There may be differences in how recurrences and metachronous tumors are identified. Recurrences seem to be more often detected through assessment of symptoms. Pairolero et al scheduled visits for their stage I NSCLC patients every 4 months for the first 2 years and then every 4 to 6 months thereafter following curative intent surgery. A history, physical examination, CXR, blood tests, urine analysis, and pooled sputum cytology were performed at each visit. Most recurrences were detected at scheduled visits (59%), but a substantial number of recurrences were detected at unscheduled visits. Most patients with recurrences were symptomatic (53%), and symptom assessment was the most sensitive method for detecting recurrences. The blood tests, urine analysis, physical examination, and sputum cytology added little to detecting recurrences. Others have reported similar findings. Chiu and colleagues followed up 38 patients following curative intent surgical resection for NSCLC with a history, physical examination, sputum cytology, CXR, and CT at 3-month intervals for 2 years and then at 6-month intervals for the next 3 years. Of the 14 patients who had recurrences, 7 patients (50%) presented with symptoms. Ichinose described a similarly intensive surveillance program and also reported that most recurrences were recognized by symptoms; neither CT nor standard blood tests provided appreciable additional benefit in identifying recurrences.
In contrast, some case series have reported that 68 to 100% of patients with metachronous lung cancers were asymptomatic and had the new primary lung cancer detected by radiographic methods. Lam-ont et al described a retrospective chart review of 124 patients following curative intent surgical resection of NSCLC. They had all been entered into a regular surveillance program, including a history, physical examination, and CXR at 4- to 6-month intervals and an annual CT. Of the 124 patients, metachronous lung cancers developed in 19 patients (15.3%; 2.1%/yr), and all 19 patients were asymptomatic at the time. Eleven of the 19 metachronous tumors were first detected by CT; 16 of the 19 patients had stage IA disease, and 14 patients underwent curative intent reoperation. Nine of 14 patients were alive without evidence of recurrent disease at a median of 20 months. These authors recommended annual CT for detecting metachronous tumors because disease can be identified early and resected, although the study was not designed to show a survival advantage for this group. Provide your patients with care of My Canadian Pharmacy.
Other studies have provided an expanded view of the methods used for detecting recurrences and/or metachronous tumors by considering the costs involved in a surveillance program. Walsh et al retrospectively evaluated the course of 358 patients following curative intent surgical resection for NSCLC. There were 135 recurrences, and most (76%) were recognized through symptoms. Although the asymptomatic patients had a longer survival time following detection of the recurrence, the authors believed that this reflected lead-time bias and not a true survival benefit. Similar percentages of symptomatic (29%) and asymptomatic (30%) patients could be treated with curative intent. Seven metachronous lung cancers were recognized in this study, but information on therapy and survival for these patients was not provided. The authors concluded that intensive surveillance was not cost-effective and suggested a reduced surveillance approach consisting of a history, physical examination, and CXR every 6 months for the first year following curative intent surgery and then annually. Egermann and col-leagues reached similar conclusions from their study of 563 patients who were cancer-free at 3 months following curative intent lobectomy for NSCLC. A history, physical examination, and CXR were performed at 3-month intervals for 2 years, and then at 6-month intervals for up to 5 years and then annually. Only 4.1% of the 361 patients had a potentially resectable lung cancer identified during follow-up. In 21 patients, metachronous tumors were detected and resected with curative intent. Survival analysis indicated a maximum survival benefit of 9 months; based on these data and estimated healthcare costs in Switzerland, a calculated cost for the surveillance plan was $56,000 (US dollars) per life-year gained. The authors believed that this cost was too high to justify this intensive follow-up and recommended follow-up at 6-month intervals. A decision-analysis model approach to estimating the cost-effectiveness of chest CT in following patients after resection of stage 1A NSCLC arrived at a similar theoretical cost ($47,676 per quality-adjusted life-year gained). However, this analysis suggested that use of chest CT in surveillance might be cost-effective in patients < 65 years old; in clinical practices where the cost of chest CT was < $700, the annual incidence of second primary lung cancers was at least 1.6% per patient, and the false-positive rate of surveillance was < 14%.
Virgo and colleagues compared two groups retrospectively following surgery for NSCLC. One group of 120 patients had intensive surveillance, consisting of at least four visits with serum chemistries and CXR per year, and annual bronchoscopy and/or sputum cytology with CT. The other group of 62 patients had less intensive surveillance, with on average only two visits with serum chemistries and CXR per year. No differences were found between the groups in either time to detection of recurrences or metachronous tumors or survival time. They agreed that intensive surveillance was not cost-effective and supported the surveillance schedule suggested by Walsh et al. Two other retrospective analyses of intensive surveillance methods provided similar results. Younes and colleagues found that intensive surveillance yielded no survival advantage and was more expensive than a symptom-based approach, although more patients in the symptom-based group had disease identified through emergency room visits. Gilbert and coworkers showed that more recurrences were found by family physicians based on symptomatic presentation than were identified through regularly scheduled surveillance visits to the surgical clinic. These investigators also found that the costs of identifying recurrences would be much lower using family physicians than intensive surveillance through the surgical clinic. Reviews of this topic have endorsed the concept of less intense surveillance because “more intensive diagnostic testing has yet to demonstrate survival and quality of life benefits.”
The concept of less intensive surveillance has been challenged by work by Westeel et al, who instituted a very intensive surveillance program in 192 patients surviving 30 days after complete surgical resection for NSCLC. Visits were scheduled every 3 months for 3 years, with history, physical examination, and CXRs. Bronchoscopy and CT were performed at 6-month intervals. From the fourth year after surgery, visits with CXRs were at 6-month intervals, and CT and bronchoscopy were performed annually. At year 8, surveillance was reduced to a visit and CXR annually. They claimed good compliance with this surveillance regimen in a subset of the entire group. Of 136 patients with recurrent cancers, 35 cases (25.7%) were asymptomatic and detected by diagnostic procedures. Of these, 15 patients (11% of recurrences) had intrathoracic recurrences that could be treated with curative intent; these were diagnosed by CXR (n = 5), bronchoscopy (n = 5), or CT (n = 5). Survival after recurrence for the 36 patients with asymptomatic recurrences was significantly better than for the 100 patients with symptomatic recurrences. In their economic analysis, Westeel et al suggested that this very intensive surveillance regimen provided an acceptable cost per additional year of life gained. However, the improved survival, as measured after time of recurrence rather than after time of resection, in the asymptomatic patients may have reflected lead-time bias, and the proposed costs for procedures used in the surveillance strategy were relatively low.
Reconciling the conflicting findings from these various studies in order to provide clinical guidance is difficult. To begin, a clinically intuitive but often not stated principle is that patients who have a poor performance status or inadequate pulmonary function are not candidates for curative resection of either recurrent or metachronous lung cancer. Consequently, such patients are not candidates for intensive and aggressive surveillance programs designed to detect asymptomatic tumors. Instead, they should be educated to seek early attention and should have ready access to their providers for follow-up of new symptoms that might herald recurrent cancer. For patients with adequate performance status and lung function, the panel recognizes that periodic patient encounters following curative intent therapy for lung cancer are essential and strongly feels that imaging studies of the chest should be included in these visits. CT is accepted as more sensitive for detecting pulmonary nodules than CXR and has been shown to be more accurate for evaluating lung cancer response during chemotherapy. Small series have shown that CT can detect changes consistent with recurrence earlier than CXR. CT is also being widely studied as a method for early detection of lung cancer (see “Screening for Lung Cancer” section). Unfortunately, the performance characteristics of CT (ie, sensitivity and specificity) for distinguishing nonspecific posttreatment changes related to surgery, radiation therapy, and/or chemotherapy from a recurrence and/or metachronous lung cancer have not been defined. Many studies report a high incidence of nodules in groups followed up with chest CT, and the appropriate protocols for differentiating benign from malignant nodules without excess morbidity and cost from diagnostic procedures have yet to be defined. Consequently, the panel was evenly divided between recommending CXR and CT as the imaging procedure of choice.
In lung cancer patients treated with curative intent therapy, and those having adequate performance and pulmonary function, surveillance with a history, physical examination, and imaging study (either CXR or CT) is recommended every 6 months for 2 years and then annually. All patients should be counseled on symptom recognition and be advised to contact their physician if worrisome symptoms are recognized. Grade of recommendation, 1C