Variation in practice in endometrial cancer and potential for improved care and equity through molecular classification

Jamieson, Amy; Huvila, Jutta; Thompson, Emily F.; Leung, Samuel; Chiu, Derek S.; Lum, Amy; McConechy, Melissa K.; Grondin, Katherine; Aguirre-Hernández, Rosalía; Salvador, Shannon; Kean, Sarah; Samouëlian, Vanessa; Gougeon, F.; Azordegan, Nazila; Lytwyn, Alice; Parra‐Herran, Carlos; Offman, Saul; Gotlieb, Walter H.; Irving, Julie; Kinloch, Mary; Helpman, Limor; Scott, Stephanie; Vicus, Danielle; Plante, Marie; Huntsman, David G.; Gilks, C. Blake; Talhouk, Aline; McAlpine, Jessica N.

doi:10.1016/j.ygyno.2022.02.001

Cited by 24 publications

(23 citation statements)

References 45 publications

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“…In addition, information from an MS7-like test in un-staged cases referred to a specialist would contribute to a more personalized approach when deciding between surveillance, interval surgical staging, and empiric radiotherapy. Unfortunately, variations in practice patterns among gynecologists and subspecialty gynecologic oncologists highlight the need for biomarkers to incrementally enhance conventional pathologic features for risk assessment [ 47 , 48 ]. We were reassured by the improved sensitivity and the high NPV of the MS7 risk score, especially when combined with MI, compared with that indicated by G3 disease, which is currently used by many gynecologists to make clinical decisions regarding referral.…”

Section: Discussionmentioning

confidence: 99%

Improving Risk Assessment for Metastatic Disease in Endometrioid Endometrial Cancer Patients Using Molecular and Clinical Features: An NRG Oncology/Gynecologic Oncology Group Study

Casablanca

Wang

Lankes

et al. 2022

Cancers

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Objectives: A risk assessment model for metastasis in endometrioid endometrial cancer (EEC) was developed using molecular and clinical features, and prognostic association was examined. Methods: Patients had stage I, IIIC, or IV EEC with tumor-derived RNA-sequencing or microarray-based data. Metastasis-associated transcripts and platform-centric diagnostic algorithms were selected and evaluated using regression modeling and receiver operating characteristic curves. Results: Seven metastasis-associated transcripts were selected from analysis in the training cohorts using 10-fold cross validation and incorporated into an MS7 classifier using platform-specific coefficients. The predictive accuracy of the MS7 classifier in Training-1 was superior to that of other clinical and molecular features, with an area under the curve (95% confidence interval) of 0.89 (0.80–0.98) for MS7 compared with 0.69 (0.59–0.80) and 0.71 (0.58–0.83) for the top evaluated clinical and molecular features, respectively. The performance of MS7 was independently validated in 245 patients using RNA sequencing and in 81 patients using microarray-based data. MS7 + MI (myometrial invasion) was preferrable to individual features and exhibited 100% sensitivity and negative predictive value. The MS7 classifier was associated with lower progression-free and overall survival (p ≤ 0.003). Conclusion: A risk assessment classifier for metastasis and prognosis in EEC patients with primary tumor derived MS7 + MI is available for further development and optimization as a companion clinical support tool.

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Section: Discussionmentioning

confidence: 99%

Improving Risk Assessment for Metastatic Disease in Endometrioid Endometrial Cancer Patients Using Molecular and Clinical Features: An NRG Oncology/Gynecologic Oncology Group Study

Casablanca

Wang

Lankes

et al. 2022

Cancers

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“…Molecular features have now been integrated into the most recent ESGO/ESTRO/ESP risk stratification and subsequent adjuvant treatment recommendations according to risk group assignment (https://ijgc.bmj.com/content/31/1/12). 24 In retrospective series looking at this 2020 system of classification, approximately 10% of cases were reassigned to higher or lower risk groups, respectively 35,36 . Jamieson et al 36 reported that ~33% of patients with POLE mutations were likely overtreated by receiving adjuvant radiation with or without chemotherapy with an unclear clinical benefit, and 42% of patients who were retrospectively recognized to have p53abn ECs had less therapy than current guidelines would have recommended, which may have contributed to adverse outcomes.…”

Section: Figurementioning

confidence: 99%

“…Because of the abundance of data on the proven value of molecular classification in EC, the focus now needs to be on strategies for implementation of/access to molecular classification for all patients with EC, ideally at the time of their initial diagnosis. Access to testing and to the downstream surgical and treatment opportunities that come with the knowledge of the molecular subtype may begin to reduce the tremendous disparities in EC cancer care that we currently observe 36,44,45 . A shift in mentality is needed to support the upfront investment of a few hundred dollars for molecular subtyping (with valuable information for hereditary cancer implications, disease prognosis, and directing treatment) rather than the high investment of complex molecular profiling at EC recurrence, which may direct a palliative treatment benefit of 3–6 months.…”

Section: Figurementioning

confidence: 99%

“…Access to testing and to the downstream surgical and treatment opportunities that come with the knowledge of the molecular subtype may begin to reduce the tremendous disparities in EC cancer care that we currently observe. 36,44,45 A shift in mentality is needed to support the upfront investment of a few hundred dollars for molecular subtyping (with valuable information for hereditary cancer implications, disease prognosis, and directing treatment) rather than the high investment of complex molecular profiling at EC recurrence, which may direct a palliative treatment benefit of 3-6 months. Some of the upfront costs could be tempered by the discontinuation of what in current practice is a tremendous volume of immunohistochemistry testing of unclear clinical relevance unrelated to molecular subtypes.…”

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confidence: 99%

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Molecular classification in endometrial cancer: Opportunities for precision oncology in a changing landscape

Jamieson

Barroilhet

McAlpine

2022

Cancer

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Lay summary Endometrial carcinoma (EC) classification and risk stratification have undergone a global transformation in the last decade, shifting from a reliance on poorly reproducible histomorphological parameters such as grade and histotype, toward a molecular classification that is consistent and biologically informative. Molecular classification enables reliable categorization of ECs, provides prognostic information, and is now beginning to drive clinical management, including surgery and adjuvant therapy. Within this framework, we now have the ability to further refine both the prognostic and predictive value of molecular classification. As we move toward the routine implementation of this classification system as a stratification tool for research, clinical trials, and patient care, it is imperative that access to these tests be equitable. Furthermore, continued education will be critical for patients and providers to understand the value that this molecular information provides.

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“…Similarly to chemotherapy, surgical therapy should be individualized based on the molecular profiles of the tumor [ 169 , 170 ]. Patients with POLE exonuclease domain mutation (EDM) may not need to undergo lymphadenectomy, as none of the POLE EDM tumors had extrauterine disease [ 171 ].…”

Section: Preoperative Prediction Of Lymph Node Metastasis and Surgica...mentioning

confidence: 99%

Therapeutic Benefit of Systematic Lymphadenectomy in Node-Negative Uterine-Confined Endometrioid Endometrial Carcinoma: Omission of Adjuvant Therapy

Otsuka

2022

Cancers

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Endometrial cancer is the most common gynecological tract malignancy in developed countries, and its incidence has been increasing globally with rising obesity rates and longer life expectancy. In endometrial cancer, extrauterine disease, in particular lymph node metastasis, is an important prognostic factor. Nevertheless, pelvic lymphadenectomy is not considered to have a therapeutic benefit, as it did not improve survival in randomized studies. However, lymphadenectomy may have a therapeutic benefit if adjuvant therapy can be omitted without decreasing oncological outcomes, as the long-term quality of life is maintained by avoiding morbidities associated with adjuvant therapy. In intermediate- and high-risk endometrioid endometrial carcinomas, adjuvant therapy may be safely omitted without decreasing long-term survival by open surgery including systematic pelvic and para-aortic lymphadenectomy when patients are node-negative. Systematic lymphadenectomy may remove undetectable low-volume lymph node metastasis in both pelvic and para-aortic regions, and open surgery may reduce vaginal recurrence even without vaginal brachytherapy. However, lymphadenectomy may not improve survival in elderly patients and patients with p53-mutant tumors. In this review, I discuss the characteristics of lymph node metastasis, the methods of lymph node assessment, and the therapeutic benefits of systematic lymphadenectomy in patients with intermediate- and high-risk endometrioid endometrial carcinoma.

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Variation in practice in endometrial cancer and potential for improved care and equity through molecular classification

Cited by 24 publications

References 45 publications

Improving Risk Assessment for Metastatic Disease in Endometrioid Endometrial Cancer Patients Using Molecular and Clinical Features: An NRG Oncology/Gynecologic Oncology Group Study

Improving Risk Assessment for Metastatic Disease in Endometrioid Endometrial Cancer Patients Using Molecular and Clinical Features: An NRG Oncology/Gynecologic Oncology Group Study

Molecular classification in endometrial cancer: Opportunities for precision oncology in a changing landscape

Therapeutic Benefit of Systematic Lymphadenectomy in Node-Negative Uterine-Confined Endometrioid Endometrial Carcinoma: Omission of Adjuvant Therapy

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