Elsevier

Gynecologic Oncology

Volume 127, Issue 1, October 2012, Pages 5-10
Gynecologic Oncology

Prospective assessment of survival, morbidity, and cost associated with lymphadenectomy in low-risk endometrial cancer

https://doi.org/10.1016/j.ygyno.2012.06.035Get rights and content

Abstract

Objective

Since 1999, patients with low risk endometrial cancer (EC) as defined by the Mayo criteria have preferably not undergone lymphadenectomy (LND) at our institution. Here we prospectively assess survival, sites of recurrence, morbidity, and cost in this low risk cohort.

Methods

Cause-specific survival (CSS) was estimated using the Kaplan–Meier method and compared using the log-rank test. Complications were graded per the Accordion Classification. Thirty-day cost analyses were expressed in 2010 Medicare dollars.

Results

Among 1393 consecutive surgically managed cases, 385 (27.6%) met inclusion criteria, accounting for 34.1% of type I EC. There were 80 LND and 305 non-LND cases. Complications in the first 30 days were significantly more common in the LND cohort (37.5% vs. 19.3%; P < 0.001). The prevalence of lymph node metastasis was 0.3% (1/385). Over a median follow-up of 5.4 years only 5 of 31 deaths were due to disease. The 5-year CSS in LND and non-LND cases was 97.3% and 99.0%, respectively (P = 0.32). None of the 11 total recurrences occurred in the pelvic or para-aortic nodal areas. Median 30-day cost of care was $15,678 for LND cases compared to $11,028 for non-LND cases (P < 0.001). The estimated cost per up-staged low-risk case was $327,866 to $439,990, adding an additional $1,418,189 if all 305 non-LND cases had undergone LND.

Conclusion

Lymphadenectomy dramatically increases morbidity and cost of care without discernible benefits in low-risk EC as defined by the Mayo criteria. In these low-risk patients, hysterectomy with salpingo-oophorectomy alone is appropriate surgical management and should be standard of care.

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.

References (45)

  • H.M. Keys et al.

    A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study

    Gynecol Oncol

    (2004)
  • P.J. DiSaia et al.

    Risk factors and recurrent patterns in stage I endometrial cancer

    Am J Obstet Gynecol

    (1985)
  • A. Mariani et al.

    Surgical stage I endometrial cancer: predictors of distant failure and death

    Gynecol Oncol

    (2002)
  • J.W. Orr et al.

    Surgical staging of uterine cancer: an analysis of perioperative morbidity

    Gynecol Oncol

    (1991)
  • H.D. Homesley et al.

    Selective pelvic and periaortic lymphadenectomy does not increase morbidity in surgical staging of endometrial cancer

    Am J Obstet Gynecol

    (1992)
  • S.E. Brooks et al.

    Resource utilization for patients undergoing hysterectomy with or without lymph node dissection for endometrial cancer

    Gynecol Oncol

    (2002)
  • M. Frumovitz et al.

    Frozen section analyses as predictors of lymphatic spread in patients with early-stage uterine cancer

    J Am Coll Surg

    (2004)
  • J.U. Shim et al.

    Accuracy of frozen-section diagnosis at surgery in clinical stage I and II endometrial carcinoma

    Am J Obstet Gynecol

    (1992)
  • J.A. Quinlivan et al.

    Accuracy of frozen section for the operative management of endometrial cancer

    BJOG

    (2001)
  • a Jemal et al.

    Global cancer statistics

    CA Cancer J Clin

    (2011)
  • P.J. Frederick et al.

    The role of comprehensive surgical staging in patients with endometrial cancer

    Cancer Control

    (2009)
  • S.M. Kehoe et al.

    The role of lymphadenectomy in endometrial cancer

    Clin Obstet Gynecol

    (2011)
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