Prospective assessment of survival, morbidity, and cost associated with lymphadenectomy in low-risk endometrial cancer
Highlights
► Lymph nodes metastases occur in less than 0.5% of patients with low risk endometrial cancer. ► Cause-specific survival is 99% in this low risk cohort when lymphadenectomy is omitted; no lymphatic recurrences were identified. ► Morbidity is significantly higher in patients who undergo lymphadenectomy with an accompanying increase in median 30-day cost of care.
Introduction
The global corpus uteri cancer burden is approaching 300,000 new cases annually. This accounts for the majority of invasive gynecologic cancers in developed countries where it is exceeded only by breast, colorectal and lung cancers [1]. Notwithstanding the regularity with which gynecologic oncologists encounter this disease, definitive management of endometrial cancer (EC) varies greatly across the international oncology community. In particular, extensive debate continues regarding the value of lymphadenectomy (LND). Utilization even at specialized centers varies from omission of LND in all cases to comprehensive assessment of all patients, even those with atypical hyperplasia in some instances [2], [3], [4], [5], [6], [7], [8], [9]. Definitions of the adequacy and extent of LND vary to an even greater degree than does indications.
Rather than investigating LND, we have focused our efforts to identify patients who will not benefit from LND or adjuvant therapy, thereby minimizing overtreatment, morbidity and cost, while preserving oncologic outcomes. There is obvious precedence for identifying a low-risk endometrial cancer subgroup as demonstrated by withholding adjuvant chemotherapy, omitting groin dissection and performing conization alone in patients with early stage ovarian, vulvar, and cervical cancer, respectively.
Collectively, 48.7% of all accrued endometrial cancers within the 26th Annual International Federation of Gynecology and Obstetrics (FIGO) report on carcinoma of the corpus uteri were FIGO stage Ia and Ib (1988 classification) with an overall 5-year survival rate of 92.6% [10], [11]. These data presuppose that a significant segment, but not all, of the stage Ia and Ib, and grade 1 and 2 endometrioid cohort is sufficiently low-risk to perhaps forego definitive surgical staging. The challenge is to accurately differentiate patients at negligible risk from patents at potential risk for lymphatic dissemination. Stage alone, as currently defined, is not adequate to identify a truly low-risk cohort. Considering the great majority of this cohort presents with multiple medical comorbidities, limiting the level of surgical complexity in this population would be advantageous. Furthermore, recent reports demonstrate significant increases in the incidence of type I endometrial cancers emphasizing the need to develop criteria for risk-stratification to allow more cost-effective personalized therapy [12], [13].
In our previous outcomes analysis of grade 1 and 2 endometrioid carcinomas with ≤ 50% myometrial invasion (MI), we observed a 5-year overall cause-specific survival (CSS) of 97% [2]. No case with a primary tumor diameter (PTD) of ≤ 2 cm had metastatic lymph node involvement detected. Our findings have been corroborated by Milan et al., who showed the prevalence of nodal metastasis in these low-risk cases to be < 1.0% [14]. In a multicenter retrospective review, Convery et al. demonstrated a 98.2% negative predictive value utilizing the above treatment algorithm [15]. On the basis of our original observations, we transitioned to omitting LND in those patients identified as having low-risk disease (type I histology, grade 1 or 2, MI ≤ 50%, PTD ≤ 2 cm, later referred to as the “Mayo criteria”) via frozen section assessment. Subsequently, cases with non-invasive type I cancers were also considered low-risk independent of grade and PTD and likewise not considered candidates for LND [16]. In this investigation we demonstrate that surgical staging in patients with low-risk endometrial cancer, as defined above, fails to improve survival in a cohort with universally excellent oncologic outcomes. Surgical staging is, however, accompanied by increased short-term morbidity and higher 30-day cost of care.
Section snippets
Materials and methods
The cohort under study was consecutive patients with endometrial cancer managed surgically at Mayo Clinic Rochester during the time interval January 1, 1999 through December 31, 2008. The technique for processing intraoperative frozen sections at Mayo Clinic has been described in detail elsewhere [17]. The longest of three tumor dimensions was recorded as the PTD. For the purpose of determining histological types, the taxonomy proposed by the World Health Organization was used [18].
Clinicopathologic characteristics
A total of 1415 women were consecutively treated with hysterectomy for epithelial endometrial carcinomas at our institution between January 1, 1999 and December 31, 2008; 22 did not grant research authorization. Of the remaining 1393, 1128 were determined to have endometrioid histology and 413 were designated low-risk as defined in Materials and methods by the Mayo criteria. However, 28 cases with synchronous or grossly apparent metastasis were excluded leaving 385 low-risk endometrioid cases
Discussion
Exemplary of the diverse strategies for endometrial cancer treatment is the continuing controversy regarding the role of LND in the surgical management of low-risk disease [2], [3], [4], [5], [6], [7], [8], [9], [15], [16], [27], [28]. Further confounding management and comparative outcomes assessments are the assorted definitions for low-risk disease [16], [29], [30], [31]. Traditionally, grade 1 and 2 endometrioid EC with myometrial invasion ≤ 50% has been considered low-risk [29] and accounts
Conflict of interest statement
The authors declare that there are no conflicts of interest.
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