Liam Davenport

September 01, 2017

UPDATED SEPTEMBER 10, 2017 // MADRID, Spain ― Current recommendations for CT scanning as part of ongoing follow-up for patients with completely resected non–small cell lung cancer (NSCLC) have been called into question, after data from a randomized trial showed that the practice offers no overall survival benefit.

Major international guidelines, including recent guidelines for NSCLC from the European Society for Medical Oncology (ESMO), recommend intensive follow-up, including CT scans, every 3 to 6 months during the first 2 years after successful surgery.

But a group of French researchers from the Intergroupe Francophone de Cancerologie Thoracique (IFCT) have shown that less intensive follow-up with clinical examinations and chest X-rays achieves comparable survival rates.

The finding comes from the IFCT-0302 study, a randomized, controlled trial of more than 1700 patients who underwent complete resection for stage I, II, or IIIA NSCLC. The study results were presented during a presidential symposium at the ESMO 2017 Congress in Madrid, Spain.

Lead author, Virginie Westeel, MD, PhD, from Centre Hospitalier Régional Universitaire, Hôpital Jean Minjoz, in Besançon, France, said in a release that, because there was no overall difference in survival with either of the two types of follow-up, "both follow-up protocols are acceptable."

There was nevertheless a signal that more intensive follow-up was associated with a survival benefit among patients who did not have a recurrence in the first 2 years after surgery, and therefore the strategy may be beneficial in those who initially do well.

"A conservative point of view would be to do a yearly CT scan, which might be of interest over the long term," she said. "However, doing regular scans every 6 months may be of no value in the first 2 postoperative years."

However, ESMO expert Floriana Morgillo, MD, PhD, from the University of Campania Luigi Vanvitelli, Naples, Italy, who was not involved in the study, pointed out that, even across the whole study population, there was a trend toward better survival with CT follow-up, suggesting it may eventually yield a benefit.

She believes that CT-based surveillance remains an appropriate choice, although patients should be informed of the associated radiation exposure.

"A significant proportion of patients with early-stage NSCLC develop second cancers between the second and fourth year after surgery," Dr Morgillo said, "and early detection of these with CT-based surveillance beyond 2 years could allow curative treatment."

During a press conference for the study, Enriqueta Felip Font, MD, PhD, head of the Lung Cancer Unit at Vall d'Hebron University Hospital in Barcelona, Spain, commented that it was an important trial and that the question the researchers are addressing is "relevant."

During a press conference for the study, Enriqueta Felip Font, MD, PhD, head of the Lung Cancer Unit at Vall d'Hebron University Hospital in Barcelona, Spain, commented that it was an important trial and that the question the researchers are addressing is "relevant."

She nevertheless agreed with Dr Morgillo that CT appears to have a long-term benefit, adding that she performs CT for patients in her clinical practice, "and probably I will not change this after this study."

Emphasizing that this is her personal opinion, she said, "Tomorrow, I will follow up my patients with a CT scan."


Study Details

The IFCT-0302 trial compared two approaches to follow-up: in the experimental arm, patients underwent clinical examination, chest X-ray, and thoraco-abdominal CT scanning, as well as optional bronchoscopy for adenocarcinomas. In the control arm, patients underwent clinical examination and chest X-ray.

The trial included 1775 patients with completely resected stage I, II, IIIA, and T4 N0-2 NSCLC. In both arms of the trial, follow-up was conducted every 6 months for 2 years, and then once a year for 5 years. In patients who developed symptoms, supplementary procedures were permitted.

The median age of the participants was 63 years, and 76.3% were men. Squamous cell and large cell carcinomas were identified in 39.5% of the patients; 68.1% had stage I disease, 13.7% stage II disease, and 18.3% stage III disease.

Lobectomy or bilobectomy was performed in 86.6% of patients. Preoperative and/or postoperative radiotherapy was performed in 8.7% of patients; 45% of participants underwent preoperative and/or postoperative chemotherapy.

There were no significant differences in baseline characteristics between patients who underwent follow-up involving CT scanning and those who underwent only clinical examinations and chest radiography.

Over a median follow-up of 8.7 years, there were no significant difference in overall survival between the two follow-up groups, at a median of 123.6 months with intensive follow-up and 99.7 months with standard care (adjusted hazard ratio [HR], 0.92; P = .27).

There were only minor differences between the groups in rates of 3-year disease-free survival, at 76.1% in the intensive arm and 77.3% among control patients. A similar pattern was seen for 8-year overall survival rates, at 54.6% and 51.7%, respectively.

However, survival outcomes differed when the patients were stratified by whether they experienced a recurrence at 24 months.

Among patients who had a recurrence at 24 months, intensive follow-up was not associated with a survival benefit, at a median overall survival of 48.3 months vs 48.4 months for standard follow-up (P = .34).

In contrast, more intensive follow-up was associated with a significant survival benefit among patients who did not have a recurrence in the first 24 months, with the median overall survival not reached compared with 129.3 months in the standard care group (P = .04).

During the press conference, Dr Westeel said that patients without a recurrence in the first 2 years of follow-up "had a higher risk of secondary primary cancer than recurrence."

"This primary cancer may be more amenable to curative treatment and therefore benefit from CT scans, which allows the earlier detection of the second primary cancer," she noted.

Dr Westeel continued: "Our suggestion for practice is that, because there is no survival difference, both follow-up protocols are acceptable."

"However, a CT scan every 6 months is probably of no value in the first 2 years, while yearly chest CT scans might benefit over the long term."

The team also notes in the release that although there was no overall survival difference in this first randomized study of follow-up in resected NSCLC, "a longer follow-up is necessary not to miss a potential long-term OS benefit of CT-scan-based surveillance."

After the study presentation, Egbert Smit, MD, PhD, from the Netherlands Cancer Institute in Amsterdam, discussed the implications of the findings.

He pointed out that the current level of evidence for the guidelines recommendations for resected NSCLC is low and that is what makes the current study "so important."

However, he noted that chest radiography cannot detect distant metastases and is less sensitive than CT in identifying secondary primary cancers, and so more intensive follow-up is "logical." Previous studies have suggested that CT is associated with a survival benefit.

Dr Smit also noted that most distant metastases are detected in the first year after resection but that secondary primary tumors take much longer to appear, which may explain why the researchers found a survival benefit with CT only in patients without early recurrence.

Moreover, evidence from several studies suggests that the treatment of late recurrences identified on CT may be more effective than that for earlier recurrences, although the current researchers did not specify what follow-up treatment was provided.

Dr Smit said that although he agreed with the overall conclusions of the study, additional data on whether CT should be abandoned during the first 2 years after resection are required, as is further research into the effect of CT after that point.

The trial was funded by the Ministère de la Santé (PHRC), Fondation de France, and Laboratoire Lilly. One coauthor received nonfinancial support from Amgen and Pfizer, personal fees from AbbVie, personal fees and nonfinancial support from Boehringer Ingelheim, nonfinancial support from BMS, and personal fees from Clovis and Lilly. All other authors have disclosed no relevant financial relationships.

European Society for Medical Oncology (ESMO) 2017 Congress. Abstract 1273O, to be presented September 9, 2017.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.