Preoperative assessment identifies patients with endometrial cancer at low risk for lymph node metastasis

Preoperative assessment of lymph node metastasis in endometrial cancer may encourage selective lymphadenectomy for low-risk patients, according to results of the PALMEC study.

The role of systematic pelvic lymphadenectomy as a staging procedure in patients with endometrial cancers has been a controversial topic among gynecologic oncologists.

“The arguments raised against routine lymphadenectomy are based on two factors: the absence of evidence showing improved survival due to the procedure and the compromised quality of life for patients who undergo lymphadenectomy,” Sokbom Kang, MD, PhD, from the gynecologic oncology research branch at Research Institute and Hospital of National Cancer Center in the Republic of Korea, and colleagues wrote. “However, many still advocate its routine use because it can provide prognostic information and allow tailoring of adjuvant therapy.”

Conversely, lymphadenectomy is not routinely used for patients without high-risk features; however, the reliability and accuracy of preoperatively identifying risk factors in this patient population has yet to be verified.

Kang and colleagues observed 529 patients with biopsy-confirmed endometrial cancer treated in Korea, Japan and China, who underwent MRI and serum cancer antigen 125 (CA-125) screening prior to surgery.

Researchers used the Korean Gynecologic Oncology Group (KGOG) criteria to identify patients whose probability of lymph node metastasis was less than 4%: endometroid-type cancer, no evidence of deep myometrial invasion on MRI, no enlarged lymph nodes on MRI, no suspicious metastasis out of the uterine corpus, and serum CA-125 levels less than 35 U/mL.

Estimation of the negative predictive value served as the primary endpoint.

According to the model’s criteria, 272 patients were categorized as low risk, including eight patients who had lymph node metastasis and were falsely categorized as low risk.

KGOG criteria demonstrated sensitivity of 84.9% (95% CI, 72.4-93.3) and specificity of 55.5% (95% CI, 50.9-60.0). However, the negative predictive value (97.1%; 95% CI, 94.3-98.7) was higher than the predefined target endpoint of 96%.

KGOG criteria had a higher diagnostic OR (7) than Society of Gynecologic Oncology (SGO; 3.7) and European Society of Medical Oncology (ESMO; 4.1) guidelines. KGOG criteria also had superior negative predictive value (97.1% vs. 96.4% vs. 95.5%).

SGO guidelines had higher sensitivity (90.6%) and ESMO guidelines yielded superior specificity (57.4%) compared with KGOG criteria, but these differences did not reach statistical significance.

Without lymphadenectomy, 24 of the low-risk patients would have been classified as high risk after surgery based on their postoperative pathologic outcomes. The rate of lymph node metastasis for these patients was 8.3%.

Of the remaining 248 low-risk patients, the rate of lymph node metastasis was 2.4%.

Kang and colleagues noted their criteria may be useful in making informed decisions by the physicians and patients.

“There have been increasing demands for surgeons to help patients make informed decisions and to provide necessary information regarding treatment options,” they wrote. “Although there is no level-one evidence showing a survival benefit of lymphadenectomy, a population-based study indicated that the morbidity of lymphadenectomy is as serious as that of radiotherapy. Therefore, such information should clearly be made available to patients before surgery, and patients should be encouraged to actively participate in decision-making.”

“Compelling” data have shown that lymphadenectomy may be diagnostic and therapeutic, David Scott Miller, MD, professor of obstetrics and gynecology at the Fred F. Florence Bioinformation Center at the University of Texas Southwestern Medical Center, wrote in an accompanying editorial.

“There is no advantage to patients to ignoring occult lymphatic metastases,” he added. “Patients with lymphatic recurrences can only occasionally be treated successfully. The promiscuous application of adjuvant therapy ignorant of the involvement of lymph nodes by cancer does not improve survival and may be associated with devastating consequences.”

In another editorial, Jean A. Hurteau, MD, gynecologic specialist at Evanston Hospital at North Shore University Health System, noted that two issues need further discussion — cost and the consideration of omitting lymph node dissection altogether as the most cost-effective strategy.

The cost of lymphadenectomy has been estimated to increase the median 30-day cost of care by approximately $4,500 per patient, he wrote.

“Proponents for routine lymphadenectomy argue that in current clinical practice, most practitioners would opt for adjuvant radiation more frequently if lymphadenectomy were omitted. The short- and long-term complications of radiation effects, such as diarrhea, enteritis, cystitis, bowel strictures, fistulas, gastrointestinal bleeding, and secondary cancers, would need to be factored into a cost analysis.” – by Kristie L. Kahl

References:

Hurteau JA. Cancer. 2016;doi:10.1002/cancer.30346.

Kang S, et al. Cancer. 2016;doi:10.1002/cncr.30349.

Miller DS. Cancer. 2016;doi:10.1002/cncr.30418.

Disclosure: The researchers, Miller and Hurteau report no relevant financial disclosures.