Gitte Ørtoft

Ultrasound Scoring to Predict High‐Risk Endometrial Cancer

Objectives To evaluate a scoring system using transvaginal ultrasound (TVS) to predict high‐risk endometrial cancer. Methods Consecutive patients with endometrial cancer/atypical hyperplasia (n = 266) were preoperatively examined by residents using TVS. Clinical parameters, endometrial morphology and Doppler scores were recorded using a gray scale and Doppler TVS and related to final histopathology at hysterectomy. Multivariate logistic regression was used to correlate imaging and clinical parameters to the presence of high‐risk endometrial cancer (defined as FIGO stage Ib‐IV or high‐grade tumors [grade 3/non‐endometroid]) to develop the High‐Risk Endometrial Cancer (HIREC) score. Results High‐risk endometrial cancer (n = 128) and lympho‐vascular space invasion (LVSI) (n = 43) were predicted by increased endometrial thickness (ET), age, and Doppler score. The HIREC scoring system, based on age, Doppler score, and ET performed well with an AUC of 78.5% (CI 95%: 73–84) to predict high‐risk cancer. By using a 2‐step strategy of (1) Preoperative identification of high‐grade tumors by biopsy, (2) Assessing the HIREC score, high‐risk endometrial cancer could be predicted at a HIREC score of ≥7 with sensitivity, specificity, and accuracy of 72.7, 88.4, and 80.8%. Low‐risk endometrial cancer was predicted at HIREC scores of <5 with sensitivity, specificity, and accuracy values of 91.4, 46.4 and 68.1%, respectively. Conclusions Low and high HIREC scores effectively predicted low‐ and high‐risk endometrial cancer. The score is a simple point system suitable for the first ultrasound assessment. It may be used in preoperative work‐up to select treatment and additional imaging, but it needs to be validated in further studies.

Vaginal and pelvic recurrences and salvage treatments in a cohort of Danish endometrial cancer patients not given adjuvant radiotherapy

In Denmark, adjuvant radiotherapy has gradually been omitted after surgery in endometrial cancer. This study analyses the impact of this strategy on patterns of recurrence and outcome after salvage radiotherapy. Moreover, the potential effect of adjuvant radiotherapy is estimated in the non-low-risk cohort. The cohort included 3723 consecutive Danish patients with endometrial cancer who had radical surgery without adjuvant treatment (2005-2012). The patients were divided into low-risk (stage 1A, endometrioid, grades 1, 2 and no lymph-vascular space invasion) and non-low-risk. Crude/actuarial recurrence rates evaluated the number of patients who might have benefited from additional adjuvant radiotherapy. Within 9 years' observation time using crude recurrence rates, 13.4% recurred.The rate of isolated vaginal recurrences was 2.9% in low-risk compared with 6.7% in non-low-risk patients. Isolated pelvic recurrences were 0.8% in low-risk compared with 2.1% in non-low-risk patients. In all, 15.8% of non-low-risk patients died from endometrial cancer, mainly due to primary or secondary non-local recurrences (a later non-local recurrence after a primary isolated local recurrence). Only 0.6% and 1.1% of all non-low-risk patients died from an isolated vaginal or pelvic recurrence, respectively. In all, 86% of all patients with an isolated vaginal recurrence were treated with curative intent. Of these, 72% were given radiotherapy with a local control rate of 91% (crude rate). However, even though only 5.8% died of an unsuccessfully treated isolated vaginal recurrence after curative intended radiotherapy, 23.1% died from a secondary non-local recurrence, while 22.3% died from other causes. The Danish strategy of omitting adjuvant radiotherapy is safe. Adjuvant external beam radiotherapy may have prevented isolated local recurrences in 8.7% of the Danish non-low-risk patients, but a majority of these patients were salvaged by curative radiotherapy with 91% and 70% crude local control rates for isolated vaginal and isolated pelvic recurrences, respectively.

Preoperative prediction of high-risk endometrial cancer by expert and non-expert transvaginal ultrasonography, magnetic resonance imaging, and endometrial histology

To identify women with high-risk endometrial cancers using expert and non-expert transvaginal ultrasonography (TVS) and MRI. Myometrial involvement was prospectively evaluated in patients with atypical hyperplasia or endometrial cancer on ultrasound by non-experts at first visit (non-expert-TVS: n = 266) and experts (expert-TVS: n = 188) at second visit. MRI (n = 175) was performed when high-risk cancer was suspected on non-expert-TVS. Preoperatively, high-risk cancer was defined as myometrial involvement ≥50 %, or preoperative unfavorable tumor histology (grade 3 endometrioid, non-endometrioid tumors, or tumor in cervical biopsies) obtained by endometrial sampling or hysteroscopic biopsies. Preoperative evaluations were compared with final histopathology obtained at surgery, high-risk cancer being defined as unfavorable tumor histology or patients with FIGO stage ≥1b. Preoperative unfavorable tumor histology was seen in 64 women and correctly identified 63 of 128 high-risk cancers. Preoperative diagnosis of unfavorable tumor histology or myometrial involvement ≥50 %, i.e. judged high-risk, had an area under the curve (AUC), sensitivity, and specificity of 79.5 %, 93.8 %, 65.2 % on non-expert-TVS; 85.5 %, 84.4 %, 86.5 % on expert-TVS, and 85.4 %, 89.6 %, 81.2 % on MRI. AUC values were not significantly different between MRI and expert-TVS, but lower on non-expert-TVS (p < 0.02). However, sensitivity was highest on non-expert-TVS, where a low cutpoint for myometrial involvement was used (included potentially deep and difficult evaluations) in contrast to an exact cutpoint of myometrial involvement ≥50 % used on expert-TVS and MRI. The highest AUC, 88.6 %, was seen when MRI was performed in patients with myometrial involvement ≥50 %, determined on non-expert TVS. Sensitivity was reduced to 85.9 %, while specificity increased to 91.3 %. Thus, MRI was needed for risk classification in only 104 (39 %) patients. Diagnostically, expert-TVS and MRI were comparable and superior to non-expert-TVS. However, non-expert-TVS classified all patients with unclear myometrial involvement ≥50 %, and thereby only misdiagnosed 6.2 % of high-risk cases. Non-expert-TVS combined with MRI when myometrial involvement was ≥50 % on non-expert-TVS was a simple and effective method comparable with expert imaging to identify low- and high-risk cancer and select patients for SLND. Addition of MRI to the diagnostic regimen was needed in only 39 % of our patients.

Predictive value of the new ESGO-ESTRO-ESP endometrial cancer risk classification on survival and recurrence in the Danish population

To compare the performance of the new ESGO-ESTRO-ESP (European Society of Gynecological Oncology-European Society for Radiotherapy & Oncology-European Society for Pathology) 2020 risk classification system with the previous 2016 risk classification in predicting survival and patterns of recurrence in the Danish endometrial cancer population. This Danish national cohort study included 4516 patients with endometrial cancer treated between 2005 and 2012. Five-year Kaplan-Meier adjusted and unadjusted survival estimates and actuarial recurrence rates were calculated for the previous and the new classification systems. In the 2020 risk classification system, 81.0% of patients were allocated to low, intermediate, or high-intermediate risk compared with 69.1% in the 2016 risk classification system, mainly due to reclassification of 44.5% of patients previously classified as high risk to either intermediate or especially high-intermediate risk. The survival of the 2020 high-risk group was significantly lower, and the recurrence rate, especially the non-local recurrence rate, was significantly higher than in the 2016 high risk group (2020/2016, overall survival 59%/66%; disease specific 69%/76%; recurrence 40.5%/32.3%, non-local 34.5%/25.8%). Survival and recurrence rates in the other risk groups and the decline in overall and disease-specific survival rates from the low risk to the higher risk groups were similar in patients classified according to the 2016 and 2020 systems. The new ESGO-ESTRO-ESP 2020 risk classification system allocated fewer patients to the high risk group than the previous risk classification system. The main differences were lower overall and disease-specific survival and a higher recurrence rate in the 2020 high risk group. The introduction of the new 2020 risk classification will potentially result in fewer patients at high risk and allocation to the new high risk group will predict lower survival, potentially allowing more specific selection for postoperative adjuvant therapy.

Survival and recurrence in stage II endometrial cancers in relation to uterine risk stratification after introduction of lymph node resection and omission of postoperative radiotherapy: a Danish Gynecological Cancer Group Study

To evaluate survival and recurrence in stage II endometrial cancer in relation to uterine risk stratification. Outcome for stage II was compared before and after the introduction of lymph node (LN) resection and omission of all postoperative radiotherapy. The cohort consisted of 4,380 endometrial carcinoma patients radically operated (no visual tumor, all distant metastasis removed) (2005-2012) including 461 stage II. Adjusted Cox regression was used to compare survival and actuarial recurrence rates. Uterine risk factors (low-, intermediate-, and high-) were the strongest predictors of survival and recurrence in stage II. Stage II low-risk having a prognosis comparable to low-risk stage I (grade 1-2, <50% myometrial invasion), whereas cervical invasion significantly increased the risk of recurrence and decreased cancer-specific survival in intermediate- and high-risk compared to the corresponding stage I risk groups. In 355 cases of 708 with cervical stromal invasion, LN-resection showed 27.9% with LN metastasis and upstaged 18.1% from stage II to IIIC resulting in longer survival and lower recurrence in LN-resected compared to non-LN resected stage II. Radical as compared to simple hysterectomy did not alter survival. Treatment with external beam radiotherapy decreased local recurrence without affecting survival. Uterine risk groups are the strongest predictors for survival and recurrence in stage II patients and should be considered when advising adjuvant therapy. LN-resected stage II had increased survival and decreased recurrence. Omitting radiotherapy increase vaginal recurrence without affecting survival.