Futile thoracotomies pose unnecessary risk and burden on patients and society. However, we demonstrate in this investigation that only 10 of 65 thoracic operations (15%) for pulmonary nodules yielding a benign diagnosis are futile. Surgical wedge resection or lobectomy led to a new diagnosis in 69% of benign cases and changed treatment in 68% of cases. In one third of cases (34%), findings directed management of an underlying disease, including concurrent extra-thoracic cancer in 26% of our benign group and transplant management in 6% (4 cases). In 6 cases (9%), resection resulted in definitive treatment. In 55 of 65 cases (85%), patients with benign diagnosis after surgical resection directly benefitted from the surgical intervention.
A prevalence of granulomatous disease within our patient population likely accounts for the relatively high benign rate in our study. The proportion of patients with granulomatous disease in this series (57%) is near the higher end of the previously reported (40–65%) ranges. 5, 7, 16
Gould et al.17
, in a meta-analysis of 10 PET imaging studies published between 1993 and 1998, found the most common benign diagnosis to be granulomatous disease (40%), with active granulomatous infection reported in only 15% of benign cases. In our study, active infection accounted for 42%; this increased prevalence deriving from a high percentage of H. capsulatum
-containing granulomata (23%) within our cohort. While Gould’s meta-analysis combined studies from a variety of geographical regions, our patient population draws from a tertiary academic medical center located in Nashville, TN. H. capsulatum
is endemic within our region, and 57–100% of the population has reported exposure.18-20
We report several cases of infectious nodules that, in hindsight, may be appropriately managed by surgical resection, although we do not assume this to be the optimal approach. Nonetheless, when antibiotic therapy is given empirically for indeterminate nodules, medical management alone has shown to provide limited benefit.5, 21
Premalignancy is another example of benign nodule pathology potentially managed with resection. Further analysis of various combined medical and surgical management approaches for infectious and premalignant nodules is needed to propose guidelines for best management of indeterminate pulmonary nodules.
Our morbidity, mortality, and cost results are particularly relevant for the development of evidence-based comparative effectiveness guidelines in the management of patients with suspicious pulmonary nodules found both in clinical practice and in CT screening programs. Prior models have calculated life expectancy of patients undergoing resection of a benign nodule resection as their normal life expectancy minus the morbidity of surgery.22, 23
The more recent model of Gould et al.24
adjusted life expectancy for quality of life using age- and sex-specific utilities and estimated health care costs for patients with benign nodules, including age-specific, annual health care expenditures. However, the assumption that outcomes of benign diagnoses correspond to the normal population has been challenged recently as oversimplification and underestimation of morbidity, mortality, and costs associated with benign diagnoses.14
Barnett et al. suggested that evaluation alone of infectious nodules incurs cost and morbidity comparable to that of malignancy. We have extended their work by specifically identifying the costs and morbidity associated with ruling out malignancy in a high-risk population and adding the value of the clinical information resulting from the pathology or microbiology reports. Since our data do not include the treatment cost of the benign diagnoses, the results represent a conservative estimate. The expenses of both ruling out malignancy and treating benign diseases must be factored into future management models for patients with indeterminate nodules in endemic areas with histoplasmosis. This data will also be applicable for determining the cost-effectiveness of CT screening programs in these geographic regions.
Several limitations of our descriptive study must be noted. The study population was specifically defined to include only those thoracotomies deemed “futile” for their benign diagnosis and those benign nodules suspicious for malignancy. “Futile thoracotomies” referring to incomplete resection of high-stage non-small cell lung cancer25
were not included. Similarly, indications for thoracic intervention other than ruling-out lung cancer, such as diagnostic wedge biopsies for diffuse infiltrates or multiple nodules were excluded. Finally, patients with benign diagnoses may have received more aggressive management than diagnostically-similar non-operative candidates because the former received multi-specialty care in a tertiary center. Therefore, our findings may not be generalizable to a broader population and should be applied within similar context. Our outcome results are also limited and potentially biased by retrospective data capture in only those patients who received an operation, so analysis did not include those followed with serial imaging. However, even if over-classification occurred, this could not explain the magnitude of our results.
Additional research is needed to elucidate reliable non-invasive alternatives to diagnostic operative resection that can identify benign diagnoses pre-operatively. Increased sensitivity for common benign diagnoses may help decision-making regarding pre-operative probability of malignancy and guide appropriate treatment of benign nodules. In particular, advances in pre-operative diagnostic discrimination between infectious granulomata and autoimmune nodules may significantly reduce the number of cases currently indicated for diagnostic operation by influencing physicians’ willingness to try anti-fungal or immunosuppressive medications when the risk involved in this therapy approaches that of surgery. A prospective study including patients managed both medically and surgically is needed to determine the best treatment options for these patients.
We conclude that patients who receive a benign diagnosis after surgical evaluation for a pulmonary nodule may benefit from this intervention with minimal surgical morbidity and mortality. In addition, obtaining this new information from surgical resection has considerable costs, and further studies are needed to determine the most cost-effective strategies for management of such patients.