Multi-Modality Mediastinal Staging for Lung Cancer Among Medicare Beneficiaries

ORIGINAL ARTICLE

Multi-Modality Mediastinal Staging for Lung Cancer Among Medicare Beneficiaries Farhood Farjah, MD, MPH,* David R. Flum, MD, MPH,*† Scott D. Ramsey, MD, PhD,‡ Patrick J. Heagerty, PhD,§ Rebecca Gaston Symons, MPH,* and Douglas E. Wood, MD储

Introduction: The use of noninvasive and invasive diagnostic tests improves the accuracy of mediastinal staging for lung cancer. It is unknown how frequently multimodality mediastinal staging is used, or whether its use is associated with better health outcomes. Methods: A cohort study was conducted using Surveillance, Epidemiology, and End Results-Medicare data (1998 –2005). Patients were categorized as having undergone single (computed tomography [CT] only), bi- (CT and positron emission tomography or CT and invasive staging), or tri-modality (CT, positron emission tomography, and invasive staging) staging. Results: Among 43,912 subjects, 77%, 21%, and 2% received single, bi-, and tri-modality staging, respectively. The use of single modality staging decreased over time from 90% in 1998 to 67% in 2002 (p-trend ⬍0.001), whereas the use of bi- and tri-modality staging increased from 10% to 30% and 0.4% to 5%, respectively. After adjustment for differences in patient characteristics, the use of a greater number of staging modalities was associated with a lower risk of death (bi- versus single modality: hazard ratio [HR] 0.58, 99% confidence interval [CI] 0.56 – 0.60; tri- versus single modality: HR 0.49, 99% CI 0.45– 0.54; tri- versus bi-modality: HR 0.85, 99% CI 0.77– 0.93). These associations were maintained even after excluding stage IV patients or adjustment for stage. Conclusions: The use of multimodality mediastinal staging increased over time and was associated with better survival. Stage migration and unmeasured patient and provider characteristics may have affected the magnitude of these associations. Cancer treatment guidelines should emphasize the potential relationship between staging procedures and outcomes, and health care policy should encourage adherence to staging guidelines. *Surgical Outcomes Research Center, †Division of General Surgery, Department of Surgery, University of Washington, Seattle, Washington; ‡Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, Washington; §Department of Biostatistics, and 储Division of Cardiothoracic Surgery, Department of Surgery, University of Washington, Seattle, Washington. Disclosure: The interpretation and reporting of these data are the sole responsibility of the authors. The views expressed in this article do not necessarily represent the official views of the National Cancer Institute, National Institutes of Health, Centers for Medicare and Medicaid Services, or the University of Washington. Address for correspondence: Douglas E. Wood, MD, University of Washington, Department of Surgery, Division of Cardiothoracic Surgery, Box 356410, 1959 N.E. Pacific Street, Seattle, Washington 98195-6410. E-mail: [email protected] Copyright © 2009 by the International Association for the Study of Lung Cancer ISSN: 1556-0864/09/0403-0355

Key Words: Lung neoplasms, Neoplasm Staging, Outcome assessment (health care). (J Thorac Oncol. 2009;4: 355–363)

M

ediastinal nodal status is an important component of lung cancer staging, and is a strong surrogate for systemic disease. As such, mediastinal staging informs the decision to recommend of one of several different therapeutic options—pulmonary resection, radiation therapy, chemotherapy, or multimodality treatment. Accurate mediastinal staging leads to appropriate treatment allocation which is expected to improve survival. Diagnostic modalities used to evaluate mediastinal lymph nodes include computed tomography of the chest (CT), positron emission tomography (PET), mediastinoscopy, endoscopic ultrasound-guided transesophageal (EUS) or transbronchial biopsy, or video-assisted thoracoscopic biopsy.1,2 The accuracy of staging has been shown to be higher with the use of complementary staging modalities.3–5 Practice guidelines have recommended direct tissue biopsy of CT and/or PET positive mediastinal lymph nodes. Current guidelines recommend routine CT and PET for all patients, and routine mediastinoscopy for T2 or greater and centrally located lung cancers.6 The frequency of use of multimodality mediastinal staging has not been well characterized,7 nor has a relationship between its use and health outcomes.8 Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to evaluate patients with nonsmall cell lung cancer (NSCLC), we describe the use of multimodality staging and the associated long-term survival for patients who received multimodality staging compared with those who did not. We hypothesized that multimodality staging would be associated with a lower risk of death.

METHODS Data Source, Study Design, and Setting A retrospective cohort study of patients diagnosed with NSCLC between 1998 and 2002 was conducted using SEERMedicare data. The generalizability, use, quality, and validity of this database have been described extensively elsewhere.9 The University of Washington Institutional Review Board approved this study.

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Patient Selection Among 129,842 patients identified with lung cancers between 1998 and 2002, the following sequential exclusions were made: patients diagnosed at autopsy/death (n ⫽ 2911), patients less than 66 years old (n ⫽ 19,167), histologic type other than NSCLC (n ⫽ 37,902), diagnosis of a second malignancy between 3 months before and 6 months after lung cancer diagnosis (n ⫽ 2507), and patients without both Part A and Part B Medicare coverage or with health maintenance organization enrollment between 1 year before and 6 months after diagnosis (n ⫽ 23,443). Medicare data do not provide complete information about all nonelderly lung cancer cases, and thus this group of patients was excluded. Because noninvasive diagnostic tests are used to evaluate other types of malignancies, and the indications for a given test are not provided within the dataset, patients with a second malignancy diagnosed within the time frame of staging and treatment ascertainment were excluded. Finally, to ensure the data accuracy and completeness when using claims data for research purposes, patients were required have complete Medicare coverage during the periods of variable ascertainment.

Ascertainment of Staging Modality Use Staging modalities were defined by claims within the Physician/Carrier and Outpatient files (Appendix) according to the Healthcare Common Procedure Coding System (HCPCS). Staging modalities were ascertained within an interval 3 months before diagnosis and the date of first therapy or 3 months after diagnosis if the patient received no therapy. An interval prior to the date of diagnosis was considered to ascertain the use of diagnostic modalities among patients who may have undergone staging for a presumptive diagnosis of lung cancer before the recorded date of diagnosis. The intervals above were based on prior estimates of the time between presentation, diagnosis, staging, and therapy.10 –12

Outcomes The primary outcome was overall survival, and the secondary outcome was lung cancer cause-specific survival. All-cause death data were available through the Medicare Enrollment Database with follow-up through 2005. Cause specific death data were available through the SEER registry with limited follow-up through 2004 only.

Covariates Sociodemographic variables were defined and categorized based on prior recommendations.13 Prior malignancy refers to any prior history of cancer other than lung cancer. The Klabunde-modified Charlson comorbidity index was calculated using claims in the year prior to diagnosis within the Physician/Carrier and Outpatient files.14 SEER abstractors recorded both stage (AJCC 6th edition) and histology based on the highest level of available information within 4 months of diagnosis—for instance that available from surgical resection rather than imaging—although there was no information within the dataset indicating which procedure(s) determined the recorded stage or histology. Lung resection, radiation therapy, and chemotherapy within 6 months of diagnosis

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were defined using HCPCS, International Classification of Diseases procedure codes, and Revenue Center Codes within the Outpatient files, and HCPCS in the Physician/Carrier files (Appendix).

Analysis The primary exposure variable was defined by three groups: patients who underwent single (CT only), bi-modality (CT and PET or CT and invasive staging), or tri-modality (CT, PET, and invasive staging) staging. All patients were assumed to have undergone single modality staging with a chest CT and included in the analysis, even though a small fraction of patients had no claim for this procedure. A sensitivity analysis excluding patients without a claim for chest CT did not impact the results. Invasive staging was defined as mediastinoscopy, mediastinotomy, EUS, and/or video-assisted thoracoscopic mediastinal biopsy. Endobronchial ultrasound guided biopsy was not included because the billing code for this procedure was not available until after the study period. STATA (Special Edition 9.2, Statacorp, College Station, Texas) was used for all statistical analyses. For comparisons of continuous and categorical variables, analysis of variance, and ␹2 tests were used respectively. Logistic regression was used to evaluate potential factors associated with multimodality staging and for trend analyses. Unadjusted survival rates were estimated using the Kaplan-Meier method, and unadjusted cause-specific survival rates were calculated based on estimates of the cumulative incidence of lung cancer deaths.15,16 Cox proportional-hazards models were used to evaluate the relationship between multimodality mediastinal staging and overall and cause-specific survival while adjusting for patient characteristics (sociodemographic variables, history of prior malignancy, and comorbidity index). Survival time was defined as the interval between date of diagnosis and death or censoring. Schoenfeld residuals were used to test the proportional hazards assumption, and extended (stratified) Cox models were fitted if the proportional hazards assumption was violated. Robust variance estimators were used for all models. Complete-case analyses were performed. The proportion of subjects with missing patient characteristics varied across staging groups (9, 7, and 7%, p ⬍ 0.001, respectively) though 5-year survival rates for patients with and without missing data did not (13% versus 13%, p ⫽ 0.38). Two-sided p-values less than 1% were considered statistically significant. Several sensitivity analyses were performed to evaluate the impact of varying assumptions on key findings. Patients who presented with metastatic disease would not be appropriate subjects to include in this study because stage IV at presentation generally obviates the need for mediastinal staging. It was not possible to exclude these patients because SEER data does not indicate whether the recorded stage is based on stage at presentation or the results of diagnostic tests and/or pathologic staging. Mediastinal staging may also be unnecessary among patients with contraindications to therapy, but SEER does not record information about important treatment selection factors such as pulmonary function, performance status, or severity of comorbid conditions. There-

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TABLE 1.

Multi-Modality Mediastinal Staging

Patient Characteristics by Mediastinal Staging Group All (n ⴝ 43,912)

Age (%) 66–70 71–75 76–80 81–85 86⫹ Mean ⫾ SD Male (%) Race (%) White Black Other Missing Income (%) Lowest quartile Missing Education (%) Lowest quartile Missing Marital status (%) Unmarried Missing Geography (%) West East Midwest South Residence (%) Metropolitan Urban Rural Prior malignancy (%) Comorbidity index (%) 0 1 2 3⫹ Stage (%) I II IIIA IIIB IV Missing Histology (%) Adenocarcinoma Squamous Large cell Undifferentiated Therapy (%) Resection Radiation therapy Chemotherapy Chemoradiation None

Single modality (n ⴝ 33,796)

Bi-modality (n ⴝ 9076)

Tri-modality (n ⴝ 1040)

p ⬍0.001

21 29 26 16 7 76 ⫾ 6 56

21 28 26 16 8 76 ⫾ 6 57

23 32 27 14 4 75 ⫾ 6 53

23 34 30 11 3 75 ⫾ 5 51

86 9 5 ⬍1

85 9 6 ⬍1

89 6 5 ⬍1

92 3 5 ⬍1

24 4

25 4

20 4

16 4

24 4

25 4

20 4

18 4

43 5

45 5

39 4

40 3

40 21 20 19

40 20 21 19

42 22 16 19

46 25 14 15

84 6 10 22

83 7 11 22

86 6 8 23

89 5 6 23

50 29 12 8

50 29 12 9

50 31 12 7

51 32 10 6

20 5 7 18 33 18

17 4 6 19 36 18

30 7 10 15 21 18

31 8 14 15 16 17

48 32 7 12

48 33 7 12

48 32 6 15

51 31 4 14

25 21 11 16 27

19 23 11 15 33

43 17 10 21 10

57 8 10 20 5

⬍0.001 ⬍0.001 ⬍0.001

⬍0.001 ⬍0.001

⬍0.001

⬍0.001

⬍0.001

⬍0.001 ⬍0.001

⬍0.001

⬍0.001

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fore, the proportion of patients who received multimodality staging was re-estimated after excluding patients with stage IV disease, excluding patients who did not receive treatment, conditioning on survival 30 days after diagnosis, or censoring for death. Analyses evaluating patient-level factors associated with the use of multimodality staging and the relationship between staging and survival, were repeated after adjusting for clustering within SEER registries to account for the possibility of correlated outcomes among patients within a given registry. Finally, multivariate analyses were also repeated after excluding stage IV patients, excluding untreated patients, or conditioning on 30-day survival because of concerns over potential confounding by patient status and disease stage at presentation, as described earlier. The primary analysis did not adjust for stage because stage, as recorded by SEER, was likely the result of mediastinal staging, if not subsequent operative therapy. Since this variable likely represents information available after mediastinal staging it would be in the hypothesized causal pathway and adjustment would not have been appropriate. Nevertheless, we considered an exploratory analysis adjusting for stage, because SEER provides no indication for how stage was ascertained and cancer stage is a strong predictor of survival.

RESULTS A total of 43,912 (median age 75 years [range 66 –105]) patients were eligible for study (Table 1). Fifty percent of patients had a comorbidity index greater than zero. The predominant histologic type was adenocarcinoma (48%). Twenty-nine percent of patients had early-stage (I/II) disease, and 25% of all patients were treated surgically. Overall 5-year survival for the entire cohort was 13% (99% confidence interval [CI] 12–13%), and lung cancer cause-specific survival was 30% (99% CI 30 –31%). A majority of patients (77%) received single modality staging whereas only 21% and 2% underwent bi- and trimodality staging, respectively. Estimates for the receipt of multimodality staging (either bi- or tri-modality) under varying assumptions were as follows: primary analysis with simple proportions and no exclusions (23%, 99% CI 23– 24%), excluding patients with stage IV disease (27%, 99% CI 26 –28%), excluding patients who did not receive treatment (29%, 99% CI 28 –29%), conditioning on 30-day survival (25%, 99% CI 25–26%), or censoring for death (25%, 99% CI 24 –25%). Clinically, these estimates were similar and thus the primary method of estimating utilization (simple proportions and no exclusions) was used for trend analyses and evaluating factors associated with the use of multimodality staging. Between 1998 and 2002, the use of single modality staging decreased from 90% to 67% (p-trend ⬍0.001), whereas the use of bi- and tri-modality staging increased from 10% to 30% and 0.4% to 5%, respectively (Figure 1). Overall use of PET over time increased from 2% to 31% (p-trend ⬍0.001), and invasive staging decreased from 9% to 8% (p-trend 0.005). Patients who underwent a greater number of staging modalities tended to be younger, more commonly white, and

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FIGURE 1. Change Over Time in the Use of Multi-Modality Mediastinal Staging. Single modality staging refers to patients who underwent chest computed tomography (CT). Bi-Modality staging refers to patients who underwent chest CT and positron emission tomography (PET) or invasive staging. Tri-Modality staging refers to patients who underwent chest CT, PET, and invasive staging.

less commonly male or in low income or education strata (Table 1). Table 2 shows a univariate analysis of factors potentially associated with multimodality mediastinal staging. In a multivariate analysis, factors associated with a lower odds of receiving multimodality staging included increasing age, male sex, nonwhite race, and patients in low income or education strata, not married at the time of diagnosis, living in the Midwest versus the West, and living in rural versus metropolitan areas (Table 3). Prior malignancy was associated with higher odds of receiving multimodality staging. Comorbidity index and urban residence were not associated with receipt of multimodality staging. Associations between the receipt of multimodality staging and age, sex, race, marital status, and prior malignancy persisted after adjusting for clustering within SEER registry. Cancer stage and management varied significantly across staging groups (Table 1). Patients in the single modality staging group had a low proportion of stage I/II cancers (25%) and patients who underwent resection (19%), whereas those in the tri-modality staging group had a high proportion of stage I/II cancers (46%) and patients who underwent resection (57%). Unadjusted overall survival rates varied significantly such that stage-based survival rates were higher for groups defined by the use of more mediastinal staging modalities (Figure 2). After adjustment for differences in patient characteristics, comparisons of bi- versus single modality staging and tri- versus single modality staging revealed a 42% and 51% lower risk of death, respectively. Patients who underwent tri- versus bi-modality staging had a 15% lower risk of death (Table 4). Sensitivity analyses excluding stage IV patients, adjusting for stage, excluding untreated patients, and conditioning on 30-day survival revealed slightly attenuated but otherwise similarly large associations. Only in the analysis adjusting for stage were differences in the risk of death no longer significant for the comparison of tri- versus bi-

Copyright © 2009 by the International Association for the Study of Lung Cancer

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TABLE 2. Univariate Analysis of Factors Potentially Associated With Multi-Modality Mediastinal Staging

Age 66–70 71–75 76–80 81–85 86⫹ Sex Female Male Race White Black Other Income Not low Low Education Not low Low Marital status Married Not married Geography West East Midwest South Residence Metropolitan Urban Rural Prior malignancy No Yes Comorbidity index 0 1 2 3⫹ Stage I II IIIA IIIB IV Histology Adenocarcinoma Squamous Large cell Undifferentiated Therapy Resection Radiation therapy Chemotherapy Chemoradiation None

Single modality (%)

Bi-modality (%)

Tri-modality (%)

75 75 76 80 88

22 23 21 18 11

2 3 3 2 1

75 78

22 20

3 2

76 85 79

21 14 19

3 1 2

75 82

22 17

3 2

TABLE 3. Factors Associated With the Receipt of MultiModality Staging

p ⬍0.001

⬍0.001

⬍0.001

⬍0.001 ⬍0.001 76 81

22 17

3 2

75 79

23 19

3 2

Multi-Modality Mediastinal Staging

⬍0.001

Age Male Race White Black Other Low income Low education Unmarried Geography West East Midwest South Residence Metro Urban Rural Prior malignancy Comorbidity index

Odds ratio

(99% CI)

0.97 0.79

(0.96–0.97) (0.74–0.84)

Referent 0.63 0.85 0.84 0.89 0.76

(0.55–0.72) (0.74–0.98) (0.77–0.93) (0.81–0.97) (0.72–0.82)

Referent 0.98 0.68 1.07

(0.90–1.07) (0.62–0.74) (0.98–1.17)

Referent 0.90 0.80 1.13 1.00

(0.79–1.03) (0.71–0.91) (1.05–1.21) (0.97–1.03)

CI, confidence interval.

⬍0.001 76 75 82 77

22 22 17 21

3 3 2 2

76 78 82

21 20 16

3 2 2

77 76

20 22

2 2

77 76 78 80

21 22 20 18

2 3 2 2

65 66 65 82 85

31 30 30 16 13

4 4 5 2 1

77 77 80 75

21 21 18 23

3 2 1 3

56 83 78 70 92

36 16 20 27 21

5 1 2 3 2

⬍0.001

0.002

⬍0.001

⬍0.001

modality staging. Adjustment for clustering within SEER registries had no bearing on associations observed in the primary analysis. An exploratory analysis adjusting for treatment was also conducted to test the assumption that the use of multiple mediastinal staging modalities leads to better health outcomes through a mechanism of more appropriate treatment allocation. If this assumption were true, then adjustment for treatment might be expected to mitigate the effect of multimodality staging on survival. The apparent effect of multimodality staging on the risk of death was attenuated but not eliminated in comparisons with single modality staging, although the apparent effect of tri- versus bi-modality staging was no longer evident. Adjustment for stage and therapy revealed similar results. Finally, analyses were repeated examining time to death due to lung cancer which yielded similar findings (Table 4).

DISCUSSION ⬍0.001

Practice guidelines and scientific evidence support the use of multimodality mediastinal staging in lung cancer management.1– 6,17 Multi-modality staging is believed to lead to better health outcomes through a mechanism of increased accuracy of staging leading to more appropriate treatment allocation. Findings from this study demonstrate that the use of multimodality mediastinal staging has increased over time, but its use varies across sociodemographic strata. As hypothesized, multimodality mediastinal staging was associated with better outcomes. The increasing use of PET over time appeared to account for the overall increase in use of multimodality staging. Two likely factors underlying rapid adoption of PET

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FIGURE 2. Stage-Based Overall Survival by Number of Staging Modalities. Panel A, stage I; Panel B, stage II; Panel C, stage III; Panel D, stage IV. Single modality staging refers to patients who underwent chest computed tomography (CT) (solid line). Bi-Modality staging refers to patients who underwent chest CT and positron emission tomography (PET) or invasive staging (long dash). Tri-Modality staging refers to patients who underwent chest CT, PET, and invasive staging (dot). TABLE 4. Relationship Between Mediastinal Staging and Survival

Bi- vs. single modality Tri- vs. single modality Tri- vs. bi-modality

Overall survival Hazard ratioa (99% CI)

Lung cancer causespecific survival Hazard ratioa (99% CI)

0.58 (0.56–0.60) 0.49 (0.45–0.54) 0.85 (0.77–0.93)

0.56 (0.54–0.58) 0.46 (0.42–0.52) 0.83 (0.74–0.93)

a Adjusted for age, sex, race, income, education, marital status, geography, area of residence, history of prior malignancy, and comorbidity index. CI, confidence interval.

include the onset of Medicare reimbursement in 1998 and a surge of publications about the diagnostic superiority of PET over CT between 1998 and 2000.2,5,17 Practice guidelines were an unlikely factor because recommendations for routine PET use were first published after the end of the study period. Even though the use of tri-modality staging increased over time, the overall use of invasive staging decreased. One explanation for this trend is that several studies have shown that PET may reduce the need for invasive staging due to a high negative predictive value for mediastinal lymph node involvement.2,5 Alternative explanations are that nonsurgical providers have limited access to specialized thoracic surgical oncologists, or that PET is being used in lieu of invasive staging because of a perception that the risks of invasive staging are too high. The latter, if true, is concerning because it would suggest that practice patterns in the community

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deviate from the findings of several meta-analyses and recent practice guideline recommendations.1,2,6 Variation in the use of multimodality staging across sociodemographic strata is concerning but consistent with prior observations about lung cancer care in the United States, particularly with regards to race. Blacks receive invasive staging,18 surgical therapy,19 and chemotherapy less often than whites.20 Reasons underlying differential management of lung cancer by race and socioeconomic level are under study and have been postulated to include factors relating to patients (i.e., baseline health status, assertiveness in seeking specialty care or higher technological interventions, or refusal of care), providers (i.e., perceptions, bias), and structural aspects of health care (i.e., insurance, access to care).21 Multimodality mediastinal staging was associated with longer survival, though likely for complex reasons. A true causal relationship is supported by a strong temporal relationship between predictor and outcome, a “dose-response” relationship (decreasing risk of death with increasing number of staging modalities), and clinical plausibility. Alternatively, these associations may have been influenced by stage migration, confounding by indication, provider effects, or lead-time bias. Stage migration is a situation in which more accurate staging results in apparently higher stage-based survival rates.22 In this study, patients who underwent staging with a greater number of modalities tended to have higher stagebased survival rates. Unmeasured patient and provider characteristics may have confounded the association between staging and survival if patients who underwent more exten-

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sive mediastinal staging were healthier and received care from high quality providers and centers of excellence. This study has several important limitations. The generalizability of our findings may be limited if patterns of mediastinal staging among patients 65 and younger or those with alternative or additional sources of insurance are dissimilar to patterns described by this study. Clinical variables such as baseline health status, tumor position (central versus peripheral), quality of imaging or nodal sampling, and/or pretest probability of nodal involvement (bulky versus not bulky) were not available in this dataset which precluded a description of patient selection factors and adequate risk adjustment. The provider (surgeon, pulmonologist, oncologist, or multidisciplinary team) driving the use of multimodality staging modalities could not be identified. Although claims data do allow identification of providers who perform or interpret tests, these providers may not have ordered the tests or subsequently acted on the results. For similar reasons, we could not reliably identify which provider and/or institution around which patients might cluster.23 Grouping patients by the number of staging modalities may not have reflected the use of different staging algorithms. For instance, patients staged by an algorithm utilizing selective mediastinoscopy for the finding of PET positive nodes might have been categorized as having received bi-modality staging or trimodality staging— depending on the results of PET scanning. Misclassification of patients in this way would likely bias the results towards the null if there were a true relationship between staging algorithm and survival. Finally, survival rates in this study seem lower than those reported by singleinstitutions24 and clinical trials.25 Death information within the SEER-Medicare database is considered robust because it was obtained from the Social Security Administration, and survival rates in this study were similar to those reported by other investigators using SEER-Medicare data.19,20,26 Differences in survival across studies and data sources may represent differences in definitions (i.e., overall versus causespecific survival), patient selection, and/or the quality of care.

Multi-Modality Mediastinal Staging

Patterns of care and associated outcomes described in this study motivate further investigation and may be used to direct quality improvement initiatives in thoracic oncologic care. A substantial degree of scientific uncertainty remains about the effects of multimodality staging on health outcomes. Observational studies have demonstrated improvements in diagnostic accuracy associated with multimodality staging,3–5 and our investigation shows an association with better survival rates. Recent randomized trials evaluating the addition of PET to conventional staging did not reveal differences in diagnostic accuracy, total number of diagnostic tests performed, costs of staging and therapy, or survival, though these trials were not necessarily powered to detect differences in the latter endpoints.27,28 However, several treatment guidelines provide clear staging recommendations and are currently the best existing evidence for staging protocols. Until a higher level of evidence is available, quality improvement initiatives should monitor compliance with current practice guidelines and focus on reducing unnecessary variability in the delivery of care. Since staging profoundly influences treatment decisions, relatively small improvements in staging might be expected to benefit a large number of patients. Accordingly, health policy directed at optimizing lung cancer staging should take high priority since improved staging may have a greater effect on survival than incremental improvements in surgery, radiation, or chemotherapy.

ACKNOWLEDGMENTS Supported by a Ruth L. Kirschstein National Research Service Award (F32 CA130434-01) and Cancer Epidemiology and Biostatistics Training Grant (T32 CA09168-30) from the National Cancer Institute (to F.F.). The authors acknowledge the efforts of the Applied Research Program, National Cancer Institute; the Office of Research, Development and Information, Center for Medicare and Medicaid Services; Information Management Services, Inc.; and the SEER Program tumor registries in the creation of the SEER-Medicare database.

APPENDIX APPENDIX. Chest computed tomography HCPCS Positron emission tomography HCPCS Mediastinoscopy/otomy HCPCS Endoscopic ultrasound HCPCS Video-assisted thoracoscopic mediastinal biopsy HCPCS Resection HCPCS

71250

71260

71270

71275

G0125

G0126

G0210

G0211

G212

39400

39000

39010

43231

43232

43242

43259

76975

32605

32606

31766 32522

32440 32525

32442 32657

32445 32663

32480

Copyright © 2009 by the International Association for the Study of Lung Cancer

G0234

78810

32484

32485

32486

32488

32500

32520 (Continued)

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APPENDIX.

(Continued)

Resection HCPCS Radiation therapy HCPCS

ICD-9 Chemotherapy HCPCS

ICD-9 RCC

31766 32522

32440 32525

32442 32657

32445 32663

32480

32484

32485

32486

32488

32500

32520

31643 77332 77404 77418 77522 77799 C1795 C1806 V58.0 92.29

77300 77333 77406 77419 77523 C1716 C1796 C2616 V66.1 92.30

77301 77334 77407 77420 77525 C1717 C1797 G0126 V67.1 92.31

77305 77336 77408 77425 77750 C1718 C1798 G0173 92.20 92.32

77310 77370 77409 77427 77761 C1719 C1799

77315 77380 77411 77430 77762 C1720 C1800

77321 77381 77412 77431 77763 C1790 C1801

77326 77399 77413 77432 77781 C1791 C1802

77327 77401 77414 77470 77782 C1792 C1803

77328 77402 77416 77499 77783 C1793 C1804

77331 77403 77417 77520 77784 C1794 C1805

95549 96425 J8610 J9091 J9190 J9350 Q0127 V58.1 0331

96400 96440 J899 J9092 J9201 J9360 Q0128 V66.2 0332

96404 96445 J9000 J9093 J9206 J9370 Q0129 V67.2 0335

96406 96450 J9001 J9094 J9208 J9375 S0178 99.25

96410 96542 J9010 J9095 J9230 J9380 S0182

92.21 92.33

92.22 92.39 96412 96545 J9045 J9096 J9250 J9390 S9329

92.23

96414 C9017 J9060 J9097 J9260 J9999 S9330

92.24

96420 J0182 J9062 J9170 J9265 Q0083 S9331

92.26

96420 J8510 J9070 J9180 J9280 Q0084

92.27

96422 J8530 J9080 J9181 J9290 Q0085

9.28

96423 J8560 J9090 J9182 J9291 Q0125

HCPCS, Health care common procedure coding system.

REFERENCES 1. Detterbeck FC, Jantz MA, Wallace M, Vansteenkiste J, Silvestri GA; American College of Chest Physicians. Invasive mediastinal staging of lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007;132(3 Suppl):202S–220S. 2. Silvestri GA, Gould MK, Margolis ML, et al. Noninvasive staging of non-small cell lung cancer: ACCP evidenced-based clinical practice guidelines (2nd edition). Chest 2007;132(3 Suppl):178S–201S. 3. Annema JT, Versteegh MI, Veselic M, et al. Endoscopic ultrasound added to mediastinoscopy for preoperative staging of patients with lung cancer. JAMA 2005;294:931–936. 4. Lardinois D, Weder W, Hany TF, et al. Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography. N Engl J Med 2003;348:2500 –2507. 5. Pieterman RM, van Putten JW, Meuzelaar JJ, et al. Preoperative staging of non-small-cell lung cancer with positron-emission tomography. N Engl J Med 2000;343:254 –261. 6. National Comprehensive Cancer Network: Clinical practice guidelines in oncology–v.2.2008: non-small cell lung cancer. http://www.nccn.org/ professionals/physician_gls/PDF/nscl.pdf. Accessed January, 2008. 7. Alzahouri K, Martinet Y, Briancon S, et al. Staging practices of primary non-small-cell lung cancer: a literature review. Eur J Cancer Care (Engl) 2006;15:348 –354. 8. Deyo RA, Jarvik JJ. New diagnostic tests: breakthrough approaches or expensive add-ons? Ann Intern Med 2003;139:950 –951. 9. Warren JL, Klabunde CN, Schrag D, Bach PB, Riley GF. Overview of the SEER-Medicare data: content, research applications, and generalizability to the United States elderly population. Med Care 2002;40(8 Suppl):IV-3–18. 10. Dische S, Gibson D, Parmar M, Saunders MI. Time course from first symptom to treatment in patients with non-small cell lung cancer referred for radiotherapy: a report by the CHART Steering Committee. Thorax 1996;51:1262–1265. 11. Myrdal G, Lambe M, Hillerdal G, et al. Effect of delays on prognosis in patients with non-small cell lung cancer. Thorax 2004;59:45– 49. 12. Quarterman RL, McMillan A, Ratcliffe MB, Block MI. Effect of

362

13.

14.

15.

16.

17.

18. 19. 20.

21. 22. 23.

preoperative delay on prognosis for patients with early stage non-small cell lung cancer. J Thorac Cardiovasc Surg 2003;125:108 –113; discussion 113–114. Bach PB, Guadagnoli E, Schrag D, Schussler N, Warren JL. Patient demographic and socioeconomic characteristics in the SEER-Medicare database applications and limitations. Med Care 2002;40(8 Suppl):IV19 –25. Klabunde CN, Potosky AL, Legler JM, Warren JL. Development of a comorbidity index using physician claims data. J Clin Epidemiol 2000; 53:1258 –1267. Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 1999;18:695–706. Marubini E, Valsecchi MG. Analyzing Survival Data from Clinical Trials and Observational Studies. Chichester, UK: John Wiley & Sons; 1995. Gould MK, Kuschner WG, Rydzak CE, et al. Test performance of positron emission tomography and computed tomography for mediastinal staging in patients with non-small-cell lung cancer: a meta-analysis. Ann Intern Med 2003;139:879 – 892. Lathan CS, Neville BA, Earle CC. The effect of race on invasive staging and surgery in non-small-cell lung cancer. J Clin Oncol 2006;24:413– 418. Bach PB, Cramer LD, Warren JL, Begg CB. Racial differences in the treatment of early-stage lung cancer. N Engl J Med 1999;341:1198 – 1205. Ramsey SD, Howlader N, Etzioni RD, Donato B. Chemotherapy use, outcomes, and costs for older persons with advanced non-small-cell lung cancer: evidence from surveillance, epidemiology and end results-Medicare. J Clin Oncol 2004;22:4971– 4978. Shavers VL, Brown ML. Racial and ethnic disparities in the receipt of cancer treatment. J Natl Cancer Inst 2002;94:334 –357. Feinstein AR, Sosin DM, Wells CK. The Will Rogers phenomenon. Stage migration and new diagnostic techniques as a source of misleading statistics for survival in cancer. N Engl J Med 1985;312:1604 –1608. Panageas KS, Schrag D, Riedel E, Bach PB, Begg CB. The effect of

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Journal of Thoracic Oncology • Volume 4, Number 3, March 2009

clustering of outcomes on the association of procedure volume and surgical outcomes. Ann Intern Med 2003;139:658 – 665. 24. Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest 1997;111:1710 –1717. 25. Ginsberg RJ, Rubinstein LV. Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ann Thorac Surg 1995;60:615– 622; discussion 622– 623. 26. Bach PB, Cramer LD, Schrag D, Downey RJ, Gelfand SE, Begg CB.

Multi-Modality Mediastinal Staging

The influence of hospital volume on survival after resection for lung cancer. N Engl J Med 2001;345:181–188. 27. Herder GJ, Kramer H, Hoekstra OS, et al. Traditional versus up-front [18F] fluorodeoxyglucose-positron emission tomography staging of nonsmall-cell lung cancer: a Dutch cooperative randomized study. J Clin Oncol 2006;24:1800 –1806. 28. Viney RC, Boyer MJ, King MT, et al. Randomized controlled trial of the role of positron emission tomography in the management of stage I and II non-small-cell lung cancer. J Clin Oncol 2004;22:2357–2362.

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