapy.

Indeed, intention-to-treat analysis showed that the local excision and total mesorectal excision groups had comparable 5-year rates of local recurrence (7 vs 7%), metastatic disease (18 vs 19%), overall survival (84 vs 82%), disease-free survival (70 vs 72%) and cancer-specific mortality (7 vs 10%).

The researchers explain that patients were classified as having had a good pathological response to chemoradiotherapy – defined as a residual tumour scar of 2 cm or smaller with no vegetative component or significant infiltration into the muscular layer (ypT0–1) or a poor response (ypT2–3 or R1).

Overall, 35% of the patients assigned to receive local excision subsequently required completion total mesorectal excision for ypT2–3 disease

And the researchers note that in as-treated analysis, patients with a poor pathological response were three times more likely to experience metastatic disease over 5 years than those with a good response (28 vs 10%, risk ratio=2.78).

Discussing the results further, the team remarks that “[t]he role of completion surgery after local excision in patients with ypT2 tumour is questionable because tumour cells are present in a very limited number of completion specimens.”

Eric Rullier et al propose that “[c]lose follow-up by MRI and endoscopy could be an alternative to completion surgery in such patients,” and say that we now await the results of the GRECCAR 12 and OPERA studies to further elucidate the impact of chemotherapy and high-dose radiotherapy, respectively, on the likelihood of organ preservation.

In addition, they suggest that further research “must investigate how best to manage patients with a subcomplete response; explore how to reduce the risk of local recurrence; and must also include patients with more advanced tumours.”

Writing in an accompanying comment, Nancy Baxter and co-authors, from the University of Toronto in Ontario, Canada, question whether the GRECCAR 2 findings change the standard of care for patients with T2T3 rectal cancers away from radical resection. 

“Given the morbidity of local excision, the inherent risk of complicating subsequent surgery, and the evolution of watch and wait, the answer today is no”, they believe.

“Perhaps patients will be better served by a strategy maximising the chance of complete clinical response that preserves surgical planes for those who require future radical surgery”, the commentators say.

“However, given the evolving evidence, we will have to wait and see.” 

References 

Rullier E, Vendrely V, Asselineau J, et al. Organ preservation with chemoradiotherapy plus local excision for rectal cancer: 5-year results of the GRECCAR 2 randomised trial. Lancet Gastroenterol Hepatol; Advance online publication 7 February 2020. doi: 10.1016/S2468-1253(19)30410-8  

Dossa F, Acuna SA, Baxter NN. Local excision after preoperative chemoradiation for T2 and T3 rectal cancers: is the wait over? Lancet Gastroenterol Hepatol; Advance online publication 7 February 2020. doi: 10.1016/S2468-1253(20)30001-7