Even in advanced stages, total tumor size can have a major impact on survival in non–small cell lung cancer (NSCLC), according to a new study.

Tumor size is not currently used to predict overall survival times for the two-thirds of lung cancer patients with locally advanced or metastatic disease. This study used data from a National Cancer Institute–sponsored phase 3 trial involving 850 patients with advanced lung cancer. The research team reviewed total tumor dimensions, which could include the primary tumor and also those in lymph nodes and other sites of metastatic disease. Total tumor measurements greater than 3 inches predicted shorter survival times.

“The traditional view is that once a cancer has spread to the lymph nodes or to other organs, tumor dimensions are unlikely to affect patient outcomes,” explained lead author David Gerber, MD, of the University of Texas Southwestern Medical Center and a member of the Harold C. Simmons Comprehensive Cancer Center, both in Dallas. “However, the survival differences we found are not only statistically significant, but also clinically meaningful.”

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In the study, published online in the British Journal of Cancer (2013; doi:10.1038/bjc.2013.472), the average total tumor dimension was 7.5 centimeters, or, roughly, 3 inches. Patients with total tumor dimensions greater than this size lived an average of 9.5 months. Patients with total dimensions less than 7.5 centimeters lived an average of 12.6 months, representing a 30% increase in survival.

When total tumor dimension was further divided into quartiles, the survival differences were even greater, ranging from 8.5 months to 13.3 months. These differences persisted even when multiple prognostic factors, such as age, gender, and type of treatment, were included in the analysis.

Gerber explained that, if confirmed in other populations, these findings could affect future clinical trials and patient care.

“Ultimately, clinical researchers might consider this information as they review outcome data, making sure survival differences are attributed to treatment effects and not to baseline differences in total tumor dimensions,” he said. “Practicing physicians may also use the information to estimate prognosis.”

Precise measurements of lung cancer tumors can be used to tailor therapy and help doctors steer patients to the best clinical trials, he added.

While the study did not seek to explain the biological reasons this size association may hold true, a number of preclinical observations link tumor size with therapeutic resistance. It is generally thought that, as tumors grow, the proportion of cells resistant to chemotherapy increases. Larger cancers may also have relatively poor blood supply and more pronounced gradients in interstitial pressure, hypoxia, and acidity, which may influence tumor cell sensitivity to chemotherapeutics and radiation treatments.