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Ann Thorac Surg 1995;60:1563-1570
© 1995 The Society of Thoracic Surgeons
Departments of Thoracic and Cardiovascular Surgery and Biomathematics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas
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Abstract |
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 TopFootnotes Abstract IntroductionPatients and MethodsResultsCommentReferences |
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Methods. Three-hundred fifty-eight consecutive patients who had undergone complete resections of non-small cell lung cancer between 1987 and 1991 were evaluated for tumor recurrence and development of second primary tumors. Recurrences were categorized by site (local or distant), mode of presentation (symptomatic or asymptomatic), treatment given (curative intent or palliative), and duration of overall survival.
Results. Recurrences developed in 135 patients (local only, 32; local and distant, 13; and distant only, 90). Of these, 102 were symptomatic and 33 were asymptomatic (most diagnosed by screening chest roentgenogram). Forty patients received treatment with curative intent (operation or radiation therapy > 50 Gy) and 95 were treated palliatively. The median survival duration from time of recurrence was 8.0 months for symptomatic patients and 16.6 months for asymptomatic patients (p = 0.008). Multivariate analysis shows that disease-free interval (greater than 12 months or less than or equal to 12 months) was the most important variable in predicting survival after recurrence and that mode of presentation, site of recurrence, initial stage, and histologic type did not significantly affect survival. New primary tumors developed in 35 patients.
Conclusions. Although detection of asymptomatic recurrences gives a lead time bias of 8 to 10 months, mode of treatment and overall survival duration are not greatly affected by this earlier detection. Disease-free interval appears to be the most important determinant of survival. Screening for asymptomatic recurrences in patients who have had lung cancer is unlikely to be cost-effective. Frequent follow-up and extensive radiologic evaluation of patients after operation for lung cancer are probably unnecessary.
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Introduction |
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TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentReferences |
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There are no medical guidelines for the appropriate and cost-effective follow-up of patients after pulmonary resection for lung cancer. Patients are monitored in an outpatient setting in an effort to detect recurrences and new primary tumors, whether bronchogenic or at other sites, at an early or potentially curable stage [1–3]. Although many patients feel a sense of security in close follow-up, many others experience intense anxiety surrounding their follow-up. Follow-up visits and testing can be expensive both to the individual, who often must travel to a tertiary care center, and to the insurance companies for the radiologic, laboratory, and professional expenses incurred.
For editorial comment, see 1557.
Escalating health care costs prompted us to conduct a retrospective study of the efficacy of routine surveillance and follow-up in our patients who had undergone resection of bronchogenic tumors. Variables examined included the incidence and the sites of tumor recurrence; symptoms, if any, at the time the recurrence was diagnosed; radiologic, laboratory, or cytologic methods of detection and diagnosis of the recurrences; and the mode of treatment of the recurrence in an effort to understand whether regular follow-up has a clinical impact on a lung cancer patient's overall survival duration.
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Patients and Methods |
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TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentReferences |
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Follow-up testing procedures and intervals varied among the different surgeons and medical oncologists. Patients monitored in an adjuvant protocol setting often underwent more intensive radiologic and laboratory investigations as dictated by the investigational study.
Patients whose tumors recurred were recorded as being either symptomatic or asymptomatic at the time of diagnosis of the recurrence. We also noted whether the recurrence was diagnosed during a scheduled or unscheduled appointment. The interval between the last normal visit and the diagnosis of cancer was recorded. The method by which the recurrence was first detected was noted; these included chest roentgenogram, computed tomographic examinations or other screening radiograph, physical examination, screening sputum cytologic analysis, laboratory tests (liver function, carcinoembryonic antigen), and others.
Recurrences were considered to be local if they were found in the previous operative field (in the surgical incision, adjacent pulmonary parenchyma if a wedge or segmental resection was performed, bronchial stump if a lobectomy or pneumonectomy was performed, or hilar or mediastinal nodes on the same side as the primary tumor). Recurrences were considered to be distant if they occurred at a site that required hematogenous spread (brain, bone, liver, or contralateral lung). A pulmonary lesion was considered to be a second primary tumor rather than a metastasis if it was of a different histologic type, was found in a different lobe or more than 3 years after the primary tumor, or was treated as such by the primary physician.
The mode of treatment of the recurrence was noted. Treatment was considered to be curative in intent if the patient underwent surgical reexcision (completion lobectomy or pneumonectomy, resection of a brain metastasis) or a high dose of radiation therapy (50 Gy or more). Palliative treatment was defined as comfort-oriented care, radiation therapy of less than 50 Gy, or chemotherapy.
In an effort to estimate the medical cost for the follow-up and management of these patients, all radiologic, laboratory, pharmacy, radiotherapy, clinic, and hospital charges for these patients (exclusive of professional fees) were obtained through computerized billing accounts and calculated from a period starting 90 days from their operation up to and including their most recent clinic visit or death.
Other malignancies that developed during the follow-up period were noted in the patient's record.
The date of operation was considered day 1. The time from operation to death or date of last observation was defined as the survival time. The disease-free interval was defined as the time from date of operation to the detection of the first confirmed recurrence or metastasis. Survival curves, starting either from the date of primary resection or from the date of recurrence, were calculated using the product-limit method of Kaplan-Meier. Survival differences between groups were evaluated (univariate analysis) by the log-rank test. Factors analyzed for prognostic significance included mode of presentation, recurrence site, treatment of recurrence, disease-free interval, T status, pathologic stage, and histology. Multivariate analysis of these prognostic variables was performed using Cox regression. Some of the variables included in the Cox proportional hazards model were believed to have clinical significance even though they may not have represented a significant risk factor in the univariate analysis. A two-sided p value less than 0.05 was considered significant. All statistical analyses were performed in the SAS statistical package (SAS Institute, Inc, SAS Cary, NC).
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Results |
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TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentReferences |
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The remaining 358 patients became the subjects of this study. The median follow-up period was 76 months (range, 2 to 92 months). The overall 5-year survival rate of this group was 54% (Fig 1
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and by T status in Figure 3.
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BY PROCEDURE.
Recurrences developed in 37% of patients who underwent segmental or wedge resections, 34% of those who underwent lobectomy (not significantly different; p = 0.63), and 54% of those who underwent pneumonectomy (p = 0.01 when compared with lesser resections). Although the rate of local treatment failure was slightly higher in the segmental/wedge resection group than in the lobectomy group (17.6% versus 11.8%), this was not significant (p = 0.21) (Table 1). The median survival duration was 59.5 months for segmental/wedge resections and has not been reached for patients undergoing lobectomy (not significant; p = 0.19). The median survival duration of patients who required a pneumonectomy was only 25 months, significantly shorter than in the lobectomy or segmental/wedge groups (p = 0.0002).
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. Chest radiographs detected recurrences in 26 (79%) of the 33 asymptomatic patients, whereas physical examination detected the recurrence in only 2 patients. No asymptomatic recurrences were detected through sputum cytologic analysis, blood work, or bone scans. Chest radiographs and computed tomographic scans (brain and chest) were the most common radiologic modalities for diagnosing recurrences in the symptomatic group. Forty-eight or nearly half (47%) of the 102 patients in whom a symptomatic recurrence developed sought medical attention before a scheduled appointment.
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shows a schematic diagram of the presentation and treatment during follow-up of this study population. Of the 102 patients with symptomatic recurrences, only 30 (29%) were treated with curative intent (median survival duration, 23.8 months from date of primary operation). These 30 symptomatic patients recurred in the brain (21), local chest (6), and other sites (3). Of the 33 patients with asymptomatic recurrences, only 10 (30%) were treated with curative intent. These 10 patients (7 with local chest recurrences and 3 with distant chest recurrences), who represent only 2.8% of the original 358, underwent curative resection based on an asymptomatic presentation of recurrence of their lung cancer and represent the only patients who received treatment with a curative intent before development of symptoms. Three of these 10 patients have died at the time of writing and 7 have had a prolonged survival. Seventy percent of both groups were treated palliatively regardless of whether they had symptoms.
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), or 7.5 months and 18.0 months, respectively, when measured from the date of recurrence (p = 0.0001).
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MODE OF PRESENTATION.
Patients whose recurrences were detected from symptoms had a median survival duration from the date of operation of 18.7 months; those whose recurrences were detected without symptoms had a median survival duration of 34.0 months (p = 0.004) (Fig 6). When measured from the date of diagnosis of the recurrence, the median survival duration of the symptomatic group was 8.0 months and that of the asymptomatic group was 16.6 months (p = 0.008) (Fig 7).
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). In patients treated palliatively, the median survival duration (from date of original operation) for those with symptoms was 16.0 months, whereas that for those without symptoms was 30.3 months (p = 0.03). In those treated with curative intent, the median survival duration increased to 23.7 months for those with symptoms, whereas the 10 patients previously mentioned who had no symptoms had not reached their median survival at the time of writing (p = 0.04). When measured from the date of diagnosis of recurrence, for the entire subgroup of patients who had recurrence, the median survival duration was 7.7 versus 15.7 months for palliative versus curative intent.
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). The disease-free interval was the most significant predictor of survival in patients whose cancers recurred (p = 0.0001) (Table 5). When the disease-free interval was held constant, those patients with a disease-free interval greater than 12 months had no difference in survival duration based on whether they presented with symptoms (43 months) or without symptoms (55 months) (p = 0.1) or based on whether they were treated with curative intent (43.5 months) or palliative intent (43.2 months); (p = 0.64) (Fig 9).
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). The yearly cost of medical follow-up for patients whose cancer did not recur was $4,379. For those who were treated palliatively, it was $10,306/year. For those who were treated with curative intent, it was $15,072/year. The overall total follow-up cost and hospital charges if treatment was required for the 358 patients in this study was $6,869,299, or an average of $19,188 per patient (Table 6).
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Nearly half of these second malignancies occurred in the aerodigestive tract (head and neck, lung, or esophagus). Although 10 patients were excluded from this study because they had had malignancy in the 5 years before their operation for their bronchogenic primary tumor, 42 (12%) who were included in this review had had 44 other malignancies more than 5 years before their operation:
Of the entire group of 358 patients in this study, 66 had one additional malignancy either during follow-up or before entry and 7 patients had two other malignancies during this period. There was a total of 80 additional primary malignancies.
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Comment |
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TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentReferences |
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A large study in the early 1980s prospectively evaluated, by surveillance sputum cytologic analysis and chest radiographs, 30,000 male smokers older than 45 years for the development of lung cancer [12, 13]. A conclusion derived from this study was that screening for lung cancer is not warranted even in this high-risk patient population [5, 14]. Can there be, therefore, any benefit to monitoring patients after surgical ``curative'' procedures? Our study indicates that our regular follow-up of patients was able to pick up recurrences at an asymptomatic stage in only 33 of 358 patients (9.2%). Of these patients, only 10 were treated with a curative intent. Therefore, in less than 3% of our patients did regular follow-up lead to a possibly different treatment strategy than would have been used if the clinician had investigated only patients who presented with symptoms. We have also seen that nearly half of the patients in whom symptoms developed returned and sought medical advice before a regularly scheduled visit. A few patients in whom localized recurrences developed in the chest benefited from an aggressive curative approach with resection or high-dose radiation therapy. The multivariate analysis revealed, however, that the mode of presentation was not a significant factor in predicting survival duration. It would appear that the disease-free interval (a direct measure of a patient's tumor biology) is the most important predictor of survival. Most recurrences were diagnosed within the first year of follow-up. Patients whose cancer recurred shortly after their operation, regardless of the tumor's initial stage, T status, and histologic type, did poorly.
Our study is retrospective and therefore necessarily complicated by lead time and length time biases. Randomized, prospective studies comparing two follow-up regimens are the only way to obtain an unconfounded estimate of the effect of follow-up. A recent prospective, randomized, controlled study of European patients with early breast cancer who were monitored postoperatively, either intensively with physician visits, bone scans, liver ultrasound, chest roentgenography, and laboratory tests or less intensively with physician visits and only clinically indicated tests, showed no difference in the primary end points of survival and health-related quality of life issues [15, 16]. These findings led the researchers to conclude that the routine use of these ``intensive'' tests should be discouraged. Although 70% of patients in the European study stated that they wanted to be seen by a physician more frequently and to undergo diagnostic tests even if they were asymptomatic, there were no differences in the quality of life indicators between the two groups. The results also fail to support the argument that intensive surveillance reassures patients, nor did frequent testing seem to increase stress and anxiety.
Although this European study clearly demonstrated that different levels of evaluation yielded no difference in survival duration, the next question that could be posed is, does physician contact add anything to periodic phone contact by a skilled nursing practitioner? In our patients, the physical examination detected a recurrence in only 2 of 33 asymptomatic patients. A prospective study that would clearly answer the question of whether follow-up affects survival duration would entail a control group of patients who are not monitored after their first postoperative clinic visit. The generally held belief of patients that regular radiologic and laboratory testing equates to quality health care delivery would not allow this study to be performed, although dwindling health care resources may force us to rethink this strategy.
In conclusion, the routine follow-up and surveillance of a large population of patients who had undergone a complete resection for lung cancer altered treatment strategy in less than 3% of the total group. Disease-free interval was the most significant predictor of survival in patients whose cancer recurred. Monitoring patients regularly is expensive and appears not to be cost-effective. Follow-up of patients with pulmonary resections may be medically unnecessary unless symptoms develop. Intensive follow-up may be warranted in research protocols in which treatment failures are used to improve our understanding of the biology and response of lung cancer, but it does not necessarily translate into a good and cost-effective clinical practice.
Our recommendation for follow-up is as follows: for the first year postoperatively the patient should have physician or nurse practitioner contact with a chest radiograph (only) every 6 months. Thereafter, yearly chest radiographs should be performed, with other radiologic evaluations only in patients in whom symptoms develop.
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Footnotes |
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TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentReferences |
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Address reprint requests to Dr Walsh, Department of Thoracic and Cardiovascular Surgery, M.D. Anderson Cancer Center, Box 109, 1515 Holcombe Blvd, Houston, TX 77030.
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References |
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TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentReferences |
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