A. Stewart

Real World Outcomes in Patients With Recurrent, Advanced, or Metastatic Endometrial Cancer Treated With Lenvatinib Plus Pembrolizumab

Patients with endometrial cancer who progress following first line therapy have improved survival outcomes with pembrolizumab and lenvatinib (pem/len) compared with standard of care chemotherapy, as demonstrated in KEYNOTE-775. This was in a group of trial patients with good performance status and excluded those with carcinosarcoma histology. In KEYNOTE-775 pem/len was associated with significant toxicity, leading to dose reductions, treatment cessation, and patient morbidity. We set out to assess the tolerability, toxicity and outcomes following pem/len for patients with recurrent, advanced or metastatic endometrial cancer in a real-world setting. UK centres treating patients with pem/len for advanced endometrial cancer within the compassionate access programme were approached. Retrospective data were analysed for those treated between May 2022 and June 2023. Data on patient demographics, treatment, toxicity and outcomes were extracted from medical records. Toxicity and tolerability were compared in those over and under the age of 70. Seven centres returned data for 70 patients. Median age of patients was 68.5 years (range 45-85) with a performance status of 0-1 in 77.1% and of 2 in 22.9%. Histological subtypes included serous (34.3%), endometrioid (32.9%), carcinosarcoma (14.3%), clear cell (7.1%), mixed (2.9%) and other (8.6%). Grade ≥3 toxicity was reported in 55.7% with any-grade toxicity observed in 85.7%. In those aged ≥70 years (n = 30) the rate of grade ≥3 toxicity was 60.0%. Rates of dose reduction of lenvatinib were 64.3%, and toxicity-related treatment interruption was 45.7%. The 6-month progression-free and overall survival rates were 54.0% (95%CI: 39.0-66.8) and 70.1% (95%CI:56.5-80.1) respectively. This real-world, observational study of pem/len showed comparable tolerability, toxicity, and outcomes to previously reported clinical trial data. Our cohort included patients with a poorer PS and a broader range of histological subtypes including carcinosarcoma.

National Survey of Current Follow-up Protocols for Patients Treated for Endometrial Cancer in the UK

The aim of this study was to establish a baseline of national practice for follow-up after treatment for endometrial cancer in the UK. An online cross-sectional survey was developed and distributed through the Royal College of Radiologists via an email link to the audit leads of radiotherapy centres in the UK. The survey was conducted from November 2021 to 5 January 2022. The main themes assessed in the survey were the form, frequency and duration of follow-up practices. There were a total of 43/61 (70%) complete responses. 93% of centres had a standard follow-up protocol and 7% who did not have a follow-up protocol discharged patients after the post-operative review. Five centres (13%) used molecular profiling to inform follow-up practices. Patient-initiated follow-up was mainly used in the cohort of patients who had surgery alone with no adjuvant treatment (68%, (19/28)). In the cohort who had face-to-face follow-up, the majority had pelvic examinations as part of their review and total follow-up for five years. 93% of respondents are interested in a national follow-up protocol. Our data shows that there is national variation in practise with regard to follow-up of women treated for endometrial cancer. Many of the follow-up practises are based on conventional follow-up regimens and these may fail to address the more holistic needs of cancer survivors. Recent publication of updated guidance from the British Gynaecological Cancer Society may help standardise practise and provide a more relevant approach to follow-up for women treated for endometrial cancer.

Endometrial Cancer: Analysing Patterns of Recurrence and Real-Life Outcome Data Using the 2020 ESGO-ESTRO-ESP Risk Stratification System

To evaluate patterns of recurrence and explore the prognostic differences between the 2018 FIGO staging system and the 2020 ESGO-ESTRO-ESP risk stratification system of endometrial cancer with an emphasis on early-stage disease. The incidence of endometrial cancer has risen by around 60% since the 90's. It is projected that by 2035 endometrial cancer will be the sixth most common cause of cancer-related death amongst females. This was a retrospective cohort study which included patients treated between 2010 and 2017. Primary endpoints were overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meyer survival analysis was used to assess OS and RFS across different risk groups. Cox proportional hazards regression was used to evaluate prognostic risk factors implicated in recurrence. Different recurrence patterns across the subgroups were analysed with Pearson's chi-square test. The study included 692 patients with a recurrence rate of 14.9%. The median time to recurrence was 17.1 months (IQR:8.8-28.4). The mean OS varied between 97.2 months in the low-risk group to 63.1 months in the high-risk group (p < 0.001). Mean RFS was 96.1 in the low-risk group and 58.9 in the high-risk group (p < 0.001). RFS was predicted by the following factors; high risk group (OR=3.87; p = 0.041), LVSI (OR=2.54, p = 0.005), carcinosarcoma (OR=2.20, p = 0.021) and serous subtype (OR=1.91, p = 0.01). Logistic regression was used to evaluate risk factors for loco-regional and distant recurrence. Patients in the low-risk group were less likely to have distant recurrence (OR=0.08, p = 0.004). Similarly, negative LVSI and Grade 1 cancers were associated with decreased risk of distant recurrence (OR=0.34, p = 0.006 and OR=0.33, p = 0.007, respectively). There were no significant risk factors for loco-regional recurrence. The 2020 ESGO-ESTRO-ESP risk stratification provides accurate estimates of recurrence risk and survival. Those treated in line with current guidance have significantly better outcomes.

The Royal College of Radiologists National Vulvar Cancer Audit

This audit examined UK vulvar cancer practice from March 2018 to January 2019 and compared it to standards from national and international recommendations. Follow-up data collection in 2020 examined patient outcomes and toxicity. Audit standards were based on Royal College of Radiologists (RCR) guidance and published literature. A web-based questionnaire was sent to the audit leads at all cancer centres in the UK. Prospective data collection included patient demographics, tumour characteristics, radiotherapy indications, dosimetry, timelines, and follow-up data. The audit targets were 95% compliance with the RCR dose/fractionation schemes in definitive and adjuvant patients, 40% use of intensity modulated radiotherapy (IMRT), 100% of radical patients treated as category 1, and 95% use of gap compensation for category 1 patients. 34/54 UK radiotherapy centres (63%) completed data entry for 152 patients. 23 out of 34 (68%) centres submitted follow-up data for 94 patients. One indicator exceeded the audit target: 98% of radical patients received IMRT. The indicators of RCR dose/fractionation compliance for adjuvant/definitive radiotherapy were achieved by 80%/43% for the primary, 80%/86% for elective lymph nodes, and 21%/21% for pathological lymph nodes. The use of concomitant chemotherapy with radical radiotherapy in suitable patients was achieved by 71%. Other indicators demonstrated that 78% were treated as category 1 and 27% used gap compensation. Acute toxicity was mostly related to skin, gastrointestinal, and genitourinary sites. Grade 3 and Grade 4 toxicities were seen at acceptable rates within the radical and adjuvant groups. Late toxicity was mostly grade 0. This audit provides a comprehensive picture of UK practice. IMRT is widely used in the UK, and treatment-related toxicity is moderate. The dose fractionation was very heterogeneous. The designation of vulvar cancer as category 1 was not regularly followed for radical/adjuvant patients, and there was minimal gap compensation during treatment.