Surgical and Radiation Therapies for High-Risk Early Lung Cancer
Name of the Trial
Phase III Randomized Study of Sublobar Resection with or without Brachytherapy Versus Stereotactic Body Radiotherapy in High-Risk Patients with Stage I Non-Small Cell Lung Cancer (ACOSOG-Z4099). See the protocol summary.
Dr. Hiran Fernando, American College of Surgeons Oncology Group
Why This Trial Is Important
For patients with stage I non-small cell lung cancer, surgical removal of the cancer-containing lobe of the lung (lobectomy) or the whole lung (pneumonectomy) can potentially cure their disease and is the current standard of care. However, patients who undergo these operations must be healthy enough to withstand the loss of lung function incurred by losing an entire lobe of a lung or a whole lung.
Stage I lung cancer patients whose medical history indicates that they would not be able to tolerate a lobectomy or a pneumonectomy are categorized as either high-risk operable or medically inoperable. High-risk operable patients can still undergo surgery to remove a segment of the affected lobe (segmentectomy) or a smaller piece of the lung in which the tumor resides (wedge resection). Although these “sublobar” resections may still cure their disease, the likelihood of recurrence in the affected lobe (local recurrence) or regional lymph nodes is greater than with resection of a whole lobe or the entire lung.
To help prevent local recurrence, some doctors have begun to incorporate a type of radiation therapy called brachytherapy into their treatment approaches. Sublobar resection with brachytherapy involves implanting radioactive seeds after surgery into the area where the tumor had been. Although the addition of brachytherapy has been reported to help prevent local recurrences, the combination of surgery and brachytherapy is not the current standard of care. Researchers hope that the results of a recently completed randomized clinical trial of sublobar resection with or without brachytherapy will help define its role in this patient population.
Patients with stage I lung cancer who are categorized as medically inoperable (unable to tolerate any surgery) may be treated—and potentially cured—with a form of high-dose radiation treatment called stereotactic body radiation therapy (SBRT).
A recent phase II trial showed that SBRT resulted in better tumor control and overall survival than what was historically seen in this patient population. Because SBRT typically produces fewer side effects than sublobar resection, doctors are questioning whether SBRT may be preferable to sublobar resection for high-risk operable patients.
Attempting to compare the two therapies by analyzing previous studies is problematic for several reasons, including differences in the way radiation and surgical oncologists have traditionally defined events such as local recurrence, differences in the patient populations treated by these approaches, and differences in the durations of follow-up in these studies.
In the current trial, patients with high-risk operable stage I lung cancer will be randomly assigned to undergo either sublobar resection (with or without brachytherapy, depending on the standard practice at each treating institution) or SBRT. Doctors will assess overall survival at 3 years and compare local and regional recurrence-free survival, disease-free survival, serious adverse events, and lung function.
“We believe that surgery confers some oncological benefits over SBRT; however, these benefits may be balanced by the lower risks of SBRT, which is a major consideration for patients who are deemed high risk,” said Dr. Fernando. “The primary aim of the study is to demonstrate that survival will not be inferior with SBRT compared to surgery.
“We also want to look at the patterns of recurrence between the two modalities, so we’ve standardized all those definitions that refer to recurrence and tumor control,” he explained. “The use of standardized definitions will allow us to develop a better understanding of how these two very different therapies compare with each other.”