In defence of one step nucleic acid amplification for intraoperative assessment of axillary lymph nodes in breast cancerBMJ 2015; 350 doi: https://doi.org/10.1136/bmj.h716 (Published 11 February 2015) Cite this as: BMJ 2015;350:h716
- Zenon Rayter, consultant surgeon1
Dixon and colleagues made several damning comments about one step nucleic acid amplification (OSNA), which is used intraoperatively to assess whether sentinel lymph nodes contain metastases.1 These are based on one seriously flawed meta-analysis.2
Firstly, it stated that many published papers on OSNA were financed by the manufacturer (Sysmex, Japan), which is untrue.
Secondly, it quoted a positive predictive value of OSNA for axillary lymph node metastasis of only 0.79 when it should have been 0.86 on the basis of the data presented in the paper. The mistake was due to tissue allocation bias—different parts of the lymph node were sampled when comparing OSNA with histology.
Thirdly, the wrong mathematical model was used to translate tumour volume into a diameter for distinguishing between micrometastasis and macrometastasis.
Dixon and colleagues then made several false statements.
Firstly, they say that OSNA is the most common method of intraoperative assessment of sentinel lymph nodes. Only 26 centres in the country use this technique, so this is unlikely.
Secondly, they quote 4700 copy numbers as the lower limit for the diagnosis of a macrometastasis when all units use 5000 as the lower limit. Most patients diagnosed with a macrometastasis have copy numbers well in excess of this value. This is important because tumour burden in the sentinel lymph node is the most powerful predictor of non-sentinel node positivity3 4 and of those patients who have four or more positive lymph nodes.5 Such patients have significantly worse prognosis, require additional radiotherapy, and make up 8-13% of the patients in the Z00116 and AMAROS7 studies. Incorporation of copy number into a predictive nomogram for non-sentinel node positivity greatly improves its predictive ability.8
Finally, the National Institute for Health and Care Excellence (NICE) guidance on OSNA was published in 2013, not 2011.
As the invited clinical lead for the NICE guidelines, I can confirm that all the published evidence was carefully evaluated. The authors note that axillary recurrence is remarkably low in these patients and that routine axillary clearance can be safely omitted in those with low tumour burden. I agree that patients should be involved in discussions about their care, including whether to test sentinel lymph nodes intraoperatively. Sentinel node surgery is the accepted gold standard in clinically node negative breast cancer even though it misses 7% of patients with a positive axillary lymph node, so it seems strange that OSNA is so heavily criticised by the authors, who have not used it in routine clinical practice.
Cite this as: BMJ 2015;350:h716
Competing interests: None declared.
Full response at: www.bmj.com/content/349/bmj.g6803/rr.