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Whole-body pet imaging with (18F) fluorodeoxyglucose in management of recurrent colorectal cancer |
Valk P E, Abella-Columna E, Haseman M K, Pounds T R, Tesar R D, Myers R W, Greiss H B, Hofer G A |
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Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology Metabolic imaging by positron emission tomography (PET) using (18F) fluorodeoxyglucose (FDG) for the detection of recurrent colorectal cancer.
Economic study type Cost-effectiveness analysis.
Study population Patients with known or suspected recurrent colorectal cancer.
Setting Hospital and outpatient tertiary referral center. The economic analysis was carried out in Sacramento, USA.
Dates to which data relate Effectiveness and resource use data were collected in the period between 27 October 1992 and 16 May 1996. The price year was not specified.
Source of effectiveness data The evidence for the final outcomes was based on a single study and an assumption made based on published surgical findings.
Link between effectiveness and cost data Costing was conducted retrospectively on the same patient sample as that used in the effectiveness analysis.
Study sample Power calculations were not used to determine the sample size. The study sample consisted of a group of 155 consecutive patients undergoing imaging for the diagnosis or staging of recurrent colorectal cancer. Twenty-one patients (14%) were excluded due to "lack of a criterion standard". An independent final diagnosis was obtained for 134 studies (86%) performed in 127 patients ( median age 67 (range: 31 - 93) years). Computed tomography (CT) scans were available for comparison for 115 patients.
Study design This was a prospective, blinded, cohort study comparing PET with CT, using histologic diagnosis, serial CT imaging, and clinical follow-up as criterion standards, with a fully blinded, retrospective reinterpretation of PET studies. The PET studies were carried out in a single centre, while the CT imaging studies were performed usually at 1 of 7 different hospital radiology departments or outpatient imaging centres in the study region. The duration of follow-up appears to have been at least 1 year. Regarding loss to follow-up, it was reported that the 21 excluded patients consisted of 6 patients who had less than 1 year of follow-up after studies with negative findings, 6 who were lost to follow-up, 5 who died without validation of sites of tumour involvement, and 4 who were treated by radiation or chemotherapy without further validation of findings. All PET images were interpreted at the time of the study by 1 or 2 of the authors who had access to clinical data. All images were reread at the conclusion of the study by 2 of 3 investigators reading independently, and without knowledge of patient's identity, clinical data, CT findings, histological data, or the results of the initial reading. CT scans were reinterpreted by 2 experienced readers to ensure uniformity of interpretation. Readers were blinded to clinical, histological, and PET data. CT studies were performed prior to PET studies with a mean delay of 22 days.
Analysis of effectiveness The principle used in the analysis of effectiveness was not explicitly specified. The clinical outcome measures were the sensitivity and specificity of the diagnostic modalities, and false-true positive and false-true negative findings. The effect of PET findings on surgical treatment was determined by review of pre- and post-PET clinical records and discussion of those records with surgeons.
Effectiveness results PET scan sensitivity was 93% and specificity was 98%. This compared to 69% and 96% for CT. 95% confidence intervals for the differences between the modalities were 16% to 32% for sensitivity and 1% to 5% for specificity. The sensitivity of both modalities varied with anatomic site of recurrence. The largest difference between the 2 modalities was found in the abdomen and pelvis, where more than one third of sites that were true positive by PET were false negative by CT. In the liver the difference between the modalities was smaller at 11% (95% CI: -1% to 22%), and in some cases resulted from difficulty in differentiating benign from malignant abnormalities by CT. In the lungs, both modalities failed to detect 1 metastatic lesion, but had more false-positive findings. PET scans were true positive in 12 out of 18 patients (67%) with elevated serum carcinoembryonic antigen levels and negative CT findings. In 23 (29%) of 78 preoperative studies in which CT showed a single site of recurrence, PET showed tumour at additional sites. At surgery, nonresectable PET-negative tumour was found in 7 of 42 patients (17%) who had PET evidence of localised recurrence only. In a management algorithm in which recurrence at more than 1 site was treated as nonresectable the PET findings in the 78 preoperative patients would translate into avoidance of surgery for nonresectable tumour in 25 patents (32%). Surgery would be avoided in 14 patients with hepatic lesions, 4 with pelvic lesions, 3 with abdominal lesions, 2 with retroperitoneal lesions, and 2 with pulmonary lesions.
Clinical conclusions Although PET is more sensitive than CT PET sensitivity is also limited by minimum detectable lesion size. The detectability of a tumour by PET depends on tumour size and uptake of FDG. Physiologic tracer accumulation in normal structures, particularly the intestine and urinary tract, is another possible source of error in the interpretation of PET images.
Methods used to derive estimates of effectiveness An assumption about effectiveness was made based on published surgical findings.
Estimates of effectiveness and key assumptions It was assumed that half of the patients with hepatic recurrence and unsuspected tumour at a second site would be found to have nonresectable tumours at surgery.
Measure of benefits used in the economic analysis No summary benefit measure was identified in the economic analysis, and only individual clinical outcomes were reported.
Direct costs Costs were not discounted because of the short time frame of the analysis. Quantities, in general categories but not in detailed resource profile, were reported separately from the costs. Some cost items were reported separately. The cost analysis covered the costs of surgical procedures and imaging modalities. The perspective adopted in the cost analysis was not explicitly specified. The effect of PET findings on the cost of patient treatment was determined based on the assumption that recurrence at more than 1 site would be regarded as nonresectable. The cost data were based on reimbursement rates for hospitalisation, professional services (surgery and anesthesia), and pathologic examination of surgical specimens. PET costs were based on average reimbursement for whole-body PET examination at the study centre. The price year was not specified.
Indirect Costs Indirect costs were not included.
Sensitivity analysis No sensitivity analysis was conducted.
Estimated benefits used in the economic analysis Cost results Potential savings resulting from the demonstration of a nonresectable tumour by PET were calculated at $3,003 per preoperative study. The total savings from avoided surgery was $374,596 compared to $140,400 for the cost of PET studies. If the 4 cases in which CT was false positive and PET was true negative were included the net saving would be $3,764 per patient.
Synthesis of costs and benefits A synthesis of costs and benefits was not included because the use of PET studies was the dominant strategy.
Authors' conclusions Positron emission tomography was more sensitive and specific than CT in the detection of recurrent colorectal cancer. Preoperative detection of a nonresectable tumour by PET may avoid unnecessary surgery, and thereby reduce the cost of patient treatment.
CRD COMMENTARY - Selection of comparators The strategy of CT imaging was explicitly regarded as the comparator because it was a procedure routinely performed in the context in question. You, as a database user, should consider whether CT imaging is a widely used health technology in your own setting. In the invited critique following the paper, it was noted that the authors elected to use their expertise against a single, poorly controlled modality rather than against any or all of the other tools that are currently available and in widespread use for the identical purpose of detecting recurrent disease.
Validity of estimate of measure of effectiveness The internal validity of the effectiveness results can not be assured due to the non-randomised nature of the study design, the lack of power calculations to justify the sample size, and the treatment completers only basis for the effectiveness analysis. Furthermore, the authors acknowledged that there were some possible sources of bias that could have favoured PET over CT, including the interval between CT and PET imaging, unequal skills in test performance, variation in CT technology, and bias in test interpretation. The critical comments pointed out the further limitation. The authors should have eliminated from their analysis those patients for whom histopathologic confirmation was not obtained. The commentator conjectured that if this had been done the sensitivity rate of PET would have approximated that of CT scanning. The follow-up period was deemed to be too short and it was not entirely clear whether re-recurrence was defined only clinically or whether it was rigorously sought. Clearly, a more accurate study would be designed to include randomisation of patients to undergo 1 of the 2 studies first, followed by the other. In such a design both scans would be performed by "experts" using the best and newest possible machines with the highest resolution, using standardised techniques and blinded to the results of the other study. The degree to which the study sample was representative of the study population cannot be objectively assessed due to the absence of adequate information about the inclusion criteria adopted in the study.
Validity of estimate of measure of benefit No summary benefit measure was identified in the economic study, and as a result, the study followed a cost-consequences design.
Validity of estimate of costs The following characteristics of the cost analysis may have undermined the validity of the cost results. A comprehensive resource use/unit cost profile was not provided, the price year and perspective adopted in the cost analysis were not specified, reimbursement data were used instead of true costs and the effects of alternative procedures on indirect costs were not addressed. In addition statistical analyses were not performed on resource use or cost data, and sensitivity analysis was not performed to assess the robustness of the study results. The critical commentary following the paper noted that the cost of additional confirmatory investigations after positive PET scan results should have been factored into the cost analysis, and the costs associated with 11 (26%) out of 42 patients in whom resection for cure was undertaken but found to be impossible and 30% of PET scan-negative patients in whom a tumour was apparently found, should be clearly factored out of the cost/savings equation.
Other issues Given the limitations of the study design, the lack of sensitivity analysis and statistical analysis of costs, and the other difficulties noted above, the study results should be treated with some degree of caution. The issue of generalisability to other settings or countries was not directly addressed. Appropriate comparisons were made with other studies.
Implications of the study In this study, PET reduced the proportion of patients with nonresectable tumour at surgery to 17%. Whether PET will also reduce the rate of recurrence by reducing the rate of undetected residual tumour after surgery remains to be determined. Hopefully, more appropriately designed prospective randomised trials will better define the role of this promising new technology, as noted by the commentary..
Source of funding Supported in part by a grant from the Sutter Institute of Medical Research, Sacramento, California, USA (Dr Valk).
Bibliographic details Valk P E, Abella-Columna E, Haseman M K, Pounds T R, Tesar R D, Myers R W, Greiss H B, Hofer G A. Whole-body pet imaging with (18F) fluorodeoxyglucose in management of recurrent colorectal cancer. Archives of Surgery 1999; 134(5): 503-511 Other publications of related interest Invited critique. Wexner S D. Archives of Surgery 1999;134:511-513.
Indexing Status Subject indexing assigned by NLM MeSH Adult; Aged; Aged, 80 and over; Carcinoembryonic Antigen /blood; Colorectal Neoplasms /blood /pathology /radionuclide imaging /surgery; Female; Fluorodeoxyglucose F18; Health Care Costs; Humans; Male; Middle Aged; Neoplasm Metastasis /radionuclide imaging; Prospective Studies; Radiopharmaceuticals; Retrospective Studies; Single-Blind Method; Tomography, Emission-Computed AccessionNumber 21999000940 Date bibliographic record published 31/07/2001 Date abstract record published 31/07/2001 |
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