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
BACKGROUND: In 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 the CK19 and 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. OBJECTIVE: To 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 SOURCES: Electronic 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 METHODS: A 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. RESULTS: A 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. LIMITATIONS: There 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. CONCLUSIONS: One-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 compensat d 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 REGISTRATION: This study is registered as PROSPERO CRD42012002889. FUNDING: The National Institute for Health Research Health Technology Assessment programme.
Citation
@article{n.2015,
author = {Huxley, N. and Jones-Hughes, T. and Coelho, H. and Snowsill,
T. and Cooper, C. and Meng, Y. and Hyde, C. and Mújica-Mota, R.},
title = {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},
journal = {Health Technol Assess},
volume = {19},
number = {2},
date = {2015},
url = {https://tristansnowsill.co.uk/a-systematic-review-and-economic-evaluation-of-interoperative.html},
doi = {10.3310/hta19020},
langid = {en},
abstract = {BACKGROUND: In 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 the CK19 and 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.
OBJECTIVE: To 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 SOURCES: Electronic 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 METHODS: A
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. RESULTS: A 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. LIMITATIONS:
There 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.
CONCLUSIONS: One-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
compensat d 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
REGISTRATION: This study is registered as PROSPERO CRD42012002889.
FUNDING: The National Institute for Health Research Health
Technology Assessment programme.}
}