Experts in endometrial cancer suggest there should be a change in the standard of care, after the largest study to date found that sentinel lymph node biopsy is as accurate for identifying metastasis as complete pelvic lymphadenectomy, which is more invasive and is the current gold standard.
The findings come from the FIRES study (Fluorescence Imaging for Robotic and Endometrial Sentinal Lymph Node Biopsy), which was published online on January 31 in Lancet Oncology.
The FIRES trial was conducted in women with early endometrial cancer who were without evidence of metastasis on physical and radiologic examination. Participants (n = 340) received sentinel lymph node mapping using cervical injection of indocyanine green, followed by fluorescence imaging of the lymphatics. They also underwent full pelvic lymphadenectomy and para-aortic lymphadectomy (when technically feasible and clinically relevant).
The study found that sentinel lymph node biopsy accurately ruled out metastasis in more than 99% of cases. The false negative rate was 3%, similar to that for cases of breast cancer, melanoma, and vulvar cancer, for which sentinel-lymph node biopsy has become the standard of care.
"I think sentinel lymph node biopsy can replace the traditional lymphadenectomy technique and should become the standard of care in endometrial cancer. It's as accurate and may be considered an improvement upon the traditional technique," first author Emma Rossi, MD, of the University of North Carolina at Chapel Hill, told Medscape Medical News.
The results showed that nodal mapping had a sensitivity of 97.2% (95% confidence interval [CI], 85.0 - 100), with a negative predictive value of 99.6% (95% CI, 97.9 - 100).
Moreover, 17% of positive sentinel lymph nodes were identified outside regions traditionally included in complete lymphadenectomy. The traditional procedure would have missed these lymph nodes, the researchers note.
The study took place at 10 tertiary academic and community nonacademic centers in the United States. Eighteen surgeons, some new to the technique, performed the procedures.
The multicenter nature of the trial and the fact that the surgeons had varying degrees of experience increase the study's generalizability and make it more likely that the findings represent "real-world" practice, according to Dr Rossi.
Less Potential for Harm, and Lower Cost
Although lymphadenectomy helps define the risk for recurrence and enables surgical staging to guide treatment decisions, the procedure carries the risk for surgical harm and lymphedema. Sentinel lymph node biopsy involves removal only of organ-specific lymph nodes, identified by injecting dye near the primary tumor. Hence, it is associated with less harm and is less costly than full lymph node dissection, the researchers point out. The main risks include allergic reaction from the dye, vascular injury, ureteral injury, and lymphedema, according to Dr Rossi.
In the FIRES study, nine percent of patients experienced an adverse event. Of 22 patients who experienced serious adverse events, in only one case was the event related to the study intervention. That event concerned ureteral injury during sentinel lymph node dissection and did not result in long-term injury.
The sentinel lymph node technique gives more information but with less morbidity," Dr Rossi emphasized.
Writing in a linked editorial, Frédéric Amant, MD, PhD, and Hans Trum, MD, both of the Netherlands Cancer Institute, in Amsterdam, agree that pelvic sentinel lymph node mapping is "probably sufficient to direct further treatment" and that the technique may change existing treatment protocols.
"[T]he sentinel-lymph-node mapping procedure is the best intermediate between complete versus no lymphadenectomy.... Based on these implications, sentinel-lymph-node mapping should be implemented in routine practice," they write.
Currently, the National Comprehensive Cancer Network endorses sentinel lymph node biopsy as an acceptable standard of care for surgical staging of endometrial cancer in select patients.
But this raises the question: which are the select patients?
Endometrial cancer is the most commonly diagnosed gynecologic cancer in the United States, affecting about 54,000 women each year. Yet only a minority of women have advanced disease. High-grade disease carries a worse prognosis and greater risk for metastasis, the editorialists note.
Some clinicians believe full lymph node dissection has therapeutic benefit in such patients. Others think that full dissection is a tool for diagnosing metastatic disease and helps guide decisions about chemotherapy. Ultimately, a large clinical trial is needed to settle the debate, Dr Rossi mentioned.
The majority of women with endometrial cancer have low-grade disease. For them, the results from the FIRES trial are potentially practice changing.
Many women who are at low risk for nodal metastases do not receive full lymphadenectomy, although in 11% of cases of low-risk endometrial tumors, lymph nodes are positive, according to research cited in the editorial.
Part of the problem concerns the surgery itself. Many women with endometrial cancer are overweight or obese (a major risk factor for the disease), which makes full dissection technically challenging.
"Women with low-grade, low-risk endometrial cancers deserve to be offered the same degree of certainty in the characterization of their cancer state (localized vs metastatic) as those women with higher-risk cancers. The sentinel node biopsy technique delivers this while minimizing their exposure to a risky, radical staging procedure," Dr Rossi emphasized.
Editorialists Dr Amant and Dr Trum appear to be in agreement.
"The need for lymph-node detection in low-risk disease deserves more attention," they write.
They also stress that outcomes are best when experienced clinicians perform the mapping. Emphasizing the importance of shared decision making, Dr Rossi added that physicians should have a full discussion with patients about the potential risks of staging inaccuracies vs surgical harms.
The study was funded by Indiana University Health, the Indiana University Health Simon Cancer Center, and the Indiana University Department of Obstetrics and Gynecology. The authors and editorialists have disclosed no relevant financial relationships.