Colorectal Cancer Upstaged with Lymphatic Mapping

SANTA MONICA, Calif., June 19--Better scrutiny of lymph nodes in colorectal cancer patients could help more accurately identify those who need adjuvant chemotherapy and those who may do just fine without it.

That's the conclusion of researchers here, reporting in the June issue of Archives of Surgery who found that one fourth of patients deemed to have stage II colorectal cancer had evidence of nodal cellular spread on ultrastaging not detected on conventional staging.

With lymphatic mapping-a technique used for staging breast cancer and melanoma-and thorough sentinel node examination, pathologists can focus on those nodes that are most likely to contain metastatic cells without adding significantly to the time or cost involved, according to Anton J. Bilchik, M.D., Ph.D., of the John Wayne Cancer Institute here, and colleagues.

"One third of patients with tumor-free lymph nodes have recurrences, and therefore, adjuvant chemotherapy may be beneficial in these patients," they wrote. "However, if all node-negative patients are treated, 70% will be subjected to unnecessary chemotherapy because surgery alone is curative. A better understanding of high-risk, node-negative patients and improved methods of lymph node evaluation are therefore needed."

Conventional node sampling methods may miss small metastases, the investigators pointed out, because nearly three-fourth of lymph nodes with tumor involvement are less than 0.5 cm in diameter, making them easy to overlook in gross dissection or microscopic examination.

Lymphatic mapping involves staining of lymphatic channels for more easy identification and retrieval of nodes. By paying particular attention to sentinel nodes with multiple sectioning and immnuohistochemistry, clinicians may be able to increase the accuracy of staging and improve the sensitivity of the pathologic exam for metastatic disease, the investigators wrote.

To see whether this kind of approach could work in colorectal cancer, they conducted a prospective phase II multicenter trial in 63 men and 69 women (median age 74) who were having standard oncologic resection for the disease.

During the surgery, the investigators performed lymphatic mapping, and the sentinel node was identified by either the surgeon or a pathologist. All lymph nodes underwent hematoxylin-eosin staining, and those that were negative on the staining were also subjected to immunohistochemistry.

The primary outcomes measure was detection of micrometastases between 0.2 mm and 2 mm, and isolated tumor cells less than 0.2 mm.

In all, 68 of the patients had a right hemicolectomy, three had a transverse colectomy, nine had a left colectomy, 15 underwent a sigmoid colectomy, 34 had a low anterior resection, one had an abdominal perineal resection, and two had a total colectomy.

There were a total of 111 evaluable primary tumors, 19 of which were T1 lesions, 17 of them T2, 72 of them T3, and three of them T4.

Thirty-three patients (30%) were classified with stage I colorectal cancer, 46 (41%) with stage II, and 32 with stage III.

The authors found that the sensitivity of lymphatic mapping and sentinel node analysis was 88.2%, with a false-negative rate of 7.4% .Of the 6 false-negative results, four were attributable to the fact that the tumor had obliterated the lymphatic channels.

As a result of the mapping and node analysis, 28 patients were staged upward on the basis of the presence of micrometastases.

"In stage II colorectal cancer, 24% of patients had nodal carcinoma cells not detected by conventional staging methods," the authors wrote. "Surgical technique (adequate lymph node retrieval) and focused pathological analysis may improve staging accuracy and the selection of patients for chemotherapy. The unnecessary toxicity and expense of chemotherapy may be avoided in those patients who are truly node negative."