ideasIdea
Molecular-class-directed adjuvant therapy in endometrial cancer
Give adjuvant treatment by the tumour's molecular class rather than by stage and grade: nothing for POLE-mutated, immunotherapy for MMRd, chemotherapy plus targeted agents for p53-abnormal, hormones for NSMP.
PORTEC-3 molecular analysis showed p53abn tumours gained the most from chemoradiation and POLEmut tumours nothing. The RAINBO programme (four parallel trials: p53abn-RED with olaparib, MMRd-GREEN with durvalumab, NSMP-ORANGE with progestin, POLEmut-BLUE de-escalation) and PORTEC-4a test this prospectively.
Hypothesis
Molecular-class-directed adjuvant therapy improves recurrence-free survival in p53abn and MMRd disease and safely omits adjuvant therapy in POLEmut disease compared with stage-based standard care.
Rationale
Retrospective PORTEC and TransPORTEC analyses consistently show class-specific benefit; the classifier is cheap (three IHC stains plus POLE sequencing).
What would test it
RAINBO and PORTEC-4a read out 2027-2030; recurrence-free survival by class.
Maturity
being tested at scale