The efficacy of postoperative vaginal irradiation in preventing vaginal recurrence in endometrial cancer

Between 1960 and 1985 hysterectomy was performed on 811 FIGO stage I and 116 stage II endometrial cancers which were divided into three groups: low-risk stage Ii (grade 1 and 2 lesions confined to the inner third of the myometrium; high-risk stage Iii (grade 3 and/or invading to the middle third of the myometrium or beyond); and FIGO stage II tumors (also high-risk). Hysterectomy was the only treatment in 492; in 145 the vaginal vault alone was radiated and in 290 the whole vagina, in each instance by an intracavity dose of 60Gy; in 34 of the latter high-risk tumors the pelvis received an additional 46Gy by external beam therapy. Forty isolated vaginal recurrences were detected; 10 in 308 low-risk and 22 in 184 high-risk tumors treated by surgery alone, and two and five in 40 low and 105 high-risk patients, respectively, who received adjuvant vault irradiation. No recurrences followed irradiation of the whole vaginal mucosa in 163 stage Ii low-risk and 40 stage II lesions and one, 9 years later, in 87 high-risk stage Iii tumors. Nearly 45% of patients with vaginal recurrence died from cancer within 1 year, 77% within 5 years and only 10% survived their recurrence 10 years. Total vaginal irradiation eliminated vaginal recurrences in low risk and reduced the incidence to 2.1% at 20 years after high-risk tumors.     

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.     

Laparoscopically assisted vaginal hysterectomy versus abdominal hysterectomy in stage I endometrial cancer

Abstract. Fram KM. Laparoscopically assisted vaginal hysterectomy versus abdominal hysterectomy in stage I endometrial cancer.
The purpose of this study was to evaluate and compare laparoscopic treatment for stage I endometrial cancer with the traditional transabdominal approach. From July 1996 to July 1998, 61 patients with clinical stage I endometrial cancer were treated at the Gynaecology Oncology Unit at the Royal North Shore of Sydney, Australia. Twenty-nine patients were treated with laparoscopic assisted vaginal hysterectomy (LAVH) and bilateral salpingo-oophrectomy (BSO) ± laparoscopic pelvic lymphadenectomy (LPLA), while 32 patients were treated with the traditional laparotomy and underwent total abdominal hysterectomy (TAH) and BSO ± pelvic lymphadenectomy (PLA). The main outcomes studied were operative time, blood loss, blood transfusion, intraoperative complications, postoperative complications, duration of hospital stay, and number of lymph nodes obtained. In conclusion, laparoscopic treatment of endometrial cancer is safe in the hands of experienced operators with minimal intraoperative and postoperative complications. This procedure is associated with significantly less blood loss and shorter hospitalization; however, it is associated with significantly longer operating time. Proper selection of patients for the laparoscopic procedure is the vital step in achieving the major goals of this approach.     

Local recurrence in high-risk node-negative stage I endometrial carcinoma treated with postoperative vaginal vault brachytherapy

OBJECTIVES: The aim of this study is to examine the patterns of failure after extended surgical staging and postoperative vaginal vault brachytherapy as the only adjuvant treatment in high-risk surgical Stage I patients with endometrial carcinoma. METHODS: The records of all patients with endometrial carcinoma (adenocarcinoma or adenosquamous) receiving vaginal vault brachytherapy as the only adjuvant treatment from January 1989 to December 1997 were examined. A total of 489 patients were found. Of these, 133 had extended surgical staging. The study group consists of 77 surgical Stage I patients with Substages IBG3 and any grade IC. Recurrences were recorded as in the vagina, pelvis, or distant. RESULTS: The mean follow-up interval was 45 months (range 14 to 96 months). Eleven patients had recurrence (14%). Median time to recurrence was 15 months (range 6 to 56 months). Recurrences occurred in the vagina in 7, pelvis in 1, and distantly in 3 patients. Five of 7 vaginal recurrences occurred within 2 years. All patients with distant recurrence died from disease. One patient with pelvic recurrence is alive with disease. Only 1 patient with vaginal recurrence died from disease. Six patients with isolated recurrences in the vagina were successfully treated with radiotherapy with or without local excision. All 6 have no evidence of disease at follow-up (median survival 29 months, range 20 to 71 months). CONCLUSIONS: The vagina remains the most common site of recurrence for high-risk surgical Stage I patients treated with postoperative vaginal vault brachytherapy. Close follow-up in the first 2 years is essential to detect isolated vaginal recurrences. These are amenable to salvage treatment with good disease-free survival.     

Surgical stage I endometrial cancer: predictors of distant failure and death

OBJECTIVES: The objective was to analyze the effect of various histopathologic characteristics on prognosis in surgical stage I (node-negative) endometrial carcinoma. METHODS: During a 10-year period, 229 patients with stage I epithelial (all subtypes) endometrial cancer had hysterectomy and node dissection. Mean number of nodes harvested was 16.2 pelvic and 5.7 paraaortic. Median follow-up was 83 months. Sixty-seven patients (29%) received adjuvant radiotherapy. RESULTS: Five-year disease-related survival (DRS) was 95%, and 5-year relapse-free survival (RFS) 91%. We observed 7 (3%) isolated vaginal recurrences, 14 (6%) distant failures, and 1 (0.4%) simultaneous recurrence at both regional (pelvic sidewall) and distant sites. Only 1 of 7 patients (14%) with vaginal failure died of the disease (median follow-up of censored patients after failure was 110 months), compared with 10 of the 15 patients (67%) with distant failure. By univariate analysis, myometrial invasion (MI) >or= 66%, nonendometrioid histology, lymphovascular invasion, absence of associated hyperplasia, and tumor diameter >2 cm were significant predictors of poor prognosis with distant failure (P or= 66% as the only independent predictor of DRS (P < 0.001, relative risk [RR] = 12.44), RFS (P < 0.001, RR = 8.67), and distant failure (P < 0.001, RR = 24.89). Only 2% of patients with MI < 66% had distant failure and died of the disease at 5 years, compared with a 29% 5-year distant failure rate and a 22% 5-year death rate among patients with MI >or= 66%. CONCLUSION: Stage I (negative nodes) endometrial cancer patients with MI >or= 66% are at significant risk for distant failure and death and should be considered candidates for new randomized trials of adjuvant systemic therapy.     

Salvage treatment with high-dose-rate brachytherapy for isolated vaginal endometrial cancer recurrence

OBJECTIVE: To evaluate the outcome of patients with recurrent vaginal endometrial cancer treated with high-dose-rate brachytherapy (HDRB) and external beam radiation therapy (EBRT). MATERIALS AND METHODS: The records of all patients diagnosed with endometrial cancer who had presented an isolated vaginal recurrence in our institution between January 1, 1997 and December 30, 2003 were reviewed. Twenty-two patients were identified; 18 (82%) received both EBRT and HDRB, and 4 (18%) received HDRB only. The median EBRT dose prescribed was 45 Gy (range: 44-50.4), and median HDRB was 26 Gy (range: 8-48). Recurrence-free intervals as well as disease-specific survival rates were noted. Complications were assessed in terms of early and late Radiation Therapy Oncology Group toxicity (grade 3 or worse) of the gastrointestinal tract, genitourinary tract and vagina. RESULTS: Median age at recurrence for the 22 patients was 72 years (range: 54-86). Median recurrence time was 20 months (range: 4-135). A complete response was achieved in 100% of patients. After a median follow-up of 32 months (range: 11-78), no patient had locoregional recurrence; 1 developed distant metastasis and died from the disease. Five-year local control, disease-free survival and disease-specific survival were 100%, 96% and 96%, respectively. Four patients (18%) presented grades 3-4 gastrointestinal toxicity, and 11 (50%), grade 3 vaginal toxicity. CONCLUSION: Recurrent vaginal endometrial cancer is amenable to salvage therapy with HDRB and EBRT.     

Analysis of vaginal recurrences in stage I endometrial adenocarcinoma

OBJECTIVE: To determine the risk of vaginal recurrence in Stage 1 endometrial cancer and treatment morbidity associated with different therapeutic approaches MATERIAL AND METHODS: Between 1995 and 2005, 341 patients with clinical Stage I endometrial cancer were treated at Istanbul Medical Faculty. One hundred and forty-four women were included in this study as the follow-ups and records were complete. The patients with no myometrial invasion received no further therapy following hysterectomy. When there was superficial myometrial invasion postoperative vaginal vault radiation was used, and if deep myometrial invasion was present, external pelvic radiation was given. RESULTS: Overall 5-year survival rate for all patients with Stage I disease was 80%. Nine patients (6.25%) developed recurrent disease, three of whom had vaginal recurrences. All three vaginal recurrences were small and diagnosed at routine follow-up exam within 51 months of primary therapy. CONCLUSION: This selective treatment protocol for patients with Stage I endometrial cancer avoided radiation entirely in 38% of the patients while achieving a very low rate of vaginal recurrence and good overall survival.     

Three classes of radical vaginal hysterectomy for treatment of endometrial and cervical cancer

OBJECTIVES: The aims of this study were to (1) describe three types of extended vaginal hysterectomy with different degree of radicality, (2) to identify possible indications for each one of them, and (3) to encourage individualization of the treatment, with special reference to the reevaluation of the role of vaginal surgery in gynecologic oncology. STUDY DESIGN: The surgical-anatomic principles of radical vaginal surgery and the techniques of three increasingly extended vaginal hysterectomies are illustrated. Possible indications are pointed out on the basis of our personal experience from previously published retrospective studies. RESULTS: Class I extended vaginal hysterectomy allows the “en bloc” dissection of the uterus along with the upper third of vagina and both the adnexa. The parametria are not removed. This procedure has proved to be of value for treatment of stage I endometrial cancer. In the class II extended vaginal hysterectomy the distal tract of the anterior and posterior parametria are preserved, whereas the cardinal ligament is entirely removed. This operation has shown promising results for treatment of stage IB-IIA cervical cancer of small volume while reducing the incidence of bladder and rectal dysfunctions. The class III procedure includes the complete removal of the parametria (anterior, lateral, and posterior). This operation has been shown to provide a high rate of cure for stage IB-IIA cervical cancer. CONCLUSIONS: In view of the several advantages of vaginal surgery, this approach should be considered in the individualized treatment of selected cases of endometrial and cervical cancers. The three classes of radical vaginal hysterectomy allow tailoring the type of vaginal operation to the clinical and physical characteristics of the patients. The combined use of extraperitoneal or laparoscopic lymphadenectomy would considerably extend the indications for radical vaginal operations. (Am J Obstet Gynecol 1996;175:1576-85.)     

Port site recurrences following laparoscopically managed early stage endometrial cancer

Faught W, Fung Kee Fung M. Port site recurrences following laparoscopically managed early stage endometrial cancer. Int J Gynecol Cancer 1999; 9: 256–258.
Laparoscopic management of endometrial cancer, although gaining in acceptance, has been associated with recurrent disease at trocar insertion sites in advanced disease. We report on a patient with a port site recurrence in early stage endometrial cancer.
An 84-year-old patient with cancer of the endometrium underwent a laparoscopic surgical staging, vaginal hysterectomy, and adjunct radiation treatment. The final surgical pathology was grade 3, stage IC endometrioid adenocarcinoma. Seven months post-treatment, she presented with bilateral port site recurrences in the lower abdominal wall.
Trocar port site recurrence in gynecologic cancer patients may be enhanced by laparoscopic management and are not limited only to patients with advanced disease.     

Abnormal cervical cytology: a risk factor for endometrial cancer recurrence

The objective of this study was to evaluate the relationship between cervical cytology, histologic type, and risk of endometrial cancer recurrence. We performed a retrospective study of patients undergoing surgery for endometrial carcinoma. Risk factors for recurrence including histology, tumor grade, nodal status, myometrial invasion, peritoneal washings, stage, and cervical cytology were assessed. Abnormal cervical cytology was defined as the presence of any endometrial cells on Pap smear. Papillary serous and clear cell carcinomas were considered high-risk histologies. Univariate and multivariate analyses of risk factors for recurrence were performed. Thirty-nine (9%) patients developed recurrent endometrial cancer. More patients with abnormal Pap smears recurred (12% versus 4%, P < 0.05). For endometrioid adenocarcinoma, abnormal cervical cytology occurred in 61% and 7% recurred, while with high-risk histologies, 84% had abnormal cervical cytology and 19% recurred (P < 0.05). Other significant predictors of recurrence on univariate analysis were myometrial invasion, nodal status, washings, stage, and histology. On multivariate analysis, only nodal status remained a significant predictor of recurrence. Abnormal cervical cytology is associated with increased risk of endometrial cancer recurrence. Abnormal cervical cytology occurs more frequently in high-risk histologies, which are known to have a higher risk of recurrence. On multivariate analysis, only nodal spread remains a significant predictor of recurrence.     

Lymphvascular space involvement—a prognostic indicator in patients with surgical stage I endometrial adenocarcinoma treated with postoperative radiation

The objective of this study was to evaluate the prognostic indices of lymphvascular space involvement (LVS), surgical substage and grade on recurrence and survival in patients with surgical stage I endometrial adenocarcinoma, who had received postoperative external beam radiation (ERT). The medical records of all patients who had surgical stage I endometrial cancer between January 1987 and December 1991 were reviewed. Prognostic indicators, ie LVS, surgical substage and grade were correlated with recurrence and survival by log-rank test. Recurrence and survival distributions were estimated using the product limit method. One hundred and twenty-two patients had surgical stage I endometrial cancer. Eight patients were excluded because of histologic types other than endometrioid adenocarcinoma. An additional 27 patients were excluded since they had surgical stage IA and grade I and had not received ERT. The remaining 87 patients who had surgical stage IB and IC and who had received ERT, are the focus of this study. Ten patients had recurrences, all of which were outside the prescribed field of radiation. Nine of II (82%) patients with LVS recurred and 8/11 (73%) patients with LVS died of disease ( P = 0.0001). Surgical substage did not correlate with risk for recurrence ( P < 0.51). Five-year survival for the study group was 92%. LVS correlated well with survival ( P < 0.0001), while grade and surgical substage were not significant indicators of survival in these patients, with surgically documented early disease ( P > 0.13 and P > 0.57). LVS appears to be an important prognostic indicator for both recurrence and survival in patients with surgical stage I endometrial adenocarcinoma who receive postoperative ERT.     

Ⅰ期子宫内膜癌128例治疗及预后临床分析

目的了解不同手术方式对Ⅰ期子宫内膜癌患者术后生存及复发的影响.方法回顾性分析Ⅰ期子宫内膜癌128例.根据手术方式不同,将其分为两组,A组;次广泛(或全子宫)+双附件切除术,80例;B组A组术式+盆腔淋巴结清扫术,48例,分析二组生存率及复发情况.结果 A、B两组的5年生存率分别为95.24%,94.87%,两组比较,差异无显著性(P>0.05),随访中,12例复发,复发率11.76%,10例在3年内复发,其中盆腔复发3例,肺转移6例,A、B两组复发率分别为7.94%,17.95%,分别比较,差异均无显著性(P>0.05).结论腹膜后淋巴结切除可明确分期,但不是Ⅰ期子宫内膜癌的治疗手段,扩大手术范围并不能显著提高患者的生存率,远处转移在术后复发中占相当比例,有高危因素时,应考虑辅助治疗.     

Prognostic significance of DNA ploidy in stage I endometrial cancer

Objective.

To improve the outcome for patients with endometrial cancer, a more accurate prognostic assessment is needed. The current study was undertaken to determine the role of flow cytometric DNA ploidy as an independent prognostic factor in patients with stage I endometrial cancer and to verify if ploidy is able to identify high-risk cases among the apparent ‘low-risk’ patients, defined as stage (IA), grade (1 or 2), and histologic type (endometrioid).

Methods.

This was a retrospective study. DNA ploidy was evaluated from tumor samples in 217 patients with stage I endometrial cancer who underwent definitive surgery as the first treatment between 2003 and 2009. Ploidy and other classic parameters were analyzed in relation to the length of recurrence-free survival.

Results.

Among the 217 evaluated patients, 184 (84.8%) had diploid tumors and 33 (15.2%) had aneuploid tumors. There were 12 recurrences during the median follow-up intervals of 42.7 months. Stage, grade, histologic type, lymphovascular space invasion (LVSI), and ploidy were significantly correlated with recurrence-free interval by univariate Cox analysis. Based on multivariate Cox analysis, ploidy was an independent prognostic factor, with a hazard ratio of 4.5 (95% confidence interval [CI], 1.3-15.3; P = 0.017) adjusted for stage, grade, histologic type, and LVSI. In low-risk patients (n = 156), the recurrence rate was 2.1% for diploid tumors and 12.5% for aneuploid tumors (P = 0.038).

Conclusions.

DNA aneuploidy is an independent prognostic factor in patients with endometrial cancer and can identify high-risk patients among those considered ‘low-risk’ with stage I endometrial cancer.     

DNA aneuploidy is associated with increased mortality for stage I endometrial cancer

OBJECTIVE: The current study was undertaken to determine if DNA ploidy is a useful prognostic variable for predicting recurrence in stage I endometrial cancer. For cancer of the endometrium, survival following recurrence may depend on a number of factors, including the pattern of recurrence and the response to second line treatment. Previous studies have demonstrated a worse survival for patients with DNA aneuploid tumors. It remains unclear, however, whether this is necessarily due to a higher risk of recurrence. This study was undertaken to assess DNA ploidy and risk of recurrence in patients with stage I endometrial cancer. METHODS: This is a retrospective study of surgically treated patients with stages IB and IC endometrial cancer treated from 1992 to 2000. All patients underwent definitive surgery, including staging lymphadenectomy. None of the patients received postoperative treatment. DNA ploidy was determined using flow cytometry and image analysis. Grade, lymph-vascular space invasion, stage (stage IB versus IC), and DNA ploidy were analyzed with regard to recurrence and survival. RESULTS: There were 100 patients with stages IB and IC endometrial cancer in this analysis. There were 17 recurrences (17%) and 10 patients that died of cancer (10%). Grade 3 and the presence of lymph-vascular space invasion were associated with increased risk of recurrence; DNA aneuploidy and stage were not. Grade, lymph-vascular space invasion, and DNA ploidy were associated with survival. These findings indicate that DNA aneuploidy does not increase the risk of disease recurrence but is associated with overall survival. CONCLUSION: Although the recurrence risk is not higher for patients with surgical stage I endometrial cancer and aneuploid tumors, overall mortality remains higher.     

The role of vaginal hysterectomy in the treatment of endometrial carcinoma

Between 1964 and 1991, vaginal hysterectomy was performed in 60 patients with clinical stage I endometrial carcinoma, who were not considered candidates for the conventional surgical approach. Of these patients, 66.7% were obese with a median weight of 235 pounds. Other risk factors included hypertension (63%), diabetes mellitus (34%), cardiac disease (28%) and pulmonary disease (12%). Operative mortality was 0%. The complication rate was 14%, with four patients requiring transfusions and four patients developing vaginal cuff cellulitis. Forty per cent of patients received adjuvant pre- or postoperative radiation therapy. Crude survival at 5 and 10 years was 91.1% and 87.1%, respectively. However, only one patient died from disease 6 years after primary treatment. Although we consider surgical staging as the standard of care for the treatment of endometrial cancer, vaginal hysterectomy has a definite place in the management of patients with good prognostic criteria who are at high operative risk for the standard surgical approach.