Predictors of Outcome in Early-Stage Papillary Serous and Clear Cell Endometrial Cancer

ObjectivesOptimal adjuvant treatment for early-stage clear cell and serous endometrial cancer remains unclear. We report outcomes for women with surgically staged International Federation of Gynecology and Obstetrics (FIGO) stage I clear cell, serous, and mixed endometrial cancers following adjuvant vaginal cuff brachytherapy with or without chemotherapy.MethodsFrom April 1998 to January 2020, women with FIGO stage IA–IB clear cell, serous, and mixed endometrial cancer underwent surgery and adjuvant vaginal cuff brachytherapy. Seventy-six patients received chemotherapy. High-dose rate vaginal cuff brachytherapy was planned to a total dose of 21 gray in three fractions using a multichannel vaginal cylinder. The primary objective was to determine the effectiveness of adjuvant vaginal cuff brachytherapy and to identify surgicopathological risk factors that could portend towards worse oncological outcomes.ResultsA total of 182 patients were included in the analysis. Median follow-up was 5.3 years (2.3–12.2). Ten-year survival was 73.3%. Five-year cumulative incidence (CI) of vaginal, pelvic, and para-aortic relapse was 1.4%, 2.1%, and 0.9%, respectively. Five-year locoregional failure, any recurrence, peritoneal relapse, and other distant recurrence was 4.4%, 11.6%, 5.3%, and 6.7%, respectively. On univariate analysis, locoregional failure was worse for larger tumors (per 1 cm) (HR 1.9, 95% CI 1.2 to 3.0, p≤0.01). Any recurrence was worse for tumors of at least 3.5 cm (HR 3.8, 95% CI 1.3 to 11.7, p=0.02) and patients with positive/suspicious cytology (HR 4.4, 95% CI 1.5 to 12.4, p≤0.01). Ten-year survival for tumors of at least 3.5 cm was 56.9% versus 86.6% for those with smaller tumors (HR 2.9, 95% CI 1.4 to 5.8, p≤0.01). Ten-year survival for positive/suspicious cytology was 50.9% versus 77.4% (HR 2.2, 95% CI 0.9 to 5.4, p=0.09). Multivariate modeling demonstrated worse locoregional failure, any recurrence, and survival with larger tumors, as well as any recurrence with positive/suspicious cytology. Subgroup analysis demonstrated improved outcomes with the use of adjuvant chemotherapy in patients with large tumors or positive/suspicious cytology.ConclusionAdjuvant vaginal cuff brachytherapy alone without chemotherapy is an appropriate treatment for women with negative peritoneal cytology and small, early-stage clear cell, serous, and mixed endometrial cancer. Larger tumors or positive/suspicious cytology are at increased risk for relapse and worse survival, and should be considered for additional upfront adjuvant treatments, such as platinum-based chemotherapy.

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Complete Response of a Mutated BRCA2 Metastatic Clear Cell Endometrial Adenocarcinoma to the Poly (ADP ribose) Polymerase (PARP) Inhibitor Olaparib

Cancer Diagnosis & Prognosis ◽

10.21873/cdp.10080 ◽

2022 ◽

Vol 2 (1) ◽

pp. 84-86

Author(s):

DIMITRI ANZELLINI ◽

GIANLUCA ARCANGELI ◽

SERGIO DEL BIANCO

Keyword(s):

Endometrial Cancer ◽

Case Report ◽

Clear Cell ◽

Early Stage ◽

Parp Inhibitor ◽

Endometrial Adenocarcinoma ◽

Abnormal Uterine Bleeding ◽

Complete Response ◽

Developed Countries ◽

Primary Therapy

Background: Cancer of the endometrium is the most common gynecologic malignancy in developed countries and the second most common in developing countries. Endometrioid tumors tend to have a favorable prognosis and typically present at an early stage with abnormal uterine bleeding. Clear cell carcinoma as well as serous endometrial carcinoma are associated with a poorer prognosis. Patients with metastatic endometrial cancer are treated with systemic therapy either following surgery or as primary therapy. As far as second-line chemotherapy is concerned, there are no general agreements on the chemotherapy to be used. Furthermore, to the best of knowledge, there are no studies on the use of poly (ADP ribose) polymerase (PARP) inhibitors in endometrial cancer even in BRCA mutated tumors. Case Report: We here present the case report of an 81-year-old woman with a mutated BRCA2 metastatic clear cell endometrial adenocarcinoma that showed an excellent clinical and radiological response to the PARP inhibitor olaparib. Conclusion: Olaparib could be successfully used in this patient setting.

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Phase III Trial: Adjuvant Pelvic Radiation Therapy Versus Vaginal Brachytherapy Plus Paclitaxel/Carboplatin in High-Intermediate and High-Risk Early-Stage Endometrial Cancer

Journal of Clinical Oncology ◽

10.1200/jco.18.01575 ◽

2019 ◽

Vol 37 (21) ◽

pp. 1810-1818 ◽

Cited By ~ 57

Author(s):

Marcus E. Randall ◽

Virginia Filiaci ◽

D. Scott McMeekin ◽

Vivian von Gruenigen ◽

Helen Huang ◽

...

Keyword(s):

Overall Survival ◽

Endometrial Cancer ◽

High Risk ◽

Confidence Limit ◽

Clear Cell ◽

Early Stage ◽

Stage I ◽

Phase Iii ◽

Phase Iii Trial ◽

Pelvic Radiation

PURPOSE The primary objective was to determine if vaginal cuff brachytherapy and chemotherapy (VCB/C) increases recurrence-free survival (RFS) compared with pelvic radiation therapy (RT) in high-intermediate and high-risk early-stage endometrial carcinoma. PATIENTS AND METHODS A randomized phase III trial was performed in eligible patients with endometrial cancer. Eligible patients had International Federation of Gynecology and Obstetrics (2009) stage I endometrioid histology with Gynecologic Oncology Group protocol 33–based high-intermediate–risk criteria, stage II disease, or stage I to II serous or clear cell tumors. Treatment was randomly assigned between RT (45 to 50.4 Gy over 5 weeks) or VCB followed by intravenous paclitaxel 175 mg/m2 (3 hours) plus carboplatin (area under the curve, 6) every 21 days for three cycles. RESULTS The median age of the 601 patients was 63 years, and 74% had stage I disease. Histologies included endometrioid (71%), serous (15%), and clear cell (5%). With a median follow-up of 53 months, the 60-month RFS was 0.76 (95% CI, 0.70 to 0.81) for RT and 0.76 (95% CI, 0.70 to 0.81) for VCB/C (hazard ratio, 0.92; 90% confidence limit, 0.69 to 1.23). The 60-month overall survival was 0.87 (95% CI, 0.83 to 0.91) for RT and 0.85 (95% CI, 0.81 to 0.90) for VCB/C (hazard ratio, 1.04; 90% confidence limit, 0.71 to 1.52). Vaginal and distant recurrence rates were similar between arms. Pelvic or para-aortic nodal recurrences were more common with VCB/C (9% v 4%). There was no heterogeneity of treatment effect with respect to RFS or overall survival among clinical or pathologic variables evaluated. CONCLUSION Superiority of VCB/C compared with pelvic RT was not demonstrated. Acute toxicity was greater with VCB/C; late toxicity was similar. Pelvic RT alone remains an effective, well-tolerated, and appropriate adjuvant treatment in high-risk early-stage endometrial carcinomas of all histologies.

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The Role of Adjuvant Chemotherapy in Surgical Stages I-II Serous and Clear Cell Carcinomas and Carcinosarcoma of the Endometrium: A Collaborative Study

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e3182094ded ◽

2011 ◽

Vol 21 (2) ◽

pp. 332-336 ◽

Cited By ~ 16

Author(s):

Ingrid Vandenput ◽

Jone Trovik ◽

Ignace Vergote ◽

Philippe Moerman ◽

Karin Leunen ◽

...

Keyword(s):

Endometrial Cancer ◽

Adjuvant Chemotherapy ◽

Clear Cell ◽

Early Stage ◽

Surgical Staging ◽

Recurrence Free Survival ◽

Type Ii ◽

Free Survival ◽

Group A ◽

Group B

Objective:To assess the impact of adjuvant chemotherapy in early surgically staged type II endometrial cancer (serous [S], clear cell carcinoma [CC]) and carcinosarcomas (CS) on recurrence and survival.Materials and Methods:Patients diagnosed with stages I-II S-CC and CS after comprehensive surgical staging were retrospectively collected. Surgical staging was defined as pelvic lymphadenectomy of more than 11 nodes harvested and exploration of the upper abdomen, with our without omentectomy. Groups with (group A) and without (group B) platinum-based chemotherapy were compared.Results:We identified 69 patients with a mean age of 66 years (range, 48-88 years). Both groups showed similar baseline characteristics. Group A consisted of 34 patients (23 S-CC, 11 CS) with 10 (29%) recurrences outside the pelvis (7 S-CC, 3 CS). Group B included 35 patients (28 S-CC, 7 CS) of which 10 (29%) developed recurrence outside the pelvis (7 S-CC, 3 CS). The median recurrence-free survival was 22 months (range, 13-51 months) for group A versus 10 months (range, 1-59 months) for group B (P= 0.437). Five patients (15%) of group A and 9 (26%) of group B died of disease after a median follow-up of 29 months (range, 20-59 months) and 17 months (range, 4-64 months), respectively (P= 0.168).Conclusion:Recurrences in early-stage type II endometrial cancer and carcinosarcomas occur irrespective of adjuvant chemotherapy, but recurrence-free survival is prolonged when adjuvant chemotherapy is administered. Only prospective randomized intergroup trials can address the benefit of adjuvant chemotherapy in early-stage high-risk endometrial cancer.

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