Advice
The technology
The technology
OSNA (one‑step nucleic acid amplification; Sysmex Corporation) is an automated molecular assay system, which is designed to detect metastatic colon cancer cells in the lymph nodes (LNs). It detects the level of expression of the cytokeratin‑19 (CK19) gene, a tissue biomarker, the levels of which correlate with the number of metastatic cells.
The system consists of the RD‑100i automated real‑time nucleic acid analyser unit and the Lynoamp HTS reagent kit, containing all the reagents needed for preparing samples and carrying out the analysis.
During surgery for colon cancer, cancerous parts of the colon and regional lymph nodes are routinely surgically removed, packed on ice, and sent directly to the histopathology laboratory. The OSNA test can be used to analyse LNs weighing 50–600 mg, which must be harvested from fresh tissue within 60 minutes of removal. Each LN is processed according to the manufacturer's instructions, giving a single sample per LN.
Up to 8 samples can be placed in the RD‑100i unit for analysis at the same time. The unit adds reagent, with the primers, nucleotides, enzyme and buffer needed for CK19 expression amplification, to the samples, and then does the test and analysis. The time taken to produce results, excluding harvesting the LNs, depends on the number of LN samples being analysed; for example, about 30–45 minutes for 8 samples and about 90 minutes for 12 samples.
Results are allocated to one of 3 categories: (++) indicates a macrometastatic tumour burden; (+) indicates a micrometastatic tumour burden; and (−) indicates no metastatic disease. Results correlate directly with the measured copy numbers of CK19 mRNA.
The OSNA technology can also be used to detect lymph node metastases in people with breast or gastric cancer, but these uses are beyond the scope of this briefing.
The innovation
In standard post‑operative histopathology, in which partial LNs are analysed, there is a risk that metastatic foci that may be unevenly distributed throughout the LN, are missed. OSNA can analyse whole or partial LNs, with the aim of eliminating or reducing the risk of tissue allocation bias.
Results of OSNA are available in a relatively short time, and so intraoperative analysis of sentinel LNs (those located near the tumour) may in future be possible, although this method of analysis has not been established in routine clinical practice.
Current NHS options
Surgical resection is the main treatment for early stage colon cancer. A pathologist assesses the resected colon tissue to grade and stage the cancer. Resected tissue is processed and cut into sections or levels, stained using haematoxylin and eosin, and examined under a microscope by a consultant histopathologist. The Royal College of Pathologists, in its standards and datasets for reporting cancers, recommends that at least 12 regional LNs from the resected tissue should be investigated. The guidance recommends embedding each whole LN, if it is less than 4 mm, or removing a central block through the longest axis for larger nodes. Typically, a single section is cut and examined from each node.
NICE guidance on diagnosing and managing colorectal cancer recommends that pathological characteristics of the lesion, imaging results and previous treatments should be considered when deciding further treatment in locally excised, pathologically confirmed stage I cancer.
Population, setting and likely place in therapy
OSNA may be used for LN analysis in people with early stage colon cancer as an alternative to standard post‑operative histopathology.
OSNA is intended for use in secondary care by pathologists or biomedical scientists, who have been trained to use the system.
Costs
Table 1 Prices of standard OSNA components (excluding VAT)
|
Product |
Price per unit |
|
RD‑100i system and ancillary equipment |
|
|
RD‑100i including image processing unit, monitor and keyboard |
£74,031.10 |
|
Fastprep‑24 complete instrument |
£7,098 |
|
Specific reagents and consumables |
|
|
Lynoamp HTS kita |
£2,284.40 |
|
Lynorhag |
£206.60 |
|
Pipette tips |
£345.70 |
|
Detector cells |
£325.10 |
|
a The Lynoamp HTS kit is for colorectal cancer only. All other components listed are generic and can also be used for other cancer analyses. |
|
The cost of additional consumables and reagents would vary depending on how many samples are tested in each batch. For example, based on analysing 12 LNs per patient, the indicative cost of disposables is £550–£590 per patient (excluding VAT). The cost could be as low as £33.50 per LN if the consumables are maximised and samples from more than 1 patient are tested in a single batch. The system has a 12‑month warranty, and the current price of an annual maintenance contract for the system (which would apply from year 2 after installation) is £6,628.48 (excluding VAT).
The manufacturer states that the lifespan of the OSNA system is at least 6 years. The test takes about 90 minutes for 12 LN samples, so samples from up to 5 patients can be analysed per day (7.5 hours), and 1,200 in 1 year (240 annual working days). Using the standard annuity method with a discount rate of 3.5%, the average cost per patient (including capital, maintenance, and disposable costs) ranges from £568–£608, depending on the cost of disposables.
The manufacturer offers procurement of the system via a 5‑year lease rental or reagent rental option (in which the analyser is provided and reagents are bought on a cost-per-test basis). For the reagent rental, the cost per patient depends on the number of patients whose samples are analysed in the centre.
Costs of standard care
NHS reference costs 2013–2014 list the cost of histopathology and histology (DAPS02) as £10, but there is no stratification of histopathology by sample type (for example, type of specimen or tissue preparation), which may affect the cost.
Resource consequences
Training is included in the purchase price and no additional facilities or devices would be needed alongside the OSNA system. Fresh tissue harvesting is not routine practice in NHS laboratories, therefore additional OSNA training includes discussion of the awareness needed to avoid contamination of molecular tests, which can be associated with fresh tissue harvesting. No other practical difficulties have been identified in using or adopting the technology.
In the absence of published economic evaluations for OSNA and post‑operative histopathology for colon cancer, the economic consequences of using OSNA in the NHS are unclear.
OSNA is currently being evaluated for use in colon cancer in 1 NHS hospital in Wales.