Discussion
Endometrioid carcinomas are the second most common epithelial ovarian cancer. in contrast to the more common serous carcinomas, endometrioid carcinomas present earlier, at a younger age and have better long-term outcomes [5-7]. Several studies have suggested that endometrioid carcinomas have higher rates of both 5-year overall survival (80.6%) and progression-free survival (68%) compared to other ovarian cancer subtype. Additionally, they have a lower recurrence rate, especially at lower grades [1, 6]. Relapse patterns appear to further differentiate endometrioid carcinomas from serous carcinomas, with endometrioid carcinomas having a much higher proportion, at nearly 50%, recurring solely in the pelvis, while serous carcinoma relapse tends to be much more diffuse [6]. Here we discuss an interesting, rare presentation of a pelvic recurrence of low grade endometrioid carcinoma.
Endometriosis is a risk factor for the development of ovarian cancer, mostly specific subtypes including endometrioid and clear cell carcinomas. Up to 42% of endometrioid adenocarcinomas are associated with endometriosis. Patients with endometrioid ovarian adenocarcinoma arising from endometriosis tend to present at a younger age, lower stage, and lower grade than those without associated endometriosis (8). The transformation from benign to atypical endometriosis to endometriosis-associated ovarian cancer involves a combination of: oxidative stress, inflammation, molecular genomic alterations, hyperestrogenism (32). Some of the molecular abnormalities encountered in endometriosis-associated ovarian cancer include: the activation of oncogenic KRAS and PI3 K pathways and the inactivation of tumour suppressor genes PTEN and ARID1A (3).ome of the key mutations involved in the malignant transformation and progression, including AT-Rich Interaction Domain 1A (ARID1A) mutations, may have potential to be effective chemotherapy targets [8, 9].
In a patient with endogenic hyperoestrogenism related to obesity, a new pelvic mass diagnosed three years from the initial surgery may represent as, rather than a recurrence, a de novo lesion progressing from benign endometriosis to atypical endometriosis and then endometrioid ovarian adenocarcinoma.
Other important pathologies have also been noted to be associated with endometrioid carcinoma that should be understood and considered, including endometrial cancer. The rare presentation of primary tumours in both the endometrium and ovary in synchronous endometrial and ovarian carcinoma, is recognised to be a separate entity to either pathology with different prognoses and treatment implications [10-12]. These tumours were previously thought to be synchronous independent tumours, however molecular analysis has established that they have a common clonal origin [13]. The 2023 FIGO staging of endometrial cancer, which incorporates molecular findings, classifies these tumours as stage IA3 when certain criteria are met: unilateral disease, no capsular spread, less than 50% myometrial invasion, absence of substantial/extensive lympho-vascular space invasion (LVSI). These tumours have a better prognosis and do not require adjuvant chemotherapy [14].
The Carboplatin/Paclitaxel regimen as adjuvant treatment has not been proven to result in survival benefit for low-grade endometrioid ovarian cancer [15]. Current National Comprehensive Cancer Network (NCCN) guidelines [16] for grade 1 endometroid ovarian carcinoma are Carboplatin/Paclitaxel or hormonal treatment, such as aromatase inhibitors, leuprolide acetate, tamoxifen. Novel, biomarker-driven therapies, are currently being investigated for this histological subtype: Bouquet (NCT04931342 GOG-3051) is a multicentre clinical trial which is currently recruiting patients with persistent or recurrent low-grade endometrioid ovarian cancer and other rare ovarian tumours that are not amenable to curative surgery.
Until new treatments options are identified, surgery with maximal cytoreductive effort remains the mainstay treatment for this histological subtype of ovarian cancer [17-25]. Achieving resection of all macroscopic disease (R0) is the single independent factor for survival. In their meta-analysis including 6885 patients with advanced ovarian cancer, Bristow et al (2023) have shown there is a 5.5% increase in median survival time with each 10% increase in maximal cytoreduction [2].
In the case we presented, a radical total exenteration was required to achieve RO. A right nephrectomy was performed to remove the right kidney, which was non-functioning. The Bricker technique for urinary diversion involved spatulation of the remaining ureter and anastomosis to a segment of descending colon used as a conduit. Total cystectomy with urinary diversion is a standard procedure in the context of anterior or total exenterations. The use of a segment of descending colon should be considered in patients undergoing end colostomy, to avoid the need for primary small bowel anastomosis.
In conclusion, ovarian endometrioid carcinoma of the ovary is an uncommon histological subtype of ovarian carcinoma for which the mainstay of treatment is surgery. Cytoreductive effort should be maximized to achieve R0, especially in young patients. The complexity of the operation should not be a deterrent factor if surgery is carried out in a multidisciplinary environment with robust clinical governance.