SAN FRANCISCO—Patients with non-small-cell lung cancer (NSCLC) who present with Stage IV disease may be able to achieve long-term survival if they undergo aggressive treatment for oligometastases, researchers reported here at the American Society for Radiation Oncology Annual Meeting (Abstract 168).
In a review of the medical literature, scientists at Western Ontario University identified 757 patients with oligometastases who were treated for NSCLC at 20 international sites, and after five years, almost 30 percent of the patients were still alive.
“That is a better outcome than patients with Stage III non-small-cell lung cancer, who have a five-year overall survival of around 15 percent,” said Allison Ashworth, MD, now Assistant Professor of Radiation Oncology at Queen's University in Kingston, Ontario.
In the meta-analysis, she and her colleagues reviewed the outcomes among patients diagnosed with oligometastatic non-small-cell lung cancer and determined that a subgroup of patients had an improved outlook over the perceived outcomes for advanced NSCLC. Of the 146 patients designated as low-risk because of being younger and having metachronous metastases and better performance status, the five-year overall survival was about 48 percent, she reported.
That contrasted with the 184 patients who presented with synchronous oligometastases, who had a five-year overall survival rate of 36 percent. However, patients who presented with synchronous oligometastases and chest lymph node involvement—i.e., N1 or N2—had a five-year overall survival rate of 13.8 percent, she said. presentation.
In an interview, though, she cautioned that the patients in the study were atypical of the patients who “walk in the door” with Stage IV NSCLC: “These were carefully selected patients. Most of the patients in the study had just a single metastasis.”
Most often that metastasis was in the brain—269 of the 757 patients. Of the patients included in the study, 668 had just one metastatic lesion. The researchers found that 63 patients who were treated had two metastatic lesions, and the remaining 26 had three to five.
The second most common lesion site was in the lungs—254 patients. The other common sites were in the adrenals—98 metastases; bone—64 metastases; and the liver and lymph nodes—18 metastases in each location.
Of the 757 patients, 635 underwent surgery to remove the primary tumor, and 339 were treated with surgery to remove the metastases. When doctors performed radiation procedures, they most often utilized high-dose, stereotactic ablative radiotherapy, Ashworth said.
About 72 percent of the patients included in the meta-analysis were men, and the median age of the patients was 61. The median progression-free survival time was 11 months; and median overall survival was 26 months. When disease recurred, in half the patients the recurrence occurred within one year of treatment.
“Our study finds that some stage IV non-small-cell lung cancer patients can achieve long-term survival after aggressive treatments,” Ashworth said. “However, it is important to note that the patients in this study are a very select minority of stage IV patients who are younger, more physically fit, with a lower tumor burden and slower pace of disease than the average stage IV patient.
“We hope our study's results will help determine which stage IV non-small-cell lung cancer patients are most likely to benefit from aggressive treatments, and equally as important, help identify those patients most likely to fail, thus sparing them from futile and potentially harmful treatments,” she said.
“Our research, however, cannot answer the question of whether the longer survival is due to the treatments or simply because these patients have less aggressive disease,” she continued. “We must await the results of randomized clinical trials to answer this question. In the meantime, it is our hope that our study will help cancer specialists in making treatment decisions and in the development of clinical trials.”
Clinical Trial Controversial
Whether there will be a randomized trial comparing patients who are treated aggressively versus those receiving standard-of-care treatment is controversial, though: “I am doubtful that we could put together a randomized trial,” said Roy Decker, MD, PhD, Associate Professor of Therapeutic Radiology at Yale University School of Medicine, who was asked his opinion for this article.
“We are treating these patients now and the national guidelines suggest we treat these patients, so I think most of us would find it very hard to randomize patients to not treat them,” he said.
Ashworth said the meta-analysis was limited because of the retrospective nature of the study and because not all the papers and sites provided complete datasets. “We propose that the overall survival risk classification scheme be considered for clinical decision-making and to guide selection/stratification of patients for clinical trials of ablative treatment,” she said.
Decker added, “We all have patients who have metastatic non-small-cell lung cancer. The classic way of looking at these patients is to say, ‘Well, the horse is out of the barn.’ But we all have seen these patients who are young and they are healthy and we really want to give them the benefit of the doubt so we treat them aggressively. Rather than just giving them chemotherapy alone, we treat them with radiation and surgery.
“We have all seen patients who are long-term survivors. We don't know if these patients are cured or they just haven't recurred yet, but the literature is full of case reports of patients who have lived 10 or 15 years.”
He said the work by Ashworth and her team represents a “systematic analysis of a large database which very nicely puts together the experience and kind of shows us that the way we have been treating these patients is probably correct.
“One of the prognostic factors that they identified was metachronous disease—basically someone who has a primary and it is surgically removed and then a year later develops a single site of disease and that is removed. What we don't know is whether these patients have curable disease or whether they have very slow-growing disease. We could just be selecting for patients with indolent disease.
“Most patients with Stage 4 non-small-cell lung cancer present with widespread disease; the average age for metastatic lung cancer is in the 70s. So this is a very young, healthy group of patients. This is for people who can undergo the local treatment,” he explained.
While the researchers identified patients who have a good risk and those with a poor risk, “even those with a poor risk have about a 13 percent long-term survival, which really is better than one would expect. I think that if you had a patient even with all those bad factors and told them they had a 13 percent chance of survival for at least five years, I think that most of them would jump at it.”