Distribution and volume of extrauterine disease in uterine serous carcinoma: is minimally invasive surgery a suitable approach?

OBJECTIVE: Minimally invasive surgery (MIS) is the preferred technique for managing endometrial cancer. Given that uterine serous carcinoma (USC) has a predilection for multiquadrant peritoneal dissemination, our objective was to estimate the potential risk for overlooking occult peritoneal spread with the use of MIS. METHODS: A single-institution, retrospective review was conducted of patients who underwent primary surgical staging for endometrial cancer via laparotomy between 1999 and 2008. Patterns of metastases were analyzed to estimate the potential risk for understaging via MIS. RESULTS: A total of 202 USC cases met inclusion criteria. Pelvic and para-aortic nodes were positive in 59 (36%) of 166 and 43 (31%) of 138, respectively. Stage IVb disease was diagnosed in 77 (38%) of 202 patients. The majority (86%, 66/77) harbored bulky and/or multisite macroscopic abdominal implants. Isolated microscopic peritoneal disease was present in 5 of 77 cases (6% of stage IV, 2% of the entire cohort) but, in all cases, was limited to the omentum; 6 of 77 cases (8% of stage IV, 3% of the cohort) harbored a single implant in the context of a negative omentum but, in all cases, were macroscopic (locations included the ileum, the diaphragm, and the base of the mesentery). CONCLUSIONS: For providers who aim to remove all visible disease in patients with USC, the rate of extrauterine disease escaping detection using MIS is low (<3%) provided an omentectomy is performed together with staging.

Comparative outcomes assessment of uterine grade 3 endometrioid, serous, and clear cell carcinomas.

OBJECTIVE: The objective of this study is to assess effects of clinicopathologic risk factors and contemporary therapeutic interventions on high-risk uterine epithelial carcinoma outcomes. METHODS: Patient-, disease-, and treatment-specific variables were annotated. Survival was estimated via the Kaplan-Meier method. Associations were evaluated with Cox proportional hazard regression and summarized using hazard ratios. RESULTS: From 1999 through 2008, therapy with curative intent was initiated for 119 grade 3 endometrioid (G3EC), 211 serous (USC), and 40 clear cell (CCC) carcinomas. Although clinicopathologic risk factors varied among the histologic subtypes, overall survival (OS) did not differ statistically between subtypes (P=.10) or in stage-for-stage comparative analyses (stage I/II, P=.45; stage III, P=.46; stage IV, P=.65). The 5-year cause-specific survival in stage I/II was 84.8%, 89.8%, and 83.9% for G3EC, USC, and CCC, respectively; multivariable modeling identified lymphovascular space involvement (LVSI) as the only independent prognostic factor (P=.02). For stage III, 5-year OS was 49.2% and 40.0% for G3EC and USC, respectively; multivariable modeling identified age (P<.001), LVSI (P<.001), unresectable nodal disease (P=.03), and regional radiotherapy (P=.01) as independent prognostic factors. For stage IV, 5-year OS was 8.7% and 12.1% for G3EC and USC, respectively; multivariable modeling identified LVSI (P=.002), cervical stromal invasion (P=.02), and adjuvant chemotherapy (P=.02) but not residual disease as independent prognostic factors. CONCLUSIONS: When controlled for disease stage, outcomes did not differ among high-risk histologic subtypes. LVSI was a significant adverse prognostic factor within all stages. The lack of improved outcomes with contemporary therapy suggests that more innovative therapeutic approaches should be given higher priority.

Impact of tubal ligation on routes of dissemination and overall survival in uterine serous carcinoma.

OBJECTIVE: Abdominal peritoneal implants are characteristic of uterine serous carcinoma (USC). The presumed mechanism of dissemination is retrograde transit via the fallopian tube. We assessed the impact of tubal ligation (TL) on the metastatic profile and survival of USC patients. METHODS: Patient risk factors, process-of-care variables, and disease-specific parameters were annotated. Categorical variables were compared using the χ(2) test. Overall survival (OS) was estimated via the Kaplan-Meier method. RESULTS: Among 211 USC patients, fallopian tube status was documented in 142 patients; 35 had a history of TL and 107 did not. When comparing patients with and without TL, positive peritoneal cytology was present, respectively, in 18.8% vs 45.0% (P=.01) and stage IV disease in 14.3% vs 34.6% (P=.02). Using Cox models, age was the sole significant determinant of OS in stage I/II USC. By contrast, age, lymphovascular space involvement, positive cytology, and TL independently and adversely affected survival in stage III/IV USC. Adjusting for these factors in a multivariable model, the association between TL and OS among patients with advanced disease yielded a hazard ratio of 8.61 (95% CI, 3.08-24.03; P<.001). The prevalence of lymphatic metastasis and nodal tumor burden was significantly greater in patients who underwent ligation. CONCLUSION: Patients with TL had significantly lower rates of positive cytology and stage IV disease than patients without TL. The lymphatic system appeared to be the dominant mode of spread after TL and was associated with a paradoxic worsening of OS, perhaps reflecting a delay in diagnosis.

Dasatinib (BMS-35482) has synergistic activity with paclitaxel and carboplatin in ovarian cancer cells.

PURPOSE: To explore the activity of dasatinib alone and in combination with paclitaxel and carboplatin in ovarian cancer cells and to determine if dasatinib activity can be predicted based on evaluation of the SRC pathway. EXPERIMENTAL DESIGN: Microarray analysis was performed for IGROV1, OVCAR3, A2780 and SKOV3 ovarian cancer cells and the status of the genomic SRC signature pathway was determined. Cells were treated with carboplatin, paclitaxel and dasatinib individually and in combination. Pre- and post-treatment phospho-SRC (pSRC) and SRC protein expression was determined. Dose-response curves were constructed, and drug interaction was assessed by the Combination Index (CI) method. RESULTS: SRC protein expression levels reflected the SRC pathway genomic signature in the cell lines with the lowest (SKOV3) and highest (IGROV1) pathway expression, but not in those with intermediate expression (OVCAR3, A2780). Dasatinib treatment caused loss of pSRC in all cell lines, with 50% growth inhibition for IGROV1 at 70 nM, OVCAR3 at 34 nM, A2780 at 4.1 µM and SKOV3 at 530 nM. Dasatinib combined with cytotoxics yielded a synergistic effect (CI=0.46 to 0.79) in all cell lines except SKOV3. CONCLUSION: Dasatinib in combination with standard chemotherapeutic agents appears to interact in a synergistic manner in some ovarian cancer cell lines. Further research is needed to evaluate tumor cell characteristics which predict response to dasatinib.