In this paper we provide population-based complication risks following CT-guided biopsy of a pulmonary nodule. While hemorrhage was infrequent (1%), pneumothorax was common (15%). Complications were associated with adverse outcomes including longer length of stay and higher rates of respiratory failure. We confirmed prior reports that older age and COPD increase complications (4
). Perhaps most importantly, we show that over 6% of CT-guided biopsies result in pneumothorax requiring chest tube. This is a clinically important complication that entails pain, serial imaging and radiation exposure, and hospitalization averaging 2-5 days (18
A recent study showed that doctors do not accurately predict pneumothorax risk following CT-guided biopsy (12
); this may in part be due to a lack of representative data. Case series over the last decade report hemorrhage in 2-10% and pneumothorax in 4-42%(4
). Some estimates are clearly lower than the risk the typical patient faces, reflecting the expertise of specialized centers. Other estimates seem high, perhaps because all complications visualized under CT-guidance were included, regardless of their clinical relevance.
Comprehensive databases offer important advantages over case series. Our analysis of essentially all CT-guided lung biopsies in four states (>15,000 biopsies) offers a more representative picture of complication risk than smaller case series of a few hundred patients. Our estimated risks of complications are more likely to be clinically important than complications defined by imaging findings at the time of biopsy (as is often done in case series), which may be irrelevant to the patient if no symptoms result. For example, in our study, hemorrhage recorded on discharge records was associated with a number of clinically important adverse events, including longer length of stay, need for blood transfusion, and respiratory failure requiring mechanical ventilation. Similarly, our estimated risk of pneumothorax requiring chest tube should be reliable and precise, since it is based on billing for a clinically important invasive procedure with coding specificity and positive predictive value of 99% and 86%, respectively (19
). Indeed, our estimated risk of pneumothorax requiring chest tube (6.6%, 95% CI 6.0-7.2%) is consistent with, but far more precise than, estimates from case series (0.2-9.0%) (4
Analyzing administrative databases has disadvantages. While they can be used to estimate short-term risks of procedures like CT-guided biopsy, these data are de-identified and cannot be linked to other sources to provide information on diagnostic yield of biopsy or long-term risks and benefits of the procedure. It is likely that some complications, particularly minor complications, are systematically undercoded. However, there has been increasing emphasis on accurately coding complications (20
), and procedure-related adverse outcomes of hemorrhage and pneumothorax have been shown to have positive predictive values over 70% (20
). Without access to clinical progress notes, we cannot be certain of the sequence of events. For example, one might wonder whether a discharge diagnosis of pneumothorax is truly a complication of CT-guided biopsy. However, our more specific sensitivity analyses, which produced little change in estimated risks, suggest it is highly likely that our reported risks of any pneumothorax and pneumothorax requiring chest tube indeed reflect complications of CT-guided biopsy.
Another disadvantage of de-identified administrative databases is the lack of clinically detailed variables to predict complications, such as previously identified patient risk factors of nodule size and location, physician characteristics such as specialty or years of experience (7
), or concentration of physicians or CT scanners in a hospital or region. The comorbidities we tested (e.g., COPD, tobacco use) may be variably coded on discharge records, and it is possible that coding of comorbidities may be more thorough on records that also show a complication. Without clinical detail, some observed associations appear counter-intuitive at first glance. For example, pleural effusion was associated with a five-fold higher likelihood of hemorrhage; however, we could not distinguish whether the effusion increased the risk of complication, or was itself the complication (i.e., hemothorax from biopsy). Although some variables associated with lower complication rates (e.g., patients undergoing concurrent bronchoscopy, biopsies performed in the midst of a hospital stay as opposed to a scheduled procedure) initially seem counter-intuitive, we believe the explanation lies in patient selection: doctors choose to perform bronchoscopy and CT-guided biopsy on the same day only in the subset of patients best able to tolerate both procedures (those with lower risk of complications); similarly, doctors tend to defer elective procedures like CT-guided biopsy in patients at high risk of complications (such as those with severe COPD) during acute hospital admissions. We suspect the lower complication risk in younger patients (age<60) represents an overall healthier population, while the lower risk of complications in older patients (age>70) suggests that doctors may reserve biopsy for the subset of older adults who are healthy enough to tolerate treatment if the nodule is malignant.
Interestingly, as shown in , low biopsy utilization states had a higher complication rate per biopsy than high biopsy utilization states (e.g., odds ratio for pneumothorax requiring chest tube given biopsy = 1.85, 95% CI 1.35-2.54 for New York vs. Florida). High biopsy utilization states likely achieved a lower rate of complications per biopsy by expanding the pool of patients undergoing biopsy to include healthier individuals with a lower risk of both cancer and complications. In support of this hypothesis is the fact that, compared to high biopsy utilization states, a greater proportion of CT-guided biopsies in New York were performed among patients with COPD and patients aged 60-79, factors associated with both lung cancer and biopsy complications. It is important to note, however, that because fewer biopsies were performed at the population level in the low biopsy utilization states, the rate of complications at the population level was lower in the low biopsy utilization states (e.g., age-adjusted relative rate of pneumothorax requiring chest tube at the population level = 0.61, 95% CI 0.50-0.73 in New York vs. Florida).
The striking variability in biopsy utilization rates between states suggests a lack of consensus on optimal management of pulmonary nodules, reflecting the paucity of evidence in this area. There have been no randomized trials comparing strategies of pulmonary nodule management (e.g., serial imaging, biopsy, early surgery) or addressing whether, when, and how to perform biopsy, and guidelines on pulmonary nodule management are based primarily on expert opinion (2
). Although full results have yet to be released, the National Cancer Institute recently stopped its National Lung Screening Trial comparing chest CT versus x-ray screening early due to a reported 20% reduction in lung cancer mortality in the CT arm (23
). This announcement received substantial media coverage and has led to renewed public and physician enthusiasm for lung cancer screening and aggressive pulmonary nodule management in general. Data from a feasibility study for this trial suggest that a third of smokers who undergo chest CT scanning have a false positive finding (a pulmonary nodule that does not turn out to be malignant over the next year) (24
). These patients will then be faced with the choice of whether or not to proceed with biopsy, an area not addressed by the design of the trial. Although our study does not address the long-term risk-benefit trade-off of whether to pursue biopsy, the population-based data we have provided on short-term risk of complications of CT-guided biopsy may help patients with pulmonary nodules and their doctors make a more informed decision.
Our data suggest that several thousand Americans experience complications of CT-guided biopsy each year. These harms will no doubt continue to rise as more patients are diagnosed with nodules and undergo biopsy. For many patients, including those with a low risk of cancer, those too frail to undergo cancer treatment, or those with a high risk of cancer who should proceed directly to surgery, this procedure may be unnecessary. Before exposing patients to potential harm from CT-guided biopsy, it is critical that physicians ensure patients understand the risks.