News item BrachyAcademy website – L.UCA.RRE conference December 5th 2025
The L.UCA.RRE conference in Nice hosted by Centre Antoine Lacassagne and the legendary Jean-Pierre Gerard brought together leading experts in organ preservation for rectal cancer, including the PIs of major Phase III trials.
Key trial represented:
• Total Neoadjuvant Therapy (TNT): ACO/ARO/AIO trials, OPRA, JANUS, PRODIGE 23
• Local Excision: OPAXX, STAR-TREC, GRECCAR 12, TAU-TEM
• Brachytherapy: MORPHEUS, OPERA, ACO/ARO/AIO-22, TRESOR, CORRECT
• EBRT Dose Escalation: WW-3, APHRODITE
A major milestone discussed at the conference: organ-preservation-intent has now been incorporated into the 2025 ESMO clinical practice guidelines for localized rectal cancer.
My main interest centered on trials evaluating non-operative management without routine induction/consolidation chemotherapy (“no TNT”) or local excision (“no TEM”).
MORPHEUS Phase III (Té Vuong):
HDR brachytherapy (BT) vs EBRT for organ preservation
• Activated in 4 centers
• 92 patients enrolled; median follow-up: 40 months
• Expected completion in ~18 months (dependent on Elekta rectal applicator 510k + MDR approval)
• Complete clinical response: 62% in Arm A (EBRT) vs 90% in Arm B (HDR brachytherapy)
Elderly and frail patients:
Given the high surgical risk, Emmanouil Fokas, MD DPhil presented the ACO/ARO/AIO-22 trial combining hypofractionated EBRT (13×3 Gy) with endorectal HDR BT (3×8 Gy). Multidisciplinary management and comprehensive geriatric assessment remain essential for proper selection.
OPERA trial impact:
As Professor Arthur Sun Myint noted, OPERA’s success led to inclusion of the contact brachytherapy (CXB) in the UK NICE guidelines. A BBC program spotlighting CXB has increased patient awareness, with some now actively requesting organ-preserving options.
OPERA has inspired several new studies:
• CORRECT (Sweden): CXB + short-course RT vs standard regimen (organ preservation + toxicity)
• TRESOR (France): CXB added to TNT to improve survival with organ preservation
Ane Appelt discussed the dose–response curve for LC in rectal cancer. BT allows the highest dose escalation and LC rates. Meanwhile, modern EBRT (SIB, CBCT-guided daily adaptation, adapted target volumes) now offers higher, safer RT doses.
APHRODITE Phase II: Primary endpoint expected at ESTRO 2026.
STARTREC-3, a Dutch study for early-stage rectal cancer patients opting for organ preservation, compares three boost strategies: CXB, EBRT, or chemotherapy.
Immunotherapy: a dedicated session covered immune checkpoint inhibition combined with CRT for both dMMR and pMMR tumors. While combinations may improve response, they also increase toxicity. More Phase III data is required.
In closing, Garcia-Aguilar Julio/Surgery summarized the field well: “These are exciting times – too many ideas to test, and not enough patients. We must choose endpoints carefully. Some patients need treatment de-escalation. Organ preservation is important, but not as important as being alive.”