Surgery Alone May Be Reasonable for Stage I Small-Cell Lung Cancer
By Fran Lowry
Medscape Medical News
February 25, 2010 — An analysis of outcomes from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database indicates that surgery without radiotherapy for stage?I small-cell lung cancer (SCLC) "appears to offer reasonable survival outcomes."
The findings led researchers to conclude that lobectomy by itself is a viable option.
The analysis, headed by James B. Yu, MD, from Yale University in New Haven, Connecticut, appears in the February issue of the Journal of Thoracic Oncology.
Traditionally, stage?I SCLC has been treated with radiation and chemotherapy, but modern studies have shown reasonable survival in patients who undergo surgery and chemotherapy. However, as the authors point out in their article, results from existing trials have been conflicting.
Dr. Yu and his colleagues were prompted to study the issue after they were presented with a patient who was originally thought to have nonsmall-cell lung cancer, which turned out to be stage?I SCLC.
"We didn't know whether there were any studies that had recently looked at whether this patient needed further radiation or not, especially in light of better chemotherapy and improved staging techniques, and that is when we decided to take a look in the SEER database," he told Medscape Oncology.
The investigators identified 247 patients with stage?I SCLC who underwent surgical resection between 1988 and 2004. Their median age was 70 years (range, 27?- 94 years). Of this codort, 205 patients (83%) had lobectomy without radiation therapy and 38 (15%) received radiation therapy; the use of radiation was unknown in 4 patients.
The researchers found that the 5-year overall survival in patients who underwent lobectomy without radiation was 50.3% (95% confidence interval [CI], 43.1%?- 57.1%); for patients who had lobectomy with radiation, the 5-year overall survival was 57.1% (95% CI, 37.4%?- 72.7%).
Dr. Yu added that the findings are provocative and open the door to a clinical trial, although he conceded that mounting such a trial would be difficult.
Two outside lung cancer experts had different opinions on the idea of a clinical trial, with one saying it was not feasible and that surgery in these patients was of "questionable value."
Limitations Stressed
Dr. Yu stressed that his study has several limitations.
"This is an analysis of the SEER database. There is inherent selection bias and there is a lot of information that we just do not know. For instance, we don't know why some patients got radiation, or what kind of radiation they did get. In addition, we have assumed that all patients got chemotherapy, but there is no information in the database about which chemotherapy they received. All we can say is that people who have a stage?I SCLC seem to have reasonable survival after surgery alone. But that is as far as we can go in terms of a conclusion."
It would be difficult to do a randomized trial.
"Most small-cell lung cancer patients present with extensive disease. Only a very small minority have true stage?I disease. We looked at the entire SEER database and only analyzed 1560 patients with stage?I small-cell lung cancer between 1988 and 2004. That is 16 years of national data, yielding only about 100 patients a year," he said.
"It would be difficult to do a randomized trial but it is possible, and it is what we definitely need to answer the question of the utility of surgery alone for such patients," Dr. Yu added.
It's Time to Fish or Cut Bait
In an accompanying editorial, Frances Shepherd, MD, from the University of Toronto in Ontario, agreed, calling for an international prospective randomized controlled trial with flexible chemotherapy and radiation protocols that would be allowed to run as long as necessary "to answer this lingering but important question."
However, Dr. Shepherd questions whether surgery is the best treatment or even necessary "in this era of platinum-based chemotherapy and the ability to administer concurrent thoracic radiotherapy in high doses safely and with acceptable levels of acute and late toxicity."
Nevertheless, it would be important to have such a trial, even though the proportion of patients with stage?I SCLC is so low.
"Very few patients fall into this subgroup (likely less than 10%), and so it would only be possible to mount a prospective randomized trial to prove or disprove that surgery is appropriate in this setting through international multidisciplinary collaboration," Dr. Shepherd writes.
There is probably only 1 more chance to mount this potentially 'landmark trial.'
It is also time to stop reporting on single-institution studies and database analyses of surgery for SCLC, she adds.
"Thoracic oncologists must decide to 'fish or cut bait.' If they decide to 'fish,' the international community must come together for a prospective trial," she concludes. "There is probably only 1 more chance to mount this potentially 'landmark trial.' Let's go fishing!"
Such a Trial Not Feasible
It would be exceptionally challenging to conduct such a trial, said Howard West, MD, from the Swedish Cancer Institute in Seattle, Washington, who was approached by Medscape Oncology for independent comment.
I think many physicians and patients would also be resistant to randomization.
"SCLC now accounts for less than 13% of lung cancers in the United States, and that proportion continues to decline. Node-negative cases that would be considered appropriate for randomization to surgery represent less than 10% of that SCLC population, so an internationally coordinated trial would be required. I think many physicians and patients would also be resistant to randomization. Overall, I fear that such a trial simply isn't feasible."
Dr. West pointed out that a significant and integral problem in interpreting the value of surgery in SCLC is that it is an option for such a small proportion of patients — about 10% — who have node-negative disease. These patients might well have disease with a very different natural history, he suggested.
"We can not and should not presume they have the same natural history as the other 90% of SCLC cases that present with more rapidly disseminating disease. The patients who present with a very localized SCLC and no nodal spread are precisely the patients who we might presume have a very atypical biology for SCLC that may have them do far better with any treatment than the more representative cases of SCLC that present with nodal involvement or more widespread disease."
Chemotherapy is a cornerstone of SCLC therapy. Dr. West cautioned about the danger of compromising the ability to deliver this treatment "in the name of a treatment that still has questionable value."
He added that radiation techniques are constantly and steadily improving, and questioned whether patients should accept the morbidity of surgery when treatments that have comparable efficacy and less toxicity are available.
Dr. Yu, Dr. Shepherd, and Dr. West have reported no relevant financial relationships.
