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More Frequent Surveillance Following Lung Cancer Resection Is Not Associated With Improved Survival

A Nationally Representative Cohort Study

McMurry, Timothy L., PhD*; Stukenborg, George J., PhD*; Kessler, Larry G., ScD; Colditz, Graham A., MD, DrPH; Wong, Melisa L., MD, MS§; Francescatti, Amanda B., MS; Jones, David R., MD||; Schumacher, Jessica R., PhD**; Greenberg, Caprice C., MD, MPH**; Chang, George J., MD, MS††; Winchester, David P., MD; McKellar, Daniel P., MD; Kozower, Benjamin D., MD, MPH

doi: 10.1097/SLA.0000000000002955
PAPERS OF THE 138TH ASA ANNUAL MEETING

Objective: To evaluate whether an association exists between the intensity of surveillance following surgical resection for non–small cell lung cancer (NSCLC) and survival.

Background: Surveillance guidelines following surgical resection of NSCLC vary widely and are based on expert opinion and limited evidence.

Methods: A Special Study of the National Cancer Database randomly selected stage I to III NSCLC patients for data reabstraction. For patients diagnosed between 2006 and 2007 and followed for 5 years through 2012, registrars documented all postsurgical imaging with indication (routine surveillance, new symptoms), recurrence, new primary cancers, and survival, with 5-year follow-up. Patients were placed into surveillance groups according to existing guidelines (3-month, 6-month, annual). Overall survival and survival after recurrence were analyzed using Cox Proportional Hazards Models.

Results: A total of 4463 patients were surveilled with computed tomography scans; these patients were grouped based on time from surgery to first surveillance. Groups were similar with respect to age, sex, comorbidities, surgical procedure, and histology. Higher-stage patients received more surveillance. More frequent surveillance was not associated with longer risk-adjusted overall survival [hazard ratio for 6-month: 1.16 (0.99, 1.36) and annual: 1.06 (0.86–1.31) vs 3-month; P value 0.14]. More frequent imaging was also not associated with postrecurrence survival [hazard ratio: 1.02/month since imaging (0.99–1.04); P value 0.43].

Conclusions: These nationally representative data provide evidence that more frequent postsurgical surveillance is not associated with improved survival. As the number of lung cancer survivors increases over the next decade, surveillance is an increasingly important major health care concern and expenditure.

*Department of Public Health Sciences, University of Virginia Health System, Charlottesville, VA

Department of Health Services, School of Public Health, University of Washington, Seattle, WA

Divisions of Cardiothoracic Surgery and Public Health Sciences, Washington University School of Medicine, St. Louis, MO

§Divisions of Hematology/Oncology, University of California San Francisco, San Francisco, CA

Commission on Cancer and Cancer Programs, American College of Surgeons, Chicago, IL

||Thoracic Surgery, Memorial Sloan Kettering Cancer Center, New York, NY

**Department of Surgery, University of Wisconsin, Madison, WI

††Department of Surgical Oncology and Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, TX.

Reprints: Benjamin D. Kozower, MD, MPH, Division of Cardiothoracic Surgery, Washington University School of Medicine. One Barnes-Jewish Hospital Plaza, Suite 3108 Queeny Tower, St. Louis, MO 63110-1013. E-mail: kozower@wustl.edu.

This work was supported by a Patient-Centered Outcomes Research Institute (PCORI) Program Award (CE-1306-00727, PI Kozower), the National Cancer Institute (UG1CA189823, Alliance for Clinical Trials in Oncology NCORP Research Base), and the Biostatistics Shared Resource, Siteman Cancer Center (CA091842).

The content is solely the responsibility of the authors and does not necessarily represent the official views of PCORI, the National Institutes of Health, the National Institute on Aging, or the National Cancer Institute.

Accepted for presentation at the American Surgical Association Meeting in Phoenix, April 19 to 21, 2018.

The authors report no conflicts of interest.

There are 13.7 million Americans currently living with a history of cancer. With continued improvements in cancer treatment and increasing life expectancy, this number is expected to reach nearly 18 million within the next decade.1 The care of these cancer patients, including surveillance during the post-treatment survivorship phase, is an increasingly important major health care concern and expenditure.2 As the fourth leading diagnosis among cancer survivors, non–small cell lung cancer (NSCLC) is a chronic problem that affects 450,000 Americans and is expected to grow 20% by 2022.3

Clinicians follow patients after NSCLC resection to detect locoregional or distant recurrence; detect a second primary lung cancer; monitor for treatment toxicities of adjuvant therapy; and manage patient anxiety and fear of recurrence.4 Although imaging is a common component of surveillance, clinical practice guidelines for surveillance imaging are inconsistent. The American College of Chest Physicians, The International Association for the Study of Lung Cancer, and the National Comprehensive Cancer Network each recommend different surveillance intensities and imaging modalities ranging from 3-month to annual surveillance with chest x-ray (CXR) or computed tomography (CT).5–7 Importantly, the National Comprehensive Cancer Network describes their recommendation as category 2A, indicating there is consensus that the intervention is appropriate but based on lower-level evidence. This issue extends beyond surveillance to the larger topic of cancer screening. Although some screening studies have compared different screening tests for their accuracy, little is known about the optimal intervals at which to screen patients for a variety of cancers.6

Because there is a paucity of high-quality data on NSCLC surveillance, practice guidelines are based on small retrospective analyses and expert opinion.5,7 This results in wide variation in practice including both underuse and overuse of surveillance services.5 This study uses a unique dataset of patients who received surgery for NSCLC and is the result of a Commission on Cancer (CoC) special study that augmented data from the National Cancer Database (NCDB). Our primary objective is to determine the association between surveillance intensity (3-month, 6-month, annual) with overall survival. A secondary outcome is the association between surveillance intensity and survival after recurrence.

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METHODS

Data Source and Patient Population

The CoC assembled a unique database through a special study mechanism as part of a quality improvement effort to better document comorbidity and cancer recurrence within the NCDB. The NCDB is a joint program of the American College of Surgeons and the American Cancer Society that captures approximately 70% of newly diagnosed cancer cases in the United States from more than 1500 CoC-accredited hospitals.8,9

Up to 10 eligible patients were randomly selected from each CoC-accredited facility for further data abstraction. Eligibility criteria included surgery for stage I to III NSCLC (1/2006–12/2007), available medical records, and complete resection with negative margins. Patients with unknown recurrence status were excluded without replacement. To ensure a minimum of 5 years available follow-up, patients were followed through 12/2012 or until first diagnosis of recurrence, new primary cancer, or death.

Registry staff abstracted complete information on perioperative comorbidity, postoperative imaging and its indication, first lung cancer recurrence, and diagnosis of new primary cancer. Because patients may have received care at multiple facilities, registry staff also obtained records from outside the facility in which initial data entry occurred. Weekly webinars educated registrars and standardized the abstraction process. The newly abstracted data were merged with corresponding NCDB records, deidentified, and transferred to our study team. Because data were deidentified, this study was exempted from institutional review board review. These efforts provide a unique dataset that allows evaluation of NSCLC surveillance practices for detection and treatment of recurrence within a representative nationwide cohort.

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Surveillance Intensity Groupings

We used imaging history and surveillance indication data to place patients surveilled with CT scans into 3 surveillance intensity groups: 3-month, 6-month, and annual, which correspond to the major guideline recommendations.5–7 Although patients can be prescribed specific follow-up intervals, real-world adherence is irregular. In addition, multiple providers (eg, surgeon, oncologist, and primary care) may follow a patient, and may change surveillance after negative imaging following new patient-reported symptoms or suspicious but inconclusive findings. Therefore, we believe that the time to first postoperative CT-surveillance imaging best captured surveillance intensity relative to current recommendations. Because most patients receive an initial postoperative follow-up approximately 30 days after surgery, patients whose first surveillance scan occurred more than 2.5 and less than 5 months postsurgery were placed in the 3-month surveillance group; if the first scan occurred 5 or more and less than 9 months they were placed in the 6-month surveillance group; and if the first scan occurred 9 or more and less than 14 months they were placed in the annual surveillance group. Registrars also recorded their confidence in obtaining the available imaging records (0%–100%).

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Analytic Methods

The primary objective was to assess the association between surveillance intensity and postoperative overall survival. Patients’ survival was then compared across follow-up groups using Cox proportional hazards survival models controlling for age, sex, comorbidities, histology, pathological stage, and surgical procedure.

The impetus for increased surveillance intensity is the hope that earlier detection can lead to improved postrecurrence outcomes. Therefore, we also evaluated the association between surveillance intensity and survival after recurrence in the subset of patients who recurred. We assessed this relationship between survival and the time between recurrence diagnosis and the most recent preceding surveillance using a Cox proportional hazards regression with time since the most recent surveillance CT scan as a covariate. Times were trimmed to a maximum of 14 months, with an additional greater than 14-month indicator variable used to model patients receiving less than annual surveillance. We controlled for the patient and disease characteristics included in the postresection survival model and symptomatic detection and locoregional versus distant site of recurrence.

All regression models used weighted and clustered survey analysis procedures, accounting for random patient sampling within CoC facilities, making results representative of the NCDB population. Proportional hazards models were stratified by pathologic stage.

There is a selection bias when grouping patients into the 3-month/6-month/annual surveillance categories. For surveillance intensity to be apparent, a patient scheduled for 6-month surveillance must remain cancer free through their first scheduled appointment, roughly 7 months postsurgery (assuming the first screening occurs 6 months after a 30-day postoperative assessment). Another patient whose physician recommended 3-month surveillance must, however, only stay healthy for roughly 4 months. To reduce this bias, when comparing the 3-month, 6-month, and annual surveillance groups, we restricted the study population to only those patients who remained disease free through 14 months postsurgery. When comparing the 3- and 6-month cohorts, we restricted to only those patients who remained disease free through 9 months postsurgery. Both analyses are included to maximize the power of the comparison between the 3- and 6-month cohorts, while also incorporating a comparison with the annual surveillance cohort.

As an alternate approach to controlling for this selection bias, we considered multiple imputation to impute surveillance times when patients recurred, developed a new primary cancer, or were lost to follow-up before surveillance was observed. For this approach, surveillance times were imputed based on patient stage, time to recurrence/new primary cancer/loss to follow-up, and the empirical distribution of surveillance times for patients who stayed healthy through 14 months.

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Missing Data

NCDB data were remarkably complete. Four percent of patients were missing chemotherapy and/or radiation treatment information. Registrars were also unable to document comorbidities for 4% of patients. These were handled by including separate “not documented” indicator variables in the regression models. One patient with unknown sex was removed.

All data cleaning and statistical analyses were performed in R (version 3.4.3) using the survival (v. 2.41–3) and survey (v. 3.32–1) packages.

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RESULTS

The special study captured data for 9668 patients. Twenty-eight of these patients were coded as having macroscopic residual tumor, and therefore did not meet inclusion criteria. Twenty-seven patients who had cancer recurrence coded after death were also excluded. Among the remaining 9613 patients, during the 5-year follow-up period, 12% developed locoregional recurrence, 21% developed distant recurrence, and 11% developed new primary cancers. The median time to recurrence was 15.7 months and median post-recurrence survival ranged between 3.0 and 19.9 months depending on whether the recurrence was distant or locoregional and on whether the patient received active treatment or only supportive care.10 Overall 5-year postsurgery survival was 64% for stage I patients, 46% for stage II patients, and 36% for stage III patients, although these estimates are somewhat upwards biased because selected patients were alive and cancer free 90 days postsurgery.

Of the 9613 patients, 5150 were not followed with CT (Fig. 1). Because CT has been shown to be superior to CXR for lung cancer screening and is increasingly being used as the imaging method of choice in postsurgical surveillance,11 our study focuses on the remaining 4463 patients from 1066 hospitals. Of these patients 1,614 were placed in the 3-month surveillance group, 1999 in the 6-month group, and 850 in the annual group (Fig. 2).

FIGURE 1

FIGURE 1

FIGURE 2

FIGURE 2

Patient demographics are shown in Table 1, overall and split by surveillance group. Comorbidities affecting more than 5% of the cohort were included. Patients are similar across the 3 groups by age, sex, race, comorbidities, histology, and surgical procedure. Higher-stage patients tend to receive more frequent surveillance (P < 0.001). The 3- and 6-month surveillance groups were most common (36% and 45%), whereas annual surveillance was less frequent (19%). Registrar confidence in imaging availability was high across all 3 groups (median 100, interquartile range: 90–100 in each group).

TABLE 1

TABLE 1

There were 3552 patients alive and cancer free 14 months postsurgery. Approximately 11.0% of these patients developed a new primary cancer and 23.8% experienced a recurrence over the remainder of the follow-up period; these rates were consistent across surveillance groups (P = 0.49). In this cohort, using Cox regression, more frequent surveillance was not associated with longer survival; the hazard ratio (HR) for 6-month follow-up relative to 3 months was 1.16 (95% CI: 0.99–1.36), whereas the HR for annual surveillance was 1.06 (CI: 0.86–1.31) (Table 2). While building the model, we performed standard regression diagnostics and observed that pathologic stage violated the proportional hazards assumption. Stage was therefore included as a stratification factor, which allows the model to control for stage, but without estimating a corresponding HR. Hence, stage does not appear in Tables 2 or 3.

TABLE 2

TABLE 2

TABLE 3

TABLE 3

In a parallel regression comparing the 3165 patients in the 3 and 6-month surveillance groups who were alive and cancer free 9 months postsurgery, more frequent surveillance also showed no survival benefit; the HR for 6-month relative to 3-month was 1.12 (CI: 0.98–1.29; P = 0.09) (Table 3). In this cohort, 10.6% of patients developed a new primary cancer, whereas 28.9% experienced a recurrence; these rates were consistent between the 3- and 6-month groups (P = 0.80).

The regression using all data and imputed surveillance times for patients who recurred, developed new primary cancers, or were lost to follow-up in the first 14 months postsurgery also showed no difference between surveillance groups (P = 0.45). The HR for 6-month surveillance relative to 3-month was 1.08 (CI: 0.95–1.22), whereas the HR for annual surveillance relative to 3-month was 1.10 (CI: 0.93, 1.32).

Table 4 shows the association between time since last surveillance and survival after recurrence among the 1056 patients with documented recurrence diagnosis dates. More recent prerecurrence imaging was not associated with postrecurrence survival (HR: 1.02/month since imaging; CI: 0.99–1.04), and patients who had gone more than 14 months without imaging were at no greater risk of death (HR: 1.01; CI: 0.62–1.65) (overall P = 0.43). Symptomatic recurrence was associated with worse survival (HR: 1.49; CI: 1.20–1.85; P < 0.01). Other factors associated with decreased survival include distant recurrence (vs locoregional), age, male sex, histology, and certain comorbidities.

TABLE 4

TABLE 4

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DISCUSSION

Post-treatment surveillance was identified as a high priority topic by the Institute of Medicine, which included cancer surveillance among their top 25 priorities for comparative effectiveness research.2 Our study, including 4463 patients surveilled with CT, and with 5-year follow-up on all patients, demonstrates that more frequent surveillance was not associated with improved overall survival or postrecurrence survival.

Although there are several studies comparing types of postoperative surveillance,12–14 there is only 1 recent systematic review and meta-analysis comparing surveillance intensity and survival for patients with lung cancer.7 The analysis included 8 small retrospective studies and 1 small prospective trial with a combined total of 1669 patients. Surveillance programs were heterogeneous and survival was not statistically associated with surveillance intensity. Importantly, the authors cautioned that better evidence was needed to confirm these findings. The current study used a much larger unique data set that explicitly captured the indication for each postoperative chest imaging study. With these data on imaging indications, our study differentiates between routine surveillance, imaging for new symptoms, and imaging unrelated to cancer.

Surveillance recommendations need to be considered in the context of potential harms and benefits to patients and their caregivers. Follow-up imaging and office visits increase cost and can lead to patient anxiety.15 Although it seems intuitive that earlier detection of asymptomatic recurrence could improve outcomes, patients with recurrent NSCLC do very poorly. This cohort had 5-year postrecurrence survival between 2.0% and 11.6% depending on whether the recurrence was distant or locoregional and whether the patient received additional treatment.10 Poor survival after recurrence helps explain why more intense surveillance after surgical resection was not associated with improvement in overall survival. However, after decades of limited progress for treating recurrence and metastatic disease, systemic therapy16 and targeted agents17 are demonstrating clinically significant survival benefits for small patient subgroups, which, in the future, may augment the benefits of early recurrence detection.

Another benefit of post-treatment surveillance is the identification of new primary lung cancers. Lung cancer survivors are the highest risk group for developing a second primary lung cancer (incidence of 2%–4% per year).5,18,19 The survival of this subgroup approaches 70% at 5 years, and guidelines recommend following these patients with at least annual CT scans.5,20 Our patient cohort had a 10% incidence of developing a second primary cancer, and 48% of these were classified and treated as metachronous lung cancers.

This retrospective, observational study has several limitations. First, patients do not consistently adhere to surveillance recommendations. We, however, believe our data are reflective of typical patient care. In a recent SEER-Medicare study, only 61% of patients received guideline-adherent surveillance during the initial 2 years after treatment.21 Another limitation is that surveillance patterns are only apparent after patients have been followed for some time. Although we believe our patient selection criteria, described in detail in the methods section, adequately controlled for the resulting biases, some patients were omitted from our analyses. In addition, the special study was performed in 2014 to 2015 on patients who underwent surgical resection in 2006 and 2007. These years were selected because there is a lag in the NCDB data, they facilitated complete 5-year follow-up required for our primary aim, and then additional time is required to clean and analyze the data. Although these resections occurred 10 years ago, there have been no systematic changes in lung cancer surveillance over the past decade. Finally, 1.1% of patients were lost to follow-up within 3 years and 5.8% were lost within 5 years. Unfortunately, no prospective trial has been funded to examine whether increased surveillance intensity improves survival. An ongoing French surveillance study is, however, prospectively comparing the effectiveness of CXR versus CT for NSCLC surveillance.13

Survival after surgical resection for NSCLC is dependent on a variety of patient and tumor-related factors.1,22 Historically, 5-year survival for the earliest stage of lung cancer, stage IA, was only 70%. Increased use of CT scanning has, however, resulted in a decrease in the median tumor size of resected NSCLC and a shift toward earlier stage disease.23,24 A longitudinal NSCLC screening study demonstrated that 10-year survival for stage I patients who underwent surgical resection was 92%.25 The National Lung Screening Trial prospectively evaluated annual low-dose screening CT scans and demonstrated a 20% reduction in mortality from lung cancer.11 This enormous improvement in survival for NSCLC patients provides great promise for the future and is likely to increase the volume of lung cancer resections performed and the number of lung cancer survivors needing routine surveillance.3 In the absence of similar prospective studies specifically focused on NSCLC surveillance after resection, we believe these results justify the use of CT scanning over CXR. Our data, combined with the results of the National Lung Screening Trial, suggest that at least annual surveillance is appropriate but that there is no benefit to more than biannual surveillance.

In conclusion, this study used a large cohort of patients who had surgical resection of their NSCLC and then underwent routine postsurgical surveillance. The study performed by the CoC allowed for accurate documentation of cancer recurrence, medical comorbidities, 5-year survival, and the indication and results of all surveillance imaging performed. Our results demonstrate that more frequent surveillance imaging was not associated with improved overall survival or postrecurrence survival.

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DISCUSSANTS

Dr M.V. Brock (Baltimore, MD):

Do have one thing to disclose. I’m a consultant with Cepheid Corporation.

Cancer surveillance of survivors is an extremely important topic since, as cancer treatment improves in the future, there will be more survivors who actually would need to be monitored for recurrence and for new cancers.

In this article, I congratulate the authors on a remarkable collaboration and a unique national data set of a thousand lung cancer surgical patients that includes, as is noted, high-quality imaging, recurrence, and survival information. This is an extremely rich data set, and the authors immediately use it to question the basic assumptions of several national guidelines which recommend that a chest CT be done after lung cancer surgery regularly and frequently in the first year postoperatively in an effort to detect lung cancer recurrence.

This recommendation from these various guidelines regarding the most effective postoperative surveillance interval of 3, 6, 9, or 12 months partially has its origins in a series of articles that date back to the 1950s that actually describe volume doubling time for malignant lung cancers. This literature, which is based primarily and initially on simple chest x-rays, suggests that bronchogenic carcinomas rarely have a volume doubling time less than a month and almost never more than a year. So, therefore, a volume change that you want to detect, it was assumed to occur sometime in between these time points, somewhere between a month and a year. This is lower-level evidence at best, and the authors are right to question it.

But my main concern about the manuscript focuses on the authors’ methodology, specifically on how they chose their cohort and some of the inherent selection bias in those patients who are left out of the data set before that endpoint actually is observed; that is, those patients that were censored. For example, if you have a patient who intended on first following-up with their surgeon at that 1-year mark, but then had a recurrence somewhere in that first 12 months, then that patient is not captured in the study as a study patient.

So my first question really is, do you have any idea on how many patients may actually have fallen into this group? And can you adequately control for the exclusion of these patients given your study design?

Finally, there is a burgeoning field of radiomics consisting of CT texture analysis in which really high-speed computers now can calculate and quantitate very, very early radiographic changes that occur at the individual pixel level where they are still invisible to the naked eye of anyone, including radiologists. This technology holds the promise that soon computer algorithms may actually be able to detect recurrent cancers developing within a very short few weeks after surgery.

My question is, do your data suggest that if a recurrent cancer is detected extremely early postoperatively and resected that this surgical intervention would not impact survival? Thank you very much.

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Dr T.L. McMurry (Charlottesville, VA):

Thank you, Dr Brock. These are really insightful comments.

To your first point that we have had to exclude some patients and that may bias our study, I think this is really an excellent point, and it illustrates one of the challenges of doing this study with retrospective data. First, I would like to say that we know of at least 4 failed attempts to get similar prospective studies funded. At this point, we think that we have the best data that are available for this purpose.

To get back to your point, the median time to recurrence in this cohort is roughly 475 days. So, even with the exclusion criteria, we capture more than half of the recurrences. I did not show it in the slides, but we also compared just the 3- and the 6-month cohorts, leaving out the annual cohort because it was smaller. We made this second comparison to make sure that if we included more of the patients in the 3 and 6-month cohorts, we would get the same results, and we got identical results. In this analysis we lost only maybe a third of the recurrences, so we were able to look at outcomes for at least two thirds of the patients who did have recurrence.

To your second question about whether very early detection could improve survival, I think it will remain an open question after this talk. With our second analysis, we tried to look to see whether having screening shortly before time of diagnosis improved outcomes, thinking that if the patient had screening a month before recurrence was diagnosed, then maybe the recurrence would have had less time to grow, and the patient might therefore have a better prognosis. We did not see any indication of improvement with more recent screening.

I think to really improve postrecurrent survival, we are going to need significant improvements in treatment. They may be coming, but it's improvements to treatment that will make a big difference.

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Dr D. Wood (Seattle, WA):

No disclosures. Very nice article, Dr McMurry, and really important data to help us beat back the unsupported enthusiasm for very aggressive follow-up after lung cancer resection.

I want to make a couple of points. One is, noticing the time frame of your cohort, 2006 to 2007, the NCCN guidelines actually then were for 3 to 4-month follow-up. Myself and others over a 3-year period managed to change these to the 6- to 12-month time interval that now exists, and that seems widely accepted by surgeons. So this audience perhaps is the choir.

Where we have had struggles is with the radiation oncologists and, to a lesser degree, the medical oncologists who, for more advanced stage tumors, want to follow those patients at 3 to 4 months. This may have muddied the waters some in your study with some of the stage 3 patients and may be a reason that the International Association for the Study of Lung Cancer has this 3-month follow-up interval as opposed to both American College of Chest Physicians and National Comprehensive Cancer Network, which have 6 months or greater in the interval.

Have you considered—or if you have not, I am going to propose that you consider—redoing your study now with more advanced stage patients, because I think there's no difficulty convincing surgeons—and your study will help do that—that a more frequent follow-up is not necessary? But I think we need the same level of data for the more advanced stage 3 and 4 tumors that are treated nonsurgically so that we get better consensus on how those patients should be followed.

Do you have a way of following those patients? And are you planning on repeating this study with more advanced stage tumors?

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Dr T.L. McMurry (Charlottesville, VA):

That is a really interesting idea. Our data are specifically focused on stages 1 to 3 patients who had a complete surgical resection. So we do not have data on stage 4 patients in this database, and it will be significant extra work to get this additional data.

It's an interesting idea, and I think it's important, but I don’t think we are prepared to do it with the data that we have.

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Dr D. Wood (Seattle, WA):

I will just close those comments with these data then may be confounded by nonsurgeons’ follow-up. Particularly, you identified that higher-stage patients are those who had the more frequent follow-up, and that may be follow-up that's being driven by medical oncologists or radiation oncologists, not surgeons.

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Dr D. Coit (New York, NY):

I won’t speak as an expert about lung cancer, but as somebody very interested in follow-up, particularly in my role on the NCCN melanoma panel. Follow-up is really intended to detect treatable recurrence, and the only way we would think that more intensive follow-up would bend the biologic trajectory of any disease is to think that the early detection is more treatable, and that outcomes are improved by more than lead-time bias.

The question is very simple. If you do not have any treatment, follow-up does not make any difference no matter how intensive it is. But in an era of emerging effective systemic therapy for lung cancer, do you think we can generalize these findings from another era to the current era of effective immunotherapy for advanced lung cancer?

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Dr T.L. McMurry (Charlottesville, VA):

This is a good point. And it may be that if these coming treatments are very effective, that we will want to reevaluate these findings.

As it currently stands, recurrence for lung cancer is very quickly fatal in almost all the patients that recurred. We looked at the cohort that recurred, and there was somewhere between a 2% and 11% five-year survival after recurrence. The range from 2% to 11% depended on whether recurrence was local or distant, and whether the patient received active treatment. Many of the deaths happened very quickly after recurrence. If treatment improves a lot, then it may well be that we want to rethink these findings.

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Dr S. Edge (Buffalo, NY):

Thank you very much. This is a wonderful article. As you know, there are studies going on in the same mechanism on breast, colon, and prostate cancer. So it's quite remarkable to see this coming out of the commission and the alliance.

As I saw your data, it appeared that the 3 groups are based on when the patients had their first imaging study after surgery, but I did not see data on the frequency of follow-up after that first examination. Do you have data? And can you share that with us on the number of CT scans that the people might have had leading up to their recurrence and the frequency with which they had those?

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Dr T.L. McMurry (Charlottesville, VA):

This is an important point. We have these data, but I do not know the numbers off the top of my head. We do see that the more frequent follow-up groups had somewhat more imaging than the less frequent follow-up groups do. But, the number of surveillance scans has the same selection bias challenge as survival. Patients who recur earlier will tend to have less surveillance imaging, and at the same time an early recurrence can only be attributed to a surveillance group if surveillance has already been observed. So, it is important to adjust for this selection bias before making comparisons.

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Dr S. Edge (Buffalo, NY):

In the breast cancer study, for example, the number of scans and the people who had scans was actually relatively low—well less than 1 a year. But I did not see the data here on how many scans a person would have received in a year. I saw when they had their first scan.

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Dr T.L. McMurry (Charlottesville, VA):

Yes. The first scan roughly reflects how many scans somebody gets. But follow-up gets more and more inconsistent as time goes out from surgery. Some patients you will see that they are very regular every 3 months for years and years and then some patients you will see that they get scans for a year and a half, and then never get seen again.

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Keywords:

computed tomography; non–small cell lung cancer; screening; surveillance

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