Maintained survival outcome after reducing lymphadenectomy rates and optimizing adjuvant treatment in endometrial cancer

Forsse, David; Berg, Hege Fredriksen; Bozickovic, Olivera; Engerud, Hilde; Halle, Mari K.; Høivik, Erling A.; Woie, Kathrine; Werner, Henrica M.J.; Haldorsen, Ingfrid S.; Trovik, Jone; Krakstad, Camilla

doi:10.1016/j.ygyno.2020.12.002

Cited by 12 publications

(20 citation statements)

References 21 publications

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“…Recently, we have reported that despite a substantial increase over time of adjuvant chemotherapy to early-stage or high-risk patients in a Norwegian tertiary hospital, survival and recurrence rates were unchanged for this group. 30 Further reduction of patients undergoing adjuvant chemotherapy may be achieved through better stratification, ideally by implementing new classifiers, such as imaging biomarkers or molecular subgroups (eg, TCGA or ProMisE) in treatment planning for these patients, 31,32 and developing and making available novel therapeutic agents to replace traditional chemotherapy where possible.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal effects of adjuvant chemotherapy and lymph node staging on patient-reported outcomes in endometrial cancer survivors: a prospective cohort study

Forsse

Barbero

Werner

et al. 2022

American Journal of Obstetrics and Gynecology

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BACKGROUND: Most patients with endometrial cancer with localized disease are effectively treated and survive for a long time. The primary treatment is hysterectomy, to which surgical staging procedures may be added to assess the need for adjuvant therapy. Longitudinal data on patient-reported outcomes comparing different levels of primary treatment are lacking, especially when adjuvant radiotherapy is omitted. OBJECTIVE: We assessed the impact of lymphadenectomy and adjuvant chemotherapy on patient-reported symptoms, function, and quality of life. We hypothesized that these treatment modalities would substantially affect patient-reported outcomes at follow-up. STUDY DESIGN: We prospectively included patients with endometrial cancer enrolled in the ongoing MoMaTEC2 study (ClinicalTrials.gov Identifier: NCT02543710). Patients were asked to complete the patientreported outcome questionnaires European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire EN24 preoperatively and at 1 and 2 years of follow-up. Functional domains and symptoms were analyzed for the whole cohort and by treatment received. To assess the effect of the individual treatment modifications, we used mixed regression models. RESULTS: Baseline data were available for 448 patients. Of these patients, 339 and 219 had reached 1-year follow-up and 2-year followup, respectively. Treatment included hysterectomy (plus bilateral salpingo-oophorectomy) alone (n¼177), hysterectomy and lymph node staging without adjuvant therapy (n¼133), or adjuvant chemotherapy irrespective of staging procedure (n¼138). Overall, patients reported improved global health status and quality of life (þ9 units; P<.001), increased emotional and social functioning, and increased sexual interest and activity (P<.001 for all) from baseline to year 1, and these outcomes remained stable at year 2. Means of functional scales and quality of life were similar to age-and sex-weighted reference cohorts. Mean tingling and numbness and lymphedema increased after treatment. The group who received adjuvant chemotherapy had a larger mean reduction in physical functioning (À6 vs þ2; P¼.002) at year 1, more neuropathy (þ30 vs þ5; P<.001; year 1) at years 1 and 2, and more lymphedema at year 1 (þ11 vs þ2; P¼.007) than the group treated with hysterectomy and salpingo-oophorectomy only. In patients not receiving adjuvant chemotherapy, patient-reported outcomes were similar regardless of lymph node staging procedures. Adjuvant chemotherapy independently increased fatigue, lymphedema, and neuropathy in mixed regression models. CONCLUSION: Patients with endometrial cancer receiving adjuvant chemotherapy reported significantly reduced functioning and more symptoms up to 2 years after treatment. For patients treated by surgery alone, surgical staging did not seem to affect the quality of life or symptoms to a measurable degree at follow-up. Therefore, subjecting patients to lymph nod...

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Section: Discussionmentioning

confidence: 99%

Longitudinal effects of adjuvant chemotherapy and lymph node staging on patient-reported outcomes in endometrial cancer survivors: a prospective cohort study

Forsse

Barbero

Werner

et al. 2022

American Journal of Obstetrics and Gynecology

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“…Pelvic lymphadenectomy with/without para-aortic lymphadenectomy was routinely performed in all patients with preoperatively defined high-risk disease (NEEC or EEC G3 histology with deep (≥ 50%) myometrial invasion assessed by MRI (MI MRI )) according to the European Society of Medical Oncology (ESMO) guidelines [8]. For patients with preoperative low-risk ESMO (EEC G1-G2 with MI MRI < 50%) and intermediate-risk ESMO (EEC G1-G2 with MI MRI ≥ 50%, or EEC G3 with MI MRI < 50%), pelvic lymphadenectomy was selectively omitted if negative imaging findings for LNM and if preserved tumor hormone receptor status (see [19] for further details). Surgical specimens were assessed by pathologists, reporting presence of deep myometrial invasion (MI ≥ 50%), cervical stroma invasion (CI), LNM, and tumor histologic subtype and grade (EEC G1-G3 or NEEC) [20].…”

Section: Patient Cohortmentioning

confidence: 99%

Preoperative pelvic MRI and 2-[18F]FDG PET/CT for lymph node staging and prognostication in endometrial cancer—time to revisit current imaging guidelines?

et al. 2022

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Objective This study presents the diagnostic performance of four different preoperative imaging workups (IWs) for prediction of lymph node metastases (LNMs) in endometrial cancer (EC): pelvic MRI alone (IW1), MRI and [18F]FDG-PET/CT in all patients (IW2), MRI with selective [18F]FDG-PET/CT if high-risk preoperative histology (IW3), and MRI with selective [18F]FDG-PET/CT if MRI indicates FIGO stage ≥ 1B (IW4). Methods In 361 EC patients, preoperative staging parameters from both pelvic MRI and [18F]FDG-PET/CT were recorded. Area under receiver operating characteristic curves (ROC AUC) compared the diagnostic performance for the different imaging parameters and workups for predicting surgicopathological FIGO stage. Survival data were assessed using Kaplan-Meier estimator with log-rank test. Results MRI and [18F]FDG-PET/CT staging parameters yielded similar AUCs for predicting corresponding FIGO staging parameters in low-risk versus high-risk histology groups (p ≥ 0.16). The sensitivities, specificities, and AUCs for LNM prediction were as follows: IW1—33% [9/27], 95% [185/193], and 0.64; IW2—56% [15/27], 90% [174/193], and 0.73 (p = 0.04 vs. IW1); IW3—44% [12/27], 94% [181/193], and 0.69 (p = 0.13 vs. IW1); and IW4—52% [14/27], 91% [176/193], and 0.72 (p = 0.06 vs. IW1). IW3 and IW4 selected 34% [121/361] and 54% [194/361] to [18F]FDG-PET/CT, respectively. Employing IW4 identified three distinct patient risk groups that exhibited increasing FIGO stage (p < 0.001) and stepwise reductions in survival (p ≤ 0.002). Conclusion Selective [18F]FDG-PET/CT in patients with high-risk MRI findings yields better detection of LNM than MRI alone, and similar diagnostic performance to that of MRI and [18F]FDG-PET/CT in all. Key Points • Imaging by MRI and [18F]FDG PET/CT yields similar diagnostic performance in low- and high-risk histology groups for predicting central FIGO staging parameters. • Utilizing a stepwise imaging workup with MRI in all patients and [18F]FDG-PET/CT in selected patients based on MRI findings identifies preoperative risk groups exhibiting significantly different survival. • The proposed imaging workup selecting ~54% of the patients to [18F]FDG-PET/CT yield better detection of LNMs than MRI alone, and similar LNM detection to that of MRI and [18F]FDG-PET/CT in all.

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“…In fact, the LNM status is closely related to poor prognosis and is an important factor in EC staging and determining the need for adjuvant therapy [8][9][10] . Two randomized trials have shown no therapeutic bene t of systemic lymphadenectomy in patients with low risk for recurrence 11,12 . It has also been reported that preoperative strati cation by imaging and histological assessments permits a reduction in lymphadenectomy to approximately 50% 11 .…”

Section: Introductionmentioning

confidence: 99%

“…Two randomized trials have shown no therapeutic bene t of systemic lymphadenectomy in patients with low risk for recurrence 11,12 . It has also been reported that preoperative strati cation by imaging and histological assessments permits a reduction in lymphadenectomy to approximately 50% 11 . However, lymphadenectomy should be performed in patients with a non-endometrioid histology or deeply in ltrating high-grade disease, both of which are known to have more aggressive behavior, even though lymphadenectomy has a 10-20% risk of lower-extremity lymphedema and a 10-25% risk of lymphocele development 12,13 .…”

Section: Introductionmentioning

confidence: 99%

Predictive model for the preoperative assessment and prognostic modeling of lymph node metastasis in endometrial cancer

Asami

Hiranuma

Takayanagi

et al. 2022

Preprint

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Lymph node metastasis (LNM) is a well-established prognostic factor in endometrial cancer (EC). We aimed to construct a model that predicts LNM and prognosis using preoperative factors such as myometrial invasion (MI), enlarged lymph nodes (LNs), histological grade determined by endometrial biopsy, and serum cancer antigen 125 (CA125) level using two independent cohorts consisting of 254 EC patients. The area under the receiver operating characteristic curve (AUC) of the constructed model was 0.80 regardless of the machine learning techniques. Enlarged LNs and higher serum CA125 levels were more significant in patients with low-grade EC (LGEC) and LNM than patients without LNM, whereas deep MI and higher CA125 levels were more significant in patients with high-grade EC (HGEC) and LNM than patients without LNM. The predictive performance of LNM in the HGEC group was higher than that in the LGEC group (AUC = 0.84 and 0.75, respectively). Patients in the group without postoperative pathological LNM and positive LNM prediction had significantly worse relapse-free and overall survival than patients with negative LNM prediction (log-rank test, P < 0.01). This study showed that preoperative clinicopathological factors can predict LNM with high precision and detect patients with poor prognosis. Furthermore, clinicopathological factors associated with LNM were different between HGEC and LGEC patients.

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Maintained survival outcome after reducing lymphadenectomy rates and optimizing adjuvant treatment in endometrial cancer

Cited by 12 publications

References 21 publications

Longitudinal effects of adjuvant chemotherapy and lymph node staging on patient-reported outcomes in endometrial cancer survivors: a prospective cohort study

Longitudinal effects of adjuvant chemotherapy and lymph node staging on patient-reported outcomes in endometrial cancer survivors: a prospective cohort study

Preoperative pelvic MRI and 2-[18F]FDG PET/CT for lymph node staging and prognostication in endometrial cancer—time to revisit current imaging guidelines?

Predictive model for the preoperative assessment and prognostic modeling of lymph node metastasis in endometrial cancer

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