Histologic Subtype Predicts Recurrence of Early Lung Adenocarcinoma

August 13, 2013

By Robert Saunders

NEW YORK (Reuters Health) Aug 13 - Recurrence after limited lung resection for small, early-stage adenocarcinoma is three times more likely when the micropapillary component of the tumor is 5% or greater compared to less than 5%, according to a retrospective analysis.

"We and many in thoracic surgery and lung-cancer community are excited about our findings, which have direct and immediate impact on lung cancer patient care," senior researcher Dr. Prasad S. Adusumilli told Reuters Health by email.

Dr. Adusumilli, at Memorial Sloan-Kettering Cancer Center in New York, and colleagues note that there have been no evidence-based criteria for choosing limited resection or lobectomy for the treatment of peripheral, early-stage lung adenocarcinoma. While limited resection preserves lung function, the recurrence rate is as high as 40%. That compares to about 15% after lobectomy.

The team therefore investigated the utility of recently proposed histologic classifications in selecting the appropriate procedure for such patients.

For their study they identified 734 patients with stage I adenocarcinoma no larger than 2 cm: 258 underwent wedge resection or segmentectomy, and 476 underwent lobectomy. Median follow-up was 37 months in the limited-resection group and 32 months in the lobectomy group.

Regression tree analysis of data from a training subset of the patients identified tumors with a micropapillary (MIP) component of 5% or more as high risk for recurrence, the team reports in the Journal of the National Cancer Institute online August 7.

In the limited-resection group of patients, the five-year cumulative incidence of recurrence (CIR) was significantly higher for those with high-risk tumors than those with low-risk tumors (34.2% vs. 12.4%, p<0.001).

"After adjustment for both vascular and lymphatic invasion, which were associated with recurrence in univariable analysis, the presence of an MIP component of 5% or greater remained independently associated with CIR (hazard ratio = 3.11; p=0.003)," according to the report. These results were replicated in a validation subset of the patients.

On the other hand, micropapillary status was not significantly associated with recurrence in patients who underwent lobectomy. The 5-year CIR was 19.1% when tumors had an MIP component of 5% or greater compared to 12.9% with tumors with a lower MIP component (p=0.13). The lack of association was also confirmed in a validation set.

"This observation, for the first time provides scientific evidence for the operating surgeons to stratify patients either for LR (limited resection) or LO (lobectomy), thereby reducing the chance of recurrence by 75%," Dr. Adusumilli stated in his email.

However, he added, "Finding of MIP requires pathological expertise, and currently can only be reported on the removed tumor."

As the authors point out, intraoperative reporting of micropapillary morphologic patterns is therefore not standard-of-care at present. "Hopefully, our findings will encourage further investigations to determine whether pathologists can recognize and report this feature on frozen sections of lung ADC," they write.

"We are now working on methods/tools to identify MIP preoperatively on imaging or intraoperatively by special staining," Dr. Adusumilli added. "This will be the ideal situation as MIP cannot be reported on few cells obtained by preoperative biopsy unless we come up with a specific marker."

Meanwhile, the researchers conclude, "Given our findings, patients treated with LR whose tumors are determined to have MIP morphologic pattern by use of permanent sections may require completion segmentectomy or LO."

SOURCE: http://bit.ly/15yvNaa

J Natl Cancer Inst 2013.

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