Diagnosis of the sentinel lymph node in breast cancer: a reproducible molecular method: a multicentric Spanish study

Bernet, Laia; Cano, Rafael; Martínez, M.B. Miguel; Dueñas, Basilio; Matías‐Guiu, Xavier; Morell, Lluisa; Palacios, José; Rezola, Ricardo; Robles‐Frías, María José; Ruíz, Irene; Velasco, Ana; Vieites, Begoña; Sevilla, Francisco J.; Torró, Josep; Medrano, J.; Ballester, Blai

doi:10.1111/j.1365-2559.2011.03836.x

Cited by 65 publications

(53 citation statements)

References 22 publications

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“…It was also noted by Bernet et al 50 that the longest and most variable time period corresponded to the stage when the node was transported from the operating room to the pathology department. The time taken for macroscopic processing of the samples could also fluctuate significantly depending on the training level of the pathologist involved.…”

Section: Assessment Of Analysis Timementioning

confidence: 83%

“…Sixteen test accuracy papers were included for OSNA, [50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65] with two papers reporting the same study. Two unpublished papers 40,66 for Metasin were identified and assessed using the Standards for the Reporting of Diagnostic Accuracy Studies (STARD) in Table 7.…”

Section: Number and Description Of Included Studiesmentioning

confidence: 99%

“…Single-gate studies The aim of a multicentre study presented by Bernet et al 50 was to compare OSNA with histology and evaluate its feasibility intraoperatively. Fifty-five SLNs were investigated using a single-gate study design; however, the results appear to include touch imprint and frozen section analysis supported by postoperative histopathology and therefore these results are not included in the review.…”

Section: Metasinmentioning

confidence: 99%

“…Single-gate studies Bernet et al 50 report two trials within one paper. For trial 1 it was unclear whether fresh or frozen sections were used as the comparator; therefore, the results from this trial are not included in the review.…”

Section: One-step Nucleic Acid Amplificationmentioning

confidence: 99%

“…The study by Bernet et al 50 has been included in the review only for the data on the time taken for OSNA analysis (see Assessment of analysis time).…”

Section: Single-gate Studiesmentioning

confidence: 99%

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A systematic review and economic evaluation of intraoperative tests [RD-100i one-step nucleic acid amplification (OSNA) system and Metasin test] for detecting sentinel lymph node metastases in breast cancer

Huxley

Jones-Hughes

Snowsill

et al. 2015

Health Technology Assessment

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BackgroundIn breast cancer patients, sentinel lymph node biopsy is carried out at the same time as the removal of the primary tumour to postoperatively test with histopathology for regional metastases in the sentinel lymph node. Those patients with positive test results are then operated on 2–4 weeks after primary surgery to remove the lymph nodes from the axilla (axillary lymph node dissection, ALND). New molecular tests RD-100i [one-step nucleic acid amplification (OSNA); based on messenger RNA amplification to identify the cytokeratin-19 (CK19) gene marker] (Sysmex, Norderstedt, Germany) and Metasin (using theCK19and mammaglobin gene markers) (Cellular Pathology, Princess Alexandra Hospital NHS Trust, Harlow, UK) are intended to provide an intraoperative diagnosis, thereby avoiding the need for postoperative histopathology and, in positive cases, a second operation for ALND.ObjectiveTo evaluate the clinical effectiveness and cost-effectiveness of using OSNA and Metasin in the NHS in England for the intraoperative diagnosis of sentinel lymph nodes metastases, compared with postoperative histopathology, the current standard.Data sourcesElectronic databases including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library and the Health Economic Evaluations Database as well as clinical trial registries, grey literature and conference proceedings were searched up to July 2012.Review methodsA systematic review of the evidence was carried out using standard methods. Single-gate studies were used to estimate the accuracy of OSNA with histopathology as the reference standard. The cost-effectiveness analysis adapted an existing simulation model of the long-term costs and health implications of early breast cancer diagnostic outcomes. The model accounted for the costs of an extended first operation with intraoperative testing, the loss of health-related quality of life (disutility) from waiting for postoperative test results, disutility and costs of a second operation, and long-term costs and disutility from lymphoedema related to ALND, adjuvant therapy, locoregional recurrence and metastatic recurrence.ResultsA total of 724 references were identified in the searches, of which 17 studies assessing test accuracy were included in the review, 15 on OSNA and two on Metasin. Both Metasin studies were unpublished. OSNA sensitivity of 84.5% [95% confidence interval (CI) 74.7% to 91.0%] and specificity of 91.8% (95% CI 87.8% to 94.6%) for patient nodal status were estimated in a meta-analysis of five studies [unadjusted for tissue allocation bias (TAB)]. At these values and a 20% node-positive rate, OSNA resulted in lifetime discounted cost-savings of £498 and a quality-adjusted life-year (QALY) loss of 0.048 relative to histopathology, that is, £4324 saved per QALY lost. The most favourable plausible scenario for OSNA in terms of the node-positive rate (range 10–40%), diagnostic accuracy values (91.3% sensitivity and 94.2% specificity, from three reports that adjusted for TAB), the costs of histopathology, OSNA and second surgery, and long-term costs and utilities resulted in a maximum saving per QALY lost of £10,500; OSNA sensitivity and specificity would need to be ≥ 95% for this figure to be ≥ £20,000.LimitationsThere is limited evidence on the diagnostic test accuracy of intraoperative tests. The quality of information on costs of resource utilisation during the diagnostic pathway is low and no evidence exists on the disutility of waiting for a second surgery. No comparative studies exist that report clinical outcomes of intraoperative diagnostic tests. These knowledge gaps have more influence on the decision than current uncertainty in the performance of postoperative histopathology in standard practice.ConclusionsOne-step nucleic acid amplification is not cost-effective for the intraoperative diagnosis of sentinel lymph node metastases. OSNA is less accurate than histopathology and the consequent loss of health benefits in this patient group is not compensated for by health gains elsewhere in the health system that may be obtained with the cost-savings made. The evidence on Metasin is insufficient to evaluate its cost-effectiveness.Study registrationThis study is registered as PROSPERO CRD42012002889.FundingThe National Institute for Health Research Health Technology Assessment programme.

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Section: Assessment Of Analysis Timementioning

confidence: 83%

Section: Number and Description Of Included Studiesmentioning

confidence: 99%

Section: Metasinmentioning

confidence: 99%

Section: One-step Nucleic Acid Amplificationmentioning

confidence: 99%

“…The study by Bernet et al 50 has been included in the review only for the data on the time taken for OSNA analysis (see Assessment of analysis time).…”

Section: Single-gate Studiesmentioning

confidence: 99%

See 3 more Smart Citations

A systematic review and economic evaluation of intraoperative tests [RD-100i one-step nucleic acid amplification (OSNA) system and Metasin test] for detecting sentinel lymph node metastases in breast cancer

Huxley

Jones-Hughes

Snowsill

et al. 2015

Health Technology Assessment

View full text Add to dashboard Cite

show abstract

Systematic review and meta-analysis of cytokeratin 19-based one-step nucleic acid amplification versus histopathology for sentinel lymph node assessment in breast cancer

Tiernan

Verghese

Nair

et al. 2014

British Journal of Surgery

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Beyond conventional pathology: Towards preoperative and intraoperative lymph node staging

Winter

Gibson

Ruszkiewicz

et al. 2014

Intl Journal of Cancer

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Accurate detection of lymph node metastases is critical for many solid tumours to guide treatment strategies and determine prognostic outcomes. The gold standard for detection of metastasis is by histological analysis of formalin-fixed paraffinembedded (FFPE) sections of removed lymph nodes; this analysis method has remained largely unchanged for decades. Recent studies have highlighted limitations in the sensitivity of this approach, at least in its current clinical use, to detect very small metastatic deposits. Importantly, the poor prognostic outcomes associated with the presence of such small tumour deposits are now well established in a number of cancers. In addition, histological analysis of FFPE sections cannot be used practically for intraoperative node assessment. Novel lymph node staging technologies are therefore actively being developed. This review critically presents the main advances in this field and discusses why these technologies have not been able to provide a better alternative to the current gold standard diagnostic technique.Localized spread of cancer cells to lymph nodes has been established as one of the most significant prognostic indicators, and consequently its identification is of the highest importance in clinical oncology and a key element of solid tumour staging. The gold standard for the detection of lymphatic involvement is the postoperative examination of formalin-fixed paraffin-embedded (FFPE) sections of the resected lymph nodes. However, recent studies have shown limitations of this technique's sensitivity to detect occult tumour deposits in lymph nodes.

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Diagnosis of the sentinel lymph node in breast cancer: a reproducible molecular method: a multicentric Spanish study

Abstract: Our multi-centric trial using the OSNA assay for sentinel node evaluation in breast cancer demonstrates that this is a highly sensitive, specific and reproducible technique that allows for standardization of the SN diagnostic procedure, a necessary, and until now unresolved, issue.

Cited by 65 publications

References 22 publications

A systematic review and economic evaluation of intraoperative tests [RD-100i one-step nucleic acid amplification (OSNA) system and Metasin test] for detecting sentinel lymph node metastases in breast cancer

A systematic review and economic evaluation of intraoperative tests [RD-100i one-step nucleic acid amplification (OSNA) system and Metasin test] for detecting sentinel lymph node metastases in breast cancer

Systematic review and meta-analysis of cytokeratin 19-based one-step nucleic acid amplification versus histopathology for sentinel lymph node assessment in breast cancer

Beyond conventional pathology: Towards preoperative and intraoperative lymph node staging

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