Enhanced Surveillance Post-Surgery Not Associated With Longer Survival in NSCLC

lung cancer

There was no overall survival (OS) improvement seen by expanding surveillance from chest x-ray to follow-up with PET-CT scan after surgery for patients with early-stage non—small cell lung cancer (NSCLC), according to data reported during the 2017 ESMO Congress.

There has not been evidence from a randomized trial to support either of the recommendations in the current guidelines, which propose follow-up by chest x-ray every 6 months for 2 to 3 years, with PET-CT allowed only when abnormalities are detected. Several guidelines also recommend follow-up by PET-CT.

A final analysis done at a median follow-up of 8 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 (95% CI, 89.1-115.5) compared to 123.6 months (95% CI, 100.9-NR), respectively, HR_adjusted0.94 (95% CI, 0.82-1.09).

The 3-year OS rates were 77.3% with minimal and 76.1% with maximal follow-up. The five- and eight-year OS rates were 66.7 versus 65.8% and 51.7% versus 54.6% in the minimal versus maximal arms, respectively.

Virginie Westeel, MD, PhD, Thoracic Oncology, University Hospital of Besançon, France, and colleagues conducted the phase III 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 (95%CI 52.1-NR) in the maximal cohorts, (P= .07). The 3- and 5-year DFS rates were 63.3% and 54.1% in the minimal arm compared to 60.2% and 49.7% in the maximal arm (HR_adjusted, 1.14).

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 (95% CI 119.3-NR) with minimal follow-up versus OS NR with maximal follow-up in patients with no recurrence at 24 months (P= .04). In patients with a recurrence at 24 months, median OS was 48.3 versus 48.4 months, respectively (P= .34).

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 1775 patients with completely resected NSCLC to the minimal (n = 888) or maximal (n = 887) follow-up programs.

These regimens were repeated every 6 months after randomization during the first 2 years, and yearly until 5 years in both arms.

The primary endpoint of the trial was OS and 2 interim analyses were planned.

All patients had undergone resection for clinical stage I, II, IIIA 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 2 arms. Overall, 76.3% of patients were male with a median age of 63 years (range, 34-88 years), and 39.5% of patients had squamous and large cell carcinomas. Stage I, II, and III disease was reported in 68.1%, 13.7%, and 18.3% of patients, respectively. Most patients (86.6%) had undergone lobectomy or bilobectomy, with 8.7% also receiving pre- and/or post-operative radiotherapy, and 45% received pre- and/or post-operative chemotherapy. Histology included squamous (34%), adenocarcinoma (57%), and large cell (5.5%).

Discussant Egbert F. Smit MD, PhD, 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 2 years of resection.”

Reference:

Westeel V, Barlesi F, Foucher P, et al. Results of the phase III IFCT-0302 trial assessing minimal versus CT-scan-based follow-up for completely resected non-small cell lung cancer (NSCLC). Presented at: 2017 ESMO Congress; September 8-12; Madrid, Spain. Abstract 1273O.