No Benefit in Increased Surveillance After Lung Cancer Surgery

More post-surgery surveillance is not necessarily better for patients with early-stage non-small cell lung cancer, according to a recent study.

Expanding surveillance after surgery from chest X-ray to follow-up with PET-CT scan did not improve overall survival (OS), researchers reported during the 2017 ESMO Congress.

Although most current guidelines recommend follow-up by chest X-ray every six months for two to three years with PET-CT allowed only when abnormalities are detected, several guidelines do recommend follow-up by PET-CT; however, evidence from a randomized trial to support either of these recommendations is lacking.

A final analysis done at a median follow-up of eight years and 10 months showed a trend toward improved OS in the experimental (maximal) follow-up arm, but did not significantly differ between minimal and maximal follow-up; median OS was 99.7 months compared to 123.6 months.

The three-year OS rates were 77.3 percent with minimal and 76.1 percent with maximal follow-up. The five- and eight-year OS rates were 66.7 versus 65.8 percent and 51.7 percent versus 54.6 percent in the minimal versus maximal arms, respectively.

Virginie Westeel, M.D., Ph.D., Thoracic Oncology, University Hospital of Besançon, France, and colleagues conducted the phase 3 IFCT-0302 trial (NCT00198341) to evaluate which follow-up regimen could improve patient outcomes. They contrasted a minimal follow-up comprising physical examination together with history and a chest X-ray with a maximal follow-up that added CT scan with contrast of the thorax and upper abdomen plus fiber optic bronchoscopy, which was optional for patients with adenocarcinoma but mandatory for squamous and large cell carcinoma.

“Although the primary endpoint was not met, a longer follow-up is needed to avoid missing a potential long-term OS benefit of CT-scan—based surveillance,” commented Westeel.

Median disease-free survival (DFS) was not reached (NR) in the minimal cohort versus 59.2 months in the maximal cohorts. The three- and five-year DFS rates were 63.3 percent and 54.1 percent in the minimal arm compared to 60.2 percent and 49.7 percent in the maximal arm.

However, DFS favored the maximal follow-up in a subset of patients who did not experience disease recurrence at 24 months. The investigators reported results from an exploratory analysis that showed median OS of 129.3 with minimal follow-up versus OS NR with maximal follow-up in patients with no recurrence at 24 months. In patients with a recurrence at 24 months, median OS was 48.3 versus 48.4 months, respectively.

Westeel commented, “This is the first large randomized trial to evaluate follow-up after surgery for NSCLC. Although no significant survival benefit was seen, there was a trend for an earlier diagnosis of recurrences and second primary cancers suggesting that maximal follow-up with CT scan may have a potential long-term benefit for patients at high risk for second primary cancers.”

The IFCT-0302 study was a multicenter trial that randomized 1,775 patients with completely resected NSCLC to the minimal (888 patients) or maximal (887 patients) follow-up programs.

These regimens were repeated every six months after randomization during the first two years, and yearly until five years in both arms.

The primary endpoint of the trial was OS and two interim analyses were planned.

All patients had undergone resection for clinical stage 1, 2, 3A or T4 (pulmonary nodules in the same lobe of the lung) N0-2 NSCLC. All perioperative treatments were allowed but patients with renal impairment or with a prior history of breast cancer or melanoma were excluded from the study.

Patient characteristics were well-balanced between the two arms. Overall, 76.3 percent of patients were male with a median age of 63 years (range, 34-88 years), and 39.5 percent of patients had squamous and large cell carcinomas. Stage 1, 2 and 3 disease was reported in 68.1 percent, 13.7 percent, and 18.3 percent of patients, respectively. Most patients (86.6 percent) had undergone lobectomy (surgical removal of a lobe on the lung) or bilobectomy (surgical removal of two lobes on the right lung), with 8.7 percent also receiving pre- and/or post-operative radiotherapy, and 45 percent received pre- and/or post-operative chemotherapy. Histology included squamous (34 percent), adenocarcinoma (57 percent), and large cell (5.5 percent).

Discussant Egbert F. Smit M.D., Ph.D., Netherlands Cancer Institute in Amsterdam, The Netherlands, who was not involved in the study, commented, “The debate between chest X-ray versus CT-based follow-up after resection of early-stage NSCLC remains unsettled; additional data are needed to abandon CT-based follow-up during the first two years of resection.”