Multimodality adjuvant therapy and survival outcomes in stage I-IV uterine carcinosarcoma.

OBJECTIVES: Uterine carcinosarcoma is a rare, aggressive form of uterine cancer with a high recurrence rate and poor survival at all stages. We sought to evaluate the outcomes of patients treated with chemotherapy versus a combination of chemotherapy and radiation (chemoradiation) to determine survival. METHODS: A multicenter retrospective analysis of patients with stage I-IV carcinosarcoma was conducted from January 2000 to December 2017. Inclusion criteria were primary surgical management, defined as hysterectomy ± salpingo-oophorectomy, comprehensive surgical staging and/or tumor debulking, followed by adjuvant chemotherapy or chemoradiation. Differences in the frequencies of stage, cytoreduction status, treatment delays and sites of disease recurrence were identified using Pearson's χ2 test. Progression-free and overall survival rates were calculated using Kaplan-Meier estimates. RESULTS: Final analysis included 148 patients; 40.5% (n=60) chemotherapy and 59.5% (n=88) chemoradiation. The mean age was 67 years (range 39-89). Stage distribution included 24.3% stage I, 12.2% stage II, 37.2% stage III, and 26.3% stage IV. There was no difference in the frequency of stage (p=0.81), cytoreduction status (p=0.61), treatment delays (p=0.57), or location of recurrence (p=0.97) between cohorts. The most frequent location of recurrence was the abdomen (50.0%). The median progression-free survival favored chemoradiation over chemotherapy (15 vs 11 months, respectively), as did the median overall survival (26 vs 20 months, respectively). Chemoradiation was associated with a statistically significant improvement in 2 year progression-free survival (22.5% vs 13.6%; p=0.006) and 2 year overall survival (50.0% vs 35.6%; p=0.018) compared with chemotherapy alone. On subanalysis of patients receiving chemoradiation, 'sandwich sequencing' (chemotherapy-radiation-chemotherapy) was associated with superior overall survival compared with alternate therapy sequences (chemotherapy-radiation and radiation-chemotherapy) (34 months vs 14 months and 14 months, respectively) (p=0.038). CONCLUSIONS: Chemoradiation was associated with improvement in both progression-free and overall survival for all stages of carcinosarcoma compared with chemotherapy alone.

A clinicopathologic study of endometrial cancer metastatic to bone: Identification of microsatellite instability improves treatment strategies.

Metastasis to bone (BM) is an uncommon manifestation of advanced endometrial cancer (EC). The present study will review the clinicopathologic features of a cohort of patients with EC and BM. We conducted a multi-center retrospective review of patients with EC and BM. Demographic and clinical information was extracted from the medical records. Survival outcomes were determined using Kaplan-Meier Curves. Final analysis included 10 patients. The median age was 65 years (range 31-71). 80% had FIGO stage III/IV disease. The most common site of BM was the spine (66%). All patients presented with extraosseous dissemination at the time of diagnosis of BM and 70% were found to have multiple sites of BM. 80% of patients were diagnosed with BM in the recurrent setting. The median time to diagnosis of bone recurrence was 14 months (range: 0-44). Median survival after diagnosis of BM was 11 months (range: 1-22 months). Patients with endometrioid histology and single site of bone metastasis experienced improved survival (p = 0.04 and p = 0.05, respectively). Eight patients had immunohistochemistry or molecular tumor profiles available for review. Seven of these patients (87.5%) were found to have microsatellite instability (MSI). The most common mutation was hypermethylation of MLH-1 (43%). To our knowledge, this is the first report demonstrating a correlation between MSI and metastasis to bone. The identification of BM in EC is uncommon, but will alter treatment strategies and dramatically impact prognosis. Molecular tumor profiling should be performed to identify targeted therapy options and optimize adjuvant treatment strategies.

Clinical comparison between neuroendocrine and endometrioid type carcinoma of the uterine corpus.

OBJECTIVE: To compare the clinicopathologic features and survival outcomes of neuroendocrine tumor of the uterine corpus (NET-U) to endometrioid type endometrial carcinoma (EC). METHODS: From 1993 to 2012, the Surveillance, Epidemiology and End Results cancer registry was queried for women diagnosed with EC or NET-U. Data regarding stage, grade, presence of extra-uterine disease, lymph node metastasis, receipt of adjuvant radiation, surgical intervention and overall survival (OS) was extracted. Chi-square tests, t-tests and Kaplan Meir curves were used for statistical analysis. RESULTS: A total of 98,363 patients were identified: 98,245 with EC and 118 with NET-U. The mean age at diagnosis for EC was 61.7 years and 64.8 years for NET-U (p=0.01). NET-U cases were more likely to be poorly differentiated (97.0% vs. 15.6%; p≤0.01) and have nodal metastasis (56.4% vs. 11.1%; p≤0.01) when compared to EC. Presence of extrapelvic disease at the time of diagnosis was observed more frequently in NET-U compared to EC, 49.1% vs. 4.8%, respectively (odds ratio=18; 95% confidence interval=13.1-27.2; p≤0.01). Significant improvement in OS was observed in NET-U patient who received radiation (OS: 7.7 vs. 3.3 years; p≤0.01) or underwent surgical management (5.6 vs. 0.9 years; p≤0.01). The OS for EC was 14.4 vs. 4.6 years for NET-U (p≤0.01). CONCLUSION: NET-U represents an aggressive form of uterine malignancy. When compared to EC, patients with NET-U present at more advanced stage, have more frequent extra-uterine disease and lower OS.

Clinicopathologic features, incidence, and survival trends of gynecologic neuroendocrine tumors: a SEER database analysis.

BACKGROUND: Primary gynecologic neuroendocrine tumors are uncommon malignant neoplasms associated with poor prognosis. Clinically, these tumors present a significant challenge because of the lack of standardized management guidelines. OBJECTIVE: The objective of this study is to evaluate the clinicopathologic features, incidence, and survival trends in gynecologic neuroendocrine tumors. MATERIALS AND METHODS: The Surveillance, Epidemiology and End Results (SEER) cancer registry was queried for women diagnosed with primary gynecologic neuroendocrine tumors from 1987 to 2012. Data regarding stage, grade, presence of extrauterine disease, receipt of adjuvant radiation, surgical intervention, incidence, and overall survival were extracted. Patients were classified as having early-stage disease (International Federation of Gynecology and Obstetrics Stage I/II) or advanced-stage disease (Stage III/IV). Extrauterine disease was defined as either regional or distant metastasis. χ2 Tests, Pearson correlation, and Kaplan-Meier curves were used for statistical analysis. RESULTS: In all, 559 cases of gynecologic neuroendocrine tumors were identified during the study period: 242 cervical, 160 ovarian, 118 uterine, and 39 vulvar/vaginal. The majority of patients in all subsets of gynecologic neuroendocrine tumors presented with poorly differentiated tumors, extrauterine disease spread, and advanced-stage disease. Poorly differentiated tumors represented 65.0% of cervical tumors, 45.3% of ovarian tumors, and 57.4% of uterine tumors. Extrauterine disease at the time of diagnosis was present in the case of 66.9% of cervical tumors, 83.5% of ovarian tumors, and 83.6% of uterine tumors. The overall incidence of gynecologic neuroendocrine tumors increased 4-fold during the study period, from 0.3 in 1987 to 1.30 per million in 2012. The study period was divided into two 13-year periods (1987-1999 and 2000-2012) for time trend mean survival analysis. We observed no significant change in overall survival across all gynecologic neuroendocrine tumor subtypes. The mean survival time of cervical neuroendocrine tumors was 74.3 vs 45.4 months (P = .31), ovarian neuroendocrine tumors 47.8 vs 41.2 months (P = .56), and uterine neuroendocrine tumors 42.9 vs 47.7 months (P = .44) for each time period, respectively. CONCLUSION: Neuroendocrine tumors of the gynecologic tract are uncommon aggressive malignancies. These poorly differentiated tumors present at advanced stage, with a high incidence of extrauterine disease. Despite 25 years of advances in cancer therapy, we observed no improvement in overall survival.

Extent of lymph node dissection and overall survival in patients with uterine carcinosarcoma, papillary serous and endometrioid adenocarcinoma: A retrospective cohort study.

OBJECTIVE: To evaluate the interaction between extent of lymph node dissection (LND) and overall survival (OS) in patients with various histologic types of uterine cancer. METHODS: We retrospectively identified 834 patients who had primary surgery in our institution for uterine carcinosarcoma (CS), papillary serous (UPSC) and endometrioid adenocarcinoma between 1984 and 2009. Stage, grade, total lymph node count (LNC), positive LNC, adjuvant therapy, age, race and OS were collected. OS was calculated using the Kaplan-Meier method. Predictive factors were compared with the log rank test and Cox regression analysis. RESULTS: Our cohort included 158 patients with CS, 115 patients with UPSC and 561 patients with endometrioid adenocarcinoma. Of the cohort, 38% of the patients had Stage III or IV disease. LND was performed in 73% of patients with CS, 68% of patients with UPSC and 79% of patients with endometrioid adenocarcinoma. LND was performed in 82% of Stage I-II and in 68% of Stage III-IV cases. The median total LNC was 13 (range 1-75) and there was no significant difference in the total LNC between the different histologies. Median OS was 21 months for CS, 18 months for UPSC and 200 months for patients with endometrioid adenocarcinoma. A positive association between the total and positive LNC was present in all three histologic types (Spearman coefficient, p < 0.001). The cohort was divided in quartiles based on the total LNC and a Kaplan-Meier survival analysis was performed. A continuum of improved OS was noted in correlation with increased LNC. OS was 27 months for the group with 0 nodes, 112 months for the group with 1-8 nodes, 117 months for the group with 9-16 nodes and 196 months for the group with >17 nodes. Doubling the total LNC was associated with 28% risk of death reduction (HR 0.724, CI 0.66-0.794, p < 0.001) for the first year and 14% risk reduction (HR 0.858, CI 0.761-0.967, p = 0.012) for the second year. CONCLUSIONS: In our cohort, the performance of LND is associated with improved OS. This effect appears to be uniform across pathology types. The extent of the LND is inversely correlated with the risk of death for the first 2 years.

External validation of a nomogram for predicting survival of women with uterine cancer in a cohort of African American patients.

OBJECTIVE: This study aimed to externally validate a nomogram for predicting overall survival of women with uterine cancer in an African American population. METHODS: After the institutional review board approval, data from the uterine cancer database from 2 major teaching hospitals in Brooklyn, NY, were analyzed. The predicted survival for each patient was calculated with the use of the nonogram; the data were clustered in deciles and compared with the observed survival data. RESULTS: High incidence of aggressive histologic types (22% carcinosarcoma, 16% serous/clear cell), poorly differentiated (53% grade 3), and advanced stage (38% stage III or IV) tumors was found in our study population. The median follow-up for survivors was 52 months (range, 1-274 months). The observed and predicted 3-year overall survival probabilities were significantly different (62.5% vs 72.6%, P < 0.001). Similarly, the observed 5-year overall survival probability was significantly lower than the predicted by the nomogram (55.5% vs 63.4%, P < 0.001). The discrepancy between predicted and observed survival was more pronounced in the midrisk groups. CONCLUSIONS: The nomogram is not an adequate tool to predict survival in the African American population with cancer of the uterine corpus. Race seems to be a significant, independent factor that affects survival and should be included in predictive models.

Transvaginal sonography of postabortal (Redo) syndrome.

Acute hematometra, also termed the postabortal syndrome or redo syndrome, is a rare immediate complication of suction curettage characterized by severe lower abdominal cramping in association with an enlarged and markedly tender uterus. We describe the transvaginal sonographic features of this syndrome.

A comparative analysis of 57 serous borderline tumors with and without a noninvasive micropapillary component.

The literature concerning serous borderline tumors with a noninvasive micropapillary component suggests an association with invasive implants. We compared the clinicopathologic features of micropapillary serous borderline tumors (MSBTs) with typical SBTs to determine the following: 1) the importance of focal micropapillary architecture in an otherwise typical SBT, 2) the behavior of low-stage MSBTs, 3) whether high-stage MSBTs are inherently more aggressive than high-stage SBTs, and 4) whether invasive implants are prevalent in an MSBT cohort without referral selection bias. The 57 borderline tumors studied were diagnosed at a university hospital between 1981 and 1998; they included 14 MSBTs, 35 SBTs, and 8 SBTs with focal micropapillary features. None of the specimens were referrals for expert pathologic consultation, thus distinguishing our study group from most of those previously reported. Neither MSBTs nor SBTs were associated with invasive implants at diagnosis (0 of 14 and 0 of 43, respectively). They also did not differ with respect to overall stage at diagnosis, but MSBTs were more frequently bilateral than SBTs (71% versus 23%, p = 0.001). There was an increased risk of recurrence in MSBT versus SBT (3 of 14 versus 1 of 43, p = 0.035), but this was stage related; there was no difference between groups when evaluating recurrence in stage I disease (0 of 8 versus 0 of 27). There was no difference in recurrence or stage at diagnosis between SBTs with focal micropapillary features and other SBTs. There was 100% survival in all groups. We conclude that high-stage MSBTs with noninvasive implants should be considered a subtype of SBTs with an increased risk of recurrence. Stage I MSBTs demonstrate clinical features that are similar to low-stage SBTs. Focal micropapillary architecture (<5 mm) has no bearing on outcome. MSBTs in the general population are not strongly associated with invasive implants.