Table 3:

Research priorities selected by the OPBC and EUBREAST panel from the 15 most important uncertainties and controversies during the consensus conference with recommended research question and study design.

Uncertainty or controversy	Research question in PICO format	Study Design	No. of votes	Yes	No	Abstain	Final voting
Q10b: Should we offer choice between observation (Z0011), axillary radiation (AMAROS) and ALND, or set hard thresholds and if we offer choice should we explore research into shared decision making and informational provision for this choice to support women?	P: Patients with clinically node-negative sentinel node-positive breast cancer I: Patient preference-guided treatment C: Physician recommendation O: Patient satisfaction	Randomized controlled trial (cluster randomization by centers with versus without patient decision aid)	62	30	28	4	48% (No consensus)
Q19b: What should be standard care in case of nodal disease left behind after axillary surgery and detected by imaging before the end of adjuvant therapy (e.g., PET-CT or planning CT for radiation): biopsy, resect, irradiate as special field or boost, observe, ignore?	P: Patients with residual suspicious findings on imaging after axillary surgery I: observe C: resect or irradiate O: regional/ axillary recurrence rate	Register on «forgotten nodes», prospective and/or retrospective	62	38	22	2	61% (Majority)
Q23b: What is the exact definition of clinical complete response (ycN0), thus allowing limited axillary surgery (i.e., SLN or TAD) with the aim of omitting ALND?	P: Patients with confirmed nodal disease at diagnosis (cN+), receiving neoadjuvant chemotherapy I: ycN status based on palpation alone C: ycN status based on palpation and imaging O: proportion ypN+ of ycN0, and ypN0 of ycN+	Substudy in AXSANA (prospective register study)	56	48	5	3	86% (Consensus)
Q29b: Is there a volume threshold of residual nodal disease after neoadjuvant chemotherapy (NACT) when radiation can replace ALND (ITC versus micrometastatic versus macrometastatic residual disease in one or more lymph nodes)?	P: Patients with confirmed nodal disease after NACT (ypN+) I: axillary radiation (or observation for low volume) C: ALND O: Disease-free survival	Pre-specified exploratory subgroup analysis of an RCT comparing axillary radiation with ALND after NACT (TAXIS)	55	48	6	1	87% (Consensus)
Q38b: In what situations can axillary radiotherapy be de-escalated?	Not applicable	Systematic review and meta-analysis to identify knowledge gaps Delphi process to prioritize Consensus conference to agree on design of clinical trials (focus on details on radiation trial)	55	47	6	2	85% (Consensus)
Q51b: What are the clinically most relevant endpoints in axillary management (survival, recurrence, lymphedema, morbidity, patient-reported outcomes)?	Not applicable	Systematic review (meta-analysis), a Delphi process including patients, and a consensus conference with patients and surgeons	50	47	2	1	94% (Consensus)