GOG 244 - The Lymphedema and Gynecologic cancer (LeG) study: The impact of lower-extremity lymphedema on quality of life, psychological adjustment, physical disability, and function.

OBJECTIVE: To assess quality of life (QOL) in patients who developed lower-extremity lymphedema (LLE) after radical gynecologic cancer surgery on prospective clinical trial GOG 244. METHODS: The prospective, national, cooperative group trial GOG-0244 determined the incidence of LLE and risk factors for LLE development, as well as associated impacts on QOL, in newly diagnosed patients undergoing surgery for endometrial, cervical, or vulvar cancer from 6/4/2012-11/17/2014. Patient-reported outcome (PRO) measures of QOL (by the Functional Assessment of Cancer Therapy [FACT]), body image, sexual and vaginal function, limb function, and cancer distress were recorded at baseline (within 14 days before surgery), and at 6, 12, 18, and 24 months after surgery. Assessments of LLE symptoms and disability were completed at the time of lower limb volume measurement. A linear mixed model was applied to examine the association of PROs/QOL with a Gynecologic Cancer Lymphedema Questionnaire (GCLQ) total score incremental change ≥4 (indicative of increased LLE symptoms) from baseline, a formal diagnosis of LLE (per the GCLQ), and limb volume change (LVC) ≥10%. RESULTS: In 768 evaluable patients, those with a GCLQ score change ≥4 from baseline had significantly worse QOL (p < 0.001), body image (p < 0.001), sexual and vaginal function (p < 0.001), limb function (p < 0.001), and cancer distress (p < 0.001). There were no significant differences in sexual activity rates between those with and without LLE symptoms. CONCLUSIONS: LLE is significantly detrimental to QOL, daily function, and body image. Clinical intervention trials to prevent and manage this chronic condition after gynecologic cancer surgery are needed.

Standardization of lower extremity quantitative lymphedema measurements and associated patient-reported outcomes in gynecologic cancers.

Practice changing standardization of lower extremity lymphedema quantitative measurements with integrated patient reported outcomes will likely refine and redefine the optimal risk-reduction strategies to diminish the devastating limb-related dysfunction and morbidity associated with treatment of gynecologic cancers. The National Cancer Institute (NCI), Division of Cancer Prevention brought together a diverse group of cancer treatment, therapy and patient reported outcomes experts to discuss the current state-of-the-science in lymphedema evaluation with the potential goal of incorporating new strategies for optimal evaluation of lymphedema in future developing gynecologic clinical trials.

GOG 244-The lymphedema and gynecologic cancer (LEG) study: Incidence and risk factors in newly diagnosed patients.

OBJECTIVES: To evaluate the incidence and risk factors for lymphedema associated with surgery for gynecologic malignancies on GOG study 244. METHODS: Women undergoing a lymph node dissection for endometrial, cervical, or vulvar cancer were eligible for enrollment. Leg volume was calculated from measurements at 10-cm intervals starting 10 cm above the bottom of the heel to the inguinal crease. Measurements were obtained preoperatively and postoperatively at 4-6 weeks, and at 3-, 6-, 9-, 12-, 18-, and 24- months. Lymphedema was defined as a limb volume change (LVC) ≥10% from baseline and categorized as mild: 10-19% LVC; moderate: 20-40% LVC; or severe: >40% LVC. Risk factors associated with lymphedema were also analyzed. RESULTS: Of 1054 women enrolled on study, 140 were inevaluable due to inadequate measurements or eligibility criteria. This left 734 endometrial, 138 cervical, and 42 vulvar patients evaluable for LVC assessment. Median age was 61 years (range, 28-91) in the endometrial, 44 years (range, 25-83) in the cervical, and 58 years (range, 35-88) in the vulvar group. The incidence of LVC ≥10% was 34% (n = 247), 35% (n = 48), and 43% (n = 18), respectively. The peak incidence of lymphedema was at the 4-6 week assessment. Logistic regression analysis showed a decreased risk with advanced age (p = 0.0467). An exploratory analysis in the endometrial cohort showed an increased risk with a node count >8 (p = 0.033). CONCLUSIONS: For a gynecologic cancer, LVC decreased with age greater than 65, but increased with a lymph node count greater than 8 in the endometrial cohort. There was no association with radiation or other risk factors.

A randomized phase II study of cabozantinib versus weekly paclitaxel in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer: An NRG Oncology/Gynecologic Oncology Group study.

INTRODUCTION: Cabozantinib is a receptor tyrosine kinases inhibitor that targets MET (c-MET), VEGF receptor 2 (VEGFR2), RET, AXL, KIT, FLT-3, and TIE-2 and previously showed promising single agent activity in recurrent ovarian cancer. METHODS: This was an open label, 1:1 randomized study of cabozantinib 60 mg orally (PO) daily versus weekly paclitaxel 80 mg/m2 given 3 out of 4 weeks (NCT01716715); 111 patients were enrolled. Eligibility included persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma and at least one but no >3 prior chemotherapy regimens. RESULTS: Median PFS was similar for both treatment groups and was 5.3 months for cabozantinib and 5.5 months for weekly paclitaxel (HR 1.11 (90% CI 0.77-1.61, p = 0.64)). Secondary analyses of overall survival (OS) and event free survival (EFS) showed that cabozantinib did not perform as well as weekly paclitaxel. Median OS for cabozantinib was 19.4 months and was not reached for weekly paclitaxel (HR 2.27 (90% CI 1.17-4.41, p = 0.04). EFS was also worse in the cabozantinib arm, 3.5 months, compared to weekly paclitaxel at 5.0 months (HR 1.81 (90% CI 1.24-2.63, p = 0.01). Overall response rate (ORR) was less for cabozantinib compared to weekly paclitaxel (7% versus 24.1%). Gastrointestinal toxicities, specifically nausea, diarrhea, and abdominal pain were worse in the cabozantinib arm. CONCLUSIONS: Median PFS was similar for cabozantinib and weekly paclitaxel. However, OS, EFS, and ORR were worse for cabozantinib compared to weekly paclitaxel. Cabozantinib given at this dose and schedule cannot be recommended as a treatment for recurrent ovarian cancer.

GOG 244 - The LymphEdema and Gynecologic cancer (LEG) study: The association between the gynecologic cancer lymphedema questionnaire (GCLQ) and lymphedema of the lower extremity (LLE).

OBJECTIVE: To explore whether patient-reported lymphedema-related symptoms, as measured by the Gynecologic Cancer Lymphedema Questionnaire (GCLQ), are associated with a patient-reported diagnosis of lymphedema of the lower extremity (LLE) and limb volume change (LVC) in patients who have undergone radical surgery, including lymphadenectomy, for endometrial, cervical, or vulvar cancer on Gynecologic Oncology Group (GOG) study 244. METHODS: Patients completed the baseline and at least one post-surgery GCLQ and LVC assessment. The 20-item GCLQ measures seven symptom clusters-aching, heaviness, infection-related, numbness, physical functioning, general swelling, and limb swelling. LLE was defined as a patient self-reported LLE diagnosis on the GCLQ. LVC was measured by volume calculations based on circumferential measurements. A linear mixed model was fitted for change in symptom cluster scores and GCLQ total score and adjusted for disease sites and assessment time. RESULTS: Of 987 eligible patients, 894 were evaluable (endometrial, 719; cervical, 136; vulvar, 39). Of these, 14% reported an LLE diagnosis (endometrial, 11%; cervical, 18%; vulvar, 38%). Significantly more patients diagnosed versus not diagnosed with LLE reported ≥4-point increase from baseline on the GCLQ total score (p < 0.001). Changes from baseline were significantly larger on all GCLQ symptom cluster scores in patients with LLE compared to those without LLE. An LVC increment of >10% was significantly associated with reported general swelling (p < 0.001), heaviness (p = 0.005), infection-related symptoms (p = 0.002), and physical function (p = 0.006). CONCLUSIONS: Patient-reported symptoms, as measured by the GCLQ, discerned those with and without a patient-reported LLE diagnosis and demonstrated predictive value. The GCLQ combined with LVC may enhance our ability to identify LLE.

A phase II study of frontline paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus, or ixabepilone/carboplatin/bevacizumab in advanced/recurrent endometrial cancer.

OBJECTIVE: Paclitaxel and carboplatin (PC) is a standard initial therapy for advanced endometrial cancer. We evaluated the efficacy and tolerability of incorporating three novel agents into initial therapy. METHODS: In this randomized phase II trial, patients with chemotherapy-naïve stage III/IVA (with measurable disease) and stage IVB or recurrent (with or without measurable disease) endometrial cancer were randomly assigned to treatment with PC plus bevacizumab (Arm 1), PC plus temsirolimus (Arm 2) or ixabepilone and carboplatin (IC) plus bevacizumab (Arm 3). The primary endpoint was progression-free survival (PFS). Comparable patients on the PC Arm of trial GOG209 were used as historical controls. Secondary endpoints were response rate, overall survival (OS), and safety. RESULTS: Overall, 349 patients were randomized. PFS duration was not significantly increased in any experimental arm compared with historical controls (p > 0.039). Treatment HRs (92% CI) for Arms 1, 2, and 3 relative to controls were 0.81 (0.63-1.02), 1.22 (0.96-1.55) and 0.87 (0.68-1.11), respectively. Response rates were similar across arms (60%, 55% and 53%, respectively). Relative to controls, OS duration (with censoring at 36 months), was significantly increased in Arm 1 (p < 0.039) but not in Arms 2 and 3; the HRs (92% CIs) were 0.71 (0.55-0.91), 0.99 (0.78-1.26), and 0.97 (0.77-1.23), respectively. No new safety signals were identified. Common mutations and rates of mismatch repair protein loss are described by histotype. Potential predictive biomarkers for temsirolimus and bevacizumab were identified. CONCLUSION: PFS was not significantly increased in any experimental arm compared to historical controls. NRG Oncology/Gynecologic Oncology Group Study GOG-86P.

A quality process study of lymph node evaluation in endometrial cancer.

Our objective was to analyze the reported lymph node counts between surgeons, histology prosectors, and pathologists using a cohort of patients enrolled on a national protocol that standardized surgical intent.This is a retrospective review of patients with uterine cancer who underwent a standardized formal staging procedure as dictated by a National Cancer Institute sponsored protocol. Patients were staged using the International Federation of Gynecology and Obstetrics 1988 guidelines. All patients required a hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic and para-aortic lymphadenectomy. Lymphadenectomy specimens were separated by the following regions: external iliac, obturator, common iliac, and periaortic. Lymph node counts were analyzed by region, surgeon, histology prosector, and pathologist.There were 78 patients enrolled in the protocol during the study period. Of them, 72 (92%) patients met the inclusion criteria. A total of 2397 lymph nodes were counted, with an average total number of 33 (SD=9) lymph nodes dissected per patient. Surgeons A, B, and C had an average lymph node count of 32, 33, and 35, respectively, with no significant difference in mean node count (P=0.66). Prosectors 1 to 4 dissected an average of 34, 33, 28, and 35 lymph nodes, respectively (P=0.091). There were 2 pathologists with ≥ 10 cases. Their mean lymph node counts were 35 and 30, respectively, with no significant difference in mean node count (P=0.079).This systematic review did not identify a discrepancy in nodal count among surgeons, prosectors, or pathologists at our institution. The methods used may be helpful in structuring interdepartmental reviews for completeness of nodal dissections in cases where surgical intent has been standardized.

Advanced cytoreductive surgery: American perspective.

Over the past 3 to 4 decades a special knowledge and understanding of the pathophysiology and behavior of gynecologic peritoneal surface malignancies has led to a significant improvement of the relevant treatment modalities, mirroring advances in chemotherapy approaches and improved knowledge of tumor biology. The surgical management of advanced ovarian, primary peritoneal, and fallopian tube cancers has evolved from the performance of basic gynecologic procedures to the incorporation of more comprehensive surgical procedures. This extensive surgical approach is of great importance for estimating the prognosis and guiding further treatment of affected patients. These complex procedures involving multi-organ resections are generally long and require excellent knowledge of upper abdominal anatomy. This article will focus on the role and program development of advanced cytoreductive surgery in patients with gynecologic peritoneal malignancies. This review is an attempt to provide guidance for the rationale and strategic approach to develop the surgical skill set, meet institutional requirements, and implement the concept of a comprehensive cytoreductive surgical team.

Multidisciplinary panel discussion of a gynecologic oncology patient: preventing wound complications.

At the 39th meeting of the Society of Gynecologic Oncologists, a multidisciplinary panel presented and discussed the current management strategies for the treatment of complex wounds. After the presentations, the panel discussed the management options for a morbidly obese endometrial cancer patient with a focus toward the complex wound that may delay discharge, healing, or the start of adjuvant treatment. This article highlights the clinical considerations discussed for these types of patients.

Topical advances in wound care.

There are fundamental differences between acute wounds that proceed to uncomplicated healing and those that become chronic wounds. Non-healing or chronic wounds can result from a combination of overlapping factors that prevent healing, including local tissue ischemia, repetitive trauma and ischemia/reperfusion injury, presence of tissue necrosis, impaired cellular and systemic host response to stress, and critical bacterial contamination. The bacterial burden in the wound contributes to a sustained inflammatory state, which inhibits normal progression to the proliferative phase of healing, thereby preventing restoration of tissue integrity. Appropriate wound bed preparation removes local barriers to healing and optimizes the tissue environment to achieve wound healing. It is an essential element of wound management that advances endogenous healing as well as the efficacy of topical and other wound therapy. This article will summarize a systematic approach to wound bed preparation using the "TIME" principle, and will highlight important advances in topical wound care.

A randomized phase III trial of VH fibrin sealant to reduce lymphedema after inguinal lymph node dissection: a Gynecologic Oncology Group study.

OBJECTIVES: To evaluate VH fibrin sealant's influence on lower extremity lymphedema after inguinal lymphadenectomy in vulvar cancer patients. METHODS: Patients undergoing an inguinal lymphadenectomy during the management of vulvar malignancy were randomized to receive sutured closure (SC) vs VH fibrin sealant sprayed into the groin followed by sutured closure (FS). Leg measurements were taken preoperatively and during postoperative encounters when surgical outcomes were assessed. Grade 2 or 3 lymphedema was defined as circumferential measurement increases of 3-5 cm and >5 cm, respectively. RESULTS: 150 patients were enrolled. 137 patients were evaluable for lymphedema analysis with 67 and 70 patients in the SC arm and FS arm, respectively. The incidence of grade 2 and 3 lymphedema was 67%(45/67) in the SC arm, and 60% (42/70) FS arm (p=0.4779). The incidence of lymphedema was strongly associated with inguinal infection (p=0.0165). Lymphedema was not statistically increased in those who received adjuvant radiation. 139 patients remained evaluable for a descriptive analysis of their surgical complications. The overall incidence of complications was 61%(43/70) and 59% (41/69) for SC and FS arms, respectively. There was no statistically significant difference in duration of drains, drain output or incidence of inguinal infections, wound breakdowns or seromas. There was an increased incidence of vulvar infections in the FS arm (23/69) vs (10/70) (p=0.0098). The utilization of a Blake drain was associated with an increase in vulvar (p=0.0157) and inguinal wound breakdown (p=0.0456). CONCLUSION: VH fibrin sealant in inguinal lymphadenectomies does not reduce leg lymphedema and may increase the risk for complications in the vulvar wound.

Costs and effectiveness of alternative strategies for cervical cancer screening in military beneficiaries.

OBJECTIVE: To estimate the potential effects, on costs and outcomes, of changes in sensitivity and specificity associated with new screening methods for cervical cancer in the military. METHODS: A Markov model of the natural history of cervical cancer was created to simulate a cohort of 100,000 military beneficiaries aged 18-85. Probability estimates for various outcomes and the accuracy of screening tests were obtained from the literature. Cost estimates were obtained from military sources where available; otherwise, civilian costs were used. The outcomes and costs of conventional cytology, liquid-based cytology, and liquid-based cytology with human papillomavirus (HPV) triage were compared at 1-, 2-, and 3-year screening frequencies. RESULTS: Marginal reductions in the incidence of cervical cancer from increasing screening sensitivity are greater than reductions in cancer mortality at every screening interval. Incremental improvements in both cancer incidence and mortality are higher at less frequent screening intervals. Increases in the ratio of low- to high-grade lesions result from increasing the sensitivity of the screening test or shortening the screening interval. Both liquid-based cytology and liquid-based cytology with HPV testing are cost effective (less than $50,000 per life-year saved) when performed at 3-year screening intervals. However, neither strategy is cost-effective when performed more frequently than every 3 years. CONCLUSION: Use of a more sensitive cervical cancer screening test increases costs. However, a more sensitive test performed less frequently may be more effective and less expensive than conventional cytology done annually. In the military setting, this has significant implications for both expense reduction and readiness enhancement.

Laparoscopic exposure in obese high-risk patients with mechanical displacement of the abdominal wall.

BACKGROUND: Patients with morbid obesity or pulmonary disease are at a higher risk for complications during advanced laparoscopic procedures. Higher intraperitoneal carbon dioxide pressures required to elevate the pannus can negatively impact hemodynamic and respiratory parameters. CASES: We describe a technique that uses a combination of a mechanical retractor and a Foley catheter inserted midway between the umbilicus and the pubic symphysis that assists in elevating the anterior abdominal wall. In 3 cases this technique allowed for a low-pressure pneumoperitoneum during advanced laparoscopic pelvic surgery, which resulted in improved hemodynamic parameters and pulmonary function in these high-risk patients. CONCLUSION: The Foley Lap-Lift facilitated laparoscopy through mechanical abdominal wall elevation and allowed for a lower-pressure pneumoperitoneum. This technique is an addition to traditional operative laparoscopy in select high-risk patients.

Bilateral and multinodular signet-ring stromal tumor of the ovary.

BACKGROUND: Signet-ring stromal tumor of the ovary is a rare, benign sex cord stromal tumor that is typically unilateral. Its distinction from malignant signet-ring cell adenocarcinoma metastatic to the ovary (Krukenberg tumor), is critical. CASE: A 69-year-old gravida 5 woman presented with a 1-week history of right lower abdominal pain. Ultrasonography revealed a 4-cm right adnexal mass. Serum CA 125 and carcinoembryonic antigen were within normal limits. An exploratory laparotomy, partial omentectomy, bilateral salpingo-oophorectomy and peritoneal washing were performed. Solid multinodular masses in both ovaries were identified that histologically corresponded to bilateral signet-ring stromal tumors. CONCLUSION: We report a rare example of signet-ring stromal tumor that is bilateral and multinodular mimicking a Krukenberg tumor. Awareness of this unusual presentation can help prevent incorrect diagnosis.

Prognostic factors for stage III epithelial ovarian cancer: a Gynecologic Oncology Group Study.

PURPOSE: Conflicting results on prognostic factors for advanced epithelial ovarian cancer (EOC) have been reported because of small sample size and heterogeneity of study population. The purpose of this study was to identify factors predictive of poor prognosis in a similarly treated population of women with advanced EOC. PATIENTS AND METHODS: A retrospective review of demographic, pathologic, treatment, and outcome data from 1,895 patients with International Federation of Gynecology and Obstetrics stage III EOC who had undergone primary surgery followed by six cycles of intravenous platinum/paclitaxel was conducted. A proportional hazards model was used to assess the association of prognostic factors with progression-free survival (PFS) and overall survival (OS). RESULTS: Increasing age was associated with increased risks for disease progression (HR = 1.06; 95% CI, 1.02 to 1.11 for an increase every 10 years) and death (HR = 1.12; 95% CI, 1.06 to 1.18). Mucinous or clear-cell histology was associated with a worse PFS and OS compared with serous carcinomas. Patients with performance status (PS) 1 or 2 were at an increased risk for recurrence compared with PS 0 (HR = 1.12; 95% CI, 1.01 to 1.24). Compared with patients with microscopic residual disease, patients with 0.1 to 1.0 cm and > 1.0 cm residual disease had an increased risk of recurrence (HR = 1.96; 95% CI, 1.70 to 2.26; and HR = 2.36; 95% CI, 2.04 to 2.73, respectively) and death (HR = 2.11; 95% CI, 1.78 to 2.49; P < .001; and HR = 2.47; 95% CI, 2.09 to 2.92, respectively). CONCLUSION: Age, PS, tumor histology, and residual tumor volume were independent predictors of prognosis in patients with stage III EOC. These data can be used to identify patients with poor prognosis and to design future tailored randomized clinical trials.

Successful management of metastatic placental site trophoblastic tumor with multiple pulmonary resections.

INTRODUCTION: Placental site trophoblastic tumor (PSTT) is an uncommon variant of gestational trophoblastic disease. Most of these tumors are confined to the uterus and treated with a simple hysterectomy. However, 30% of these patients will present with metastatic disease. These patients are typically treated with a hysterectomy followed by adjuvant multiagent chemotherapy. Unfortunately, PSTT is relatively resistant to chemotherapy when compared to other forms of gestational trophoblastic disease. Consequently, these patients have a poor prognosis. CASE: We present a case report of a 26-year-old female with multiple metastatic lesions to the lungs unresponsive to chemotherapy who was managed with multiple pulmonary resections. She has remained clinically free of disease at 28 months of follow up. CONCLUSION: A patient with metastatic PSTT was successfully managed with radical surgical resection of chemotherapy-resistant sites.

Papillary serous adenocarcinoma of the ovary diagnosed after malignant pericardial tamponade and embolic stroke.

BACKGROUND: Epithelial carcinomas of the ovary are predominantly an intraperitoneal disease. Reports of epithelial ovarian carcinomas metastatic to the pericardium are rare. CASE: A 43-year-old woman was admitted with symptoms of a pericardial tamponade, as well as an embolic cerebrovascular accident, and transferred to the ICU where a pericardiocentesis was performed. Cytology revealed malignant cells in the pericardial fluid. CT scan of the abdomen and pelvis revealed bilateral pelvic masses. A laparotomy revealed a papillary serous adenocarcinoma of ovarian primary and an infarcted spleen with capsular tumor metastases. The malignant cells in the pericardial fluid were consistent with the ovarian primary. CONCLUSION: Ovarian cancer metastasis to the heart and pericardium presented an aggressive variant of tumor spread with significant morbidity and subsequent mortality.

Modified technique for urinary diversion with incontinent conduits.

BACKGROUND: Incontinent urinary diversions are frequently performed in gynecologic oncology. The incontinent urinary diversions generally utilize a short segment of distal ileum or colon as a conduit. Conduit complications such as anastomosis leaks and strictures may be related to the technique utilized for inserting and securing the ureters and the degree of postimplant manipulation. TECHNIQUE: We describe a technique using a metal Yankaur suction device placed through the conduit's matured stoma to facilitate the mucosa-to-mucosa anastomosis of the ureters. This procedure allows for tension-free ureteral anastomoses, the isolation of the ideal conduit length, optimal stomal maturation, and reduced manipulation of the conduit after the ureteral anastomoses. CONCLUSION: This modification provides an elegant, yet simple and expedient, method of ureteral anastomosis to the incontinent urinary conduit.

Adenosquamous histology predicts a poor outcome for patients with advanced-stage, but not early-stage, cervical carcinoma.

BACKGROUND: The objective of this study was to compare survival between patients with adenocarcinoma and patients with adenosquamous carcinoma of the cervix. METHODS: Patients who were diagnosed with invasive cervical carcinoma from 1988 to 1999 were identified from the Automated Central Tumor Registry for the United States Military Health Care System. Clinical data, including race, age at diagnosis, histology, tumor grade, disease stage, lymph node status, treatment modality, and survival, were collected. Survival analysis was performed with Kaplan-Meier survival curves and compared using the log-rank test. RESULTS: A total of 273 women were identified, 185 women with a histologic diagnosis of adenocarcinoma (AC) and 88 women with a diagnosis of adenosquamous carcinoma (ASC). Among the women with ASC, only 5% had Grade 1 tumors, and 66% had Grade 3 tumors. By comparison, among the women with AC, 37% had Grade 1 tumors, and 26% had Grade 3 tumors (P < 0.001). There was no difference in the incidence of positive lymph nodes or in the number of patients who underwent radical hysterectomy as primary treatment between patients with ASC and patients with AC. More patients with ASC received radiation therapy (51% vs. 28%) or chemotherapy (29% vs. 12%) as treatment (P < 0.001). Patients who had tumors with ASC histology had a significantly decreased 5-year survival rate compared with patients who had tumors with AC histology (65% vs. 83%; P < 0.002). When patients with early-stage cervical carcinoma (International Federation of Gynecology and Obstetrics [FIGO] Stage I) were examined separately, there was no statistically significant difference in the 5-year survival rate (AC, 89%; ASC, 86%; P = 0.644). However, when patients with advanced-stage disease (FIGO Stages II-IV) were analyzed, ASC was associated with a significant decrease in median and overall survival (P = 0.01). When the results were analyzed by grade, patients who had tumors with ASC histology had a shorter survival compared with patients who had AC histology of any grade; however, this was a significant difference only for patients with Grade 1 tumors: The 5-year survival rate for patients with Grade 1 AC was 93%, compared with 50% for patients with Grade 1 ASC (P < 0.01). CONCLUSIONS: ASC histology appears to be an independent predictor of poor outcome in women with cervical carcinoma compared with their counterparts who have pure AC. The significant decrease in survival was observed only in patients with advanced-stage cervical carcinoma. This decreased survival may be related mainly to the grade of ASC.