Tuesday, May 1, 2012
Abstract & Commentary
By Robert L. Coleman, MD, Professor, University of Texas; M.D. Anderson Cancer Center, Houston, is Associate Editor for OB/GYN Clinical Alert.
Dr. Coleman reports no financial relationships relevant to this field of study.
Synopsis: The merits of sentinel-node technology -- including more efficient nodal isolation, reduction of lymphatic dissection in low-risk patients, and tailored therapy -- may be relevant in endometrial cancer.
Source: Ballester M, et al. Detection rate and diagnostic accuracy of sentinel-node biopsy in early stage endometrial cancer: A prospective multicentre study (SENTI-ENDO). Lancet Oncol2011;12:469-476.
Previous studies have demonstrated the feasibility of identifying sentinel lymph nodes (SLN) in the pelvic and para-aortic nodal basins in women with endometrial cancer. However, these data have been generated from multiple techniques explored in single institutions and reported as hypothesis-generating retrospective studies. To assess the detection rate and diagnostic accuracy of the SLN procedure in predicting the pathological pelvic-node status in patients with early-stage endometrial cancer, patients with stage I-II endometrial cancer underwent SLN assessment via cervical injection of dye and radionuclide. SLNs, if identified, were characterized prior to systematic pelvic lymphadenectomy. All lymph nodes were histopathologically examined, and SLNs were serial sectioned and examined by immunochemistry (IHC). The primary endpoint was estimation of the negative predictive value (NPV) of sentinel-node biopsy per hemipelvis. The multi-institutional study enrolled 133 patients; at least one SLN was detected in 111 of 125 eligible patients (89%). Pelvic node metastases were identified in 20 eligible patients and in 19 patients where a SLN was detected (17%). Of these 19, nine were detected by IHC alone. Five of 111 patients (5%) had an associated SLN in the para-aortic basin. NPV was 100% and sensitivity 100%, when evaluated with respect of the hemipelvis. However, false-negative sentinel nodes were found in three patients (two in the contralateral pelvis and one in the para-aortic chain), producing a NPV of 97% and sensitivity of 84% when considering the patient as the index. SLN biopsy upstaged 10% of patients with low-risk and 15% of those with intermediate-risk endometrial cancer. The authors concluded that SLN biopsy could be a trade-off between routine systematic lymphadenectomy and no dissection at all in patients with endometrial cancer of low or intermediate risk.
The sentinel node concept makes a lot of practical sense in situations where routine complete extraction of a tumor's nodal basin are unrelated to disease outcome..sup.1 The advantage under the hypothesis that a limited number of "high-risk" nodes are preferentially receiving drainage from the primary tumor is that more information may be gained about tumor biology with less disruption and morbidity. In several solid tumors, the concept has been validated and, in many, is now the standard of care (melanoma, breast cancer). In gynecologic oncology, the technique also appears to be valid for vulva cancer..sup.2 However, examination of the pelvic organs are trickier because the central location and multiple potential draining basins place a premium on false-negative exams and require a much broader investigation intraoperatively. In addition, re-operation to explore high-risk clinical scenarios or underassessment is impractical relative to more superficial nodal basins examined in vulva or breast cancer. Nevertheless, carcinoma of the uterus fulfills many of the assumptions that would promote investigation in this manner: lymph node metastases are uncommon; lymphadenectomy has not proved to alter overall survival, yet routine lymphadenectomy is associated with morbidity; and tailored therapy based on improved assessment could impact long-term outcomes..sup.3 The latter underscores the ultimate impact, which was not addressed in the current study and should be the next step. Also, one must be cautious not to overstate the concept is validated. Nodal risk was very low in this study (< 20%) and would require many more dissections to establish a confident "per patient" false-negative predictive value (3% in the current study). This parameter is much more important as the outcome in the nodal basin from the SLN is not known at the time of sampling. Also limiting is the fact that nearly half of the SLN determined with metastases were found by IHC techniques. This is much more difficult to obtain at the time of operation, and eliminating it until final postsurgical pathological assessment would increase the intraoperative false-negative rate or raise the question we already struggle with in patients who have not been formally staged: reoperation vs overutilization of postoperative therapy.
Coleman RL, et al. Current perspectives on lymphatic mapping in carcinomas of the uterine corpus and cervix. J Natl Compr Canc Netw 2006;4:471-478.
Van der Zee AG, et al. Sentinel node dissection is safe in the treatment of early-stage vulvar cancer. J Clin Oncol 2008;26:884-889.
Barlin JN, et al. The importance of applying a sentinel lymph node mapping algorithm in endometrial cancer staging: Beyond removal of blue nodes. Gynecol Oncol 2012 Feb 22 [Epub ahead of print].
"Sentinel-Node Biopsy in Endometrial Cancer: Valid Approach?" OB/GYN Clinical Alert 1 May 2012. Health Reference Center Academic. Web. 1 May 2012.
Gale Document Number: GALE|A288121616