Postop Opioid Use Tied to NSCLC Recurrence

TAMPA -- Non-small cell lung cancer (NSCLC) patients who experienced disease recurrence half a decade after surgery received a significantly higher dose of opioids postoperatively, researchers said here.

In a retrospective study among patients treated for early-stage NSCLC, recurrence occurred in 26 who received a mean dose of 232 mg of opioids in the 96 hours after surgery compared with 124 mg of opioids administered to the 73 patients in whom there was no recurrence in 5 years (P=0.020), reported Dermot Maher, MD, from Cedars-Sinai Medical Center in Los Angeles, and colleagues.

"A suggested mechanism is the opioid-induced inhibition of natural killer cell's ability to scavenge tumor cell emboli during the 'decisive period,'" the authors wrote in a poster presentation at the annual scientific meeting of the American Pain Society.

Maher said that in the decisive period right after surgery, natural killer cells find and destroy cancer cells that might have spilled during the perioperative period. Maher said that opioids tend to inhibit the natural killer cell activity.

The inhibition period is about 4 days, he said, so his group studied opioid use in the 96-hour period after surgery.

"We knew that opioid-sparing anesthetic techniques can reduce the recurrence rate of certain cancers, so we decided to look at outcomes in NSCLC," he told MedPage Today.

Maher's group looked at outcomes of 444 stage I or stage IIa NSCLC patients who underwent video-assisted thoracoscopic lobectomy procedures.

"We focused on early stage I, stage II lung cancer, using the same surgeon at the same site and performing the same surgery; only four anesthesiologists handled the patients preoperatively. Postoperatively, the patients pain scores were the same," Maher said.

The average age of the patients was about 68. Nearly half of the men were recurrence-free (49%) versus 31% who experienced recurrence (P=0.148). There were no statistical differences in other demographics of the patients. For example, 77% of each group had a history of smoking.

Based on a multivariable regression analysis, predictors of NSCLC recurrence 5 years postoperatively were:

• Total postoperative opioid administration: odds ratio 1.003 (95% CI 1.000-1.006)
• Number of pack-years smoked: OR 1.027 (95% CI 1.000-1.056)
• Clinical stage Ia: OR 0.117 (95% CI 0.014-0.941)
• Clinical stage Ib: OR 0.086 (95% CI 0.009-0.780)
• Clinical stage IIa: OR 0.387 (95% CI 0.032-4.74)

Maher noted that all the confounding variables, except treatment of breakthrough pain, were the same, giving the researchers a clean analysis of the possible effect of opioid administration to outcomes.

"But at [4 a.m.] in the morning when [residents are] treating the patients, they may have different ideas on what they are going to do to treat the patients' pain," he explained.

"Future prospective randomized controlled trials are needed to establish causatory link between non-small cell lung cancer recurrence and increased postoperative opioid administration," his group wrote.

"This is a very important finding," said Samer Kaba, MD, vice president for neurosciences at Medpace, a clinical research organization in Cincinnati. Kaba was not involved in the current study.

However, Kaba cautioned that "we do need a prospective study looking at this. As a retrospective study, there are possible faults and biases that can arise, but there is a critical need to study this."

The study results have been accepted for publication by the British Journal of Anaesthesia, the authors reported.

Comment