No chemo needed for truly node-negative colon cancer

Last Updated: 2015-05-28

By Larry Hand

NEW YORK (Reuters Health) - Stage I and II colon cancer patients who undergo adequate surgery and have at least 12 negative lymph nodes are not likely to benefit from adjuvant chemotherapy, according to a new international study.

"If a pathology report shows fewer than 12 lymph nodes, then the clinician should be telling the pathologist to look more closely for more than 12 lymph nodes," senior investigator Dr. Anton J. Bilchik, of the John Wayne Cancer Institute, Santa Monica, California, told Reuters Health in a telephone interview.

"Clinicians can also be telling patients that if they've had more than 12 lymph nodes removed and, in fact, the lymph nodes are truly negative, that they really are unlikely to benefit from chemotherapy," he added. "In fact, you'll have to treat a hundred patients to benefit fewer than two."

The researchers recruited adults with adenocarcinoma of the colon in the U.S., Serbia, and Israel between 2001 and 2014. The cohort was about evenly split between males and females, with a median age of 68.

Of 442 patients screened, 203 had at least 12 hematoxylin and eosin (H&E)-negative lymph nodes. Nine patients turned out to have micro-metastases >0.2mm, leaving 194 patients for analysis.

None of the patients received adjuvant chemotherapy.

The investigators established up front that surgeons would do a standard and adequate resection and that pathologists would find at least 12 lymph nodes in the tumor specimen, Dr. Bilchik said.

"The second thing we did was to standardize our pathology, not only to look very carefully for metastasis in the lymph nodes but actually to do multiple sectioning" to look for occult metastasis, he added.

In this cohort, 42 patients did have occult metastases on pan-cytokeratin immunohistochemistry or molecular staging of H&E-negative nodes. These patients were comparable to the 152 without occult disease except for higher rates of lympho-vascular invasion (17.1% vs 6.4%; p=0.045) and pT3-pT4 Stage (85.7% vs 62.3%; p=0.007).

At a median follow-up of 37.6 months (range 0-97 months), the mean disease-free survival as estimated on Kaplan-Meier analysis was 92.9 months for patients without occult disease, vs 71.8 months for patients with nodes ultimately found to contain single tumor cells or clusters smaller than 0.2mm.

Disease recurred in 2.6% of truly node-negative patients compared with 16.7% of patients with nodes containing single or small clusters of tumor cells (p<0.0001).

Six patients died from the disease, the authors reported online May 18 in the Journal of the American College of Surgeons.

"What we found was that if a surgeon does a complete oncologic resection, and if the pathologist does a very thorough job of looking for even the smallest cancer cell, if the lymph nodes are negative, and if you have more than 12 lymph nodes removed, there is no benefit to giving chemotherapy in that group, because 97.4% of patients were disease-free at a mean follow-up of close to four years," Dr. Bilchik said.

"The recurrence rate in patients with more than 12 lymph nodes that were staged negative by both standard techniques as well as immunohistochemistry was only 2.6%. So that's really the central message, which had never been evaluated in a prospective trial," he added.

"One of the issues with colon cancer and the management of colon cancer is that most of the clinical trials that have led to the approval of chemotherapy drugs or biologic drugs for colon cancer have not taken into account surgical quality measures and pathological quality measures," Dr. Bilchik continued. "We've found over the past 10 years that surgical quality measures impact survival and the way a pathological specimen is examined also is important in terms of accurate staging for colon cancer."

He said current research is focusing on trying to determine which groups of patients to treat based on the biological characteristics of the primary tumor and which patients are more likely cured by surgery alone and don't need additional chemotherapy.

After this trial, he said, "I strongly believe that in clinical trials that are designed to evaluate colon cancer drugs, there needs to be very close attention to both surgical and pathology quality measures up front."

The United States Military Cancer Institute, the National Cancer Institute, and the California Oncology Research Institute supported this research.

SOURCE: http://bit.ly/1GDR61A

J Am Coll Surg 2015.