Survival among patients treated with total mesorectal excision or selective watch-and-wait after total neoadjuvant therapy: A pooled analysis of the CAO/ARO/AIO-12 and OPRA randomized phase II trials Journal Article
| Authors: | Williams, H.; Fokas, E.; Diefenhardt, M.; Lee, C.; Verheij, F. S.; Omer, D. M.; Lin, S. T.; Dunne, R. F.; Marcet, J.; Cataldo, P.; Polite, B.; Piso, P.; Polat, B.; Dapper, H.; Ghadimi, M.; Hofheinz, R. D.; Qin, L. X.; Saltz, L. B.; Wu, A. J.; Gollub, M. J.; Smith, J. J.; Weiser, M. R.; Rödel, C.; Garcia-Aguilar, J. |
| Article Title: | Survival among patients treated with total mesorectal excision or selective watch-and-wait after total neoadjuvant therapy: A pooled analysis of the CAO/ARO/AIO-12 and OPRA randomized phase II trials |
| Abstract: | Background: Prospective data comparing watch-and-wait (WW) to mandatory total mesorectal excision (TME) in patients with locally advanced rectal cancer (LARC) remain limited, as randomized control trials assessing these two treatment approaches are considered impractical. This pooled analysis of the CAO/ARO/AIO-12 and OPRA trials analyzes survival outcomes among LARC patients managed with either a selective WW or mandatory TME strategy following total neoadjuvant therapy (TNT). Patients and methods: The CAO/ARO/AIO-12 and OPRA trials were multicenter, phase II trials that randomized patients with stage II/III rectal cancer to receive either induction or consolidation chemotherapy as part of TNT. All patients in the CAO/ARO/AIO-12 trial underwent TME within 6 weeks of completing TNT. The OPRA trial allowed patients with a complete or near-complete response to enter WW while those with an incomplete response proceeded to TME. The primary endpoint of the present pooled analysis was disease-free survival (DFS). Secondary endpoints included distant recurrence-free survival (DRFS), local recurrence-free survival (LRFS) and overall survival (OS). Results: This pooled analysis included 628 patients (n = 304 CAO/ARO/AIO-12; n = 324 OPRA). Median follow-up was 3.6 [interquartile range (IQR) 1.13] years and 5.1 (IQR 2.2) years, respectively. Patients in the CAO/ARO/AIO-12 trial were more likely to have cT3/4 and cN-positive disease while patients in the OPRA trial had tumors closer to the anal verge. Compliance to TNT and rates of grade 3+ adverse events were similar between studies. There were no differences in DFS, DRFS, LRFS or OS based on treatment strategy or TNT treatment arm. Conclusions: This pooled analysis demonstrated equivalent oncologic outcomes between patients treated with mandatory TME and selective WW strategies following TNT. These results strengthen available evidence indicating that WW is a safe treatment option for patients with an excellent response to neoadjuvant therapy. © 2025 European Society for Medical Oncology |
| Keywords: | adult; cancer survival; controlled study; aged; middle aged; major clinical study; overall survival; clinical feature; fluorouracil; advanced cancer; capecitabine; cancer patient; disease free survival; neoadjuvant therapy; cancer staging; nuclear magnetic resonance imaging; follow up; cancer grading; retrospective study; watchful waiting; intermethod comparison; rectum cancer; sigmoidoscopy; induction chemotherapy; total mesorectal excision; pathological complete response; randomized controlled trial (topic); phase 2 clinical trial (topic); clinical outcome; local recurrence free survival; consolidation chemotherapy; nonoperative management; locally advanced rectal cancer; human; male; female; article; total neoadjuvant therapy; distant recurrence free survival; watch-and-wait |
| Journal Title: | Annals of Oncology |
| Volume: | 36 |
| Issue: | 5 |
| ISSN: | 0923-7534 |
| Publisher: | Oxford University Press |
| Date Published: | 2025-05-01 |
| Start Page: | 543 |
| End Page: | 547 |
| Language: | English |
| DOI: | 10.1016/j.annonc.2025.01.006 |
| PUBMED: | 39848335 |
| PROVIDER: | scopus |
| PMCID: | PMC12034476 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is Julio Garcia-Aguilar -- Source: Scopus |
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