May 2020's 'Paper of the Month' presents a French multicenter randomised controlled trial assessing the effect of the time leg between completion of radiation therapy and surgery on oncological outcomes of patients with locally advanced rectal cancer.

Does A Longer Waiting Period After Neoadjuvant Radio-chemotherapy Improve the Oncological Prognosis of Rectal Cancer?: Three Years' Follow-up Results of the Greccar-6 Randomized Multicenter Trial

Jérémie H Lefèvre, Laurent Mineur, Marine Cachanado, Quentin Denost, Philippe Rouanet, Cécile de Chaisemartin, Bernard Meunier, Jafari Mehrdad, Eddy Cotte, Jérome Desrame, Mehdi Karoui, Stéphane Benoist, Sylvain Kirzin, Anne Berge, Yves Panis, Guillaume Piessen, Alain Saudemont, Michel Prudhomme, Frédérique Peschaud, Anne Dubois, Jérome Loriau, Jean-Jacques Tuech, Guillaume Meurette, Renato Lupinacci, Nicolas Goasguen, Ben Creavin, Tabassome Simon, Yann Parc, The French Research Group of Rectal Cancer Surgery (GRECCAR)

Ann Surg 2019 Nov; 270(5):747-754. doi: 10.1097/SLA.0000000000003530.

What is known about the subject?

Numerous studies have shown that complete pathological response following long course neoadjuvant radiotherapy is associated with improved prognosis. Several studies, mostly retrospective, have suggested that a longer time lag between completion of radiation and surgery may increase complete response rate, while other studies, including the current Greccar-6, did not show this effect. It was unclear however if the potential effect of lag time on the rate of pathological complete response could be translated into improved (or potentially worse) oncological outcome.

What the study adds?

This French multicentre trial randomized 265 patients undergoing neoadjuvant long course radiotherapy for locally advanced rectal cancer into two groups: surgery within 7 weeks of completion of radiotherapy, or surgery within 11 weeks. The GRECCAR group published short-term outcomes in 2016, showing no significant differences in rate of complete pathological response. The current paper provides the first insight into the effect of lag time between radiation and surgery on oncological outcome using a prospective randomized trial design. Results showed that there was no significant difference in the rate of overall survival, disease-free survival and local recurrence between the two groups at an average follow-up of 32 months.

Implications for colorectal practice

The optimal lag time between completion of neoadjuvant radiation therapy and surgery is controversial. Longer time periods may allow extended effect of radiation therapy on the death of malignant cells but may also allow residual viable cells to regrow and delay systemic therapy. The GRECCAR 6 follow up study suggests that there is no oncologic benefit nor deleterious effect to longer lag time. The study is a significant contribution in this controversy, but has several limitations, including the fact that the sample size was not calculated for oncologic outcomes, and the fact that contrary to several other studies, there was no difference in complete pathological response rate. In addition, current studies are assessing the option of adding consolidation chemotherapy between completion of radiation and surgery, which may potentially improve oncologic outcomes.

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