Early-stage NSCLC: the role of radiotherapy and systemic therapy

Although surgical resection offers the best opportunity for cure in early-stage non-small cell lung cancer, long-term survival remains less than 50% for all but clinical stage IA disease. Nearly 80% of relapses occur in distant sites. Thus, investigators have turned to chemotherapy or radiotherapy to prevent relapse and extend survival. Chest radiotherapy has proven to significantly reduce local relapse, but with a negative impact on survival. This harmful effect may be caused by toxicity associated with older, wide-field techniques; however, no randomized study has shown a beneficial effect on survival. Postoperative chemotherapy with alkylating agent-based therapies yielded an increased risk of death, also probably caused by toxicity. Frequent metastatic relapse has led researchers to focus on incorporating chemotherapy into treatment for early-stage disease. Modern two-drug platinum-based combinations improved survival in the three most recent randomized trials. Induction chemotherapy offers several potential advantages to adjuvant chemotherapy. Retrospective series, as well as randomized trials, show consistent benefit, but these trials suffer from small numbers of patients. More recently, phase II trials have confirmed the feasibility of this strategy in patients with stage IB-IIIA disease, with nearly all patients completing induction chemotherapy and no apparent increase in operative mortality. Ongoing trials continue to assess the role of preoperative and postoperative chemotherapy or radiotherapy in early stage non-small cell lung cancer.