Concentration of uterine cancer surgical care among the elderly: a population-based perspective.

OBJECTIVES: To characterize the primary surgical care and short-term outcomes for uterine cancer in women age > or = 80 years compared to younger women. METHODS: A statewide hospital discharge database was used to identify women that underwent primary surgery for uterine cancer from 1994 to 2005. Logistic regression models were used to evaluate for significant differences in demographic characteristics and short-term outcomes comparing women aged > or = 80 years with those aged < 80 years. RESULTS: A total of 6181 women were identified, women aged > or = 80 years comprised 10.6% (n=656) of cases. Elderly women were 1.3 times more likely to be managed by high volume surgeons (41% vs. 35%, p=0.00). The 30-day mortality rate was 4.3 fold higher for the elderly group (4.27% vs. 1.03%, p=0.00). Among the elderly group, there was a 62% reduction in the risk of 30-day mortality when they were managed at high volume hospitals (95% CI: 0.18-0.80, p=0.01), and a 44% reduction in the risk of 30-day mortality when management was performed by high volume surgeons (95% CI: 0.21-1.48, p=0.22). The cost of care among elderly women managed at high volume centers ($10,425 vs. $9454, p=0.02) and by high volume surgeons ($11,260 vs. $9400, p<0.00) was higher when compared to the low volume groups. CONCLUSIONS: Primary surgical care of elderly women with uterine cancer by high volume providers is associated with better short-term outcomes but increases healthcare expenditure compared to low volume providers. Increased efforts to concentrate the operative care of this patient population in experienced, high volume centers are warranted.

Predictors of extended intensive care unit resource utilization following surgery for ovarian cancer.

OBJECTIVE: To identify perioperative variables associated with length of stay in the surgical intensive care unit (SICU), and overall cost of hospitalization in order to optimize resource utilization among patients undergoing surgery for ovarian cancer. METHODS: A retrospective analysis of patients admitted to the SICU immediately after surgery for ovarian cancer between 1/1/94 and 6/30/04 was performed. Patients admitted to the SICU were categorized in two groups. Those admitted for < 48 h were compared patients requiring a SICU stay > or = 48 h. Perioperative variables were compared across the two groups by univariate and multivariate logistic regression analysis. RESULTS: A total of 95 patients were admitted to the SICU immediately after surgical management for ovarian cancer, with 57% requiring a stay > or = 48 h. Patient age = 63 years was associated with an increase risk of admission to the SICU for > or = 48 h (OR: 5.9, 95% CI: 1.72-20.50, p=0.005). Patients with administration of > or = 5 l of crystalloid solution during surgery were 8 times more likely to have prolonged admission to the SICU (95% CI: 2.34-27.57, p=0.001). Furthermore, a preoperative serum albumin level > or = 3.5 g/dl was associated with a reduction in the risk of prolonged admission to the SICU (OR: 0.23, 95% CI: 0.07-0.77, p=0.02). The average cost of hospitalization per patient was $33,086. Cost of hospital care was strongly associated with SICU length of stay (p=0.005). CONCLUSION: Extensive fluid resuscitation during surgery, poor nutritional status, and > or = 63 years are associated with a prolonged postoperative SICU stay. These data may facilitate a reduction in unnecessary ICU admissions for patients without these risk factors and thereby optimize resource utilization following surgery for ovarian cancer.

Clinical significance of Her-2/neu overexpression in uterine serous carcinoma.

OBJECTIVE: To evaluate the clinico-pathologic characteristics and survival outcome associated with overexpression of Her-2/neu in patients with uterine serous carcinoma (USC). METHODS: Twenty-five patients with a confirmed pathologic diagnosis of USC and available paraffin embedded tissue samples treated at the Johns Hopkins Medical Institutions from 1/1/1992 through 12/31/2000 were identified retrospectively. Her-2/neu expression was evaluated by immunohistochemistry using HercepTest (DAKO). Clinical data were abstracted from medical records. Clinico-pathologic characteristics associated with Her-2/neu overexpression like staging, histology, lymph-vascular space involvement, and myometrial invasion were evaluated using logistic regression analysis and Fisher's exact test. Analyses of overall survival time were performed using the Kaplan-Meier method and Cox proportional hazards regression models. RESULTS: Twelve (48%) of the 25 USC cases demonstrated Her-2/neu overexpression. There was a significant difference in Her-2/neu overexpression and surgical staging (81.8% vs. 28.6%, P = 0.01). Survival analysis according to primary tumor characteristics revealed that overexpression of Her-2/neu was significantly associated with a worse survival outcome (HR = 6.58, 95%CI: 1.36-31.89, P = 0.02). CONCLUSIONS: Her-2/neu overexpression is associated with advanced surgical stage USC and poor survival outcome. These data may be useful in guiding the clinical management of patients with USC and have potential implications for the development of novel treatment strategies.

Surgical care of elderly women with ovarian cancer: a population-based perspective.

OBJECTIVE: To characterize the primary surgical care and short-term outcomes for ovarian cancer in women aged 80 years and older compared to women younger than 80 years. METHODS: A statewide hospital discharge database was used to identify women undergoing primary surgery for ovarian cancer from 1990 to 2000. Logistic regression models were used to evaluate for significant differences in demographic characteristics and short-term outcomes comparing women aged > or = 80 years with those aged <80 years. RESULTS: A total of 2417 women were identified; women aged > or = 80 years comprised 7.0% (n = 168) of cases. Compared to younger women, those aged > or = 80 years were significantly more likely to be admitted under emergent conditions (25.6% vs. 14.9%, P < 0.0003) and less likely to undergo surgery at a university hospital (6.6% vs. 18.6%, P = 0.001). Ovarian cancer patients aged > or = 80 years were significantly more likely to have a longer hospital stay (median 10 days vs. 7 days, P < 0.0001) and a higher adjusted cost of hospital related care (median dollar 76,760 vs. dollar 52,649, P < 0.0001). The 30-day mortality rate was 2.3-fold higher for women aged > or = 80 years (5.4% vs. 2.4%, P = 0.036). For women aged > or = 80 years, there was a trend toward a higher risk of peri-operative death among low-volume hospitals (8.8%) compared to high-volume hospitals (3.0%, P = 0.16). CONCLUSION: Primary surgical care for ovarian cancer in women aged > or = 80 years is associated with utilization of significant health care resources and worse short-term outcomes compared to younger women. Additional research is needed to identify opportunities for improving the cost-effectiveness of care in this population.

Abdominal carcinomatosis in women with a history of breast cancer.

OBJECTIVES: The goals of this study were to: (1) characterize the etiology of abdominal carcinomatosis, (2) identify clinical features predictive of primary ovarian/peritoneal cancer, and (3) evaluate the survival impact of cytoreductive surgery among patients with advanced ovarian/peritoneal cancer and a history of breast cancer. METHODS: Patients with a history of prior breast cancer undergoing surgical exploration for abdominal carcinomatosis between 1/1/88 and 12/31/02 were retrospectively identified from tumor registry databases. Logistic regression analysis was used to explore clinical characteristics predictive of primary ovarian/peritoneal cancer versus recurrent breast cancer. Survival analyses and comparisons were performed using the Kaplan-Meier and Cox proportional hazard models. RESULTS: Seventy-nine patients underwent surgery for abdominal carcinomatosis a median of 5.39 years after initial breast cancer diagnosis. Abdominal carcinomatosis was due to primary ovarian/primary peritoneal cancer in 74.7% of cases. A history of Stage I breast cancer [OR = 10.73, 95%CI = 2.6-43.7, P < 0.001] and the lack of a prior breast cancer recurrence [OR = 10.60, 95%CI = 2.5-45.2, P < 0.001] were independently predictive of primary ovarian/peritoneal cancer. Among patients with primary ovarian/peritoneal cancer, optimal (< or =1 cm) cytoreductive surgery was associated with a median survival of 44.0 months compared to 18.0 months for patients with suboptimal residual disease [HR = 6.81, 95%CI = 3.37-13.77, P < 0.0001]. Recurrent breast cancer was associated with a median survival time of 6.4 months. CONCLUSIONS: Among patients with prior breast cancer presenting with abdominal carcinomatosis, early-stage disease and the absence of a prior recurrence were predictive of primary ovarian/peritoneal cancer. Optimal cytoreductive surgery was associated with a significant survival advantage for patients with primary ovarian/peritoneal cancer.

Cancer of the uterine corpus among Hispanic women living in the United States: patterns of staging, diagnosis, and primary treatment.

OBJECTIVES: To evaluate the demographic characteristics, clinico-pathological features, and patterns of care of uterine cancer among Hispanic women living in the United States. METHODS: The National Cancer Institute (NCI)'s Surveillance, Epidemiology, and End Results Program (SEER), was used to identify 1618 Hispanic, 17,814 non-Hispanic white (NHW), and 1477 non-Hispanic black (NHB) women diagnosed with primary carcinoma of the uterus during 1996-2000. Data derived from hospital registries was analyzed, for differences in case presentation, staging, and primary treatment by race/ethnicity and age. Statistical analysis was performed using the IBM PC packages, Stata, and the SAS system. RESULTS: Hispanic women were statistically significantly more likely to present with uterine cancer at a younger age compared to non-Hispanic groups. Hispanic women with early stage disease (stage I-II) were also statistically significantly more likely to be younger than 55 years at the time of diagnosis (NHW: OR=0.40, 95% CI: 0.35-0.45; P = 0.0000, NHB: OR=0.45, 95% CI: 0.38-0.55; P=0.0000). Hispanics were statistically significant less likely than NHB to present with advanced stage disease, high tumor grade, and receive radiation therapy for uterine cancer. CONCLUSIONS: Hispanic women are more likely to be diagnosed with uterine cancer at a younger age than other ethnic groups. The etiologic factors related to this presentation have yet to be precisely defined. Additional epidemiological and demographic studies, addressing such factors as body mass index and other medical co-morbidities, are needed to identify opportunities for improved cancer prevention and control in this population of women.

Ovarian cancer surgery in Maryland: volume-based access to care.

PURPOSE: To characterize the patterns of primary surgical care for ovarian cancer in a statewide population according to annual surgeon and hospital case volume. METHODS: The Maryland hospital discharge database was accessed for annual surgeon and hospital ovarian cancer case volume for the time intervals: 1990-1992, 1993-1995, 1996-98, and 1999-2000. Annual surgeon case volume was categorized as low (/=10). Annual hospital case volume was categorized as low (/=20). Logistic regression models were used to evaluate for significant trends in case volume distribution over time and factors associated with access to high-volume care. RESULTS: Overall, 2417 cases were performed by 531 surgeons at 49 hospitals. The distribution according to annual surgeon case volume was low (56.3%), intermediate (9.2%), and high (34.5%). Between 1993 and 2000, there was no significant increase in the proportion of cases performed by high-volume surgeons (OR = 1.03, 95% CI = 0.81-1.33, P = 0.79). Access to high-volume surgeons was positively associated with care at high-volume hospitals and negatively associated with residence >/=50 miles from a high-volume hospital. The overall hospital volume case distribution was low (49.6%), intermediate (27.6%), and high (22.8%). There was a statistically significant decrease in access to high-volume hospitals between 1990 and 1998 (OR = 0.39, 95% CI = 0.30-0.50, P < 0.0001). CONCLUSION: A large proportion of primary ovarian cancer surgeries are performed by low-volume surgeons at low-volume hospitals. In light of positive volume-outcomes data for malignancies treated with technically complex operative procedures, increased efforts to concentrate the surgical care of women with ovarian cancer are warranted. Condensed abstract. A large proportion of primary ovarian cancer surgeries are performed by low-volume surgeons at low-volume hospitals. In light of positive volume-outcomes data for malignancies treated with technically complex operative procedures, increased efforts to concentrate the surgical care of women with ovarian cancer are warranted.

Phase I and clinical pharmacology of a type I and II, 5-alpha-reductase inhibitor (LY320236) in prostate cancer: elevation of estradiol as possible mechanism of action.

OBJECTIVES: To study the safety, pharmacokinetics, biologic activity, and preliminary efficacy of the bispecific 5-alpha-reductase inhibitor (LY320236) in prostate cancer. METHODS: Fifty-one patients with recurrent or metastatic prostate cancer were sequentially (nonrandomly) assigned in cohorts to receive one of five single daily oral doses of LY320236 (10, 50, 150, 250, and 500 mg). Serial evaluations included serum testosterone, dihydrotestosterone, androstenediol glucuronide, estradiol, and pharmacokinetics on days 1, 29, and 57. Toxicity assessments, x-rays/scans, and blood tests, including serum prostate-specific antigen (PSA) determination, were done at regular intervals. RESULTS: Overall, treatment was well tolerated, with 3 of 51 patients developing reversible grade 3-4 toxicity (one diarrhea, two elevated liver enzymes). Peak blood levels (2 to 3 hours after drug administration) were greater for doses of 150 mg or greater compared with less than 150-mg doses with slow accumulation. Serum levels of testosterone, dihydrotestosterone, and androstenediol glucuronide did not change significantly during treatment; however, a statistically significant increase occurred in serum estradiol levels in both the castration and noncastration groups. One of 26 in the noncastration group and 4 (27%) of 15 in the castration group with baseline PSA levels of 5 ng/mL or greater had a 50% or greater PSA decline for 4 weeks or longer. CONCLUSIONS: LY320236 treatment is associated with modest reversible toxicity. An elevation of estradiol levels was seen in both castration and noncastration groups, although PSA declines were primarily seen in the castration group. The absence of cardiovascular toxicity suggests that this agent may be a promising alternative to exogenous estrogens in patients with prostate cancer who demonstrate evidence of disease progression after initial androgen deprivation treatment.

Clinically occult recurrent ovarian cancer: patient selection for secondary cytoreductive surgery using combined PET/CT.

OBJECTIVE: The aim of this study was to evaluate the utility of combined positron emission tomography/computed tomography (PET/CT) for identifying ovarian cancer tumor masses > or =1 cm in patients with clinically occult recurrent disease by conventional CT imaging. METHODS: Twenty-two patients with epithelial ovarian cancer, rising serum CA125 levels, and negative or equivocal conventional CT imaging > or =6 months after primary therapy underwent combined PET/CT imaging followed by surgical reassessment. Fisher's exact test was used to measure the ability of PET/CT to predict macroscopic disease > or =1 cm. RESULTS: The median patient age was 55 years, and 91% of patients had FIGO Stage IIIC/IV disease. The median increase in serum CA125 was 24 U/ml (range 10 to 330 U/ml). Conventional CT was reported as negative (n = 15) or equivocal (n = 7) in all cases. Eighteen patients were ultimately found to harbor recurrent ovarian cancer measuring > or =1 cm at the time of surgery, with a median maximal tumor diameter of 2.3 cm (range 1.5 to 3.2 cm). The overall patient-based accuracy of PET/CT in detecting recurrent disease > or =1 cm was 81.8%, with a sensitivity of 83.3% and positive predictive value of 93.8% (P = 0.046). Of patients with recurrent ovarian cancer > or =1 cm, complete cytoreduction to no gross residual tumor was accomplished in 72.2%. CONCLUSION: PET/CT imaging demonstrates high sensitivity and positive predictive value in identifying potentially resectable, macroscopic recurrent ovarian cancer among patients with biochemical evidence of recurrence and negative or equivocal conventional CT findings. In appropriately selected patients, early identification of macroscopic recurrent disease may facilitate complete surgical cytoreduction.

Recurrent micropapillary serous ovarian carcinoma.

BACKGROUND: The objectives of the current study were to: 1) characterize the clinical outcome of patients with recurrent micropapillary serous ovarian carcinoma (MPSC) and 2) evaluate the survival impact of secondary cytoreductive surgery and other prognostic variables. METHODS: Twenty-six patients with recurrent MPSC were identified retrospectively from hospital and tumor registry databases. Survival curves were generated from the time of tumor recurrence using the Kaplan-Meier method and statistical comparisons were performed using the log-rank test, logistic regression analysis, and the Cox proportional hazards regression model. RESULTS: The median age of the patients at the time of recurrence was 46 years. The mean progression-free interval was 31.6 months, and 92% of patients had advanced stage disease at the time of the initial diagnosis. Twenty-one patients underwent secondary cytoreductive surgery; tumor debulking was performed in 90.5% of cases and 52.4% of patients required an intestinal resection. Optimal resection (residual disease < or = 1 cm) was achieved in 15 patients (71.4%). Patients undergoing optimal secondary cytoreduction had a median survival time of 61.2 months from the date of disease recurrence, compared with 25.5 months for those patients in whom suboptimal residual disease remained (P < 0.02) and 29.9 months for nonsurgical patients (P < 0.01). On multivariate analysis, optimal secondary cytoreduction was found to be the only independent predictor of survival. Salvage chemotherapy produced an objective response in 25% of patients with measurable disease. The administration of chemotherapy prior to surgical intervention was associated with a trend toward worse survival and a lower likelihood of optimal secondary cytoreduction. CONCLUSIONS: Optimal secondary cytoreductive surgery is feasible in the majority of patients with recurrent MPSC and is an independent predictor of subsequent survival. Surgical intervention should be considered for those patients with recurrent MPSC. [See editorials on pages 675-6 and 677-80, this issue.]

Micropapillary serous ovarian carcinoma: surgical management and clinical outcome.

OBJECTIVES: The objectives of this study were to characterize the prognostic features of micropapillary serous ovarian carcinoma (MPSC), examine the clinical impact of surgical staging, and define the role of cytoreductive surgery for patients with advanced disease. METHODS: Fifty-one patients with MPSC were identified from hospital and tumor registry databases. Demographic, operative, pathologic, and follow-up data were abstracted retrospectively. Survival curves were generated using the Kaplan-Meier method, and statistical comparisons were performed using the log rank test, logistic regression analysis, and the Cox proportional hazards regression model. RESULTS: The median age at diagnosis was 45 years, and follow-up extended to a median of 43.0 months. Stage I/II disease was present in 25.5% of patients and no disease-related deaths were observed in this group. Stage III disease was discovered in 29.4% of patients with tumor clinically confined to the ovaries. Stage III/IV disease (74.5% of cases) was associated with median progression-free and overall survival times of 32.8 and 114.2 months, respectively. Menopausal status and the anatomic extent of disease were significantly associated with survival outcome. However, the strongest independent predictor of survival for patients with advanced disease was the amount of residual tumor. Median overall survival for patients with optimal cytoreduction (residual disease 1 cm residual tumor (P < 0.0002). CONCLUSIONS: MPSC carries a significant risk of extraovarian spread; however, adequately sampled Stage I/II disease is associated with a favorable prognosis. Optimal cytoreduction is associated with improved survival and should be the primary therapeutic objective for patients with advanced-stage MPSC.