Intra-operative tumor spillage in minimally invasive surgery for endometrial cancer and its impact on recurrence risk.

OBJECTIVE: The prognostic impact of intra-operative tumor spillage (ITS) during minimally invasive surgery (MIS) for endometrial cancer (EC) is not well studied. The objective of this study was to determine if there is an association between ITS and EC recurrence. METHODS: We performed a case-control study of patients with a laparoscopic or robot-assisted hysterectomy with EC on final pathology between 2017 and 2022 and compared those with (case) and without (control) a subsequent EC recurrence. Electronic medical records were reviewed for demographic, intra-operative and pathologic details, and recurrence status. ITS was defined as uterine perforation with a manipulator, presence of extra-uterine tumor after colpotomy or specimen delivery, exposure of uncontained specimen into peritoneum, and/or pathology/operative reports noting specimen fragmentation. Conditional logistic regression was used to determine odds ratios for the association of cancer recurrence with ITS. We adjusted for >50% myoinvasion, tumor size, and adjuvant treatment. RESULTS: 1057 patients underwent MIS for EC. Approximately 8% (n = 86) developed recurrent cancer and 172 patients were selected as controls. Twenty percent of recurrent cases (17/86) had ITS compared with 4% of nonrecurrent controls (7/172). When adjusted for tumor size, deep myoinvasion, and adjuvant treatment, patients with ITS had a 5.6 times increased odds (aOR 5.63, 95% CI 1.52-20.86) of recurrence compared to patients without ITS. CONCLUSIONS: In patients with EC, we found an association between ITS and cancer recurrence. These findings warrant further investigation to determine if adjuvant therapy or surgical technique should be altered to improve outcomes.

Surveillance of gynecologic cancer patients post-COVID-19 vaccine: Are CA-125 levels reliable?

Objective: The COVID-19 vaccine is known to instigate an inflammatory response that impacts cancer testing. We aimed to evaluate carbohydrate antigen 125 (CA-125) trends in gynecologic oncology patients in surveillance following COVID-19 vaccination to inform clinical practice. Methods: This was a single institution retrospective study of patients who received a COVID-19 vaccine while undergoing surveillance of gynecologic cancers with serial serum CA-125 measurements. CA-125 levels from the three months before and after vaccination were included in analysis. Differences between mean and median pre- and post-vaccination CA-125 levels for each patient were calculated. The mean and median of these differences were calculated, as well as the distribution of change. Demographic and cancer-related variables were also recorded. Results: Twenty-six patients who received a COVID-19 vaccine and were followed with surveillance serum CA-125 levels were identified. The mean age was 68.2 years; 92 % received a two-vaccine series. Forty-six percent had endometrial cancer and 54 % had ovarian cancer. The mean change from pre- to post-vaccine mean CA-125 level was 0.16 (±7.17) U/mL and the median change from pre- to post-vaccine median CA-125 level was -0.30 (IQR 3.66) U/mL. The range in change from pre- to post-vaccine mean was -16.50 to 24.00 U/mL, with 73 % of patients between -4 and +4 U/mL. Conclusion: We found no clinically significant change in CA-125 level after patients under surveillance for gynecologic cancers were vaccinated against COVID-19, suggesting that that the vaccine does not impact the utility of CA-125 as a tool to monitor disease in this population.

Key concepts in management of vulvar cancer.

Vulvar carcinoma is an uncommon tumor that is seen most often in older women. Subtle symptoms such as pruritus should prompt examination and targeted biopsy in all women as this disease can be successfully treated even in elderly, frail individuals. Vulvar cancer has a bimodal age distribution and is seen in both young and older women with risk factors including human papillomavirus (HPV) infection, smoking, and vulvar skin diseases (i.e., lichen sclerosus). This cancer is staged surgically, with an update in 2009 incorporating prognostic factors. The treatment of vulvar carcinoma has evolved to include more conservative surgical techniques that provide improved cure rates with emphasis on minimizing morbidity. Advanced and metastatic lesions are now treated with chemoradiation which produces substantial cure rates with decreased morbidity. Promising areas of research in vulvar cancer include refinement of sentinel lymph node biopsy, prevention of lymphedema, and preservation of sexual function following treatment.

Dual mTORC1/2 inhibition in a preclinical xenograft tumor model of endometrial cancer.

OBJECTIVES: Up to 70% of endometrioid endometrial cancers carry PTEN gene deletions that can upregulate mTOR activity. Investigational mTOR kinase inhibitors may provide a novel therapeutic approach for these tumors. Using a xenograft tumor model of endometrial cancer, we assessed the activity of mTOR and downstream effector proteins in the mTOR translational control pathway after treatment with a dual mTOR complex 1 and 2 (mTORC1/2) catalytic inhibitor (PP242) compared to that of an allosteric mTOR complex 1 (mTORC1) inhibitor (everolimus, RAD001). METHODS: Grade 3 endometrioid endometrial cancer cells (AN3CA) were xenografted into nude mice. Animals were treated with PP242, PP242 and carboplatin, carboplatin, RAD001, and RAD001 and carboplatin. Mean tumor volume was compared across groups by ANOVA. Immunoblot analysis was performed to assess mTORC1/2 activity using P-Akt, P-S6 and P-4E-BP1. RESULTS: The mean tumor volume of PP242+carboplatin was significantly lower than in all other treatment groups, P < 0.001 (89% smaller). The RAD001+carboplatin group was also smaller, but this did not reach statistical significance (P = 0.097). Immunoblot analysis of tumor lysates treated with PP242 demonstrated inhibition of activated P-Akt. CONCLUSIONS: Catalytic mTORC1/2 inhibition demonstrates clear efficacy in tumor growth control that is enhanced by the addition of a DNA damage agent, carboplatin. Targeting mTORC1/2 leads to inhibition of Akt activation and strong downregulation of effectors of mTORC1, resulting in downregulation of protein synthesis. Based on this study, mTORC1/2 kinase inhibitors warrant further investigation as a potential treatment for endometrial cancer.

Surgical options for recurrent uterine sarcomas.

Leiomyosarcoma, the most frequent pure uterine sarcoma, is an aggressive tumor with a tendency toward early relapse. Survival for patients with recurrent disease is poor. In contrast, endometrial stromal sarcoma, the second most common uterine sarcoma, is a more indolent malignancy with a tendency toward recurrence after a long latency period. The relative infrequency of both diseases makes the study and standardization of treatment for recurrent disease challenging. Treatment of recurrence with cytotoxic chemotherapy, radiation therapy, or hormone therapy produces modest to poor response rates. Surgical resection is one treatment modality offering the potential for cure and perhaps a more durable response than is seen with medical management. Although initial studies focused on pulmonary metastasectomy in recurrent soft tissue sarcoma, an increasingly large body of data specifically evaluating outcomes after both thoracic and extrathoracic metastasectomy in patients with recurrent uterine sarcoma is now available. Though no prospective trials have been conducted, retrospective comparisons of chemotherapy or radiation therapy with surgery for recurrent uterine sarcoma suggest improvement in disease-specific survival for the surgery group. Clearly defined factors are associated with better prognosis after surgical resection of recurrence, including a prolonged disease-free interval and complete resection of disease. In properly selected women, surgery and even repeated metastasectomy for recurrent disease may improve survival and should be considered.

Targeting the mTOR/4E-BP pathway in endometrial cancer.

Endometrial cancer is the most common gynecologic malignancy. Although it is highly treatable in the early stages of disease, therapies for advanced and recurrent disease are rarely curative. A molecular and genetic understanding of endometrial cancer involves the mTOR signaling pathway, an emerging target for treatment of type I disease (the most common presentation). Endometrial cancers show a significant reliance on the mTOR pathway for survival, and studies to date have revealed a clinical advantage in targeting this pathway. Less well developed in the study of endometrial cancer is an understanding of mTOR signaling to its major downstream effector, translational control. Given the poor rate of success for treatment of late-stage endometrial cancer, increasing attention is being directed to the development of new therapeutic approaches, including targeting the mTOR pathway. Here, we discuss the potential benefit of targeting mTOR combined with existing chemotherapies by monitoring its impact on translational regulatory pathways and key translation targets in endometrial cancer. We also highlight laboratory and clinical research findings that will provide new avenues for future research and clinical development.