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OBJECTIVE: To compare strategies for diagnosing cancer in primary care patients with low back pain. Strategies differed in their use of clinical findings, erythrocyte sedimentation rate (ESR), and plain x-rays prior to imaging and biopsy.
DESIGN: Decision analysis and cost effectiveness analysis with sensitivity analyses. Strategies were compared in terms of sensitivity, specificity, and diagnostic cost effectiveness ratios.
MEASUREMENTS: Estimates of disease prevalence and test characteristics were taken from the literature. Costs were represented by the Medicare reimbursement for the tests and procedures employed.
MAIN RESULTS: In the baseline analysis, using magnetic resonance imaging (MRI) as the imaging procedure prior to a single biopsy, strategies ranged in sensitivity from 0.40 to 0.73, with corresponding diagnostic costs of $14 to $241 per patient and average cost effectiveness ratios of $5,283 to $49,814 per case of cancer found. Incremental cost effectiveness ratios varied from $8,397 to $624,781; 5 strategies were dominant in the baseline analysis. Use of a higher ESR cutoff point (50 mm/hr) improved specificity and cost effectiveness for certain strategies. Imaging with MRI, or bone scan followed in series by MRI, resulted in a fewer unnecessary biopsies than imaging with bone scan alone. Cancer prevalence was an important determinant of cost effectiveness.
CONCLUSIONS: We recommend a strategy of imaging patients who have a clinical finding (history of cancer, age ≥=50 years, weight loss, or failure to improve with conservative therapy) in combination with either an elevated ESR (>50 mm/hr) or a positive x-ray, or using the same approach but imaging directly those patients with a history of cancer.
Low back pain is a common complaint among primary care outpatients; estimates of the cumulative lifetime prevalence range from 13.8% for persistent pain 1 to as high as 80% for any episode of pain. 2 In the majority of cases of back pain, a specific diagnosis is not made, 3 and patients usually recover within a few weeks of the onset of symptoms. 4
An important goal of diagnostic testing is to identify the serious systemic causes of back pain, such as malignancy, infection, and inflammatory disease. 3,5 Although malignancy is the most common of these systemic problems,5 the prevalence of spinal malignant neoplasms (usually metastatic disease) among primary care patients with low back pain is less than 1%.6 An important goal of early diagnosis and treatment of spinal metastasis is to prevent complications, which may include pain, pathologic fracture, weakness, sensory loss, paralysis, and bowel or bladder dysfunction. 7,8 Among patients who develop epidural spinal cord compression, those who are diagnosed early, while still able to ambulate, are the most likely to remain ambulatory following treatment. 9,10 The ideal diagnostic strategy would detect the few cases of cancer among primary care patients with low back pain, while minimizing unnecessary diagnostic testing.
Several strategies have been proposed for detecting spinal malignancy in patients with back pain and a known history of cancer9,11; these strategies may involve exhaustive testing to rule out spinal malignancy with a high degree of certainty.9However, only one large study has addressed the issue in a primary care population. In that study, Deyo and Diehl 6 looked at 1,975 patients with a chief complaint of back pain who presented for care to the walk-in clinic of a public hospital; only 13 (0.66%) of those patients were found to have cancer as the underlying cause. The four clinical findings with the highest likelihood ratios for predicting cancer were a previous history of cancer, age 50 years and older, failure to improve with conservative therapy (having sought medical care within the past month and not improving), and unexplained weight loss of more than 10 pounds in 6 months. In their study, all patients with cancer had at least 1 of these 4 findings. Deyo and Diehl 6 proposed an algorithm (see Fig. 1(A)) for detecting cancer which employed these clinical findings, Westergren erythrocyte sedimentation rate (ESR), and plain spine radiographs (x-rays).
Figure 1(A). Strategy A (“selective testing”), adapted from Deyo and Diehl6 with the addition of imaging and biopsy. Strategy A2 (“revised selective testing”) is identical to Strategy A except that patients with a history of cancer go directly to imaging.
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In our analysis, we used decision analytic methods to compare several diagnostic strategies, including the above-mentioned algorithm, for finding cancer in primary care patients with low back pain. We assumed that these patients had no red flags 12 for other potentially serious conditions such as cauda equina syndrome, spinal fracture, or infection. Strategies were compared in terms of overall sensitivity, specificity, and diagnostic cost effectiveness. Costs were represented by the year 2000 Medicare reimbursement for the tests and procedures employed, and therefore represent the payer's perspective. Effectiveness was defined as cases of cancer found. The costs of treatment were not included in our analysis.
Most spinal malignancies are metastatic; primary tumors include breast, lung, and prostate cancers, lymphoma, myeloma, and a number of other types. 13 Following Deyo and Diehl, 6 we considered the various forms of metastatic and primary cancers together as a group for the purpose of this analysis. The term “spinal cancer” therefore comprises a collection of neoplasms, each with its own natural history and clinical features, but similar in their association with back pain. The specific management and prognosis of these disorders depend upon the particular diagnosis.
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Cost effectiveness analysis can indicate a set of diagnostic strategies that are dominant in terms of incremental cost effectiveness ratios, but does not provide a criterion for choosing a single best strategy from this set of optimal strategies. The choice of strategy involves a trade-off between sensitivity, specificity, and cost. Policy makers can use cost effectiveness analysis to “maximize the net health benefit for a target population derived from a fixed budget”.37 From the payer's perspective, available resources may dictate the choice of strategy from a set of optimal strategies. However, the physician must act in the best interest of the individual patient. For physician and patient, the goal is to maximize sensitivity while avoiding the discomfort, inconvenience, and risk of unnecessary biopsy.
The most sensitive approach (strategy C) would image everyone with a clinical finding using MRI or bone scan alone; however, this would result in a substantial number of unnecessary biopsies (20.4 per 1,000 patients for MRI, 123 per 1,000 patients for bone scan). When this strategy is applied using serial imaging, the number of unnecessary biopsies is lower (6.1 per 1,000 patients) but still exceeds the number of cases found. Many would consider the incremental cost effectiveness ratios for this strategy prohibitive compared with the next most effective strategy; depending upon the ESR cutoff point, these exceed $218,000 per additional case found when imaging with bone scan, $305,000 with serial imaging, and $454,000 with MRI.
The most specific strategy of serial testing with ESR followed by x-ray, and imaging only if both are positive (strategy F, image if ESR+ and x-ray+), is inexpensive but has poor sensitivity. Fewer than half of cancer cases are found, even with repeat biopsy. In our opinion, better sensitivity is needed.
The algorithm proposed by Deyo and Diehl 6 (strategy A, selective testing) finds slightly more than half of cancers under baseline assumptions at low cost, and with few unnecessary biopsies; this is a reasonable choice if one is willing to accept the limited sensitivity. We advise an ESR cutoff point of 20 mm/hr for this strategy because of the loss of sensitivity that results from the higher cutoff point. Although this strategy is highly specific, imaging with bone scan alone still results in more unnecessary biopsies (4.6 per 1,000 patients) than cases of cancer found.
Of the strategies considered, we recommend strategies B (image if ESR+ or x-ray+) and B2 (image if HxCa+ or ESR+ or x-ray+) because they offer the best balance between sensitivity and specificity with acceptable cost. For these strategies, we advise the higher ESR cutoff point of 50 mm/hr; in our opinion, the small sacrifice in sensitivity is justified by the marked improvement in specificity and cost effectiveness ratios. The choice between these 2 strategies, and between imaging with MRI or serial imaging, can be based upon whether greater sensitivity or greater specificity is desired (see Table 3). We would not recommend imaging with bone scan alone due to the larger number of unnecessary biopsies (9.6 per 1,000 patients for strategy B, 15.1 for B2).
Our reasoning regarding the choice of imaging gives considerable weight to the number of unnecessary biopsies that result when bone scan alone is used for imaging. Because we did not quantify the patient concern, inconvenience, and discomfort of unnecessary biopsy in our analysis, the higher false-positive rate of bone scan was offset by its lower cost. However, unnecessary biopsy does carry intangible (nonmonetary) costs as well as a small but finite risk of serious complications. For all strategies with sensitivity greater than 50%, unnecessary biopsies exceeded cases found when bone scan alone was used for imaging. Magnetic resonance imaging offers greater specificity than bone scan, with comparable sensitivity and the added advantage of providing anatomic detail in all patients imaged. Serial imaging with bone scan followed by MRI offers the greatest specificity. The choice between these imaging options could also be influenced by considerations that were not included in our decision model. For example, if nonspinal metastases are suspected, then serial imaging might be chosen. If myeloma is suspected based upon clinical presentation, then MRI would be a better choice. Decision models and cost effectiveness analyses provide a framework for clinical decision making but do not relieve the physician of the need to exercise clinical judgement.
Disease prevalence is a critical determinant of cost effectiveness in diagnostic testing. This impact is not only on average cost effectiveness ratios; incremental cost effectiveness ratios are lower at higher disease prevalence. This reflects the essentially reciprocal relationship between disease prevalence and the cost per case detected by a diagnostic test. Liang and Komaroff 40 observed a similar effect in their analysis of spinal roentgenograms. At the prevalence of 0.66% for spinal malignancy assumed in our analysis, the cost effectiveness ratios are extremely sensitive to small changes in cancer prevalence.
One may question whether the use of these diagnostic strategies might increase the costs of managing back pain. Using the strategies we have recommended (B and B2) with an ESR cutoff point of 50 mm/hr, 38% to 40% of patients with low back pain would undergo x-ray to look for cancer, including most patients over 50 years of age. This represents a substantial increase in x-ray use over that observed in several outpatient settings. Frazier et al 41 found that application of 11 published criteria for spinal x-rays would have increased spinal roentgenogram use from 21% to 46% in a series of outpatients with back pain. Schroth et al. 42 used similar criteria and found both underutilization and overutilization of radiography and imaging; however, radiographs were obtained in only 29% of patients with an indication for plain radiography. The effect on levels of utilization would depend upon the practice setting and specialty. Carey et al. 43 found marked differences across specialties in the use of spinal radiography and CT or MRI; radiography use ranged from 19% by HMO providers to 72% by orthopedists for an episode of acute low back pain, and Computed Tomography (CT) or MRI use ranged from 6% to 17%.
Our study has certain limitations. We did not consider the costs of treatment or the utilities associated with treatment outcomes; neither did we include the costs associated with missed diagnoses of cancer. Incidental findings on MRI scan, such as disc protrusion not associated with nerve root impingement and disk degeneration, could lead to patient concern, additional care-seeking, and follow-up imaging without significant clinical benefit to the patient. The additional costs associated with such incidental findings were not included in our analysis. The sensitivities of the clinical findings used in the analysis were estimated from small numbers of patients and therefore had wide confidence intervals. Because spinal malignancy includes a diverse group of neoplasms, the test characteristics may not uniformly apply. For certain malignancies (e.g., myeloma) MRI is more sensitive than bone scan. Although we assumed conditional independence of tests, the actual degree of dependence among tests must be established by observation. Studies that focus on this aspect of multiple testing are essential to the construction of accurate decision models.
Current guidelines recommend that cost effectiveness analyses be done from the societal perspective, in which all costs and all health outcomes are taken into account. 38 We used Medicare reimbursement as a measure of costs in our analysis; the perspective is therefore that of the payer. This, as well as our use of an intermediate outcome (cases of cancer found), limits the ability to compare the cost effectiveness of these diagnostic strategies with other potential uses of health care resources. Our analysis accounts for only a portion of the cost of evaluating the patient with low back pain. Cancer is 1 of several possible causes of low back pain in primary care patients, and the search for underlying cancer is part of a larger diagnostic algorithm. Despite these limitations, the comparison of strategies in this analysis should complement the broader recommendations for the management of low back pain published in 1994 by the Agency for Health Care Policy and Research12 and provide some insight into the costs associated with the implementation of that guideline.
Are these costs reasonable? This question can only be answered in the context of patient and societal preferences. Studies of mammographic screening for breast cancer have shown cost effectiveness values of $7,000 to $25,500 per case of cancer found, 44 and $3,400 to $83,830 per life-year saved.45 Direct comparison with these figures is difficult; unlike metastatic spinal malignancy, breast cancer is often cured by early therapy. Although treatment of spinal metastatic disease will primarily impact upon quality of life rather than survival, these benefits can be substantial. Three-year survival for patients with spinal metastases, measured from the time of bone scan positivity, varies with cancer type but has been shown to be as high as 48% for breast cancer and 56% for prostate cancer.46 The potential gain in quality of life from early treatment to relieve pain and prevent spinal cord compression offers a compelling argument in favor of early diagnosis of spinal malignancy before the onset of neurologic compromise. In our opinion, the associated diagnostic costs are reasonable and justified.
In summary, our baseline analysis identified 5 dominant strategies for finding cancer as a cause of low back pain in primary care patients. Sensitivity analysis identified additional strategies that are optimal in terms of cost, effectiveness, and false-positive rate. We recommend a strategy of imaging patients who have 1 or more clinical finding (history of cancer, age ≥ 50 years, weight loss, or failure to improve with conservative therapy) in combination with either an elevated ESR (>50 mm/hr) or a positive x-ray, or using the same approach but imaging directly without intervening testing those patients with history of cancer. A selective testing algorithm6 that incorporates clinical findings, ESR (>20 mm/hr), and x-ray prior to imaging is a reasonable, although less sensitive, option. Strategy sensitivity can be improved with a modest increase in cost by repeating the biopsy when initially negative. Imaging with MRI, or bone scan followed in series by MRI, leads to fewer unnecessary biopsies than imaging with bone scan alone.