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One of the most important risk factors associated with recurrence and survival among patients with endometrial cancer is stage. The extent and distribution of tumor tissue in advanced stage disease define use of postoperative adjuvant therapies. Stages III and IV disease have different clinical behaviors, prognoses, and response to adjuvant chemotherapy. There is high risk of disease recurrence and a poor prognosis for stages III and IV disease in patients with intraperitoneal (IP) involvement; reported 5-year survival rates range from 5% to 20%.A Gynecologic Oncology Group (GOG) trial published in 2004 demonstrated that in patients with stage III-IV endometrial cancer, use of the 3-drug paclitaxel, doxorubicin, and cisplatin (TAP) regimen produced improved response rates, progression-free survival (PFS), and overall survival (OS) compared with doxorubicin and cisplatin: response rate, 57% versus 34%; PFS, median, 8.3 versus 5.3 months; and OS, median, 15.3 versus 12.3 months. These results led to the TAP regimen being considered a new standard of care. However, the complete response rate with TAP was still low (<25% in patients with measurable disease), and about 50% of stage III patients and 90% of stage IV patients had a recurrence and died of their disease. Intraperitoneal disease spread appears to be responsible for this poor outcome.The investigators hypothesized that the addition of IP drug delivery to the TAP regimen would be effective therapy for advanced-stage endometrial cancer and could reduce the toxicity observed with the intravenous (IV) TAP regimen. Dosing and toxicities of the IP regimen, cisplatin and paclitaxel, have been well studied in other tumors; however, this regimen has not been well studied in endometrial cancer.The present phase 1 study was conducted to determine the maximum tolerated dose of a modified TAP regimen, which incorporated IP paclitaxel or IP paclitaxel/cisplatin (IV/IP-based TAP regimen) in advanced-stage endometrial cancer. Participants had histologically confirmed endometrial cancer and FIGO (1998) stage IIIA/IIIC with positive cytologic washings/ascites, adnexal spread, or serosal involvement or stage IV (IP disease spread). A 3 + 3 dose escalation study was conducted for the dose escalation phase of the study; 5 dose levels were evaluated. A total of 6 cycles were administered to all patients on a 21-day schedule. Patients received cycles 1 to 2 with standard IV TAP and cycles 3 to 6 with IV/IP-based TAP regimen. Adverse events reported on cycles 3 and 4 were evaluated for dose-limiting toxicity (DLT) and decisions on dose escalation.Between 2008 and 2014, 21 eligible patients were enrolled; 17 of these patients were evaluable for DLT. Among these 17, 13 patients (76%) had stage IV disease, and 10 (59%) had serous or clear cell histology. The maximum tolerated dose for the IV/IP-based TAP regimen was determined to be at dose level 3 (cycles 3-6 including IP paclitaxel 90 mg/m2, IV doxorubicin 45 mg/m2, and IV cisplatin 50 mg/m2). Three DLT events occurred that were related to grades 3 to 4 metabolic (electrolyte) toxicities. Although 1 patient developed a grade 2 sensory neuropathy event, none developed grades 3 to 4 sensory neuropathy, and myelosuppression was tolerable without the need for granulocyte colony-stimulating factor. Fifteen of the evaluable patients (88%) received all 6 cycles of IV/IP. At a median follow-up time of 22 months, 46% of patients remained progression-free at 2 years. The 2-year survival rate was 55%, with a median OS of 30 months.These findings suggest that treatment of advanced-stage endometrial cancer with an IV/IP based-modification of a standard TAP regimen may enhance efficacy and reduce toxicity. Further study of IP therapy in endometrial cancer is warranted based on the high rate of completing 6 cycles of therapy, low rates of neuropathy, and tolerable myelosuppression, as well as promising PFS and OS.

Stage is the strongest prognostic factor among patients with endometrial cancer, irrespective of histology or grade. Patterns of metastasis, however, vary by tumor subtype suggesting that characterizing routes of metastasis may help improve staging procedures and lead to better management. Metastasis of endometrial cancer occurs via lymphatics, blood vessels, invasion through the uterine wall, or passage through the fallopian tube into the peritoneum. The importance of the fallopian tube as a conduit for the spread of endometrial carcinoma into peritoneal cavity is ill defined. Assessment of the tube’s role in metastasis of this cancer could have implications for staging, management, and understanding of its pathogenesis.The present study was designed to test the hypothesis that tubal ligation (TL), which should impede transtubal passage of tumor cells, is associated with lower endometrial carcinoma stage at presentation and, consequently, lower mortality. Associations between TL, cancer stage, extrauterine metastasis, and mortality in patients with endometrial cancer were examined. Participants in the NRG Oncology/Gynecologic Oncology Group (GOG) 210 Trial were women with presurgical diagnoses of endometrial carcinoma (carcinoma or carcinosarcoma) who were eligible for surgery. None had undergone prior retroperitoneal surgery or pelvic/abdominal radiation.Four thousand four hundred eighty nine eligible patients from 62 US institutions were available for analysis.Cases were oversampled for aggressive tumor types. After exclusions, patients completed a risk factor questionnaire that included TL history. Twenty-eight percent of the subjects reported a previous TL at a median age of 32 years. Pathology data derived from clinical reports and central review were examined. Tumor subtypes, including high-grade endometrioid, serous, and clear cell carcinomas, were examined as an effect modifier of relationships between TL, stage, and peritoneal metastasis.Logistic regression models were used to assess associations between TL with stage and peritoneal metastasis, overall and by tumor subtype. Cox proportional hazards regression models were used to assess the relationship between TL and mortality.All statistical tests (Pvalues) were 2-sided.There was an inverse relationship between TL and both stage III (odds ratio [OR], 63; 95% confidence interval [CI], 0.52–0.78) and stage IV carcinomas (OR, 0.14; 95% CI, 0.08–0.24) overall and among individual tumor subtypes compared with stage I. Tubal ligation was also inversely associated with peritoneal metastasis overall (OR, 0.39; 95% CI; 0.22–0.68) and among serous carcinoma cases (OR, 0.28; 95% CI, 0.11–0.68). Cox multivariable models adjusted for covariates except stage showed an inverse association between TL and endometrial carcinoma–specific mortality; the hazard ratio was 0.74, with a 95% CI of 0.61 to 0.91. After adjustment for stage, however, this survival advantage was eliminated. Similar relationships were observed with all-cause mortality.These findings provide evidence that transtubal spread is an important mechanism for metastasis of aggressive histological types of endometrial carcinoma. The association of TL with lower stage and mortality among women with aggressive endometrial carcinomas may have prognostic implications.

To compare stages IB1 and IB2 cervical cancer, the authors conducted a review of all patients with stage IB cancer of the cervix who underwent a type III radical hysterectomy with bilateral pelvic lymphadenectomy at their institutions between 1990 and 2000. They identified 195 patients who had no gross extrauterine disease and sufficient data for analysis. One hundred seventy-seven (91%) subjects also underwent a bilateral paraaortic lymphadenectomy. No patient received preoperative radiation therapy.

More than 10 of cancer patients have venous thromboembolism (VTE). There is a clear relationship between VTE and several types of solid tumors; VTE negatively impacts survival. This disorder is the second leading cause of death in cancer patients. Some studies have reported that the solid tumor with the highest rate of VTE is ovarian cancer. Few studies have evaluated the contribution of VTE timing to survival in patients with solid tumors. A substantial proportion of deaths in cancer patients may be preventable with improved and tailored thromboprophylaxis.

In the past 28 years, there has been a marked increase in the prevalence of in situ and invasive vulvar carcinoma with the increase of in situ disease occurring primarily in the under 65 age group and peaking at 40 to 49 years. The striking increase in the rates of premalignant lesions in women younger than 50 and other accumulating evidence suggests that the pathogenesis of vulvar cancer may be different in younger and older women. To investigate whether the pathogenesis may be different in these 2 age groups, this retrospective review evaluated prognostic and environmental risk factors associated with squamous cell vulvar cancer in a population of women at age 45 years or younger. The study population was comprised of 56 patients who were diagnosed with the cancer between 1994 and 2006. Their median age was 38 (range: 19–45). Demographic data that were collected and analyzed included a history of smoking, human papillomavirus infection and immunosuppression, and vulvar intraepithelial neoplasia. The median follow-up period was 25.3 months.

Many elderly cancer patients are managed less aggressively than younger ones, despite the fact that studies indicate that they have outcomes similar to their younger counterparts when treated similarly. Older patients often are viewed as being less tolerant of intensive surgical and chemotherapeutic interventions. In addition, the medical comorbid conditions that accompany advancing age create a perception of increased risk. This retrospective review of clinical records examined outcomes in 65 patients who were diagnosed at age 80 or older as having uterine cancer (UC); their mean age was 84 years. Parity averaged 2.4, and the body mass index, 27. Two-thirds of patients had comorbid medical conditions, most commonly hypertension and diabetes.