Long-term survival following chemoradiation for inoperable non-small cell lung cancer

Although lung cancer is not Australia’s most common cancer, it is the commonest cause of cancer death, with 7264 deaths recorded in 2004.1 The survival time of patients with lung cancer is among the poorest of any cancer, and it has only marginally improved in the past 15 years. In Victoria, 5-year relative survival increased slightly from 8% in 1990 to 11% in 2004.2 These grim statistics create a sense that treatment is ineffective, engendering a sense of nihilism among patients and their doctors, especially if the cancer cannot be surgically removed. As an example, a recently published book on interpreting cancer imaging includes the statement that “surgery offers the only chance of cure in non-small cell lung cancer”.3

Patients with locoregional non-small cell lung cancer (NSCLC) whose disease is inoperable are usually treated primarily with radiotherapy. For these patients, recent meta-analyses indicate that the combination of chemotherapy given concomitantly with radiotherapy is superior not only to radiotherapy alone4 but also to the combination of radiotherapy and chemotherapy administered sequentially.5 These studies demonstrated a statistically significant survival benefit at 3 years of 3.2% comparing concomitant chemoradiation with radiotherapy alone (16.6% v 13.4%), and 6.6% comparing concomitant chemoradiation with sequential radiotherapy and chemotherapy (24.8% v 18.2%).

While these survival benefits are important, longer-term benefits of treatment are also of interest to patients when making a decision about choice of treatment. In a survey of patients with a variety of advanced cancers, 85% wanted to know the longest possible survival time with treatment.6

At our dedicated cancer hospital in Victoria, studies of various concomitant chemoradiation strategies for inoperable NSCLC have been conducted by the multidisciplinary Lung Service since the early 1990s. Two groups of patients enrolled in prospective studies in the late 1990s have now been followed for a minimum of 9 years; here, we report their survival.

Although 27 of 33 patients treated in the two trials reported here died within the first 5 years, the remaining six surviving patients have been followed for a minimum of 9 years. Thus, the proportion of patients still alive after 9 years is 18%. While falling well short of the success rates reported with the treatment of other common cancers, these survival data challenge some widely held beliefs about the incurability of inoperable NSCLC, and represent important information to have on hand when discussing treatment options with patients who have inoperable NSCLC.

A recently completed larger study (but with shorter follow-up) has reported similar survival rates. This was a trial in which 191 patients in one arm were randomly assigned to receive chemoradiation without surgery; estimated survival at 5 years for these patients was 20.3%.7

The term “cure” is a contentious one in oncology, and this is particularly true for NSCLC, where competing causes of death from other smoking-related comorbidities can confound the interpretation of survival data. Five-year survival probability is often used as a surrogate for “cure”, as relapse following radiotherapy-based treatment is unusual after this time, although it can occur.8 Informing patients of the longest observed survival time is an alternative way of presenting them with prognostic information. In a study of patient preferences in the setting of metastatic disease from a variety of cancers, patients more often wanted to know the longest survival time with treatment than the 5-year survival rate.6

The strengths of our study are that it is based on two prospectively conducted trials using contemporary treatment techniques, and the survival analysis is based on intention-to-treat. Its weaknesses include the small sample size and the absence of a no-treatment control arm.

It might be argued that in the absence of a control arm of untreated patients, the survival reported here may reflect the natural history of a carefully selected group of patients, rather than being a consequence of treatment. This seems unlikely, given that the 5-year relative survival of untreated patients with locally advanced NSCLC recorded in a large United States database ranged from 1% to 4%, depending on stage and histology.9 This is similar to the 5-year survival rate of 1% observed in patients treated with palliative radiotherapy.10

The outcomes for good performance-status patients with NSCLC who have locoregional disease that cannot be resected are poor, but not hopeless. Treatment with a combination of chemotherapy and radical radiotherapy may offer the prospect of long-term survival for almost one in five patients.

2 Overall survival of patients from both studies combined

Grey lines indicate 95% confidence intervals.