Cost-Effectiveness of Alternative Management Strategies for Patients with Solitary Pulmonary Nodules

  1. Michael K. Gould, MD, MS;
  2. Gillian D. Sanders, PhD;
  3. Paul G. Barnett, PhD;
  4. Chara E. Rydzak, BA;
  5. Courtney C. Maclean, BA;
  6. Mark B. McClellan, MD, PhD; and
  7. Douglas K. Owens, MD, MS
  1. From Veterans Affairs Palo Alto Health Care System, Palo Alto, California, and Stanford University, Stanford, California.
    1. Figure 1. The recommended sequence of tests when CT results are possibly malignant ( ) and when CT results are benign ( ) is shown. Subsequent test selection is shown to be a function of pretest probability and the corresponding post-test probability once the results of CT are known. Note that surgery is preferred when positron emission tomography (PET) results are positive, biopsy is preferred when PET results are negative, and watchful waiting is preferred when biopsy results are nondiagnostic. Recommendations are based on the assumption that society is willing to pay $100 000 per quality-adjusted life-year gained. Results were very similar when willingness to pay was assumed to be $25 000 or $50 000 per quality-adjusted life-year gained. FDG-PET = positron emission tomography with 18-fluorodeoxyglucose.
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      Figure 1. The recommended sequence of tests when CT results are possibly malignant ( ) and when CT results are benign ( ) is shown. Subsequent test selection is shown to be a function of pretest probability and the corresponding post-test probability once the results of CT are known. Note that surgery is preferred when positron emission tomography (PET) results are positive, biopsy is preferred when PET results are negative, and watchful waiting is preferred when biopsy results are nondiagnostic. Recommendations are based on the assumption that society is willing to pay $100 000 per quality-adjusted life-year gained. Results were very similar when willingness to pay was assumed to be $25 000 or $50 000 per quality-adjusted life-year gained. FDG-PET = positron emission tomography with 18-fluorodeoxyglucose. Recommended sequence of diagnostic testing in patients who are at average risk for surgical complications, according to pretest probability and the results of computed tomography (CT).topbottom
    2. Figure 2. The algorithm pertains to patients with low (10% to 50%), intermediate (51% to 76%), and high (77% to 90%) pretest probability of malignancy. Note that in patients with very low pretest probability (<10%), biopsy is preferred when computed tomography ( ) results are possibly malignant and watchful waiting is preferred when CT results suggest a benign diagnosis. In patients with very high pretest probability (>90%), surgery without diagnostic testing is the preferred strategy. FDG-PET = positron emission tomography with 18-fluorodeoxyglucose.
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      Figure 2. The algorithm pertains to patients with low (10% to 50%), intermediate (51% to 76%), and high (77% to 90%) pretest probability of malignancy. Note that in patients with very low pretest probability (<10%), biopsy is preferred when computed tomography ( ) results are possibly malignant and watchful waiting is preferred when CT results suggest a benign diagnosis. In patients with very high pretest probability (>90%), surgery without diagnostic testing is the preferred strategy. FDG-PET = positron emission tomography with 18-fluorodeoxyglucose. Suggested algorithm for clinical management of patients with solitary pulmonary nodules who are at average risk for surgical complications.CT
    3. Appendix (Figure 1). The square decision node ( ) indicates that computed tomography ( ), observation (watchful waiting), surgery, positron emission tomography with 18-fluorodeoxyglucose ( ), or transthoracic needle biopsy may be selected as the initial diagnostic test. If CT is selected first, the result may be possibly malignant or benign. Observation, surgery, biopsy, or FDG-PET may be the next diagnostic test, depending on the results of CT ( ). If FDG-PET is selected as the first test, results may be positive or negative; CT, observation, surgery, or biopsy may be selected as the next test, depending on results ( ). Observation, surgery, or biopsy may be selected after both CT and FDG-PET have been performed ( ).
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      Appendix (Figure 1). The square decision node ( ) indicates that computed tomography ( ), observation (watchful waiting), surgery, positron emission tomography with 18-fluorodeoxyglucose ( ), or transthoracic needle biopsy may be selected as the initial diagnostic test. If CT is selected first, the result may be possibly malignant or benign. Observation, surgery, biopsy, or FDG-PET may be the next diagnostic test, depending on the results of CT ( ). If FDG-PET is selected as the first test, results may be positive or negative; CT, observation, surgery, or biopsy may be selected as the next test, depending on results ( ). Observation, surgery, or biopsy may be selected after both CT and FDG-PET have been performed ( ). Decision model.ACTFDG-PETBCD
    4. Appendix (Figure 2). Needle biopsy may result in fatal or nonfatal complications or no complications (biopsy subtree). If no fatal complications occur, the biopsy may be diagnostic or nondiagnostic, depending on whether it yields a specific malignant or benign diagnosis. If the biopsy reveals malignancy, we assumed that surgery would be performed. If the biopsy reveals a specific benign diagnosis, we assumed that the patient would be treated accordingly and monitored with serial chest radiographs. After a nondiagnostic biopsy, surgery or observation may be selected as the next diagnostic option. Surgery may result in fatal or nonfatal complications, or no complication (surgery subtree). At surgery, most malignant nodules will be local-stage lung cancer, but metastases to regional lymph nodes may be detected in some cases. Some nodules will be benign, depending on the prevalence of benign disease in the target population.
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      Appendix (Figure 2). Needle biopsy may result in fatal or nonfatal complications or no complications (biopsy subtree). If no fatal complications occur, the biopsy may be diagnostic or nondiagnostic, depending on whether it yields a specific malignant or benign diagnosis. If the biopsy reveals malignancy, we assumed that surgery would be performed. If the biopsy reveals a specific benign diagnosis, we assumed that the patient would be treated accordingly and monitored with serial chest radiographs. After a nondiagnostic biopsy, surgery or observation may be selected as the next diagnostic option. Surgery may result in fatal or nonfatal complications, or no complication (surgery subtree). At surgery, most malignant nodules will be local-stage lung cancer, but metastases to regional lymph nodes may be detected in some cases. Some nodules will be benign, depending on the prevalence of benign disease in the target population. Decision model subtrees.
    5. Appendix (Figure 3).
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      Appendix (Figure 3). Markov model.
    6. Appendix (Figure 4). Survival curves for patients with pathologically staged lung cancer (T1N0M0), pathologically staged regional lung cancer (any T N1–3 M0), and distant lung cancer (any T any N M1) are from the linked Medicare claims–Surveillance, Epidemiology and End Results ( ) tumor registry. Modeled survival was based on Markov transition probabilities. For patients with local and regional lung cancer, modeled survival closely approximated observed survival.
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      Appendix (Figure 4). Survival curves for patients with pathologically staged lung cancer (T1N0M0), pathologically staged regional lung cancer (any T N1–3 M0), and distant lung cancer (any T any N M1) are from the linked Medicare claims–Surveillance, Epidemiology and End Results ( ) tumor registry. Modeled survival was based on Markov transition probabilities. For patients with local and regional lung cancer, modeled survival closely approximated observed survival. Observed and modeled survival for patients with local, regional, and distant lung cancer.SEER
    7. Appendix (Figure 5). The frequency plot demonstrates the distribution of observed doubling times for 67 pulmonary nodules and mass lesions from the Veterans Administration–Armed Forces Cooperative Study on Asymptomatic Pulmonary Nodules . The monthly probability of disease progression ( ) was assumed to be a function of the tumor doubling time.
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      Appendix (Figure 5). The frequency plot demonstrates the distribution of observed doubling times for 67 pulmonary nodules and mass lesions from the Veterans Administration–Armed Forces Cooperative Study on Asymptomatic Pulmonary Nodules . The monthly probability of disease progression ( ) was assumed to be a function of the tumor doubling time. Distribution of tumor doubling times and corresponding probabilities of disease progression during the observation period.(20)black circles
    8. Appendix (Figure 6). The ROC curves illustrate the tradeoff between sensitivity and specificity as the threshold that defines a positive test result varies from most stringent to least stringent. The ROC curve for FDG-PET is shown with 95% CIs ( ). Black diamonds represent individual study estimates of sensitivity and specificity. Four studies reported perfect sensitivity and specificity ( ). The point on the summary ROC curve that corresponds to the median specificity reported in 13 studies of FDG-PET for pulmonary nodule diagnosis is shown ( ). At this point, sensitivity and specificity were 94.2% and 83.3%, respectively.
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      Appendix (Figure 6). The ROC curves illustrate the tradeoff between sensitivity and specificity as the threshold that defines a positive test result varies from most stringent to least stringent. The ROC curve for FDG-PET is shown with 95% CIs ( ). Black diamonds represent individual study estimates of sensitivity and specificity. Four studies reported perfect sensitivity and specificity ( ). The point on the summary ROC curve that corresponds to the median specificity reported in 13 studies of FDG-PET for pulmonary nodule diagnosis is shown ( ). At this point, sensitivity and specificity were 94.2% and 83.3%, respectively. Summary receiver-operating characteristic (ROC) curve for positron emission tomography with 18-fluorodeoxyglucose (FDG-PET).dotted linesblack squareblack circle
    9. Appendix (Figure 7). The ROC curve for CT is shown with 95% CIs ( ). Black diamonds represent individual study estimates of sensitivity and specificity. The black circle represents the point on the summary ROC curve that corresponds to the median specificity reported in 12 studies of noncontrast CT and high-resolution CT for pulmonary nodule diagnosis. At this point, sensitivity and specificity were 96.5% and 55.8%, respectively. Note that the summary ROC curve for CT is not symmetrical.
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      Appendix (Figure 7). The ROC curve for CT is shown with 95% CIs ( ). Black diamonds represent individual study estimates of sensitivity and specificity. The black circle represents the point on the summary ROC curve that corresponds to the median specificity reported in 12 studies of noncontrast CT and high-resolution CT for pulmonary nodule diagnosis. At this point, sensitivity and specificity were 96.5% and 55.8%, respectively. Note that the summary ROC curve for CT is not symmetrical. Summary receiver-operating characteristic (ROC) curve for computed tomography (CT).dotted lines
    10. Appendix (Figure 8). Average monthly Medicare expenditures for 1207 patients with surgically treated, T1N0M0 lung cancer ( ); 1954 patients with surgically staged, regional lung cancer ( ); and 10 835 patients with distant lung cancer ( ), from the linked Medicare claims–Surveillance, Epidemiology and End Results tumor registry database. SPN = solitary pulmonary nodule.
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      Appendix (Figure 8). Average monthly Medicare expenditures for 1207 patients with surgically treated, T1N0M0 lung cancer ( ); 1954 patients with surgically staged, regional lung cancer ( ); and 10 835 patients with distant lung cancer ( ), from the linked Medicare claims–Surveillance, Epidemiology and End Results tumor registry database. SPN = solitary pulmonary nodule. Health care costs for patients with malignant pulmonary nodules.black circlesblack squaresblack triangles
    11. Appendix (Figure 9). Test selection is shown to be a function of pretest probability and the corresponding post-test probability once the results of CT are known. Recommendations are similar regardless of whether societal willingness to pay is $50 000 or $100 000 per quality-adjusted life-year ( ) gained. Note that surgery is preferred when positron emission tomography ( ) results are positive, biopsy is preferred when PET results are negative, and watchful waiting is preferred when biopsy results are nondiagnostic. FDG-PET = positron emission tomography with 18-fluorodeoxyglucose.
      View larger version:
      Appendix (Figure 9). Test selection is shown to be a function of pretest probability and the corresponding post-test probability once the results of CT are known. Recommendations are similar regardless of whether societal willingness to pay is $50 000 or $100 000 per quality-adjusted life-year ( ) gained. Note that surgery is preferred when positron emission tomography ( ) results are positive, biopsy is preferred when PET results are negative, and watchful waiting is preferred when biopsy results are nondiagnostic. FDG-PET = positron emission tomography with 18-fluorodeoxyglucose. Recommended sequence of diagnostic testing in patients who are at average risk for surgical complications, according to pretest probability, computed tomography (CT) results, and threshold that determines cost-effectiveness.QALYPET
    12. Appendix (Figure 10). Test selection is shown to be a function of pretest probability and the corresponding post-test probability once the results of CT are known. Positron emission tomography with 18-fluorodeoxyglucose ( ) is recommended over a wider range of post-test probabilities when societal willingness to pay is $100 000 per quality-adjusted life-year ( ) gained. Note that surgery is preferred when PET results are positive, biopsy is preferred when PET results are negative, and watchful waiting is preferred when biopsy results are nondiagnostic.
      View larger version:
      Appendix (Figure 10). Test selection is shown to be a function of pretest probability and the corresponding post-test probability once the results of CT are known. Positron emission tomography with 18-fluorodeoxyglucose ( ) is recommended over a wider range of post-test probabilities when societal willingness to pay is $100 000 per quality-adjusted life-year ( ) gained. Note that surgery is preferred when PET results are positive, biopsy is preferred when PET results are negative, and watchful waiting is preferred when biopsy results are nondiagnostic. Recommended sequence of diagnostic testing in patients who are at high risk for surgical complications, according to pretest probability, computed tomography (CT) results, and threshold that determines cost-effectiveness.FDG-PETQALY
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    1. Ann Intern Med May 6, 2003 vol. 138 no. 9 724-735
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