Opra trial

This survey. The consolidation arms of these trials demonstrated significantly higher rates of pCR (AIO-12) or cCR (OPRA) when compared to induction chemotherapy. In addition, 53% of patients in the consolidation arm of the OPRA trial avoided surgery at 3-year follow-up making this regimen attractive for those aiming for non-operative management (NOM), an approach that can improve quality of life by reducing low anterior resection syndrome (LARS). However, it must be noted that neither of these phase 2 trials significantly improved DFS or OS, and most centres do not recommend NOM unless as part of a clinical trial. Notably, at the American Society of Clinical Oncology (ASCO) 2023 conference, the 5-year OPRA update showed persistent differences in organ preservation using the consolidation approach (54% vs 39% with induction TNT) and lower rates of local regrowth (29% vs 44% with induction TNT). Furthermore, there was no oncologic detriment in either arm when integrating a watch-and-wait approach with salvage surgery for regrowth [18].More than 60% of colorectal surgeons in this survey preferred a consolidation TNT approach, despite historical concerns about the potential risk of pelvic fibrosis as the time interval between radiation and surgery is extended. The French GRECCAR-6 trial showed greater surgical complications and morbidity when waiting for 11 weeks, as opposed to 7, after neoadjuvant chemoradiotherapy, which may partly explain the preference for the induction PRODIGE regimen in France. However, several trials have not demonstrated increased surgical difficulty or compromised R0 resection rates with a consolidation TNT approach [19,20,21].Specialists in this survey demonstrated a low preference for the PRODIGE regimen, especially for advanced-risk disease for which it was chosen by less than 10%, surprising considering the robust data supporting this approach. PRODIGE-23, a phase 3, randomized controlled trial of induction FOLFIRINOX chemotherapy followed by LCCRT, demonstrated superior pCR rates (28% vs 12%, p p = 0·034) and metastasis-free survival (hazard ratio 0·64, p = 0·017) compared to LCCRT alone. Furthermore, since conducting our survey, additional follow-up data presented at ASCO 2023 demonstrated a significant increase in 5-year overall survival (6.9%), the only TNT trial to do so [22].In the setting

Approach for a patient with a stage II-III ESMO EARLY (GOOD) risk category rectal cancer (cT3a/b in mid- or high rectum, N0 (or also cN1 if high), MRF clear, no EMVI). a. Upfront surgery b. Short course radiotherapy (SCRT) followed by surgery c. Long-course chemoradiotherapy (LCCRT) followed by surgery d. Total Neoadjuvant Therapy (TNT) If choosing a TNT approach, which protocol would you prefer in this case? a. PRODIGE 23 (FOLFIRINOX – LCCRT – Surgery – FOLFOX) b. RAPIDO or STELLAR (SCRT – FOLFOX or CAPOX – Surgery) c. Induction OPRA or CAO/ARO/AIO-12 (FOLFOX – LCCRT – Surgery) d. Consolidation OPRA or CAO/ARO/AIO-12 (LCCRT – FOLFOX – Surgery) Case 2 – Indicate your preferred approach for a patient with an ESMO INTERMEDIATE risk category rectal cancer (cT3a/b if low rectum, levators clear, MRF clear OR cT3a/b in mid- or high rectum, cN1-2 (not extra-nodal), no EMVI). a. Upfront surgery b. Short course radiotherapy (SCRT) followed by surgery c. Long-course chemoradiotherapy (LCCRT) followed by surgery d. Total Neoadjuvant Therapy (TNT) If choosing a TNT approach, which protocol would you prefer in this case? a. PRODIGE 23 (FOLFIRINOX – LCCRT – Surgery – FOLFOX) b. RAPIDO or STELLAR (SCRT – FOLFOX or CAPOX – Surgery) c. Induction OPRA or CAO/ARO/AIO-12 (FOLFOX – LCCRT – Surgery) d. Consolidation OPRA or CAO/ARO/AIO-12 (LCCRT – FOLFOX – Surgery) Case 3 – Indicate your preferred approach for a patient with an ESMO BAD risk category rectal cancer (cT3c/d or very low localisation, levators threatened, MRF clear OR cT3c/d mid-rectum, cN1–N2 (extra-nodal), EMVI + OR limited cT4aN0). a. Upfront surgery b. Short course radiotherapy (SCRT) followed by surgery c. Long-course chemoradiotherapy (LCCRT) followed by surgery d. Total Neoadjuvant Therapy (TNT) If choosing a TNT approach, which protocol would you prefer in this case? a. PRODIGE 23 (FOLFIRINOX – LCCRT – Surgery – FOLFOX) b. RAPIDO or STELLAR (SCRT – FOLFOX or CAPOX – Surgery) c. Induction OPRA or CAO/ARO/AIO-12 (FOLFOX – LCCRT – Surgery) d. Consolidation OPRA or CAO/ARO/AIO-12 (LCCRT – FOLFOX – Surgery) Case 4 – Indicate your preferred approach for a patient with an ESMO

Of TNT with selective nonoperative management (NOM) for patients with (near) clinical complete response, as reported in the recent OPRA trial [14] and currently investigated in our ongoing ACO/ARO/AIO-18.1 trial (NCT04246684), sustained local control without regrowth (i.e., TME-free survival) and disease-free survival including NOM and events of salvage surgery [4] have been incorporated as relevant clinical endpoints. Supplementary MaterialsThe following are available online at Figure S1. (A) Discrimination ability of non-pCR for disease-free survival in the CAO/ARO/AIO-12 trial. (B) Discrimination ability of non-pCR for disease-free survival in Arm A and Arm B of the CAO/ARO/AIO-12 trial. Supplementary Methods: Time-dependent ROC curve analysis. Supplementary results of the time-dependent discrimination ability of pCR for DFS.Author ContributionsConceptualization, M.D., C.R. and E.F.; methodology, M.D., C.R., E.F. and R.-D.H.; software, M.D.; validation, C.R. and E.F.; writing—original draft preparation, M.D., C.R. and E.F.; writing—review and editing, A.S.-L., T.K., S.K., P.P., W.O.B., G.H., M.G. and R.-D.H. All authors have read and agreed to the published version of the manuscript.FundingThe CAO/ARO/AIO-12 trial was funded by grant 110-460 from German Cancer Aid.Institutional Review Board StatementThe CAO/ARO/AIO-12 trial was approved by the Ethics’ Committee of the University Hospital Frankfurt on 19 January 2015 (Ethic Code: 406/14, EudraCT-Nr: 2011-006310-13).Informed Consent StatementInformed consent was obtained from all subjects involved in the study.Data Availability StatementThe data are not publicly available.Conflicts of InterestAll other authors have no conflict of interest or financial ties to disclose.ReferencesKasi, A.; Abbasi, S.; Handa, S.; Al-Rajabi, R.; Saeed, A.; Baranda, J.; Sun, W. Total Neoadjuvant Therapy vs Standard Therapy