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Surgery improves outcomes in advanced NSCLC, yet remains underutilized
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Patients with advanced non–small cell lung cancer who underwent surgery achieved superior survival outcomes compared with those who did not, according to retrospective study results.
However, the use of multimodality regimens including surgery has decreased, and a significant proportion of patients received no treatment at all, results showed.
Elizabeth A. David
“We have a treatment that we know improves survival when offered to appropriate candidates, but we’re offering it to fewer people,” Elizabeth A. David, MD, FACS, assistant professor of surgery at UC Davis Health System, said in a press release. “We need to understand why this is happening.”
NSCLC is the leading cause of cancer death worldwide, causing more than 1.4 million deaths each year.
Chemotherapy and radiation therapy remain the standards of care for NSCLC. The role of surgical resection in this patient population has not been properly defined.
David and colleagues sought to evaluate treatment trends in patients with NSCLC, as well as the impact of treatment modalities on outcomes. They hypothesized that treatment platforms involving surgery led to increased OS but may be underutilized.
The researchers used the California Cancer Registry to identify 34,106 patients (54.2% men; 65% non-Hispanic white; 37.7% aged younger than 65 years) diagnosed with stage IIIA, stage IIIB or stage IV NSCLC between 2004 and 2012.
Researchers categorized patients by treatment group — no treatment, chemotherapy alone, surgery alone, radiation alone or any combination of therapies — and calculated trends and predictors of treatment groups.
Regression modeling was used to determine the influence of treatment modalities on OS.
Twenty-seven percent of patients (n = 9,223) received no treatment for their disease, and the percentage of patients receiving no treatment rose commensurate with stage (P < .0001).
“As practitioners, we need to be aware of these disparities and make sure all groups have the same access to care,” David said. “That 27% number has room for improvement.”
A total of 25.7% of the cohort (n = 8,768) received combined chemotherapy and radiation, without surgery. More than 10,000 patients received either chemotherapy alone (n = 6,930) or radiation alone (n = 4,299).
Eleven percent of the cohort underwent surgery, either alone (n = 1,261), with
chemotherapy (n = 1, 243), with radiation (n = 189), or with chemotherapy and radiation (n = 1,022).
The researchers observed a 0.6% increase in treatment with chemotherapy over time (P < .001), whereas treatment with radiation alone (P = .011), surgery alone (P < .001) or any combination therapy significantly decreased.
Patients who received surgery alone or in any combination exhibited significantly increased OS compared with patients who received any nonsurgical treatment option (P < .001).
Among the entire cohort, patients treated with surgery and chemotherapy had the longest survival, with a median OS of 40.7 months. Patients treated with chemotherapy, radiation, and surgery had a median OS of 33.3 months, whereas patients treated with surgery alone had a median OS of 28.8 months. Patients treated with radiation and surgery had a median OS of 18.6 months.
In contrast, patients who received chemoradiation achieved a median OS of 11.9 months. The median OS associated with chemotherapy alone was 10.5 months and for radiation alone was 3.7 months.
Untreated patients had a median OS of 2.1 months.
The researchers conducted analyses to identify predictors of treatment groups, which showed that increasing age appeared associated with an increased likelihood of receiving no treatment. Compared with patients in the highest socioeconomic status subgroup, patients in all other socioeconomic subgroups were more likely to not receive treatment.
Further, patients with stage IIIB or stage IV disease were more likely to not receive treatment than patients diagnosed with stage IIIA disease.
Study limitations include the researchers’ inability to access information regarding treatment decisions, as well as the potential underreporting of chemotherapy data. Only 20% of patients had lymph node sampling, which may reflect NSCLC understaging.
“We’re continuing to look at how the decision is made to involve surgery,” David said. “Surgery is not right for all patients with advanced-stage lung cancer, but we want to ensure that patients are being evaluated properly. We want to see if we can create a decision tool that helps physicians decide who is suitable for surgery.” – by Cameron Kelsall
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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Brendon Stiles, MD
Surgery is often viewed as “aggressive” treatment by the lay public, and even by some referring physicians, whereas nonsurgical treatment approaches may be viewed differently. The lung cancer patient population tends to be older and to have comorbidities, and there has been a tendency to shy away from surgery for many of these patients. However, the realities of the risks and benefits associated with surgery in 2016 are very different than they were 10 years ago. With the availability of minimally invasive surgery, improved pain management, better postoperative care and increased attention to pulmonary and physical therapy rehabilitation, thoracic surgery has been made much safer.
A recent study by Elizabeth A. David, MD, FACS, and colleagues showed a significant survival benefit for patients with non–small cell lung cancer treated with surgery, either exclusively or in combination with other modalities. This benefit may be driven in large part by selection bias, with only the healthiest patients or those with the least disease burden receiving surgical treatment. However, the improved survival is still an important finding to note, and suggests that surgery should be seriously recommended to carefully selected patients with relatively low disease burdens.
The concept of the benefit of local control in advanced disease was further supported by an abstract at this year’s ASCO Annual Meeting. Daniel Gomez, MD, presented data from a randomized trial of patients with stage IV NSCLC that questioned the value of “local therapy” — surgery or radiation to treat a specific area of disease — in patients with limited residual disease after chemotherapy or targeted therapy. PFS strongly favored the arm that received local therapy (14.4 months vs. 3.9 months; P = .013). These patients, as well as the patients on the study by David and colleagues, were carefully selected, and results must be interpreted cautiously. Still, these two studies should set the stage for more trials of surgery or focused radiation therapy for patients with relatively limited advanced disease in need of local control.
The study by David and colleagues also found that 27% of patients received no surgical or medical treatment at all. This is problematic, and the reasons for such undertreatment should be carefully investigated. Certainly, some patients with lung cancer may be too sick for any therapy, and others may decline therapy for personal reasons. However, numerous studies showed that in addition to prolonging life, medical therapy for advanced cancer improves quality of life. I suspect, unfortunately, that therapeutic nihilism remains toward patients with lung cancer, given the historically high mortality rate associated with the disease. The improvements in care delivery, as well as the record number of new drugs approved for lung cancer in recent years, leaves me optimistic that the number of untreated patients will decrease.
Medical and surgical oncologists already work very well together to evaluate the best treatment options for these complex patients. The key to treating patients with lung cancer is a team-based approach in which medical oncologists, radiation oncologists and thoracic surgeons — as well as radiologists and pathologists — all weigh in on individual patients. This is common at many busy academic centers, as evidenced by previous studies, which showed that patients treated at academic centers were more likely to be treated with surgery and multimodal treatment in general. Many patients with advanced lung cancer would likely benefit from referral to high-volume specialty centers, particularly for consideration of whether surgery could be safely performed.
We need to ensure that appropriate patients are considered for surgery, especially those with stage IIIA disease. A clear benefit exists for those patients who can be treated with lobectomy. For patients with stage IIIB or stage IV NSCLC, the role of surgery is not firmly established. Local consolidative therapy, either with surgery or stereotactic radiation, should be considered by a multidisciplinary tumor board more often for well-selected patients. With recent advances in systemic treatment, targeted therapy and immunotherapy extending the lives of patients with advanced disease, I expect to see more clinical trials to evaluate local consolidative therapy in these patients.
Reference:
Gomez D, et al. Abstract 9004. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.
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