NO BENEFIT OF EXTENDED LYMPHADENECTOMY FOR ESOPHAGEAL CANCER

Extensive lymph node removal during surgery for esophageal cancer might not necessarily improve survival, according to new findings.

In a study of 606 patients, the extent of lymphadenectomy was not significantly associated with 5-year all-cause or disease-specific mortality.

These results are seemingly in conflict with the currently accepted standard of care, according to the study authors, led by Jesper Lagergren, MD, PhD, from Guy's and St. Thomas' NHS Foundation Trust in London, United Kingdom.

The results, published online September 2 in JAMA Surgery, showed that 5-year survival was similar in patients who had 21 to 52 nodes resected and in those who had 0 to 10 nodes resected.

However, increased mortality rates were associated with a greater number of metastatic nodes and a higher positive- to negative-node ratio.

"These results challenge current clinical guidelines," according to the study authors.

"The conclusions of the study are in some conflict with previous findings, but the existing evidence for extensive lymphadenectomy is limited," Dr Lagergren told Medscape Medical News. "One single study cannot change clinical practice, but together with our previous study [J Natl Cancer Inst. 2015;107:djv043], the results do call into question the need for extensive lymphadenectomy as part of esophagectomy for cancer."

In that study, Dr Lagergren and his team found no association between survival and the number of lymph nodes resected in 1044 Swedish patients with esophageal cancer. It is too early to make clinical recommendations, Dr Lagergren said, "but the results do indicate the need for further studies."

Conflicting Results, Questions Unanswered

The conclusion of the study authors — that these data challenge current clinical guidelines — is echoed by Marco G. Patti, MD, from the University of Chicago Pritzker School of Medicine, in an accompanying editorial.

Clinical guidelines currently advocate transthoracic esophagectomy with two-field lymphadenectomy as the standard of care. Dr Patti points out that in a consensus statement developed by physicians from 13 institutions in China, Europe, and the United States, it is recommended that a minimum of 10 nodes be resected for T1 cancer, 20 nodes for T2 cancer, and 30 or more nodes for T3/T4 cancers (Ann Surg. 2010;251:46-50).

"Clearly, these studies have conflicting results so that the main question is still unanswered," writes Dr Patti. "Does the more extensive lymph node resection improve survival or rather does it just allow for better staging and migration?"

Dr Patti said he thinks it is not so much the operation that makes the difference, but rather the tumor biology and the stage of the tumor at the time the patient undergoes surgery.

"Until a definitive answer is given, surgeons should perform either a transhiatal or a transthoracic esophagectomy based on the patient's status and their own preference," he writes.

Replicating Results

The findings from the Swedish cohort provided impetus for the current study. Dr Lagergren and his colleagues wanted to test whether the Swedish results could be replicated with another design and a different population.

To do this, the team used prospective and comprehensive clinical data obtained from a high-volume surgery center in London that specialized in esophageal cancer.

Of the 606 patients involved in the study, 506 (83.5%) had a diagnosis of adenocarcinoma of the esophagus, 92 (15.2%) had a diagnosis of squamous cell carcinoma, and eight (1.3%) had a diagnosis adenosquamous carcinoma.

All participants underwent esophagectomy for cancer from 2000 to 2012 and were followed until 2014.

In the study cohort, 323 patients (53%) died within 5 years of surgery, and 235 (39%) of these deaths were related to tumor recurrence. Preoperative chemotherapy was more common in patients treated from 2000 to 2006 than in those treated from 2007 to 2012 (77% vs 53%).

The median number of removed nodes during the study was 14 (range, 0 - 52), and the in-hospital postoperative mortality rate was 3% (18 patients).

There were strong dose–response associations between the number of metastatic nodes and mortality, as well as the ratio of positive and total number of lymph nodes and mortality, the authors note. In addition, there were generally no major differences between all-cause and disease-specific 5-year mortality.

As noted, all-cause 5-year mortality was not significantly lower in patients who had 21 to 52 nodes removed than in those who had 0 to 10 nodes removed (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.63 - 1.17). This was particularly true for the 2007 to 2012 period, compared with the 2000 to 2006 period (HR, 0.98; 95% CI, 0.57 - 1.66).

The authors note that in other cancers, such as breast, endometrial, and those of the gastrointestinal tract, more extensive lymphadenectomy has not been associated with improved survival. "It is possible that lymphadenectomy does not improve survival in esophageal cancer simply because positive nodes represent a disseminated disease, while nonmetastatic nodes do not need to be removed," they conclude.

The study was funded by the Swedish Research Council and the Swedish Cancer Society. The authors and Dr Patti have have disclosed no relevant financial relationships.

JAMA Surg. Published online September 2, 2015. Abstract, Editorial