Creation of Appropriate Use Criteria for Management of Uterine Clear Cell and Serous Carcinomas

Document Type

Conference Proceeding

Publication Date

10-1-2021

Publication Title

Cancer Clin Trials

Abstract

Background: Uterine serous carcinomas (USC) and uterine clear cell carcinomas (UCCC) represent a subset of endometrial cancers that have a high propensity for peritoneal, lymphatic and distant spread, tend to be more advanced at presentation, and carry a higher risk of recurrence and death compared with most estrogen-mediated endometrioid carcinomas. Both USC and UCCC have typically been pooled into studies that include other high-risk uterine cancers, but neither histology has been exclusively studied in large prospective clinical trials. Thus, the optimal treatment paradigm for each individual histology remains somewhat undefined, especially in early stage disease limited to the uterus. Adjuvant treatment options include chemotherapy, vaginal cuff brachytherapy (VBT) and pelvic +/- para-aortic external beam radiotherapy (EBRT), or both, with multimodality therapy typically considered for these aggressive tumors. Objectives: We sought to rate the appropriateness of treatment procedures for a variety of USC and UCCC cases by a multidisciplinary expert panel including gynecological oncologists and radiation oncologists with expertise in the treatment of uterine cancer. Methods: An extensive and updated analysis of current medical literature from peer-reviewed journals was conducted from 1/1/1996-1/28/2020 using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to search the PubMed, Embase and Web of Science databases to retrieve a comprehensive set of relevant articles. We developed strategies using subject and combinations of keywords search terms. We reviewed the bibliographies of full articles for a comprehensive survey, and relevant studies were included. The literature was reviewed for quality of study design, cohort size, selection bias, variability of evaluation of participants in regard to time from exposure, and methods of assessments. In addition, two significant studies published in 12/20 and 2/21 were selectively included during writing of the manuscript. A well-established consensus methodology (modified Delphi) was used to rate the appropriateness of treatment procedures by the expert panel. Results: The panel recommends strongly vaginal cuff brachytherapy (VBT) alone or systemic therapy + VBT as adjuvant treatment for a noninvasive surgically staged FIGO stage IA UCCC or USC. The panel recommends strongly that adjuvant chemotherapy and radiation therapy is usually appropriate for a typical case of FIGO stage IB UCS and UCCC; an exception is the option for pelvic EBRT alone for a surgically staged IB UCCC with minimal risk features. The panel recommends strongly that tumor volume-directed radiation treatment is usually appropriate in the adjuvant setting of patients with advanced stage USC or UCCC. IMRT is the recommended treatment technique when EBRT is recommended. For patients who undergo pelvic and para-aortic lymph node sampling and are pN0, the panel recommends strongly omitting the para-aortics from the external beam field, while there was some disagreement on whether to target para-aortic lymph nodes when the pelvic lymph nodes are known to be involved yet the para-aortic sampling was negative. The panel strongly recommends against the routine use of adjuvant WART outside of a clinical trial setting. Conclusions: Due to the rarity of uterine clear cell and serous carcinomas, there is a paucity of prospective trials focusing exclusively on management of these aggressive histologies and hence there is no standard consensus for treatment strategy in patients with uterine clear cell and serous carcinoma. Given the aggressive nature of these malignancies, and until further research determines the most appropriate adjuvant therapy, it may be reasonable to counsel patients about combined modality treatment with systemic chemotherapy and RT. Further prospective studies or multi-institutional retrospective studies are warranted to determine optimal sequencing of therapy and appropriate management of patients based on their unique risk factors.

Volume

44

Issue

10

First Page

S15

Last Page

S16

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