Table 1:
Final ranking of uncertainties and controversies prioritized during the Delphi process
| Question | Ranking× | Average Median Likert Rating | Average Mean Likert Rating |
|---|---|---|---|
| (Q1) Should imaging-based staging of the axilla at initial diagnosis and/or after neoadjuvant therapy be standard care and what is the best imaging modality? | 1 | 8.33 | 7.84 |
| (Q25) Should targeted axillary dissection (TAD versus SLN only or ALND) be standard care in initially cN+ converting to ycN0 and is TAD oncologically safe compared to ALND? | 2 | 8.00 | 7.80 |
| (Q51) What are the clinically most relevant endpoints in axillary management (survival, recurrence, lymphedema, morbidity, patient-reported outcomes)? | 3 | 8.00 | 7.68 |
| (Q38) In what situations can axillary radiotherapy be de-escalated? | 4 | 8.00 | 7.66 |
| (Q10) Should we offer patients a choice between observation (Z0011), axillary radiation (AMAROS) and ALND, or should we 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? | 5 | 8.00 | 7.45 |
| (Q19) 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? | 6 | 8.00 | 7.31 |
| (Q26) Should use of the SLN or TAD procedures with the aim of omitting ALND in patients with cN+ converting to ycN0 depend on the initial clinical tumor load (e.g., large number of initially suspicious lymph nodes, cN2/3, cT4)? | 7 | 7.67 | 7.30 |
| (Q47) What is the best technique for pathology assessment of the SLN and should it be standardized? | 8 | 7.67 | 7.17 |
| (Q20) What is the contemporary morbidity of the SLN procedure versus ALND and SLN procedure versus no axillary surgery and its impact on quality of life? | 9 | 7.67 | 7.07 |
| (Q2) Should there be development of baseline standards for axillary imaging (e.g., similar to false-negative rates for the SLN-procedure)? | 10 | 7.33 | 7.33 |
| (Q22) When will we be able to banish most of the remaining routine indications for radical ALND from clinical practice to improve patient-reported quality of life without jeopardizing survival and oncologic safety (e.g., palpable disease in the adjuvant setting or residual disease in the neoadjuvant setting)? | 11 | 7.33 | 7.28 |
| (Q29) 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)? | 12 | 7.33 | 7.20 |
| (Q31) What is standard of care for suspicious findings in internal mammary or supraclavicular lymph nodes on imaging? | 13 | 7.33 | 7.13 |
| (Q24) Should measures to decrease the false-negative rate of the SLN procedure in initially cN+ converting to ycN0 be standard of care, such as use of dual tracer or removal of a minimum of 3 negative SLNs? | 14 | 7.33 | 7.11 |
| (Q23) 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? ⸸ | 15 | 7.33 | 7.08 |
| (Q9) Should the ACOSOG Z0011 protocol be considered standard of care around the world? ± | 16 | 7.33 | 6.89 |
| (Q34) Are there subgroups of Z0011-eligible patients that should receive axillary radiation, and should axillary radiation in Z0011-eligible patients –if indicated- be combined with extended regional nodal irradiation (e.g., levels 1–4, levels 3–4, internal mammary nodes, and combinations)? | 17 | 7.33 | 6.83 |
| (Q45) What is the best method to mark the sampled node and the best imaging modality to localize it? | 18 | 7.33 | 6.71 |
| (Q12) What is the role of imaging-guided localization and selective removal of non-palpable biopsy-positive or suspicious nodes in the upfront surgery setting? | 19 | 7.00 | 7.04 |
| (Q11) What is standard care for non-palpable ultrasound-detected lymph node metastases in a Z0011-eligible patient? | 20 | 7.00 | 6.83 |
| (Q36) What are the side effects of axillary radiation using modern techniques? * | 21 | 7.00 | 6.83 |
| (Q30) What is the maximum volume of residual nodal disease after neoadjuvant hormonal therapy (NET) that radiation can control (ITC versus micrometastatic versus macrometastatic residual disease in one or more lymph nodes), thus allowing omission of ALND? | 22 | 7.00 | 6.81 |
| (Q17) Should invasive lobular breast cancer be managed in the same way as invasive ductal carcinoma regarding omission of ALND? | 23 | 7.00 | 6.76 |
| (Q35) What is the optimal patient selection for ERNI in general and for specific ERNI protocols in particular (e.g., levels 1–4, levels 3–4, internal mammary nodes, and combinations)? | 24 | 7.00 | 6.74 |
| (Q16) Should tumor biology have an impact on eligibility of the Z0011 protocol? | 25 | 7.00 | 6.68 |
| (Q7) What is the role of axillary surgery in ipsilateral in-breast recurrence after previous breast-conserving surgery and SLN procedure? | 26 | 7.00 | 6.60 |
| (Q33) What is the best nodal irradiation technique? | 27 | 7.00 | 6.56 |
| (Q28) How many suspicious nodes on imaging should be marked (e.g., clipped) in a patient undergoing neoadjuvant chemotherapy (NACT)? | 28 | 7.00 | 6.55 |
| (Q42) Should level II be included in standard ALND? | 29 | 7.00 | 6.47 |
| (Q46) Should the biopsied lymph node be marked (e.g., clipped) immediately or after histologic confirmation of metastasis? | 30 | 7.00 | 6.47 |
| (Q37) What is the risk of lymphedema in a patient who develops recurrence in the axilla after radiation of the axilla and undergoes ALND? | 31 | 6.67 | 6.72 |
| (Q21) What is the impact of the lack of knowledge of the exact number of positive and negative nodes on use of molecular tests (e.g., Oncotype DX®, Mammaprint®) and adjuvant therapy decisions? | 32 | 6.67 | 6.45 |
| (Q40) How can we prevent axillary web syndrome? | 33 | 6.67 | 6.44 |
| (Q5) Should we omit the SLN procedure in a clinically node-negative (cN0) patient with triple-negative (TNBC) or Her-2 positive breast cancer and a high likelihood of pathologically negative nodes after neoadjuvant chemotherapy? | 34 | 6.67 | 6.42 |
| (Q44) What is the best tracer to mark sentinel nodes and when should we use dual tracer? | 35 | 6.67 | 6.38 |
| (Q13) Should we apply the Z0011 protocol to cN- patients with pathologically positive SLNs who were not eligible for Z0011 (e.g., mastectomy, cT3 cancer, >2 positive SLNs, gross extranodal disease, partial breast or intraoperative radiotherapy)? | 36 | 6.67 | 6.29 |
| (Q48) Is there a role for nomograms that predict the likelihood of nodal metastases based on patient, tumor and treatment variables in contemporary axillary management? | 37 | 6.67 | 6.28 |
| (Q4) Is there an optimal age, size or frailty threshold to omit the SLN procedure? | 38 | 6.67 | 6.17 |
| (Q14) Should we apply the Z0011 protocol to cN- patients with microscopic extranodal extension in SLN metastases? | 39 | 6.67 | 6.00 |
| (Q32) What is the best axillary surgery procedure after neoadjuvant radiation therapy? | 40 | 6.33 | 6.41 |
| (Q8) What is standard of care in case of aberrant drainage with internal mammary or contralateral axillary SLNs on lymphoscintigraphy in ipsilateral in-breast recurrence after previous breast-conserving surgery and SLN procedure? | 41 | 6.33 | 6.40 |
| (Q3) What is the clinical implication of discordant axillary imaging before surgery (e.g., node suspicious on magnetic resonance imaging [MRI], but not seen on ultrasound [US]? | 42 | 6.33 | 6.18 |
| (Q15) Should the ratio of positive to negative SLNs have an impact on eligibility of the Z0011 protocol (e.g., 2 of 2 versus 2 of 5 removed SLNs are positive)? | 43 | 6.33 | 6.16 |
| (Q39) Should intercostobrachial nerves be preserved during ALND? | 44 | 6.33 | 6.07 |
| (Q27) Should the finding of nodal pCR by use of the SLN or TAD procedure with the aim of omitting ALND in patients with cN+ converting to ycN0 depend on the documentation of regressive changes in the lymph node by the pathologist? | 45 | 6.00 | 6.24 |
| (Q41) Should lymphatic vessels be preserved during ALND, e.g. by using axillary reverse mapping or stepwise limited ALND? | 46 | 6.00 | 6.20 |
| (Q49) What is the optimal follow-up interval and imaging modality for patients after axillary surgery? | 47 | 6.00 | 5.82 |
| (Q18) In which non-Z0011 eligible patients should intraoperative frozen section analysis of the SLN be standard care? | 48 | 6.00 | 5.68 |
| (Q50) How should we address lack of sensitivity of axillary imaging during follow-up? | 49 | 6.00 | 5.61 |
| (Q6) Should we evaluate omission of axillary surgery by delaying the SLN procedure after evaluation of breast pathologic complete response during primary surgery? | 50 | 6.00 | 5.57 |
| (Q43) When should level III be included in ALND? | 51 | 5.67 | 5.41 |
×
Ranking based on importance, which is defined as need for evidence-based expert consensus recommendations to standardize international clinical practice.
The 15 most important questions that were brought forward to the consensus conference were highlighted in bold font.
⸸
Q23 was re-prioritized to be within 15 most important questions during Delphi round 2, while being ranked number 16 in round 1.
±
Q9 ranked top 3 by surgeons and accordingly, added to the 15 most important questions even though only ranked number 16 overall
*
Q36 ranked top 3 by patient advocates and accordingly, added to the 15 most important questions even though only ranked number 21 overall