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Role of Adjuvant Therapy in Resected Stage II/IIIA Non-Small-Cell Lung Cancer

Role of Adjuvant Therapy in Resected Stage II/IIIA Non-Small-Cell Lung Cancer

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.[1] 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[2] 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 (Platinol), given at 60 mg/m² every 28 days, and
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.

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