Risk factors of endometrial cancer in Palermo

A case-control study on 150 cases and 300 non-neoplastic controls admitted to the Obstetric and Gynaecologic Clinic B of the University of Palermo from 1977 to 1986 was carried out in order to assess the risk factors of corpus uteri cancer in Palermo area. Age at menarche less than 11, menopausal status, nulliparity, diabetes and obesity were found significantly associated with the risk of cancer; family history of neoplastic disease was slightly under statistical significance. It can be concluded that the same etiologic factors of endometrial cancer, as in other areas, may be operating in Palermo women.     

Assessment of prognostic factors in stage IIIA endometrial cancer

OBJECTIVE: The objective of this study was the assessment of prognostic factors in stage IIIA endometrial cancer. METHODS: Between 1984 and 1993, 51 patients with stage IIIA endometrial cancer received definitive treatment at our institution. Thirty-seven patients had positive peritoneal cytologic findings only (stage IIIA1), and 14 had adnexal or uterine serosal involvement (USI) (stage IIIA2). Median follow-up of surviving patients was 82.5 months. RESULTS: The 5-year disease-related survival (DRS) and recurrence-free survival (RFS) were 88 and 73%, respectively. RFS was 79% in patients with stage IIIA1 disease, compared with 57% in patients with stage IIIA2 disease (P = 0.04). However, DRS did not significantly differ between stages IIIA1 and IIIA2. In the 37 patients with stage IIIA1 tumors, histologic grade 3, nonendometrioid histologic subtype, and lymphovascular invasion (LVI) significantly predicted a poor prognosis, with extraabdominal sites of failure (P < 0.05). Of the 22 patients who had stage IIIA1 disease with endometrioid histologic subtype and without LVI, none had recurrence [17 had whole abdominal irradiation (WAR) or intraperitoneal injection of (32)P, 2 had pelvic external radiotherapy (PRT)]. By contrast, of the 15 patients with either nonendometrioid histologic subtype or LVI, 9 (60%) had recurrence and 7 (47%) died of disease (12 had WAR or (32)P). An extraabdominal component was present in 7 of the 9 recurrences observed in this subgroup. Among the 14 patients with stage IIIA2 tumors (6 had WAR, 6 had PRT), those with USI had a 5-year DRS of 83% and a rate of extraabdominal failure of 83%, compared with 100 and 12.5% in patients without USI (P < 0.05). CONCLUSION: Patients with stage IIIA endometrial cancer who have endometrioid tumors, no LVI, and positive peritoneal cytologic findings as the only sign of extrauterine disease have an excellent prognosis. Nonendometrioid histologic subtype, LVI, and USI are strong predictors of distant failures and poor prognosis. Patients with either of these histologic factors should be considered candidates for systemic adjuvant therapy.     

Risk factors and recurrent patterns in Stage I endometrial cancer

Clinical Stage I carcinoma of the endometrium was evaluated in 222 patients. Twenty-five percent of patients were found to have pathologic findings thought to require postoperative external irradiation; of these, 20 of 57 (35%) had recurrence. During the 36- to 72-month follow-up period, only 14 of 165 (8.3%) treated only with operation (68 patients or 31%) or operation plus intracavitary radium (97 patients or 44%) manifested a recurrence. Furthermore, of all recurrences, 27 of the 34 (79%) were outside the pelvis. In these surgically staged cases, the absence of definable, demonstrable extrauterine disease was associated with a 7% recurrence rate versus a 43% recurrence rate if disease was found anywhere outside the uterus. Recurrence and death were correlated with other prognostic factors, which are outlined in this report.     

Survival of women with surgical stage II endometrial cancer.

OBJECTIVE: The aim of this study was to report survival and determine prognostic factors and results of therapy in women with surgical stage II endometrial cancer. METHODS: Forty-eight consecutive women with surgical stage II endometrial cancer treated at the University of Vermont between March 1984 and March 1998 were reviewed. Patients' characteristics, surgical procedure, postoperative treatment and its complications, and tumor recurrence and its treatment were recorded. In addition, a formal review of their pathological material for confirmation of the diagnosis was performed. RESULTS: The median duration of follow-up was 6.2 years. Three patients (6.3%) had tumor recurrence and two (4.2%) died of their disease. The estimated 5-year overall survival and disease-free survivals were 92.1% (SE = 5.5%, 95% confidence interval: 81.3, 100%) and 89.9% (SE = 5.8%, 95% confidence interval: 78.5%, 100%), respectively. None of the patients treated by total abdominal hysterectomy followed by both whole pelvic and vaginal cuff radiation therapy (the main line of treatment for patients in whom cervical involvement was diagnosed following hysterectomy, n = 20) or by radical hysterectomy (the main line of treatment for patients in whom cervical involvement was known before hysterectomy, n = 11) had tumor recurrence. Three of 17 (17.6%) patients treated with total abdominal hysterectomy followed by either whole pelvic (n = 13) or vaginal cuff (n = 4) radiation therapy had tumor recurrence. The difference between those two groups was statistically significant (0/31 versus 3/17, P = 0.02). There was no difference in survival among women with stage IIA and IIB or women who underwent radical abdominal hysterectomy and those who underwent total abdominal hysterectomy with postoperative pelvic and vaginal cuff radiation. Morbidity secondary to therapy was mild. Age, depth of myometrial invasion, tumor histology, and grade were not significantly related to recurrence. CONCLUSIONS: Survival of women with surgical stage II endometrial cancer is excellent especially among those treated with total abdominal hysterectomy followed by both pelvic and vaginal cuff radiotherapy or by radical abdominal hysterectomy.     

Risk factors for young premenopausal women with endometrial cancer

OBJECTIVE: Endometrial cancer is the most common gynecologic malignancy in the United States. The mean age at diagnosis is 61 years; however, 5-30% of women are aged younger than 50 years at the time of diagnosis. The objective of this study was to conduct a clinical and pathologic review of endometrial cancers diagnosed in premenopausal women aged younger than 50 years, to better identify the risk factors for this subgroup of women. METHODS: We conducted a retrospective cohort study of patients with histologically confirmed endometrial cancer treated at the University of Texas, M. D. Anderson Cancer Center from 1989 to 2003. Clinical characteristics including age, body mass index (BMI), parity, diabetes, and personal or family history of cancer were obtained from the medical record. Pathologic information was obtained from pathology reports. RESULTS: Twelve percent (188/1531) of all patients with endometrial adenocarcinoma were aged younger than 50 years. The mean age at diagnosis was 41 years (range 21-49 years). Mean BMI was 34 kg/m(2) (range 18-68); 58% of patients had a BMI of 30 or greater. Fifty-five percent were nulliparous and 39% reported irregular menstrual cycles. The incidence of both diabetes and hypertension was 23%. Thirty-six patients (19%) had synchronous ovarian cancers. CONCLUSION: We found that the majority of patients diagnosed with endometrial cancer at a young age were obese and nulliparous. In addition, we found a high incidence of synchronous primary ovarian cancers in this cohort of young, premenopausal women.     

Adjuvant chemotherapy as treatment of high-risk stage I and II endometrial cancer

OBJECTIVE: This study was performed to define the subgroups of patients who benefit from postoperative adjuvant chemotherapy in stage I and II endometrial carcinoma. METHODS: A retrospective review of 170 International Federation of Gynecology and Obstetrics (FIGO) stage I and II endometrial carcinoma patients treated between 1988 and 2000 at Niigata University Hospital was performed. All patients underwent surgery, of which 41 patients underwent adjuvant chemotherapy, consisting of intravenous cisplatin, doxorubicin, and cyclophosphamide. Multivariate analysis was performed for the prognostic factors and actuarial techniques were used for the survival and recurrence rates. RESULTS: The patients were divided into low-risk and high-risk groups based on the number of prognostic factors (tumor grade G3, outer half myometrial invasion, lymph-vascular space involvement (LVSI), and cervical invasion). The 5-year disease-free survival and the 5-year overall survival for the low-risk group were 97.4%, and 100%, respectively, which were significantly better than 77.4% and 88.1% for the high-risk group (P < 0.0001, P < 0.0001), respectively. Among high-risk group patients, the 5-year disease-free survival and the 5-year overall survival were 88.5% and 95.2% in 26 patients treated with adjuvant chemotherapy, and 50.0% and 62.5% in eight cases who underwent only surgery (P = 0.0150, P = 0.0226). Disease recurrence occurred in 7 (20.6%) of 34 high-risk group patients. Four of seven recurrences occurred in patients who did not receive postoperative chemotherapy, in which all four were distant failure. In the remaining three patients who were in the CAP group, two had vaginal wall recurrence and only one had pulmonary recurrence. Three recurrences were also observed in the 133 low-risk group patients. Only isolated vaginal wall recurrence occurred in three patients without adjuvant chemotherapy after the initial surgery. CONCLUSIONS: There is possibility that postoperative adjuvant CAP may be omitted in surgical stage I or II endometrial cancer patients with 0 or 1 prognostic factor. The high-risk group of patients should be treated with postoperative adjuvant CAP to decrease distant failure and improve prognosis.     

Treatment of stage II endometrial carcinoma

The optimal management of stage II carcinoma of the endometrium remains to be established. We reviewed our experience in treating 42 patients with stage II endometrial cancer by surgery, radiation, or combined radiation and surgery at the Hospital of the University of Pennsylvania. The overall 5-year survival was 47.6%. The 5-year survivals of patients treated by surgery only, radiation only, or combination radiation and surgery were 68.5, 36.5, and 46.1%, respectively, which were not significantly different. Histologic grade was found a significant prognostic factor but type of cervical involvement was not. Major complication rates were similar in each treatment group. We conclude that the majority of patients with stage II endometrial carcinoma are best treated by combination radiation and surgery, but in a select subset of patients, radical hysterectomy and lymphadenectomy constitute a reasonable treatment option.     

Risk factors for lymphatic complications following lymphadenectomy in patients with endometrial cancer

ObjectiveLymph node (LN) metastasis is among the important prognostic factors for survival in endometrial cancer (EC). This study aimed to evaluate the occurrence of lymphatic complications following lymphadenectomy in patients with EC.Materials and methodsEC patients were retrospectively evaluated. Lower extremity lymphedema (LEL) and pelvic lymphocele (PL) were evaluated according to the International Society of Lymphology guidelines and the National Cancer Institute Common Terminology Criteria for Adverse Events, respectively.ResultsA total of 289 patients were enrolled. Surgery was performed via laparotomy and laparoscopy in 200 (69.2%) and 89 (30.8%) patients, respectively. LEL and PL occurred in 43 (14.9%) and 33 (11.4%) patients, respectively. In multivariate logistic regression analysis, circumflex iliac node (CIN) removal (odds ratio [OR]: 3.22; 95% CI: 1.43–7.98; P = 0.004) was an independent risk factor for LEL, while the surgical approach (OR: 4.46; 95% CI: 1.13–29.9; P = 0.004) was an independent risk factor for PL.ConclusionCIN dissection was a significant risk factor for LEL, while laparotomy was an independent risk factor for PL compared to laparoscopy in EC patients. This suggests that laparoscopic surgery combined with sentinel lymph node navigation surgery will prevent lymphatic complications in low-risk EC patients.     

Risk factors for endometrial hyperplasia and cancer among women with abnormal bleeding

OBJECTIVE: To identify independent risk factors for endometrial neoplasia in women with abnormal perimenopausal or postmenopausal bleeding and to use those factors to develop and test a predictive model. METHODS: We conducted a case-control study of women with abnormal perimenopausal or postmenopausal bleeding who had endometrial samplings; cases had endometrial cancer or complex hyperplasia and controls had benign endometrial histologies. Multivariate logistic regression models identified factors associated with risks of endometrial neoplasia. The predictive abilities of our models and a published model were assessed using the area under receiver operating characteristic (ROC) curves, for which an area of 1.0 indicated perfect positive predictive ability and an area of 0.5 was expected by chance. RESULTS: There were 57 cases of endometrial hyperplasia or cancer and 137 controls. Parity was related inversely (odds ratio [OR] 0.70; 95% confidence interval [CI] 0.56, 0.88; P = .002) and weight directly (OR 1.02 per kg; 95% CI 1.01, 1.04; P = .018) to the risk of endometrial neoplasia. Age (OR 1.04 per year; 95% CI 1.00, 1.08; P = .06) and diabetes (OR 3.50; 95% CI 0.99, 12.33; P = .052) were significant marginally. The area under the ROC curve for our model was 0.75, indicating moderate predictive ability; the area under the ROC curve for the published model was lower at 0.66. CONCLUSION: Current clinical predictive models based on case-control studies do not have sufficient predictive ability to determine if women with abnormal perimenopausal or postmenopausal bleeding should have diagnostic testing.     

Prognostic factors in endometrial cancer

The 5 year survival rates of 228 patients with endometrial cancer treated in the period 1978-1982 according to the prognostic factors (stage, grade, depth of myometrial invasion, lymph node metastasis) is presented. All patients were treated with primary surgery consisting of classical Wertheim operation with lymphadenectomy (98 cases-43%), total abdominal hysterectomy with bilateral salpingo-oophorectomy with lymphadenectomy (52 cases-48%) and without lymphadenectomy (55 cases-52%) and vaginal hysterectomy with bilateral salpingo-oophorectomy (23 cases-10%). All patients except 6.6% were postoperatively irradiated. The 5 year survival for all stages was 74.6%. In SI cases it was 83.8%, in SII 57.9% and only 37.5% in SIII group. The survival was 90.1% in patients with superficial myometrial invasion and 56.4% in cases of deeper invasion. The survival of patients with node metastasis (8.6%) was only 39.5%, irrespective of the type of surgery and postoperative external irradiation. Vaginal recurrences were observed in 3.9%, and all the patients died. To improve the results it is necessary to individualize the treatment according to the pathologic and clinical prognostic factors.     

Phase II trial of vaginal cuff brachytherapy followed by chemotherapy in early stage endometrial cancer patients with high-intermediate risk factors

Objective

To determine the progression free survival (PFS), toxicity, and patterns of failure for early stage, high-intermediate risk (H-IR) patients in a phase II trial with adjuvant vaginal cuff brachytherapy (VCB) and three cycles of carboplatin and paclitaxel.

Methods

Surgically staged patients with stage I-IIb endometrial cancer with H-IR factors were treated with VCB (2100 cGy) followed by three cycles of carboplatin (AUC 6) and paclitaxel (175 mg/m²). The primary endpoint was PFS at 2 years, with toxicity and sites of failure as secondary endpoints. Toxicity was assessed by patient report (CTCAE v. 3) as well as by delays or dose modifications in treatment.

Results

All patients completed VCB and 19/23 (83%) completed both VCB and 3 cycles of chemotherapy. Mean time to complete VCB was 14.5 days with minimal acute toxicity noted. At 6 months, all toxicity related to VCB had resolved. In total 60 cycles of chemotherapy were given, with one dose reduction (1.6%) for grade 2 neuropathy and seven delays (11.6%) in treatment due to hematologic toxicity. At a median follow-up of 44.5 months, 91% of patients remained progression free at 2 years. Four patients experienced a recurrence; they recurred both locally and distant.

Conclusions

Adjuvant therapy with VCB and chemotherapy is well tolerated in a population of patients with H-IR endometrial carcinoma and provides 2 year PFS of 91%. A randomized trial is currently underway to assess whether combined VCB and chemotherapy reduces the rate of recurrence compared to external beam radiation therapy (EBRT) in this patient population.     

Histomorphologic prognostic factors in stage I endometrial cancers

The prognostic significance of qualitative and quantitative morphological tumour characteristics for endometrial carcinoma of stage I (FIGO) is to be ascertained from the available 230 operation specimens from 1976 to 1983 (inclusive). The fundamental objective is to design a standardized and reliably reproducible histological technique. By utilizing a multi-dimensional statistical comparison (multiple regression analysis), the maximal relative extent of the endometrial invasion as a determinant prognostic feature shall also be ascertained. Furthermore, the degree of differentiation (Grading) and tumour type (Typing) influence the survival rate whereas the maximal superficial extension of the carcinoma has no significant prognostic importance.     

Laparoscopic-assisted vaginal hysterectomy versus abdominal hysterectomy in patients with stage I and II endometrial cancer

The purpose of this study was to evaluate and compare the outcomes of laparoscopic surgery with those of conventional abdominal surgery in patients with early endometrial cancer. From 1997 to 2003, 79 patients underwent laparoscopic-assisted vaginal hysterectomy with or without lymphadenectomy. Laparoscopy was performed on patients deemed clinical stage I in preoperative studies. Of the 79 patients, 74 found to be surgical stage I or II were enrolled in the comparative study. As a control group, we selected 168 laparotomy cases at the same disease stage as the laparoscopy group. Operation time, amount of blood transfusion, and hemoglobin changes were similar for both groups. In the laparoscopy group, the number of lymph nodes obtained was significantly higher, and the number of postoperative complications was lower compared to the laparotomy group. The hospital stay was significantly shorter for laparoscopy group. Three-year recurrence-free survival rates were similar, being 97.5% for the laparoscopy group and 98.6% for the laparotomy group. We conclude that laparoscopic surgery for treatment of early endometrial cancer is a safe and effective alternative to laparotomy in terms of perioperative complications. Three-year recurrence-free survival did not differ significantly between the groups. However, long-term survival and risk of recurrence have yet to be determined.