PET-CT Is Better for Preoperative Staging of Lung Cancer

Nick Mulcahy

July 01, 2009

July 1, 2009 — The frequency of futile thoracotomies is reduced by use of combined positron-emission tomography and computed tomography (PET-CT) compared with conventional staging in patients with non–small-cell lung cancer (NSCLC), according to a new study.

PET-CT also reduced the total number of thoracotomies and improved diagnostic accuracy compared with conventional staging.

However, the use of this more expensive technology in the staging of these patients did not significantly affect overall survival, write the authors of the study in the July 2 issue of the New England Journal of Medicine.

Nevertheless, the authors of the study emphasize the benefits of PET-CT, including the fact that improved diagnostic accuracy can help avoid "resections of benign nodules and early local and distant relapse after surgery with curative intent." The authors were led by Barbara Fischer, PhD, from the department of oncology at the Odense University Hospital, in Copenhagen, Denmark.

The primary end point of the study, futile thoracotomy, is "controversial" in so far as it does not have a completely agreed-upon definition in the field, suggest the authors. In the study, a thoracotomy was considered futile in the event of any of the following clinical findings or results: a benign lung lesion, pathologically proven mediastinal lymph node involvement (stage IIIA [N2]), stage IIIB or IV disease, inoperable T3 or T4 disease, or recurrent disease or death from any cause within 1 year of randomization.

If that definition is accepted and futile thoracotomy is indeed considered a valid end point, write the authors, "the significantly higher number of early deaths and relapses in the conventional-staging group than in the PET-CT group was not due to chance or more successful surgery in the PET-CT group but instead reflects a better selection of patients for surgery in the PET-CT group."

Specifically, after staging, 60 patients in the PET-CT group (out of a total of 98) and 73 in the conventional-staging group (out of a total of 91) were considered to have operable disease and underwent thoracotomy.

Of the 60 patients in the PET-CT group, the thoracotomy was futile in 21 (35%), and of the 73 patients in the conventional-staging group, the procedure was futile in 38 (52%) (P = .05).

For the PET-CT group, the diagnostic accuracy and sensitivity were 79% and 64%, respectively. For the conventional-staging group, the accuracy and sensitivity were 60% and 32%, respectively.

Confirms Another Study

The new study's findings are similar to the results of another trial. That study, led by Harm van Tinteren, MD, from the Comprehensive Cancer Center Amsterdam, in the Netherlands, involved a similar number of patients (188) with NSCLC, although 70% of these patients had localized disease vs 34% in the latest study. Nevertheless, that study yielded a similar result and showed that staging with stand-alone PET resulted in an absolute risk reduction of futile thoracotomy by 20% (van Tinteren H et al. Lancet. 2002;359:1388-1393).

But there is 1 other trial that is comparable to these 2 studies that had different results. In an Australian study of 184 patients, 92% of whom had localized disease, there was no difference in number of thoracotomies between the 2 randomized comparison groups: patients who underwent staging with stand-alone PET and those who underwent conventional staging (Viney RC et al. J Clin Oncol. 2004;22;2357-2362).

However, this Australian study did not use confirmatory invasive procedures — only 10 of the 184 patients underwent mediastinoscopy, the authors of the latest study point out. In their own study, 94% of the patients underwent mediastinoscopy, which was "one of the strengths of the study," Dr. Fischer and colleagues comment. Eleven percent of the patients had positive lymph nodes on mediastinoscopy. Thus, these patients were considered to have inoperable disease in the current study but would have not been so classified in the Australian study; in short, the lack of mediastinoscopy weakens the Australian findings, Dr. Fischer and colleagues suggest.

One of the limitations of the current study is that it did not meet enrollment goals and was closed due to slow accrual.

The study was designed so that 215 patients would be randomized to each group (for a total of 430 patients), thus allowing enough power to detect a difference of 15% in the number of futile thoracotomies between the 2 groups, write the authors. However, the study was closed after enrolling only 189 patients. The published study is the first analysis of the data.

No Significant Difference in Survival

The staging of NSCLC was 1 of the first approved indications for PET, the authors observe. The combined PET-CT "has rapidly replaced stand-alone PET" since 2001, they add. The diagnostic capability has been proven to be superior to either PET or CT alone, they add. The advantage is mainly based on the superior assessment of tumor stage, the authors write.

Despite being the standard of care, there has been uncertainty about whether or not improved diagnostic accuracy translates into improved management of patients. The findings of the current study suggest that management is improved. However, there were no significant differences in survival between the 2 groups, with a median survival of 31 months in the PET-CT group and 49 in the conventional staging group (P = .29).

The study was supported by grants from the Danish Cancer Society and the Danish Center for Health Technology Assessment. One of the coauthors has received lecture fees from AstraZeneca. No other financial relationships were disclosed.

New Engl J Med. 2009;361:32-39.

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