Standard (8 weeks) vs long (12 weeks) timing to minimally-invasive surgery after NeoAdjuvant Chemoradiotherapy for rectal cancer: a multicenter randomized controlled parallel group trial (TiMiSNAR)

Igor Monsellato, Filippo Alongi, Elisa Bertocchi, Stefania Gori, Giacomo Ruffo, Elisa Cassinotti, Ludovica Baldari, Luigi Boni, Graziano Pernazza, Fabio Pulighe, Carlo De Nisco, Roberto Perinotti, Emilio Morpurgo, Tania Contardo, Enzo Mammano, Ugo Elmore, Roberto Delpini, Riccardo Rosati, Federico Perna, Andrea Coratti, Benedetta Menegatti, Sergio Gentilli, Paolo Baroffio, Piero Buccianti, Riccardo Balestri, Cristina Ceccarelli, Valter Torri, Davide Cavaliere, Leonardo Solaini, Giorgio Ercolani, Elena Traverso, Vittorio Fusco, Maura Rossi, Fabio Priora, G Numico, Paola Franzone, Sara Orecchia, Igor Monsellato, Filippo Alongi, Elisa Bertocchi, Stefania Gori, Giacomo Ruffo, Elisa Cassinotti, Ludovica Baldari, Luigi Boni, Graziano Pernazza, Fabio Pulighe, Carlo De Nisco, Roberto Perinotti, Emilio Morpurgo, Tania Contardo, Enzo Mammano, Ugo Elmore, Roberto Delpini, Riccardo Rosati, Federico Perna, Andrea Coratti, Benedetta Menegatti, Sergio Gentilli, Paolo Baroffio, Piero Buccianti, Riccardo Balestri, Cristina Ceccarelli, Valter Torri, Davide Cavaliere, Leonardo Solaini, Giorgio Ercolani, Elena Traverso, Vittorio Fusco, Maura Rossi, Fabio Priora, G Numico, Paola Franzone, Sara Orecchia

Abstract

Background: The optimal timing of surgery in relation to chemoradiation is still controversial. Retrospective analysis has demonstrated in the recent decades that the regression of adenocarcinoma can be slow and not complete until after several months. More recently, increasing pathologic Complete Response rates have been demonstrated to be correlated with longer time interval. The purpose of the trial is to demonstrate if delayed timing of surgery after neoadjuvant chemoradiotherapy actually affects pathologic Complete Response and reflects on disease-free survival and overall survival rather than standard timing.

Methods: The trial is a multicenter, prospective, randomized controlled, unblinded, parallel-group trial comparing standard and delayed surgery after neoadjuvant chemoradiotherapy for the curative treatment of rectal cancer. Three-hundred and forty patients will be randomized on an equal basis to either robotic-assisted/standard laparoscopic rectal cancer surgery after 8 weeks or robotic-assisted/standard laparoscopic rectal cancer surgery after 12 weeks.

Discussion: To date, it is well-know that pathologic Complete Response is associated with excellent prognosis and an overall survival of 90%. In the Lyon trial the rate of pCR or near pathologic Complete Response increased from 10.3 to 26% and in retrospective studies the increase rate was about 23-30%. These results may be explained on the relationship between radiation therapy and tumor regression: DNA damage occurs during irradiation, but cellular lysis occurs within the next weeks. Study results, whether confirmed that performing surgery after 12 weeks from neoadjuvant treatment is advantageous from a technical and oncological point of view, may change the current pathway of the treatment in those patient suffering from rectal cancer.

Trial registration: ClinicalTrials.gov NCT3465982.

Trial registration: ClinicalTrials.gov NCT03465982.

Keywords: Minimally invasive surgery; Neoadjuvant treatment; Radiation therapy; Rectal cancer; Robotic surgery; TaTME; Timing to surgery.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart of TiMiSNAR Trial

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Source: PubMed

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