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Letters to the Editor |
City of Hope National Medical Center, 1500 East Duarte Road 91010, Duarte, CA USA
Received 4 March 2008; accepted 12 March 2008.
* Corresponding author. Tel.: +1 626 359 8111x64119; fax: +1 626 301 8855. (Email: fgrannis{at}coh.org).
Key Words: Lung cancer • Non-small cell lung cancer (NSCLC) • Stage IA • Size • Survival • Screening
Medical publications contain conflicting evidence on the important question of whether NSCLC size within stage IA impacts survival. Veeramachanenia et al. from Washington University present important new data to answer this question in February's EJCTS entitled ‘Risk factors for occult nodal metastasis in clinical T1N0 lung cancer: a negative impact upon survival [1].’
Their retrospective review of 292 patients with clinical stage IA NSCLC demonstrates that a size increase of 1 cm increases the risk of nodal metastasis by a factor of 3.5. Such occult nodal metastasis results in strikingly reduced survival. Because cases with nodal enlargement on CT or hilar or mediastinal PET uptake were excluded, and because systematic mediastinal node dissection was not routinely performed, this figure may underestimate occult nodal metastasis. In their literature review, the authors cite multiple prior studies offering similar data and conclusions.
But does not this information merely confirm common-sense notions regarding tumor biology? Why is this information important?
Although most publications, including this one, suggest decreasing survival as small NSCLC grow larger, two influential articles from Duke University dispute this association. In 2000, Patz published a review of 510 NSCLC patients with pathologic stage IA disease and found no association between size and survival [2]. In 2001, the same investigators reviewed 620 NSCLC 3 cm or smaller and concluded that increasing size within the group had no significant effect on final stage of tumors [3]. They conclude that, because they found no evidence that size matters with regard to either stage or survival, the theoretical benefit of detecting very small lung cancers by computerized tomographic screening is questionable. One of the Duke investigators, Philip C. Goodman MD, has included this data and conclusions prominently in paid depositions and courtroom testimony for tobacco companies in two lawsuits that seek jury verdicts compelling tobacco companies to pay for medical monitoring of individuals with high lung cancer risk.
Who is correct? With regard to survival, the 2000 Duke data contains a very important intrinsic bias. By excluding clinical IA cases that subsequently are classified in higher final pathological stages, they publish misleading data leading to incorrect conclusions. The Washington University investigators have not repeated this mistake, carefully identifying those patients who are so reclassified and the resulting wide variance in survival. With regard to size and stage, the issue is more complex. In the 2001 Duke series, 16.8% of cIA NSCLC had pII-IV comparable to 16.1% in the Washington series but patients upstaged to IB are not identified, nor is survival of 104 higher-stage patients displayed. Furthermore, their statistical analysis contains a questionable manipulation of data. Although a statistically significant increase in stage IIIB by size is noted, they conclude that ‘with stage IIIB patients being excluded, no statistically significant difference was found to exist.’
My conclusion is that size does appear to matter, and that Veeramachanenia et al. have demonstrated that a striking increase in nodal metastasis with increasing size at least partially explains why this is true.
Footnotes
The authors of the original paper [1] were invited to comment on this Letter to the Editor but declined the offer.
I am a principle investigator in the International Early Lung Cancer Action Program (IELCAP) lung cancer screening project. I have received $30,000 in data management support as well as travel, meals and accommodations to semi-annual IELCAP meetings. Last week an article in the New York Times revealed that IELCAP had accepted a gift of $2.4 million from a foundation created largely by the Vector Corporation, parent company to Liggett Tobacco in 2000 and subsequently another $1.1 million. I was not aware of this tobacco industry funding before the Times article. This money comprises approximately 6% of IELCAP funding.
References
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