Debating Pros and Cons of Total Neoadjuvant Therapy in Rectal Cancer

Francesco Sclafani, Claudia Corrò, Thibaud Koessler, Francesco Sclafani, Claudia Corrò, Thibaud Koessler

Abstract

Recently, two large, randomised phase III clinical trials of total neoadjuvant therapy (TNT) in locally advanced rectal cancer were published (RAPIDO and PRODIGE 23). These two trials compared short-course radiotherapy (SCRT) followed by chemotherapy with standard chemoradiotherapy (CRT) and chemotherapy followed by CRT with standard CRT, respectively. They showed improvement in some of the outcomes such as distant recurrence and pathological complete response (pCR). No improvement, however, was observed in local disease control or the de-escalation of surgical procedures. Although it seems lawful to integrate TNT within the treatment algorithm of localised stage II and III rectal cancer, many questions remain unanswered, including which are the optimal criteria to identify patients who are most likely to benefit from this intensive treatment. Instead of providing a sterile summary of trial results, we put these in perspective in a pros and cons manner. Moreover, we discuss some biological aspects of rectal cancer, which may provide some insights into the current decision-making process, and represent the basis for the future development of alternative, more effective treatment strategies.

Keywords: PRODIGE-23; RAPIDO; chemoradiotherapy; consolidation chemotherapy; induction chemotherapy; rectal cancer; short-course radiotherapy; total neoadjuvant therapy.

Conflict of interest statement

T.K. reports receiving consulting fees from Bayer, Lilly, Merck, MSD, Roche, Boehringer Ingelheim, Vifor, BMS and a leadership role as Co-Chair of the EORTC Colon Cancer Task Force. F.S. reports receiving consulting fees from Amal Therapeutics, Bayer; travel expenses from Bayer, Lilly; institutional research funding from Amgen, AstraZeneca, Bayer, BMS, Roche, Sanofi; and a leadership role as Co-Chair of the EORTC Colon Cancer Task Force. C.C. has no other personal or financial conflicts of interest to disclose. The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Study design of the PRODIGE 23 and RAPIDO trials.

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