Is hormonal therapy after risk-reducing salpingo-oophorectomy associated with an increased risk of malignancy in pathogenic variant carriers?

OBJECTIVES: This study aimed to assess the association between hormone replacement therapy and the incidence of subsequent malignancies in patients who underwent risk-reducing salpingo-oophorectomy and had mutations predisposing them to Müllerian cancers. METHODS: This Institutional Review Board-approved retrospective study was performed at five academic institutions. Women were included if they were age 18-51 years, had one or more confirmed germline highly penetrant pathogenic variants, and underwent risk-reducing salpingo-oophorectomy. Patients with a prior malignancy were excluded. Clinicodemographic data were collected by chart review. Patients with no documented contact for one year prior to study termination were called to confirm duration of hormone use and occurrence of secondary outcomes. Hormone replacement therapy included any combination of estrogen or progesterone. RESULTS: Data were analyzed for 159 women, of which 82 received hormone replacement therapy and 77 did not. In both groups an average of 6 years since risk reduction had passed. The patients treated with hormone replacement therapy did not have a higher risk of subsequent malignancy than those not treated with hormone replacement therapy (6 out of 82 vs. 7 out of 77, P = .68). Patients who received hormone replacement therapy were younger than those who did not receive hormone replacement therapy (39.0 vs. 43.9 years, P < .01) and were more likely to have undergone other risk reductive procedures including mastectomy and/or hysterectomy, though this difference was not statistically significant (69.5% vs. 55.8%, P = .07). CONCLUSIONS: In this multi-institution retrospective study of data from patients with high-risk variant carriers who underwent risk-reducing salpingo-oophorectomy, there was no statistically significant difference in the incidence of malignancy between women who did and did not receive hormone replacement therapy.

Recurrence, death, and secondary malignancy after ovarian conservation for young women with early-stage low-grade endometrial cancer.

OBJECTIVE: To examine the association between ovarian conservation and oncologic outcome in surgically-treated young women with early-stage, low-grade endometrial cancer. METHODS: This multicenter retrospective study examined women aged <50 with stage I grade 1-2 endometrioid endometrial cancer who underwent primary surgery with hysterectomy from 2000 to 2014 (US cohort n = 1196, and Japan cohort n = 495). Recurrence patterns, survival, and the presence of a metachronous secondary malignancy were assessed based on ovarian conservation versus oophorectomy. RESULTS: During the study period, the ovarian conservation rate significantly increased in the US cohort from 5.4% to 16.4% (P = 0.020) whereas the rate was unchanged in the Japan cohort (6.3-8.7%, P = 0.787). In the US cohort, ovarian conservation was not associated with disease-free survival (hazard ratio [HR] 0.829, 95% confidence interval [CI] 0.188-3.663, P = 0.805), overall survival (HR not estimated, P = 0.981), or metachronous secondary malignancy (HR 1.787, 95% CI 0.603-5.295, P = 0.295). In the Japan cohort, ovarian conservation was associated with decreased disease-free survival (HR 5.214, 95% CI 1.557-17.464, P = 0.007) and an increased risk of a metachronous secondary malignancy, particularly ovarian cancer (HR 7.119, 95% CI 1.349-37.554, P = 0.021), but was not associated with overall survival (HR not estimated, P = 0.987). Ovarian recurrence or metachronous secondary ovarian cancer occurred after a median time of 5.9 years, and all cases were salvaged. CONCLUSION: Our study suggests that adoption of ovarian conservation in young women with early-stage low-grade endometrial cancer varies by population. Ovarian conservation for young women with early-stage, low-grade endometrial cancer may be potentially associated with increased risks of ovarian recurrence or metachronous secondary ovarian cancer in certain populations; nevertheless, ovarian conservation did not negatively impact overall survival.

Type II endometrial cancers with minimal, non-invasive residual disease on final pathology: What should we do next?

There are minimal data regarding the management of high risk endometrial cancer histologies lacking invasive disease on the final pathology specimen. This study examines a cohort of these patients and assesses outcomes including time to recurrence and risk of death after management with and without adjuvant therapies. Endometrial cancer patients with minimal or no remaining invasive disease on final pathologic specimen from 1995 to 2010 were included. Surgical procedure was at the discretion of the operating physician. Electronic medical records were used to abstract relevant clinicopathologic data and standard statistical methods were employed. 70 patients met inclusion criteria, of which 26 were high grade histologies. Adjuvant therapies were given in 12 of 26 patients. 6/26 patients recurred, of which 50% were salvaged with therapy at time of recurrence. Overall deaths occurred in 3 of 26 patients in the high risk cohort. Less than half of the high risk cohort received adjuvant therapies after surgical management. No histologic type was found to increase risk of recurrence, and treatment with initial adjuvant therapy did not significantly reduce recurrence risk. Large scale prospective trials are needed to aid in management of this unique endometrial cancer population.

Inpatient management of hypercalcemia portends a poor prognosis among gynecologic oncology patients: A trigger to initiate hospice care?

We aim to describe survival outcomes of gynecologic oncology inpatients treated with intravenous bisphosphonates for hypercalcemia and develop a risk stratification model that predicts decreased survival to aid with goals of care discussion. In a single-center, retrospective cohort study of gynecologic oncology patients admitted for bisphosphonate therapy for hypercalcemia. Survival from hypercalcemia to death was assessed by Kaplan-Meier method and log-rank test. Univariate log-rank test and Cox proportional hazards modeling were used to develop a risk stratification model. Sixty-five patients were evaluable with a median follow-up of 83.5 months. Mean age was 59.2 years, 64.6% had recurrent disease, and 30.8% had ≥2 previous lines of chemotherapy. Median survival was 38 days. Our analysis identified four risk factors (RFs) [brain metastasis, >1 site of metastasis, serum corrected peak calcium >12.4 (mg/dL), and peak ionized calcium >5.97 (mg/dL)] that predicted survival and were used to build a risk stratification score. Sum of RFs included 35 patients with 1 RF, 11 had 2 RFs, and 19 had ≥3 RF. Median survival for 1, 2, or ≥ 3 RFs was 53, 28, and 26 days respectively (p = .009). Survival at 6 months was 28.6%, 18.2%, and 5.3% for each group respectively. Hospice enrollment was 26.2%, and did not vary by group (p = .51). Among gynecologic oncology patients, inpatient management of hypercalcemia with bisphosphonates portends poor prognosis. Individualized risk stratification may help guide end-of-life discussions and identify patients who may benefit most from hospice care.

Palliative Care in Gynecologic Oncology.

The integration of palliative care and hospice into standard gynecologic oncology care is associated with cost-savings, longer survival, lower symptom burden, and better quality of life for patients and caregivers. Consequently, this comprehensive approach is formally recognized and endorsed by the Society of Gynecologic Oncology, the National Comprehensive Cancer Network, and the American Society of Clinical Oncology. This article reviews the background, benefits, barriers, and most practical delivery models of palliative care. It also discusses management of common symptoms experienced by gynecologic oncology patients.

Association between body mass index and surgical menopausal symptoms in patients with early stage endometrial cancer.

OBJECTIVES: Premenopausal women may undergo surgical menopause after staging for their endometrial cancer. Our aim was to determine the association between body mass index (BMI) and surgical menopausal symptoms. METHODS: We report a retrospective review of endometrial cancer patients whom underwent menopause secondary to their surgical staging procedure. Symptoms were classified as severe if treatment was prescribed, or mild if treatment was offered, but declined. Univariate analysis was performed with ANOVA and Chi-square tests as appropriate. Relative risks (RR) were generated from Poisson regression models. RESULTS: We identified 166 patients in whom the BMI (kg/m2) distribution was as follows: 33 (19.9%) had BMI <30, 49 (29.5%) had BMI 30-39.9, 50 (30.1%) had BMI 40-49.9, and 34 (20.5%) had BMI ≥50. There were no differences in race, age, or adjuvant treatment among the groups. Overall, 65 (39.2%) women reported symptoms of surgical menopause, including 19 (11.4%) mild and 46 (27.7%) severe. Symptom type did not differ by BMI; however, the prevalence of severe menopausal symptoms decreased with increasing BMI: <30 (45.5%), 30-39.9 (30.6%), 40-49.9 (22%), and ≥ 50 (14.7%); P = 0.002. Multivariate analysis confirmed that symptom prevalence decreased with increasing BMI. Compared to women with a BMI of <30, those with a BMI 40-49.9 (RR = 0.39, 95% CI: 0.17-0.87) or ≥ 50 (RR = 0.24, 95% CI: 0.08-0.70) were significantly less likely to experience menopausal symptoms. CONCLUSIONS: Women younger than 50 with BMI >40 and stage I endometrial cancer are significantly less likely than women with BMI <30 to experience menopausal symptoms after oophorectomy. This information may assist in peri-operative counseling.

Gynecologic Oncologists' Perceptions of Palliative Care and Associated Barriers: A Survey of the Society of Gynecologic Oncology.

OBJECTIVES: Gynecologic oncologists frequently care for patients at the end of life with the aid of palliative care (PC) specialists. Our primary objectives were to identify perceived barriers to integrating specialty PC into gynecologic cancer care. MATERIALS AND METHODS: Members of the Society of Gynecologic Oncology (SGO) were invited to participate in an anonymous online survey. A Likert scale captured perceptions regarding primary and specialty PC, frequent barriers to use of PC, and potential interventions. RESULTS: A total of 174 (16%) gynecologic oncologists completed the survey. The majority (75%) agreed or strongly agreed that PC should be integrated into cancer care at diagnosis of advanced or metastatic cancer. The most frequently perceived PC barriers included patients' unrealistic expectations (54%), limited access to specialty PC (25%), poor reimbursement (25%), time constraints (22%), and concern of reducing hope or trust (21%). The most agreed upon potential intervention was increased access to outpatient PC (80%). CONCLUSIONS: According to this cohort of SGO members, families' or patients' unrealistic expectations are the most frequent barriers to specialty PC. Understanding this communication breakdown is critically important.