Using clinical features or tests to screen for serious pathologies in low back pain patients involves identifying features which, when present, raise the index of suspicion and when absent, lower the index of suspicion of having the disease. For malignancy in particular, raising the index of suspicion is most important due to the prevalence of the disease within this patient group being around 1%. The results of this systematic review identified a number of features, which raise the probability of malignancy, however these features are not equally useful for this purpose. The LR+ of the features ranged from 1.7 to 55.6 and this needs to be appreciated when judging the clinical importance of a red flag identified in a clinical assessment.
Age ≥50 years, no improvement after 1 month, a previous history of cancer, and no relief with bed rest are commonly suggested “red flags” for malignancy in clinical guidelines [17
], and are supported by the results of this review. Of these four red flags, a previous history of cancer is the most informative with a pooled LR+ of 23.7. The other three all had LR+ about 3. Other common “red flags” include unexplained weight loss, fever, thoracic pain, or being systematically unwell [17
]. Being systemically unwell was not evaluated by any of the eligible studies, and the other features did not significantly raise or lower the probability of having malignancy [6
While laboratory tests are not recommended routinely in low back pain patients [13
] tests for ESR and anaemia were found to be useful screening tools for malignancy. Hematocrit <30% (LR+ = 18.2) and WBC ≥12,000 (LR+ = 4.2) also significantly raise the suspicion of malignancy [6
]. In the study, which evaluated these laboratory tests, however, the decision to perform them was based on clinician judgement [6
] and the results would therefore be subject to a form of filter bias [14
]. Overall clinician judgement for the presence of malignancy also had significant LR+ of 12.1 [16
] but the details of what factors and other features were contained within this overall judgement were not reported.
Providing data, such as likelihood ratios, on the diagnostic accuracy of clinical features to screen for malignancy allows clinicians to evaluate whether further testing is warranted in patients with low back pain. The results of this review show that whilst a number of features have significant likelihood ratios, only four features; a previous history of cancer, an elevated ESR, low hematocrit, and clinician judgement are able to raise the post-test probability of malignancy to a clinically significant level when used in isolation (Table ). This process is illustrated in Table , which shows the post-test probability of cancer in patients with a positive response to each red flag. The analysis is conducted for pre-test probabilities of 1 and 5%. For example, if the prevalence of malignancy (pre-test probability) in a low back pain patient is presumed to be 1%, and the patient is aged ≥50 years, the (post-test) probability would only increase to 2.2%. In fact all but one of the red flags from the clinical assessment had only modest predictive ability. The exception is if a patient has a previous history of cancer, where the probability will be raised to 19.2%, a change in disease probability that would be sufficiently large to warrant further investigation.
Application of red flags to clinical decision making
Clearly it would be helpful to have a clinical screening tool with greater accuracy than the clinical red flags in Table . One strategy would be to rely upon combinations of red flags an approach more analogous to overall clinician judgement. The only combination of features that was evaluated had a significant LR+ of only 2.4 and a significant LR− of 0.06, as the focus was on increasing the sensitivity [6
]. Further study is needed which focuses on raising the suspicion of malignancy by investigating to what effect combinations of features can increase the post-test probability. Almost three-quarters of the clinical features identified by this review were investigated in only one study [6
], and it is possible that other features not previously evaluated may be useful in the diagnosis of malignancy. Due to the low prevalence of the disease, large-scale high quality studies need to be performed for practitioners to have further confidence in their ability to screen for serious pathologies such as malignancy. Another area of research would be the investigation of the salient features that are considered when clinicians form an overall judgement that the patient may have cancer especially as this ‘test’ was the second most informative clinical test to identify patients with cancer. This test was found to be quite informative in two studies but neither outlined the cues the clinicians were considering when forming this judgement.
The quality of the studies included in the review is an important consideration because certain methodological shortcomings can have large effects on estimates of diagnostic accuracy [14
]. The largest of these effects are caused by studying a non-representative sample of patients, or failing to apply the same reference standard to the entire cohort or a random sample of the population [3
]. Only one eligible study reported performing the same reference standard (X-ray) on all patients in their cohort [12
]. The other studies combined the use of X-ray as a reference standard with clinical follow-up [5
]. As clinical follow-up may fail to identify false-negative test results, the diagnostic performance of the test will be overestimated [14
]. Overall, the reporting of design-related characteristics of the studies was poor, and the methodological quality was low.
To increase the external validity of our findings, we excluded case-control studies, and only extracted data from studies of clinical populations of low back pain patients. The use of clinical features for detecting serious spinal pathology is presumably most useful in the community primary care setting as this is where patients with low back pain are usually managed [13
]. However, there were no studies identified by this review that were performed on a consecutive series of low back pain patients presenting to community primary care providers.
In conclusion malignancy is rare in low back patients. The most informative tests to screen for malignancy are a previous history of cancer, overall clinician judgement, elevated ESR, and reduced hematocrit. Popular red flags such as unexplained weight loss, age >50, and failure to improve after 1 month have only modest predictive ability and on their own are not useful to screen for cancer.