Impact of histology and surgical approach on survival among women with early-stage, high-grade uterine cancer: An NRG Oncology/Gynecologic Oncology Group ancillary analysis☆
Introduction
Uterine cancer is not a single disease, but consists of several histologic subtypes, with different risk factors, precursor lesions, molecular and genetic profiles, and clinical outcomes. Epithelial uterine cancer has been historically classified into two subtypes, Type I and Type II, based on histologic and molecular characteristics [1], [2]. Observations by Lauchlan, Hendrickson, and Bokhman led to the description of these two distinct types, with Type I, commonly referred to as the endometrioid type, comprising 80–90% of all uterine cancers, and Type II, most often non-endometrioid tumors, encompassing the remaining 10–20% of endometrial tumors [3], [4], [5]. The most common histologies of this latter subtype include uterine serous carcinoma (USC) and clear-cell carcinoma (CCC). Additionally, carcinosarcoma (CS), a biphasic, high-grade epithelial uterine tumor, behaves similarly to the Type II tumors and is often classified as such [6].
In general, Type II uterine neoplasms are associated with more aggressive tumor biology and clinical behavior than Type I tumors, accounting for more than 40% of all uterine cancer deaths. However, this has not been observed in all studies [3], [4], [5], [7], [8]. At least one study from the Gynecologic Oncology Group (GOG) suggested the association between tumor type and prognosis was weak for patients with advanced/recurrent uterine cancer [9]. Additionally, although it is often labeled as a Type II cancer, grade 3 endometrioid adenocarcinoma is an entity that may defy categorization, despite its endometrioid histotype. Some studies demonstrate that USC and CCC are associated with an unfavorable prognosis compared with grade 3 endometrioid cancer, while a recent clinicopathologic analysis revealed no difference in outcome between these histologies [7], [8], [10].
Survival outcomes for the GOG LAP-2 study, a multicenter phase III study of women with apparent early-stage, grade 1–3 uterine cancer randomized to laparoscopy versus laparotomy, have been previously reported [11]. While the authors suggest that histologic cell type should not necessarily be a factor in the decision to offer minimally invasive surgery, detailed data regarding the women with high-grade disease from the LAP-2 cohort remains unexplored. There are few large prospective studies describing the impact of high-risk uterine cancer histologies on patient prognosis. There are even fewer published reports evaluating the role of minimally invasive surgery in the management of high-grade uterine malignancies [12]. Therefore, the primary study aim was to examine the clinicopathologic features and prognostic differences among histologic cell types in women with high-grade uterine cancer enrolled in a cooperative group trial. A secondary aim was to compare the oncologic outcomes of this same population staged by minimally invasive approaches versus laparotomy.
Section snippets
Methods
This was an institutional review board exempt study. An ancillary analysis of the GOG LAP-2 trial, a multicenter phase III study of women with apparent early-stage uterine cancer randomized 2:1 to laparoscopy versus laparotomy was performed. Data was collected on patients with high-grade malignancies; specifically, grade 3 endometrioid, and those with Type II uterine cancers, including USC, CCC and carcinosarcoma. Representative slides from the hysterectomy specimens were submitted for central
Results
Of 2600 patients enrolled in the LAP-2 trial, we identified 753 patients with high-grade disease: 350 were diagnosed with endometrioid; 289 with USC; 72 with carcinosarcoma; and 42 with CCC. Laparoscopy was performed in 507 patients and laparotomy in 246. Demographic and clinicopathologic data stratified by uterine tumor histology is shown in Table 1. Compared with the grade 3 endometrioid cohort, those with “other” Type II uterine cancers were more likely: older (median age 69.4 vs 61.8,
Discussion
While most uterine corpus cancers are early-stage, low-grade Type I tumors with an excellent prognosis, grade 3 endometrioid adenocarcinoma, USC, CCC and carcinosarcoma have been identified as distinct, high-risk variants, each with a poorer prognosis than the Type I cancers [8], [11]. Although these high-grade subtypes account for fewer than 25% of all uterine cancers, they collectively account for more than 50% of uterine cancer deaths [12], [19]. Thus, it is paramount that cancer centers and
Conflicts of interest
Dr. Nick Spirtos receives per capita reimbursement to the Women's Cancer Center, travel supplement as Gyn Onc Committee Chair, co-operative research funding on a per capita basis from GOG Foundation, Inc., and royalties from Wiley Health Services for Bonney's Gynaecological Surgery.
Dr. Michael Pearl receives grant money from the GOG/NRG. He also serves as a consultancy for Ethicon, provided expert testimony for legal expert review, and has grants/grants pending from NIH, small foundations, as
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These findings were presented at the Society of Gynecologic Oncology's 45th Annual Meeting on Women's Cancer in Tampa, Florida, March 22–25, 2014.
This study was supported by National Cancer Institute grants to the University of Oklahoma (1CA65221), the Gynecologic Oncology Group (GOG) Administrative Office (CA 27469), the Gynecologic Oncology Group Statistical Office (CA 37517), NRG Oncology (1U10 CA180822) and NRG Operations (U10CA180868). The following Gynecologic Oncology Group (GOG) institutions participated in the GOG 2222 (LAP2) study: Abington Memorial Hospital, Walter Reed Army Medical Center, University of Minnesota Medical School, University of Mississippi Medical Center, University of Pennsylvania Cancer Center, University of California at San Diego, University of Iowa Hospitals and Clinics, University of Texas Southwestern Medical Center at Dallas, Indiana University School of Medicine, University of California Medical Center at Irvine, Tufts–New England Medical Center, Rush–Presbyterian–St Luke's Medical Center, University of New Mexico, The Cleveland Clinic Foundation, State University of New York at Stony Brook, Washington University School of Medicine, Memorial Sloan-Kettering Cancer Center, Columbus Cancer Council, MD Anderson Cancer Center, University of Massachusetts Medical School, Women's Cancer Center, University of Oklahoma, Tacoma General Hospital, Tampa Bay Cancer Consortium, Gynecologic Oncology Network, Fletcher Allen Health Care, University of Wisconsin Hospital, Women and Infants Hospital, and Community Clinical Oncology Program.
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Dr. Stephanie Ricci is currently at Cleveland Clinic Foundation; Dr. Christina L. Kushnir is currently at Women's Cancer Center of Nevada.