Cervical Cancer: Targeted Sampling Detects Involved Nodes in Unusual Places (2009)

Figure: No Caption Available.ORLANDO, FL—It's not exactly a needle in a haystack, but a sentinel pelvic lymph node in a woman with early-stage cervical cancer might be found in some unexpected places. French researchers here at the ASCO Annual Meeting reported that lymph node mapping of women with early-stage cervical cancer can identify sentinel lymph nodes and detect small isolated tumor cells and micrometastases in atypical areas such as common iliac, internal iliac, para-aortic, and parametrial territories, as effectively as full pelvic lymph node dissection. The prospective Senticol trial, conducted in seven centers in France, compared results using sentinel node mapping versus results from biopsies after full pelvic lymphadenectomy in 128 women. The major finding was that using sentinel lymph node biopsy in women with early-stage cervical cancer to detect metastases, instead of the standard pelvic lymphadenectomy, is very accurate, and that it is safe and effective for the majority of patients. Outside the Ilio-Obturator Region But also important was the detection of sentinel nodes in an unusual territory, defined as outside the ilio-obturator region. Sentinel lymph node biopsy identified at least one sentinel node in an unexpected territory in 48 of the 128 patients (38%)—primarily outside the external iliac and interiliac regions. Three of those were positive: a micrometastasis in a right internal iliac sentinel node; one in a left common iliac sentinel node; and macrometastases in a left interiliac and in a para-aortic sentinel node. The biopsies had a sensitivity of 91% and negative predictive value of 98%, leading the researchers to recommend the removal of only sentinel lymph nodes (SLNs) for biopsy to assess metastasis in women with early-stage cervical cancer rather than pelvic lymphadenectomy. “Targeted node sampling may be more relevant than full node dissection,” said lead author Fabrice Lecuru, MD, PhD, Professor of Obstetrics and Gynecology at Georges Pompidou European Hospital in Paris. “These data suggest that the majority of women with Stages Ia1 or Ib1 epidermoid cancer or adenocarcinoma or adenosquamous cervical cancer can safely undergo SLN biopsy rather than the more invasive pelvic lymphadenectomy.” He and his colleagues estimated that pelvic node dissection could have been avoided in 104 of the patients (81%) with negative nodes, potentially decreasing treatment-associated morbidity. Mapping Lymphatic Drainage Through Unusual Pathways SLN biopsy is common in surgery for breast cancer and melanoma, and previous studies have shown it can be used in early-stage cervical cancer to predict cancer spread to lymph nodes in pelvic areas most likely to be involved, Dr. Lecuru noted. “But 10% to 15% of women with no pathological nodes still experience recurrence of cervical cancer.” One reason may be that positive nodes are located outside the dissection field in areas such as common iliac, internal iliac, para-aortic, and parametrial territories.Figure: FABRICE LECURU, MD, PhD: “Targeted node sampling may be more relevant than full node dissection. These data suggest that the majority of women with Stages Ia1 or Ib1 epidermoid cancer or adenocarcinoma or adenosquamous cervical cancer can safely undergo SLN biopsy rather than the more invasive pelvic lymphadenectomy.”“Besides allowing women with early-stage cervical cancer to avoid full pelvic lymph node dissection, SLN biopsy would also be more effective in mapping lymphatic drainage through unusual pathways, which is important since 25% of patients have lower limb edema,” Dr. Lecuru said. The risk of edema increases with the number of removed nodes. Sentinel lymph nodes were detected peri-operatively in the pelvic and para-aortic territories by a combination of blue-dye labeling and endoscopic technetium gamma probe. Additional Results Among the 128 women, the researchers identified 26 positive sentinel lymph nodes (6% of all sentinel nodes) in 21 patients (16%). Eight of the 26 positive sentinel nodes contained isolated tumor cells (i.e., less than 0.2 mm); eight contained micrometastases (0.2 to 2 mm); and 10 contained macrometastases (greater than 2.0 mm). Dr. Lecuru said these sentinel lymph nodes in unexpected territories were twice as likely to be found by lymphoscintigraphy than intraoperatively. They were also twice as likely to be found by gamma probe than by blue dye. Complications of SLN biopsy and lymphadenectomy occurred in about 20% of procedures and 17% of patients. The most common by far was urinary tract infection, in 14 of the 128 women. There were three cases of obturator nerve injury; four cases of bleeding; two hemoperitoneum; and two cases of lower limb edema. Discussant: Standardize Technique First Lymphedema occurs quite frequently in patients with early-stage cervical cancer after full lymphadenectomy and radiotherapy, said the Discussant for the study, Ate G.J. Van der Zee, MD, Professor of Obstetrics and Gynecology in the Department of Gynecologic Oncology at University Hospital Groningen in The Netherlands. Using the sentinel lymph node biopsy with combined radiolabeling and blue dye to detect involved nodes goes far to spare patients the morbidity associated with lymphadenectomy, Dr. Van der Zee said. But he said he was concerned about the reproducibility of sentinel node detection in cervical cancer, given that some studies have shown very little correlation between the lymphoscintigraphy and intraoperative findings with the gamma probe. “There are really some issues with respect to standardizing the technique for sentinel node detection in cervical cancer, and it relates to where and how deep to perform the tracer injection, the optimal technique for injecting the tracer, and who should carry out the node sampling.” The study's strengths, Dr. Van der Zee said, are that it was prospective and multicenter and had a very clear protocol and a short accrual period. Its weaknesses, he said, included the small number of patients in whom isolated tumor cells or micrometastases were found. The significance of finding isolated tumor cells or micrometastases remains to be established. Phase III trials may be too ambitious, given the numbers of patients required, and future studies might well be observational studies, he said. “I think at the present time, in patients with early-stage cervical cancer, sentinel node detection should be performed only within the protection of clinical trials.”