CT screening catches small cell lung cancers earlier

In one of the largest studies yet to focus on a rare type of lung cancer, radiologists from Columbia University in New York City found that CT screening and treatment when indicated may spare the lives of patients with small cell lung cancer (SCLC).

CT screening corresponded to significantly lower disease stage at diagnosis. In fact, most of the handful of early-stage SCLC patients who underwent resection are still alive five years later, the researchers found.

The screening results compared favorably to data from patients who received standard care, in which CT was used for staging rather than screening of small cell lung cancers. The comparison data came from a large 2007 study by Shepherd et al from the International Association for the Study of Lung Cancer (IASLC) database.

The IASLC study performed survival analyses for clinically staged lung cancer patients. It concluded that stage distribution in SCLC correlated significantly with prognosis. Five-year survival for stage I SCLC was 28%, stage II was 21%, stage III was 10%, and stage IV was 1% (Journal of Thoracic Oncology, December 2007, Vol. 2:12, pp. 1067-1077).

To date, most lung cancer screening studies have sought to assess the potential benefits of early detection of non-small cell lung cancers, which are far more common than SCLCs and less closely associated with tobacco use. SCLC occurs almost exclusively in long-term smokers.

SCLCs also tend to grow and spread more quickly than their non-small cell counterparts, potentially diminishing any mortality benefit that might eventually be shown to result from interval screening of smokers and former smokers with CT.

“If there’s any subcohort within lung cancer that you’d think would not be a group to screen it would be small cell carcinoma,” said Dr. John Austin, professor of radiology and director of thoracic imaging at Columbia University Medical Center in New York City.

Austin recently presented the first results of his group’s review of subjects who underwent interval screening for five years in the International Early Lung Cancer Action Program (I-ELCAP), a multinational, multi-institutional lung cancer study led by Dr. Claudia Henschke, Ph.D., that has screened approximately 43,000 individuals, mostly smokers and former smokers.

Austin and colleagues Rowena Yip, Dr. Belinda D’Souza, and Dr. Jianwei Yang, with the assistance of I-ELCAP researchers Dr. David Yankelevitz and Henschke from New York-Presbyterian Hospital and Weill Medical College in New York City, assessed the utility of CT screening for the detection of SCLC in asymptomatic smokers and ex-smokers.

The findings were compared to those from 7,960 TNM (tumor, node, metastasis)-staged SCLC patients reported by Shepherd et al in the 2007 IASLC study, which represents the current standard of care. In that study, CT screening was not used; instead, patients were staged after reporting with symptoms.

Of 581 patients with lung cancer identified in the I-ELCAP trial, 43 (7.4%) were diagnosed with SCLC (median age, 68 years). About 45% of the subjects were current smokers, 35% were ex-smokers, and 10% had occupational or other risk factors. Individuals diagnosed with SCLC had a mean 59 pack-years of smoking history.

“I would say that small cell is the really committed smokers’ cancer,” Austin said.

The study aimed to “look at the frequency of small cell lung carcinomas picked up at screening and look at stage distribution compared to the absence of CT screening,” Austin said in a presentation at the 2008 RSNA meeting.

The records of I-ELCAP subjects with a diagnosis of SCLC were reviewed by an international panel of five expert pulmonary pathologists, who generally have no trouble diagnosing small cell cancers, he said.

“We looked at how many cancers — not at baseline but detected in annual follow-up screening — were visible in retrospect,” he said. “And we also looked at examples and at the treatment provided to stage I patients.”

Of approximately 43,000 subjects, there were 43 small cell cancers, or one in 1,000 screened subjects, he said. Five patients had both small cell and non-small cell cancers, which are treated as small cell, he said.

Of the 43 cases, 53% (23/43) were found in baseline screening, 40% (17/43) in annual follow-up screening, and 7% (3/43) were symptom-prompted and interim-diagnosed cases. Each was staged according to the TNM staging system, and stage distribution was compared with that of the 7,960 SCLC cases in the IASLC series, using either chi-square or Fisher exact testing, as appropriate.

SCLC detected in I-ELCAP and IASLC patients by stage

SCLC stage I-ELCAP (all T1N0M0) IASLC (2.7% T1N0M0) P-value
Stage I 42% (18/43) 6.7% [ 0.0001
Stage II 12% (5/43) 4.1% 0.03
Stage III 33% (14/43) 32.3% Not significant
Stage IV 14% (6/43) 56.9% [ 0.0001

While baseline screening detects both slow-growing and fast-growing tumors, “ongoing follow-up means you’re going to have a chance to pick up fast-growing tumors,” Austin explained. As a result, he said, it was not surprising to see a significant shift toward early-stage SCLC in the I-ELCAP cohort compared to the IASLC cohort.

Half of the 18 stage I SCLC cases (all stage IA) were evident in retrospect, he said. And I-ELCAP’s 14% of patients with stage IV disease was a far cry from the approximately 60% distribution of advanced-stage cancers that Austin said he was taught 40 years ago.

Five years after diagnosis, eight out of 10 (80%) of the I-ELCAP SCLC patients with stage I disease who had their cancers resected were still alive, Austin said. In contrast, the eight stage I patients who did not undergo resection had died.

“These are small numbers but extraordinarily optimistic results,” he said.

Five-year survival for the stage I patients plus seven additional stage II and stage III patients whose cancer was resected was 36%, he said. Overall, 51% of I-ELCAP cases were early-stage compared with 11% of the control group.

CT screening of at-risk subjects detects SCLC at earlier stages than in a usual-care population, the study concluded.

By Eric Barnes
AuntMinnie.com staff writer
February 10, 2009