Treatment of limited-stage small cell lung cancer in the elderly, chemotherapy vs. sequential chemoradiotherapy vs. concurrent chemoradiotherapy: that’s the question

Small cell lung cancer (SCLC) is an aggressive pulmonary tumor characterized by a rapid doubling time, high growth fraction, and the early development of widespread metastases. It represents approximately 15% of new lung cancer diagnosis each year and its incidence increases with age, about 45% of these involved patients older than age 70 years (1). According to the Veteran’s Administration Lung Study Group’s 2-stages classification scheme, the extension of disease in patients with SCLC is distinguished in: limited disease (LD)-SCLC, defined as a tumor that is confined to ipsilateral hemithorax, mediastinal, or supraclavicular lymph nodes, which can be safely encompassed within a radiation field (about one-third of cases), and extensive disease (ED), where the tumor is not confined to one hemithorax or has malignant pleural or pericardial effusion or hematogenous metastases (2). Chemotherapy (CT) is the mainstay of the treatment in LD- and ED-SCLC patients, while concurrent chemoradiotherapy (CRT) is the standard of care in healthy patients with LD. In 1992, two meta-analyses were published regarding the role of thoracic radiotherapy in addition to CT in LD-SCLC (3,4). The first meta-analysis, including 2,140 patients with LD-SCLC from 13 trials (433 patients with ED-SCLC were excluded), evaluated the hypothesis that thoracic radiotherapy contributes to a moderate increase in overall survival (OS) (3). The relative risk of death in the combined-therapy group as compared with the CT group was 0.86 [95% confidence interval (CI), 0.78–0.94; P<0.001], corresponding to a reduction of 14% in the mortality rate. The benefit in term of 3-year survival rate was 5.4%±1.4%, although it wasn’t evident in patients older than age 70 years: the relative risk of death in the combined-therapy group as compared with the CT group ranged from 0.72 in patients younger than 55 years (95% CI, 0.56–0.93) to 1.07 for those over 70. This result was probably, but not confirmed, related to increased toxicity in the older patients (3). The second meta-analysis reported a small but significant improvement in survival and a major improvement in local (intrathoracic) tumor control in patients receiving CRT treatment, although it was associated with a small increase in treatment-related mortality (4)