Objective: Biomarkers reflecting real-time response to therapy and recurrence are lacking.We assessed the clinical value of detecting cell-free circulating tumor DNA (ctDNA) mutations in endometrial cancer (EC) and ovarian cancer (OC) patients. Methods: EC/OC patients undergoing primary surgery were consented for tissue banking and 2-year serial blood draws. Tumor tissue DNA and plasma ctDNA underwent next generation sequencing using a targeted gene panel for somatic mutations. Results: Of 44 patients (24 EC, 17 OC, 2 synchronous endometrial and ovarian carcinomas [SEOC] and 1 endocervical adenocarcinoma [EA]) at least one somatic mutation was identified in tumor tissue in 40 (91%, 20/24 EC, all OC/SEOC/EA), and in preoperative plasma ctDNA in 12 (27%) patients (6/24 [25%] EC and 6/17 [35%] OC). Detection of preoperative ctDNA mutations was associated with advanced stage, higher preoperative CA125, and subsequent disease recurrence. In 5/12 (42%) patients with preoperative ctDNA mutations, examination/imaging suggested clinical stage I however final pathology revealed stage II/III. In 11 patients where serial timepoints were assessed during treatment for ctDNA and CA125, ctDNA clearance preceded normalization of CA125. Thirteen patients developed recurrent disease (4 EC, 8 OC, 1 EA); 8 in whom ctDNA mutations were detected postoperatively, and 4 followed through time of recurrence with ctDNA mutations identified 2–5 months prior to clinical/radiologic/biomarker progression in 3. Conclusion ctDNA can reflect larger tumor volume/metastases, treatment response and subsequent disease recurrence in EC and OC. Careful patient selection is critical to direct resources to patients most likely to benefit, considering disease burden and risk group.

Objective: Biomarkers reflecting real-time response to therapy and recurrence are lacking.We assessed the clinical value of detecting cell-free circulating tumor DNA (ctDNA) mutations in endometrial cancer (EC) and ovarian cancer (OC) patients. Methods: EC/OC patients undergoing primary surgery were consented for tissue banking and 2-year serial blood draws. Tumor tissue DNA and plasma ctDNA underwent next generation sequencing using a targeted gene panel for somatic mutations. Results: Of 44 patients (24 EC, 17 OC, 2 synchronous endometrial and ovarian carcinomas [SEOC] and 1 endocervical adenocarcinoma [EA]) at least one somatic mutation was identified in tumor tissue in 40 (91%, 20/24 EC, all OC/SEOC/EA), and in preoperative plasma ctDNA in 12 (27%) patients (6/24 [25%] EC and 6/17 [35%] OC). Detection of preoperative ctDNA mutations was associated with advanced stage, higher preoperative CA125, and subsequent disease recurrence. In 5/12 (42%) patients with preoperative ctDNA mutations, examination/imaging suggested clinical stage I however final pathology revealed stage II/III. In 11 patients where serial timepoints were assessed during treatment for ctDNA and CA125, ctDNA clearance preceded normalization of CA125. Thirteen patients developed recurrent disease (4 EC, 8 OC, 1 EA); 8 in whom ctDNA mutations were detected postoperatively, and 4 followed through time of recurrence with ctDNA mutations identified 2–5 months prior to clinical/radiologic/biomarker progression in 3. Conclusion ctDNA can reflect larger tumor volume/metastases, treatment response and subsequent disease recurrence in EC and OC. Careful patient selection is critical to direct resources to patients most likely to benefit, considering disease burden and risk group.

Objective: Biomarkers reflecting real-time response to therapy and recurrence are lacking.We assessed the clinical value of detecting cell-free circulating tumor DNA (ctDNA) mutations in endometrial cancer (EC) and ovarian cancer (OC) patients. Methods: EC/OC patients undergoing primary surgery were consented for tissue banking and 2-year serial blood draws. Tumor tissue DNA and plasma ctDNA underwent next generation sequencing using a targeted gene panel for somatic mutations. Results: Of 44 patients (24 EC, 17 OC, 2 synchronous endometrial and ovarian carcinomas [SEOC] and 1 endocervical adenocarcinoma [EA]) at least one somatic mutation was identified in tumor tissue in 40 (91%, 20/24 EC, all OC/SEOC/EA), and in preoperative plasma ctDNA in 12 (27%) patients (6/24 [25%] EC and 6/17 [35%] OC). Detection of preoperative ctDNA mutations was associated with advanced stage, higher preoperative CA125, and subsequent disease recurrence. In 5/12 (42%) patients with preoperative ctDNA mutations, examination/imaging suggested clinical stage I however final pathology revealed stage II/III. In 11 patients where serial timepoints were assessed during treatment for ctDNA and CA125, ctDNA clearance preceded normalization of CA125. Thirteen patients developed recurrent disease (4 EC, 8 OC, 1 EA); 8 in whom ctDNA mutations were detected postoperatively, and 4 followed through time of recurrence with ctDNA mutations identified 2–5 months prior to clinical/radiologic/biomarker progression in 3. Conclusion ctDNA can reflect larger tumor volume/metastases, treatment response and subsequent disease recurrence in EC and OC. Careful patient selection is critical to direct resources to patients most likely to benefit, considering disease burden and risk group.

Endometrial cancer (EC) is the fifth most common cancer in women worldwide. Global estimates show rising incidence rates in both developed and developing countries. Most women are diagnosed postmenopausal, but 14–25% of patients are premenopausal and 5% are under 40 years of age. Established risk factors include age and hyperestrogenic status associated with nulliparity, obesity, and metabolic syndrome. Standard treatment for EC, which involves total hysterectomy and bilateral salpingo-oophorectomy, has excellent survival outcomes, particularly for low-grade endometrioid tumors. However, it leads to permanent loss of fertility among women who wish to preserve their reproductive potential. With current trends of reproductive-age women delaying childbearing, rising EC incidence rates, and a growing epidemic of obesity, particularly in developed countries, research on conservative non-surgical treatment approaches remains a top priority. Fertility-sparing treatment predominantly involves the use of oral progestins and levonorgestrel-releasing intrauterine devices, which have been shown to be feasible and safe in women with early stage EC and minimal or no myometrial invasion. However, data on the efficacy and safety of conservative management strategies are primarily based on retrospective studies. Randomized clinical trials in younger women and high-risk obese patients are currently underway. Here, we have presented a comprehensive review of the current literature on conservative, fertility-sparing approaches, defining the optimal candidates and evaluating tumor characteristics, reproductive and oncologic outcomes, and ongoing clinical trials. We have also summarized current guidelines and recommendations based on the published literature.

Endometrial cancer (EC) is the fifth most common cancer in women worldwide. Global estimates show rising incidence rates in both developed and developing countries. Most women are diagnosed postmenopausal, but 14–25% of patients are premenopausal and 5% are under 40 years of age. Established risk factors include age and hyperestrogenic status associated with nulliparity, obesity, and metabolic syndrome. Standard treatment for EC, which involves total hysterectomy and bilateral salpingo-oophorectomy, has excellent survival outcomes, particularly for low-grade endometrioid tumors. However, it leads to permanent loss of fertility among women who wish to preserve their reproductive potential. With current trends of reproductive-age women delaying childbearing, rising EC incidence rates, and a growing epidemic of obesity, particularly in developed countries, research on conservative non-surgical treatment approaches remains a top priority. Fertility-sparing treatment predominantly involves the use of oral progestins and levonorgestrel-releasing intrauterine devices, which have been shown to be feasible and safe in women with early stage EC and minimal or no myometrial invasion. However, data on the efficacy and safety of conservative management strategies are primarily based on retrospective studies. Randomized clinical trials in younger women and high-risk obese patients are currently underway. Here, we have presented a comprehensive review of the current literature on conservative, fertility-sparing approaches, defining the optimal candidates and evaluating tumor characteristics, reproductive and oncologic outcomes, and ongoing clinical trials. We have also summarized current guidelines and recommendations based on the published literature.