Effectiveness of cyanoacrylate microbial sealant in the reduction of surgical site infection in gynecologic oncology procedures: A phase III single institution prospective randomized trial.

OBJECTIVES: Surgery is a cornerstone for patients with gynecologic malignancies. Surgical site infections (SSI) remain a source of post-operative morbidity. Consequences range from escalated costs, delay in adjuvant therapy, and increased morbidity. Our primary objective was to evaluate the effectiveness of a cyanoacrylate microbial sealant (CMS) to reduce post-operative SSI following laparotomy for suspected gynecologic malignancy. METHODS: Patients were randomized using a 1:1 allocation to receive either standard skin preparation or standard preparation with CMS and stratified by BMI. Patients were followed for 6weeks for SSI. Demographic data was collected through the EMR. Associations between SSI, use of CMS, and clinicopathologic factors were explored using descriptive statistics, chi-square and multivariate analysis. RESULTS: 300 patients underwent randomization. Median age of the cohort was 58. Arms were matched and there was no difference in rate of medical comorbidities. Mean BMI was 38.8kg/m2 in patients randomized to BMI≥30 and 26.3kg/m2 randomized to BMI<30. Surgical characteristics for the entire cohort: 66% malignancy, 91% clean-contaminated, 21% bowel surgery, 25% transfusion. Seventy-six (25%) patients developed a SSI: 43 patients (28%) treated with CMS, compared to 33 (21%) patients treated without CMS (p=0.18). Multivariate model demonstrated that BMI≥30 (p<0.005), surgery for malignancy (p=0.010), transfusion in the OR (p<0.001), and closure with staples (p=0.0005) were associated with post-operative SSI. CONCLUSIONS: Patients presenting to a gynecologic oncologist for surgery frequently present with multiple risk factors for SSI and laparotomy is complicated by surgical-site complications in up to 30% of cases. The addition of CMS alone does not appear to reduce risk of overall SSI. Additional risk-reducing strategies including use of antimicrobial agents and optimization of modifiable risk factors prior to surgery should be explored as pathways for reducing this significant post-operative morbidity.

A phase I study of intraperitoneal nanoparticulate paclitaxel (Nanotax®) in patients with peritoneal malignancies.

PURPOSE: This multicenter, open-label, dose-escalating, phase I study evaluated the safety, tolerability, pharmacokinetics and preliminary tumor response of a nanoparticulate formulation of paclitaxel (Nanotax®) administered intraperitoneally for multiple treatment cycles in patients with solid tumors predominantly confined to the peritoneal cavity for whom no other curative systemic therapy treatment options were available. METHODS: Twenty-one patients with peritoneal malignancies received Nanotax® in a modified dose-escalation approach utilizing an accelerated titration method. All patients enrolled had previously received chemotherapeutics and undergone surgical procedures, including 33 % with optimal debulking. Six doses (50-275 mg/m(2)) of Cremophor-free Nanotax® were administered intraperitoneally for one to six cycles (every 28 days). RESULTS: Intraperitoneal (IP) administration of Nanotax® did not lead to increases in toxicity over that typically associated with intravenous (IV) paclitaxel. No patient reported ≥Grade 2 neutropenia and/or ≥Grade 3 neurologic toxicities. Grade 3 thrombocytopenia unlikely related to study medication occurred in one patient. The peritoneal concentration-time profile of paclitaxel rose during the 2 days after dosing to peritoneal fluid concentrations 450-2900 times greater than peak plasma drug concentrations and remained elevated through the entire dose cycle. Best response assessments were made in 16/21 patients: Four patients were assessed as stable or had no response and twelve patients had increasing disease. Five of 21 patients with advanced cancers survived longer than 400 days after initiation of Nanotax® IP treatment. CONCLUSIONS: Compared to IV paclitaxel administration, Cremophor-free IP administration of Nanotax® provides higher and prolonged peritoneal paclitaxel levels with minimal systemic exposure and reduced toxicity.

Ridaforolimus as a single agent in advanced endometrial cancer: results of a single-arm, phase 2 trial.

BACKGROUND: This open-label, multicentre, phase 2 trial evaluated the efficacy and tolerability of the mammalian target of rapamycin inhibitor ridaforolimus in women with advanced endometrial cancer. METHODS: Women with measurable recurrent or persistent endometrial cancer and documented disease progression were treated with ridaforolimus 12.5 mg intravenously once daily for 5 consecutive days every 2 weeks in a 4-week cycle. The primary end point was clinical benefit response, defined as an objective response or prolonged stable disease of 16 weeks or more. RESULTS: In all, 45 patients were treated with single-agent ridaforolimus. Clinical benefit was achieved by 13 patients (29%), including 5 (11%) with confirmed partial responses and 8 (18%) with prolonged stable disease. All patients with clinical benefit response received ridaforolimus for more than 4 months. In this heavily pretreated population, the 6-month progression-free survival was 18%. Ridaforolimus was generally well tolerated: adverse events were predictable and manageable, consistent with prior studies in other malignancies. Overall, the most common adverse events were diarrhoea (58%) and mouth sores (56%); most common grade 3 or higher adverse events were anaemia (27%) and hyperglycaemia (11%). CONCLUSION: Single-agent ridaforolimus has antitumor activity and acceptable tolerability in advanced endometrial cancer patients. Further clinical evaluation of ridaforolimus is warranted.

Do uterine risk factors or lymph node metastasis more significantly affect recurrence in patients with endometrioid adenocarcinoma?

OBJECTIVES: Controversy continues over the importance of lymph node (LN) status in treating and predicting recurrence in endometrial cancer. Several predictive models are available which use uterine factors to stratify risk groups. Our objective was to determine how LN status affects recurrence and survival compared to uterine factors alone. METHODS: A retrospective review was performed of patients undergoing complete surgical staging for clinical stage 1 endometrioid adenocarcinoma of the uterus. Patients were assessed based on PORTEC 1 high intermediate risk (H-IR) criteria (2 factors : age>60, grade 3, >50% DOI), GOG-99 H-IR criteria (age >70+1 factor, age 50-70+2 factors, any age +3 factors: grade 2 or 3, LVSI, >50% DOI), and PORTEC 2 criteria. Rates of nodal involvement, recurrence rates, PFS, and OS were compared. RESULTS: We identified 352 clinical stage I patients with positive LN in 24% (87). 175 patients met PORTEC 1 eligibility and 66 met H-IR criteria. Rates of LN positivity were similar among groups (18.4% vs 19.7%, p=0.83) but recurrence rates were dissimilar (7.4% vs 27.3%, p=0.0004). Only 93 met PORTEC 2 criteria for treatment with no association between LN status, recurrence, and eligibility. 188 patients met H-IR eligibility criteria for GOG-99 with LN positive and recurrence rates higher in the H-IR group compared to GOG-99 eligible (34.6% vs 16.3%, p=0.0004, 28.3% vs. 10.6%, p=0.0002). CONCLUSIONS: Patients with H-IR disease based on uterine characteristics alone have substantial risk of nodal involvement. Knowledge of LN status may better define risk, prognosis, and postoperative treatment.

Single-agent trabectedin as second-line therapy of persistent or recurrent endometrial cancer: results of a multicenter phase II study.

OBJECTIVE: To assess the efficacy and safety of single-agent trabectedin in women with persistent or recurrent endometrial cancer. METHODS: In this open-label, phase II multicenter trial, women with persistent or recurrent endometrial carcinoma were administered trabectedin as a 3-hour intravenous infusion every 21 days at a starting dose of 1.3 mg/m(2) with dexamethasone pretreatment. Clinical objective response was the primary efficacy endpoint. Secondary endpoints were time to progression (TTP), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: The median age of the 50 women entering the study was 63 years (range, 22-87), with all having history of prior chemotherapy (92% combination regimens) and the majority having undergone surgery (92%) or radiation therapy (68%). Patients received trabectedin for a median duration of 6.8 weeks (range, 3-20). A median of 2 cycles (range, 1-6) was administered, with a median dose intensity of 0.4 mg/m(2) per week (range, 0.27-0.43) and a median relative dose intensity of 92% (range, 61.5-100.2%). One patient exhibited a complete response for an objective response rate of 2.2% (95% confidence interval [CI]: 0.1%, 11.5%). Median TTP and PFS were both 1.8 months (95% CI: 1.4, 2.9), and median OS was 6.7 months (95% CI: 5.2, 13.9). Most frequent adverse events were nausea (62%), asthenia (50%), vomiting (42%), and increased alanine aminotransferase (40%). CONCLUSION: Single-agent trabectedin displayed minimal antitumor activity in this pretreated population of women with persistent or recurrent endometrial cancer.

Intraperitoneal chemotherapy for patients with advanced epithelial ovarian cancer: a review of complications and completion rates.

OBJECTIVE: Intraperitoneal (i.p.) chemotherapy has a clear survival advantage in patients with advanced ovarian cancer, but the high rate of complications has discouraged widespread acceptance. The purpose of this study was to review the completion rate of patients receiving i.p. chemotherapy as first line treatment at a single institution and determine what factors prohibit completion of therapy. METHODS: Patients receiving i.p. chemotherapy from 1993 to 2006 were identified by hospital registries for a retrospective review. Charts were abstracted for patient demographics, clinical and pathologic findings, surgical intervention, treatment modalities, and toxicity. RESULTS: Eighty-three patients were identified who received front line treatment with i.p. chemotherapy. All patients received a platinum and taxane agent. Port placement (single lumen, venous access device) was completed at time of cytoreductive surgery (33%, n=27) or by mini-laparotomy (67%, n=56). Fifty patients (60%) completed a minimum of 6 cycles of treatment with a mean of 5 cycles. Eleven patients (13%) discontinued treatment due to catheter-related complications including infection (n=4), access difficulties (n=3), grade 4 abdominal pain (n=1), port leaking (n=1), and development of a peritoneal-vaginal fistula (n=1). Sixteen patients (19%) did not complete i.p. treatment because of chemotherapy-related toxicity. The remaining six patients did not complete chemotherapy due to disease progression or other reasons unrelated to modality of treatment. CONCLUSIONS: Few catheter-related complications were encountered in a review of front-line i.p. chemotherapy administration at a single institution using a single lumen venous access device. The majority of failures were due to persistent grade 3-4 chemotherapy toxicity. i.p. chemotherapy can be safely administered by a dedicated health-care team committed to i.p. chemotherapy as a front-line treatment.

A Phase II study of trabectedin single agent in patients with recurrent ovarian cancer previously treated with platinum-based regimens.

The objective of this study was to determine the objective response rate in patients with platinum-sensitive and platinum-resistant recurrent ovarian cancer to treatment with trabectedin (Yondelis) administered as a 3-h infusion weekly for 3 weeks of a 4-week cycle. We carried out a multicentre Phase II trial of trabectedin in patients with advanced recurrent ovarian cancer. Trabectedin (0.58 mg m(-2)) was administered via a central line, after premedication with dexamethasone, to 147 patients as a 3-h infusion weekly for 3 weeks followed by 1-week rest. Major eligibility criteria included measurable relapsed advanced ovarian cancer and not more than two prior platinum-containing regimens. Patients were stratified according to the treatment-free interval (TFI) between having either platinum-sensitive (>/=6 months TFI) or platinum-resistant disease (<6 months TFI)/platinum-refractory disease (progression during first line therapy). In the platinum-sensitive cohort, 62 evaluable patients with measurable disease had an overall response rate (ORR) of 29.0% (95% CI: 18.2-41.9%) and median progression-free survival (PFS) was 5.1 months (95% CI: 2.8-6.2). Four patients with measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST) criteria had no follow-up scans at the end of treatment. In the platinum-resistant/refractory cohort, 79 patients were evaluable with an ORR of 6.3% (95% CI: 2.1-14.2%). Median PFS was 2.0 months (95% CI: 1.7-3.5 months). Two patients with measurable disease per RECIST criteria had no follow-up scans at the end of treatment. The most frequent (>/=2% of patients) drug-related treatment-emergent grade 3/4 adverse events were reversible liver alanine transferase elevation (10%), neutropaenia (8%), nausea, vomiting, and fatigue (5% each). Trabectedin is an active treatment, with documented responses in patients with platinum sensitive advanced relapsed ovarian cancer, and has a manageable toxicity profile.

Salvage of isolated vaginal recurrences in women with surgical stage I endometrial cancer: a multiinstitutional experience.

The objective of this study was to evaluate the treatment outcomes and risk factors of women with surgical stage I endometrial adenocarcinoma who were initially treated with surgery alone and subsequently developed isolated vaginal recurrences. Patients with surgical stage I endometrial adenocarcinoma diagnosed from 1975 to 2002 were identified from tumor registry databases at seven institutions. All patients were treated with surgery alone including a total hysterectomy, bilateral salpingo-oophorectomy, pelvic (+/- para-aortic) lymph node dissection, and peritoneal cytology and did not receive postoperative radiation therapy. Vaginal recurrences were documented histologically. Metastatic disease in the chest and abdomen was excluded by radiologic studies. Overall survival was calculated by the Kaplan-Meier method. Sixty-nine women with surgical stage I endometrial cancer with isolated vaginal recurrences were identified. Of the 69 patients, 10 (15%) were diagnosed with stage IA disease, 43 (62%) were diagnosed with stage IB disease, and 16 (23%) were diagnosed with stage IC disease. Patients diagnosed with grade 1 disease were 22 (32%), grade 2 disease were 26 (38%), and grade 3 disease were 21 (30%). Among women, 81% with isolated vaginal recurrences were salvaged with radiation therapy. The mean time to recurrence was 24 months, and the mean follow-up was 63 months. Among women, 18% died from subsequent recurrent disease. The 5-year overall survival was 75%. The majority of isolated vaginal recurrences in women with surgical stage I endometrial cancer can be successfully salvaged with radiation therapy, further questioning the role of adjuvant therapy for patients with uterine-confined endometrial cancer at the time of initial diagnosis.

Ovarian cancer metastatic to the brain: what is the optimal management?

PURPOSE: To better define determinants of survival and optimal management strategies for patients with ovarian cancer and brain metastases. METHODS: A review of literature using Medline identified 15 case series of ovarian cancer patients with brain metastases (OBM). Each article was abstracted for survival data, and in all cases, the intervals between ovarian cancer diagnosis and brain metastasis identification, and between brain metastasis identification and last follow-up were recorded. Cases were categorized by patient characteristics and treatment modality for brain metastases. Estimated survival probabilities were plotted using the Kaplan-Meier method with differences between subgroups analyzed by the log-rank test. Cox proportional hazards model was used to identify independent prognostic factors age, number of metastasis, and treatment modality associated with survival. RESULTS: The median interval from ovarian cancer diagnosis to brain metastasis in 104 identified patients was 19.5 months. Brain metastasis was single in 43%, multiple in 41%, and not reported in 16% of cases. About 81.7% of patients were treated for their brain metastases using external radiation therapy (XRT), chemotherapy, and surgery. XRT was utilized in 76% of 104 patients and in 93% of treated patients. The most commonly used modalities were XRT alone (40%) and craniotomy and XRT (17%). The median survival (MS) for all patients regardless of treatment type was 6 months. Patients who received any treatment lived longer than those not receiving surgery/chemotherapy/XRT (MS; 7 months vs. 2 months, P = 0.0001). Patients with single brain metastasis had a longer median survival (21 months vs. 6 months, P = 0.049) when treated with craniotomy plus radiation and/or chemotherapy compared to treatment regimens that excluded craniotomy. In a multivariate analysis, only treatment type was significant in predicting survival. CONCLUSION: OBM portends a poor prognosis, however, long-term survival is possible. Patients appear to benefit from therapy, especially selected groups of OBM patients with single brain metastasis treated with radiation therapy and surgery.

Nodal distribution and its significance in FIGO stage IIIc endometrial cancer.

OBJECTIVE: The aim of this study was to describe the distribution of nodal disease in FIGO Stage IIIc endometrial cancer (EC) and to evaluate whether nodal distribution is related to recurrence and survival. METHODS: Charts from EC patients with FIGO Stage IIIc disease from 1989 to 1998 were abstracted for clinicopathologic data, pelvic (PLN) and para-aortic (PALN) nodal involvement, number of positive/removed nodes, and extranodal disease spread. Patterns of nodal distribution were evaluated for site of first recurrence and survival. Associations between variables were tested by chi(2) and Wilcoxon rank sums. Survival analyses were performed by the Kaplan-Meier method. RESULTS: Of 607 EC patients evaluated, 47 were identified with FIGO Stage IIIc disease. All 47 patients underwent hysterectomy and PLN sampling, and 42/47 had PALN sampling. The median number of PLN removed was 16 (range 2-35), and the median number of PALN was 7 (0-18). Stage IIIc disease was defined by positive PLN alone in 43%, positive PLN and PALN in 40%, and positive PALN alone in 17%. Positive peritoneal cytology and/or adnexal metastasis were present in 12 patients. Only 1/12 of these patients had isolated positive PLN whereas 11/12 had positive PALN (P = 0.007). An increasing number of positive PLN was associated with PALN metastasis (P = 0.0001), and of the 10 patients with bilateral PLN involvement, 9/10 also had positive PALN (P = 0.001). Sites of first recurrence were similar regardless of whether PALN were positive. At a median follow-up of 37 months, the 3-year survival estimate was 70% for patients with positive PALN versus 87% for those with isolated PLN disease (P = 0.22). For all patients neither the total number of positive PLN nor the total number of PLN or PALN removed was associated with survival. CONCLUSIONS: PALN involvement is common in patients with FIGO Stage IIIc endometrial cancer, suggesting that PLN sampling alone may result in underdiagnosis of disease. Patients with positive PALN had more extensive disease, but survival and patterns of failure were not significantly different from those with disease confined to PLN, suggesting that lymph node dissection may have a therapeutic role.

Analysis of FIGO Stage IIIc endometrial cancer patients.

OBJECTIVE: The aim of this study was to analyze FIGO Stage IIIc endometrial cancer (EC) patients to better define clinicopathologic associations, patterns of failure, and survival. METHODS: Charts were abstracted from EC patients with lymph node metastasis from 1989 to 1998. Data on clinicopathologic variables, adjuvant treatment, site of first recurrence, and survival were collected. Associations between variables were tested by chi(2) and Wilcoxon rank sums. Survival analyses were performed by the Kaplan-Meier method, and multiple regression analysis was done by the Cox proportional hazards model. RESULTS: From 607 EC patients evaluated, 47 (8%) were identified with FIGO Stage IIIc disease. All 47 underwent hysterectomy and pelvic lymph node (PLN) sampling, and 42/47 had para-aortic lymph node (PALN) sampling. Stage IIIc disease was defined by positive PLN alone in 38%, positive PLN and PALN in 41%, and positive PALN alone in 17%. Twelve of 47 also had positive peritoneal cytology and/or adnexal metastases. Grade III tumors were present in 56% and >50% myometrial invasion in 61%. No association between depth of invasion (DOI) and grade was seen, however. Nearly 1/3 of cases had papillary serous or clear cell histology. Postoperative adjuvant treatment included whole abdominal radiation (36%), pelvic radiation with (19%) and without (17%) extended field, chemotherapy (17%), and oral progestins (11%). The 3-year and 5-year survival estimates for all patients were 77 and 65%, respectively. At a median follow-up of 37 months, 5 patients are alive with disease, and 10 are dead of disease. A distant site of first recurrence was most common (21%), followed by pelvic failure (9%). Only 1 patient has had an abdominal recurrence. Univariate predictors of survival included age, DOI, and extranodal disease, but not grade, histology, or PALN involvement. For the 12 patients with nodal disease and positive cytology and/or adnexa, 3-year survival was 39% versus 93% for those patients without evidence of extranodal disease. In a multivariate analysis only DOI was an independent predictor of survival (P = 0.03). CONCLUSIONS: Once lymph node involvement occurs, the importance of additional extranodal disease increases. Consideration of substaging Stage IIIc patients based on positive adnexa or cytology is supported by the data. The extent which adjuvant treatments contributed to the 77% 3-year survival remains to be defined. The patterns of failure suggest a possible role for combined modalities in future treatments.

Bowel resection at the time of primary cytoreduction for epithelial ovarian cancer.

BACKGROUND: The purpose of this study was to determine the morbidity and survival associated with bowel resection at the time of primary cytoreductive surgery for ovarian cancer. STUDY DESIGN: We reviewed all patients undergoing bowel resection by gynecologic oncology faculty at the time of primary cytoreduction for advanced epithelial ovarian cancer diagnosed between 1983 and 1995. RESULTS: There were 105 patients meeting the above criteria. The median age was 65 years (range 34 to 85 years). There were 76 stage III and 25 stage IV cancers. The primary indication for bowel resection was tumor debulking in 92% of the patients. Seventy patients had segmental resection of the colon only, and 22 patients underwent resections that included the large and small bowels. Mean operating time was 260 minutes and mean estimated blood loss was 1,447 mL. Thirty-three (31%) patients were optimally cytoreduced to less than 1 cm residual disease. Ten patients experienced major complications directly related to bowel resection, including bowel fistula (4 patients), early postoperative bowel obstruction (5 patients), and stomal hernia (1 patient). Other morbidity included ileus for more than 10 days (18 patients), cardiac complications (17 patients), pneumonia (8 patients), sepsis (5 patients), and thromboembolism (4 patients). Six patients died and five patients required reexploration within 30 days of operation. Patients with preoperative bowel obstruction and suboptimal residual disease were more likely to have postoperative morbidity. Median survival in the optimally debulked patients was 35 months compared with 18 months in patients suboptimally cytoreduced (p = 0.006). Multivariate analysis demonstrated that optimal debulking (p = 0.009) and platinum chemotherapy (p = 0.00006) were independently associated with improved survival. Age, International Federation of Gynecologia Oncologists stage, American Society of Anesthesiologists class, and paclitaxel chemotherapy did not influence survival. CONCLUSIONS: In patients undergoing bowel resection at the time of primary cytoreduction for ovarian cancer, optimal cytoreduction to less than 1 cm residual disease results in improved survival. Morbidity is common but is comparable to other published series of ovarian cancer patients undergoing primary cytoreductive surgery without bowel resection. Additionally, patients with preoperative bowel obstruction and suboptimal residual disease are more likely to have serious morbidity.

Retrospective review of gynecologic oncology patients with therapy-induced neutropenic fever.

We reviewed the course and outcome of gynecologic oncology patients with neutropenic fever (NF), and identified low-risk patients who might be candidates for outpatient management. Charts from patients with the discharge diagnosis of NF from 1990 to 1994 were reviewed for variables related to the febrile neutropenic episode. Outcome was evaluated in terms of the duration of neutropenia, length of hospital stay, NF treatment result, incidence of positive blood cultures, dose reduction in the subsequent course of chemotherapy, and death. Statistical associations between variables and outcome parameters were examined by the Student t test and chi 2 or Fisher's exact tests as indicated. Multivariate analysis by logistic regression was done to determine independent significance of variables. Forty-five episodes of NF were identified involving 40 patients. The median duration of neutropenia following the diagnosis of NF was 2.5 days. The source of fever was unexplained by exam or cultures in 25/45 (56%) episodes. There were two (4%) deaths. In 16/45 episodes, patients had been treated with at least one prior regimen of chemotherapy (median, eight courses). Episodes of NF in patients receiving second-line chemotherapy were associated with a prolonged time of neutropenia (> 3 days, P = 0.058); however, this did not translate into increased hospital stay, treatment failure, or death. Thirteen of 45 (29%) NF episodes developed in patients while already hospitalized for medical or surgical conditions. In this group, cultures were positive in 64% of cases. The remaining 32 NF episodes developed in patients while at home. Patients who developed outpatient NF (ONF) had positive cultures in 23% of cases (P = 0.08) and had a median hospital stay of 4 days. No patient with ONF who remained hemodynamically stable during the first 12 hr of admission suffered serious morbidity. In a multivariate analysis, only bacteremia approached statistical significance in predicting a longer hospital stay (P = 0.07), and no variable studied was predictive of prolonged NF in the ONF group. Our retrospective analysis indicates that patients with ONF who remain stable during the initial 12 hr of hospitalization might safely be discharged home with appropriate antibiotics. Prospective study of outpatient management of NF is required to confirm these findings.

Endometrioid adenocarcinoma of the ovary and its relationship to endometriosis.

In order to better understand the clinical presentation and biologic behavior of ovarian carcinomas arising in endometriosis, we performed a historical cohort study of all women with endometrioid adenocarcinoma of the ovary (ECO) diagnosed between 1979 and 1991 at our institutions. A review of pathology reports determined the presence or absence of coexisting endometriosis. Cancers adjacent to endometriosis on the same ovary or arising within endometriosis were labeled endometriosis-associated endometrioid adenocarcinoma (EAEA), while all others were considered typical endometrioid adenocarcinoma (TEA). Associations between tumor type and clinicopathologic variables were analyzed by chi 2 and Fisher's exact tests as indicated. Disease-free interval (DFI) and overall survival were estimated using the Kaplan-Meier method. The independent prognostic significance of clinicopathologic variables was determined by multivariate analysis using the Cox proportional hazards regression model. Of 91 ECO patients identified, 63 (69%) had TEA and 28 (31%) had EAEA. Significant differences between TEA and EAEA existed for age at diagnosis (greater than 55 years; 56 vs 32%, P = 0.039), nulliparity (19 vs 46%, P = 0.007), stage (I and II combined; 37 vs 70%, P = 0.004), and disease status at completion of primary surgery (complete tumor resection; 47 vs 70%, P = 0.04). Synchronous atypical endometrial hyperplasia or uterine carcinoma was found in 7/63 (11%) TEA versus 7/28 (25%) EAEA cases (P = 0.054). Estimated 5-year DFI by life table analysis was significantly longer in the EAEA than in the TEA cohorts (57 vs 25%, P = 0.02); however, the 5-year survival difference was not significant (59 vs 45%, P = 0.18). Multivariate analysis identified only stage as an independent prognostic factor in predicting both DFI and survival. In conclusion, women with EAEA are significantly younger, present with earlier stage disease, and have a longer disease-free survival than those with TEA. These factors may reflect a more favorable biologic behavior of ECO when arising in association with endometriosis.