Dr. Movsas has written a thorough, accurate description of the state of the art on postoperative, adjuvant therapy for resected "high risk" non-small-cell lung carcinoma (NSCLC). Management of this common situation indeed remains an "art," since the results of "scientific" randomized trials have been singularly disappointing.
Why has there been detectable progress in the management of inoperable or marginally resectable stage III NSCLC, while postoperative interventions have largely failed? Why does adjuvant therapy succeed against other common solid tumors, such as breast and gastrointestinal cancers, but not NSCLC? Should the concept of postoperative therapy for NSCLC be discarded, instead focusing all clinical trials on neoadjuvant treatment and screening?
An Exhausted Population
Patients with NSCLC typically have significant chronic obstructive pulmonary disease and other tobacco-induced comorbidities that are not commonly seen in people undergoing surgery for breast cancer, gastrointestinal cancers, or most other malignancies. The trauma of a thoracotomy and resection can further injure one’s overall physiologic status. The 30-day mortality rates for pneumonectomy and lobectomy are approximately 11% and 4%, respectively. Significant morbidity, such as life-threatening pneumonias, arrhythmias, or embolic events, occur in at least 25% of patients.
It is likely that most patients who are convalescing from major lung cancer surgery will not tolerate aggressive adjuvant therapy of the type used in stage III unresectable NSCLC. Indeed, in the Eastern Cooperative Oncology Group (ECOG)/Intergroup study capably discussed by Dr. Movsas, only 69% of patients received all four cycles of adjuvant chemotherapy, despite a relatively modest dose-intensity schedule of cisplatin(Drug information on cisplatin) (Platinol), given at 60 mg/m² every 28 days, and etoposide(Drug information on etoposide). In the combined-modality arm, toxicity was clearly at the limits of acceptability; yet there was no hint of a benefit to chemotherapy. There was satisfactory compliance with radiotherapy in both arms of this trial.
Postoperative Radiotherapy: A ‘Dead’ Issue?
In an effort to maximize local control, the Intergroup trial utilized postoperative radiotherapy in both arms. The use of postoperative radiotherapy was seriously questioned by the postoperative radiotherapy (PORT) meta-analysis, which has been appropriately critiqued by Dr. Movsas. However, several critical points deserve emphasis.