Definitive radiotherapy for stage I non-small cell lung cancer: ain't nothing like the real thing?

In contrast to the guarded outlook for the majority of patients diagnosed with non-small cell lung cancer (NSCLC), the prospect for a cure is excellent after anatomic resection for pathologic stage I disease. 1 Nevertheless, a substantial number of patients with early-stage NSCLC suffer from cardiopulmonary disease and/or other medical comorbidities, rendering them unsuitable for lobectomy. 2 Treatment philosophies vary widely for the “medically inoperable” population. Although still frequently encountered in clinical practice, a nihilistic approach is not justified because the majority of patients with untreated stage I NSCLC die from lung cancer, not from comorbid illnesses. Moreover, recent observations suggest poorer outcomes for the cohort of patients that do not receive any therapy. 3,4 Fractionated external-beam radiotherapy has been the most frequently employed treatment option by far, with outcomes contingent on patient selection, tumor burden, and, perhaps, radiotherapy dose. 5,6 As the importance of this patient population has become apparent, several alternatives have emerged, including (thorascopic) wedge resection with or without permanent brachytherapy, heavy-particle therapy (proton and carbon ion), stereotactic radiosurgery, and radiofrequency ablation. 7–12 Particularly encouraging is the development of prospective multi-institutional cooperative group trials specific to this population. Most trials are in progress or have recently completed accrual. CALGB 9335, which assessed video-assisted thorascopic wedge resection and postoperative radiotherapy for high-risk patients with pathologic stage IA NSCLC, is unique in providing long-term outcomes for patients with well-defined cardiopulmonary dysfunction. 13 Five-year survival was 29% for the cohort of 31 patients. This is in stark contrast to the 50% survival reported in retrospective single-institution studies and illustrates the need for carefully conducted prospective research. 14,15 The relative merit of radiotherapy versus (limited) surgery for elderly and high-risk patients has long been debated, with selected retrospective series used to defend opposing viewpoints. 16,17 The mature results of ongoing prospective phase II studies should finally shed some light on the issue, although the standard caveats apply regarding patient selection and the use of pathologic versus clinical staging. In this issue of the Journal of Thoracic Oncology, Graham et al. 18 report a retrospective comparison of surgery and radiotherapy in stage I NSCLC treated at different centers in Australia during the 1990s. Median and 5-year survival were 67 months and 54% for the surgery cohort (n 68) compared with 43 months and 30% for the radiotherapy cohort (n 39). On multivariate analysis, the only significant factor was performance status, and cancer-specific 5-year survival for surgery and radiotherapy were similar at 59 and 53%, respectively. The authors attribute their encouraging results to modern radiotherapy techniques and to having accelerated the course of radiotherapy such that treatment was completed in 5 weeks. Prospective dose-escalation trials from the University of Michigan and the Radiation Therapy Oncology Group (RTOG) show that doses up to 102.9 Gy could be given to limited target volumes with three-dimensional conformal radiotherapy. 19 –21 Median survival ranged from 21 to 27 months for early-stage medically inoperable