12. Fragile Patients/Geriatric Assessment. – Endometrial Cancer

Although the evidence base for older patients with endometrial cancer is limited, there are an increasing number of study results, some of them interventional, of older patients with oncological diseases. These have meanwhile found their way into national and international evidence-based oncological guidelines [906][907][863][912].

Identification of the fragile patient is achieved with the help of the comprehensive Geriatric Assessment (GA) or with an upstream validated screening tool. The GA is a multidimensional diagnostic process that attempts to capture relevant aspects of the elderly patient with validated tools that are relevant to the therapy of the elderly patient. The individual tests available including their test sizes can be found in the S1 Guideline “Geriatric Assessment Level 2” [912]. According to the SIOG (International Society of Geriatric Oncology) screening tools do not replace a comprehensive GA but are suitable in everyday life to identify elderly patients who benefit from a GA  [907]. Screening tools that have been well studied in oncology patients include the G8, the VES-13 or the Groningen Frailty Indicator (GFI) [907].

Bourgin et al. published a review on the surgical approach to the elderly patient with endometrial cancer in 2016 [909]. The authors' conclusions were based on 16 surgical studies of older patients. The lower limit of age for patient inclusion varied from 63 to 80 years. The studies included between 115 and 1682 female patients. 2 studies were prospectively randomized, 2 retrospective studies were based on prospective databases, 7 studies were prospective cohort studies and 5 were retrospective cohort studies. 8 studies compared different surgical approaches, whereas the remaining 8 studies compared different age subgroups. Laparoscopic access was used in 8 studies, robotic access in 4 studies, open access in 2 studies, and vaginal access in 2 studies. The authors reached the following conclusions. The older patient with endometrial carcinoma suffers from a biologically more aggressive malignancy and is often undertreated. The more aggressive tumor type requires optimal surgical management based on the oncologic findings, which may include lymphadenectomy. The surgical approach should be laparoscopic and include a GA to determine fragility [909].

In 2018, Ahmed et al. published preliminary results of a prospective, multicenter cohort study of a total of 189 patients older than 70 years with a pre-operative suspected diagnosis of advanced endometrial cancer or ovarian cancer [911]. Patients received a short-form GA, which quantifies the extent of fragility with a score of 0-10. The primary endpoint of the study was an association between abnormal GA and postoperative complication rate. In the overall cohort of all patients, shortened GA was not associated with this (p=0.134). Due to a relatively large proportion of patients with benign disease (21.4%), two unplanned subgroup analyses were performed. In the cohort gynecologic malignancies of all stages, there was no statistically significant association between GA and complication rate (HR: 1.195; 95%-CI: 0.963 – 1.488; p= 0.089 per increasing point in GA). In the cohort of advanced stage III/IV gynecologic malignancies, a statistically significant association was identified (HR: 1.290; 95%-CI: 1.006 – 1.674; p=0.0456 per increasing point in GA) [911].

In 2017, Driver et al. published the results of a retrospective cohort study of 88 patients with endometrial cancer older than 60 years [910]. In this cohort, the presence of at least one marker of fragility (hypoalbuminemia, anemia, BMI ≤ 20kg/m2, unintentional weight loss, ECOG 2 and greater, osteopenia or osteoporosis and Charlson Comorbidity Score) was associated with a worse prognosis (recurrence, disease-specific survival, overall survival) [910].

In 2018, the American Society of Clinical Oncology (ASCO) published a guideline on the care of older patients who should receive chemotherapy [906]. In summary, patients 65 years of age and older should be referred to a GA to identify non-oncologic problems. At a minimum, a GA should include assessment of function, secondary diseases, falls, depression, cognition and nutrition. Either the Cancer and Aging Research Group (CARG) tool or the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) should be used to assess the risk of experiencing adverse effects from the intended system therapy. The G8 Screening Test or Vulnerable Elders Survey-13 (VES-13) can be used to estimate the impact of frailty on mortality (2). Furthermore, a tool will be used to estimate life expectancy without considering oncologic prognosis. In summary, these measures bundled with the oncological situation should lead to an individualized indication of system therapy and furthermore non-oncological problems should be solved in an interdisciplinary way [906].

In 2020, Nadaraja et al. published a monocenter randomized study with 114 patients older than 70 years with gynecological, urological malignancies and non-small cell lung cancer [908]. In the standard arm, patients received system therapy as prescribed by the investigator. In the experimental trial arm, participants first received the G8 screening test and underwent geriatric assessment (GA) if abnormalities were detected, and then received system therapy. There was no difference with regard to the primary endpoint, protocol-compliant performance of indicated system therapy. Patients in the intervention arm showed a clinically but not statically significant lower rate of grade 3 and grade 4 adverse events (p=0.055). Performing GA led to intervention such as changing concomitant medication, initiating rehabilitation and nutritional counseling in 75% of patients. Four patients (8%) received system therapy at the dose-reduced dosage due to GA [908].