Can Staging for Lung Cancer Better Guide Treatment Decisions?

An analysis from the CONVERT trial found that patients with stage I to II small-cell lung cancer (SCLC) have relatively long-term survival when treated with chemoradiotherapy. Their outcomes were significantly better than patients with stage III disease, calling into question the practice of combining these patients into one prognostic group.

“To date, there are no data on the proportion or outcome of patients with stage I to II disease included in trials that established chemoradiotherapy as a standard treatment, limiting the evidence to guide stage I to II SCLC management,” wrote study authors led by Ahmed Salem, FRCR, of the University of Manchester in the United Kingdom. The researchers conducted a secondary analysis of the phase III CONVERT trial, which compared once-daily and twice-daily radiotherapy given concurrently with chemotherapy. The results were published in JAMA Oncology.

For this new analysis, a total of 509 patients with TNM staging information available were included. Of those, 86 patients (16.9%) had stage I to II disease (4 with stage I, 82 with stage II). Of those early-stage patients, 40.7% were randomized to receive twice-daily radiotherapy, and 59.3% received once-daily radiotherapy; both received a chemotherapy regimen of cisplatin and etoposide.

The median gross tumor volume was smaller in stage I to II patients, at 38.4 cm³ compared with 93 cm³ in stage III patients (P < .001). There were no other differences in baseline or treatment characteristics.

The median overall survival (OS) was 50 months in those with stage I to II disease, and 25 months in those with stage III disease, for a hazard ratio of 0.60 (95% CI, 0.44–0.83; P = .001). At 2 years, the OS rate was 64% in stage I to II patients and 51% in stage III patients; at 5 years, these rates were 49% and 28%, respectively.

Among the early-stage patients, there was no significant survival difference between the two trial arms, with a median OS of 39 months with once-daily radiotherapy and 72 months with twice-daily radiotherapy (P = .38). The incidence of both acute and late treatment-related toxic effects were similar between stage I to II and stage III patients.

“Patients with stage I to II SCLC in CONVERT achieved long-term survival with acceptable toxic effects after chemoradiotherapy. Concurrent chemoradiotherapy followed by prophylactic cranial irradiation may be considered as a treatment option in this patient group,” the authors wrote, adding that a randomized clinical trial will still be required to guide treatment between surgical and non-surgical approaches.

In an accompanying editorial, Howard (Jack) West, MD, of the Swedish Cancer Institute in Seattle, noted that stage I to II patients are typically lumped together with stage III as “limited-stage” SCLC. “These results imply that we may do our patients a disservice by dispensing with clinically relevant staging information that can lead to a more refined assessment of prognosis and optimal treatment. Although most future practice-changing advances are likely to emerge from identification of molecular and immunologic features of different subgroups of patients with SCLC, we cannot overlook opportunities to refine management based on obvious issues, such as more precise staging, particularly when they are accompanied by distinctions in prognosis and potentially tumor biology.”