Therapeutic Role of Lymph Node Resection in Endometrioid Corpus Cancer

Abstract & Commentary

By Robert L. Coleman, MD, Associate Professor, University of Texas; M.D., Anderson Cancer Center, Houston, is Associate Editor for OB/GYN Clinical Alert.

Dr. Coleman is on the speaker's bureau for GlaxoSmithKline, Bristol-Myers Squibb, and Ortho Biotech.

Synopsis: The findings of the current study suggest that the extent of lymph node resection improves the survival of women with intermediate/high-risk endometrioid uterine cancer.

Source: Chan JK, et al. Therapeutic role of lymph node resection in endometrioid corpus cancer: a study of 12,333 patients. Cancer. 2006;107:1823-1830.

The therapeutic role of lymphadenectomy in patients with endometrial cancer is controversial and challenging to study given the relative infrequency of metastatic disease and the generally good prognosis of newly diagnosed patients. Nevertheless, prior work in limited sized cohorts has suggested that the number of nodes resected may be prognostic and informative in planning subsequent adjuvant treatment. To address these questions, Chan and colleagues evaluated over 12,000 women registered in the SEER database in whom nodal sampling accompanied their primary surgical procedure from 1988-2001. Patients with Stage I to IV disease and endometrioid histology (all grades) were included in the study cohort. Importantly, women with uterine serous histology and uterine sarcoma were excluded. In light of the large sample size, 5 categories of node counts could be evaluated. Risk groups were considered as well, defined as: Low Risk (Stage IA, all grades, Stage IB, Grade 1-2), Intermediate Risk/High risk (Stage IB, Grade 3, Stage IC-IV, all Grades) and High Risk (Stage IIIC-IV). The authors documented that the percentage of patients undergoing nodal sampling significantly increased over the years of the study (23% to 41%; P < 0.001). The number of nodes resected was significantly associated with improved survival for intermediate/high-risk and high-risk patients. No benefit in disease-specific survival was seen for the low-risk cohort. Age at diagnosis, race, year of diagnosis, grade, identified metastatic nodal disease, and adjuvant therapy were significant covariates in the study; however, in the multivariate analysis, node count remained a significant prognostic factor to disease specific survival in the intermediate/high-risk cohort after adjustment for these effects. The authors concluded that node count acts as a surrogate for extent of node resection and improves the survival of women with intermediate/high-risk endometrioid uterine cancer.

Commentary

One of the most important prognostic factors for uterine cancer limited to the corpus is identification of extrauterine disease, particularly retroperitoneal adenopathy. Fortunately, the identification of metastatic disease occurs in just 1 in 5 women with endometrioid primary cancers. However, the price for undetected metastatic disease is high. This has led to two approaches or management philosophies regarding intervention: broader application of more extensive nodal sampling or more frequent utilization of adjuvant therapy in patients where staging information is missing. Both approaches have merit but risk overtreatment. The former strategy ensures accurate diagnostic information in all cases but 80% of women will receive limited benefit from the procedure; the latter, ensures high-risk areas are treated without the attendant morbidity of extensive surgery but does so blindly as the target volume is "guesstimated" (vaginal cuff and/or pelvis field and/or paraortic field). The current article provides some guidance to this dichotomous treatment approach for women with endometrioid tumors.

One relevant observation the authors identify is that there appears to be a cohort of patients (totaling 5,556/12,333 or 45% of the population) in whom nodal sampling or dissection offers no therapeutic value—patients with stage IA, all grades and stage IB, grades 1 and 2. Survival in this low-risk cohort ranges from 94% to 97%, irrespective of the extent of nodal resection. However, for all other risk cohorts, node count has a profound effect on survival. Most impressive is the effect of node count on patients with identified metastatic disease. Of 1221 patients with stage IIIC/IV disease, 5-year disease-specific survival ranged from 51% in women with 1 resected node to 72% in women with more than 20 resected nodes. To minimize sampling bias, they additionally evaluated the ratio of positive nodes to the total number of nodes resected. In this analysis women in whom the metastatic node ratio was greater than 20% had a survival of 51% compared to those in whom the number of metastatic nodes were 5% or less of the total node resection. While this kind of analysis can be confounded by misclassification of patients with high positive node counts, their specific occurrence is historically uncommon and may still be positively offset by more thorough lymphadenectomy.

The second point raised in this analysis is that patients without formal staging may be misclassified as having optimistic outcomes in apparent early stage disease and poor outcome in advanced stage disease. Women undergoing formal evaluation by lymphadenectomy resulting in an early stage (Stage I) designation similarly have favorable outcomes; however, the survival for those identified advanced disease (Stage II-IV) is substantially better. This result is likely the combination of stage migration and the therapeutic value of resection—even unaffected nodes. It also speaks to better defining the treatment volume of "at-risk" tissues, which has the potential to reduce treatment-related toxicity.

This current report suffers the fate of similar SEER-based analyses with inconsistent or absent central pathology review, missing data of adjuvant hormonal and chemotherapy, undefined skills of the surgeon, unknown progression-free survival and incomplete detail of subsequent therapy for recurrence. In addition, while node counts may serve as a surrogate of completeness of resection, it is highly operator-dependent. Large node counts can be achieved if they are specifically sought in gross processing, particularly if defattying agents are utilized. Reproducible criteria which ensure the completeness of resection are unavailable and probably better represented by specified sampling in specific nodal regions such as: external iliac, obturator, junctional, common iliac, low paraortic (below the inferior mesenteric artery) and paraortic (ovarian). However, the data are provocative and are positive reinforcement for the trend identified in this study of a greater proportion of patients being referred for expert surgical care by trained gynecologic oncologists.

References

  1. Trimble EL, et al. Lymph node sampling and survival in endometrial cancer. Gynecol Oncol. 1998;71:340-343.
  2. Kilgore LC, et al. Adenocarcinoma of the endometrium: survival comparisons of patients with and without pelvic node sampling. Gynecol Oncol. 1995;56:29-33.
  3. McMeekin DS, et al. Nodal distribution and its significance in FIGO stage IIIC endometrial cancer. Gynecol Oncol.2001;82:375-379.