An historical perspective of multi-modality treatment for resectable non-small cell lung cancer.

We examine the origins of surgical therapy, radiotherapy, and chemotherapy as they were applied to lung cancer in the mid-portion of this century. Surgical therapy for lung cancer started in the 1930s with pneumonectomies. The prognostic significance of nodal metastases was soon recognized, and surgical staging procedures became an important part of patient workup. Radical radiotherapy for potential cure of lung cancer began in the 1950s with megavoltage linear accelerators. The first application of chemotherapy for lung cancer was the use of nitrogen mustards in the 1940s. Single modality surgical therapy has become the treatment of choice for Stages I and II non-small cell lung cancer, but 50% of clinical Stage I patients die of recurrent disease, and 70% of those recur outside the chest. Biologic markers may identify high risk subgroups of Stage I and II patients who may benefit from adjuvant chemo- or radiotherapy. Within the last decade, several single and multi-institutional Phase II trials and two single institution Phase III trials have reported improved survival in Stage IIIA patients treated with cisplatin-based neoadjuvant chemotherapy prior to surgical resection. These trials have reported high response and resectability rates, but at a substantial toxicity. A new standard of care for Stage IIIA disease has not been conclusively established.