The role of preoperative brachytherapy as an adjunct to surgery and postoperative radiotherapy in the treatment of stage I endometrial carcinoma

PURPOSE: Between 1978 and 1993, 817 cases of endometrial carcinoma were treated with simple hysterectomy with bilateral salpingo-oophorectomy. Five hundred and twenty-six cases had preoperative brachytherapy (Preo), and 291 cases underwent surgery without preoperative radiotherapy (Nopre). The aim of the study was to compare disease-free survival of the two groups. METHODS AND MATERIALS: Survival comparison of the two groups was controlled for postoperative treatment type, according to stage, histological type, degree of differentiation, depth of myometrial invasion and age. The life-table method was used for survival analysis. Cumulative disease-free survival probabilities were calculated as a function of the proportion of normal remaining life elapsed from the time of diagnosis. RESULTS: Five-year disease-free survival of patients with and without preoperative brachytherapy in stage IA, IB and IC was 93 and 93.6%, 93 and 94%, and 80 and 65%, respectively. In well differentiated tumors and poorly differentiated tumors, there was no difference in disease-free survival between patients with and without preoperative brachytherapy. Patients with moderately differentiated tumor treated with preoperative brachytherapy had significantly better disease-free survival than those without preoperative radiotherapy, however, this was confounded by uneven distribution of invasion depth. CONCLUSION: Preoperative brachytherapy plays a limited role in the treatment of early stage endometrial carcinoma.     

Postoperative radiotherapy in stage I endometrial adenocarcinoma

OBJECTIVE: To evaluate postoperative whole pelvic radiation for high-risk patients with Stage I endometrial adenocarcinoma. METHODS: One hunderd and twenty-two patients with irregular premenopausal or postmenopausal haemorrhage were included into the study. Fractional curettage was performed in all cases. When the pathohistological report confirmed endometrial adenocarcinoma, abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. Low-risk patients include women with Stage IA tumours and Stage IB grade 1 or 2 histology. High-risk group include patients with Stage IB grade 3 tumours and Stage IC carcinomas. High-risk patients received whole pelvic radiotherapy between two and four weeks after surgery. RESULTS: Eighty-two patients (67.21%) were low-risk and forty patients (32.79%) were high-risk. In the low-risk group of patients, CA-125 was negative in ten cases and positive in 72 patients with a mean value of 30.12 +/- 12.42 U/ml serum. In the high-risk group of the patients, CA-125 was negative in two cases and positive in 38 patients with a mean value of 60, 48 +/- 20, 14 U/ml serum. Locoregional recurrences were diagnosed in four patients (4.87%) in the surgery group and in two patients (5.00%) assigned to radiotherapy. The incidence of distant metastases was 2.43% in the surgery group and 2.50% in the radiotherapy group. Overall survival at five years was 90.25% in the low-risk group and 87.50% in the high-risk group of patients. CONCLUSION: Five-year overall survival, locoregional and distant metastasis were similar in the low-risk and high-risk groups of patients. That emphasizes the value of whole pelvic radiation in patients with unfavourable prognostic factors in Stage I endometrial cancer.     

Treatment of stage I endometrial carcinoma

Cases of stage I endometrial carcinoma treated at Columbia-Presbyterian Medical Center, New York, between 1966 and 1980 were evaluated with regard to clinical parameters, surgicopathologic findings, treatment modalities and survival. Four factors significantly influenced survival: tumor grade, patient's age, uterine size and addition of postoperative external radiotherapy in cases of significant myometrial invasion or a poorly differentiated lesion. No deaths or significant morbidity resulted from the use of adjuvant whole pelvic radiation.     

Estrogen replacement therapy following treatment for stage I endometrial carcinoma

One hundred forty-four patients with clinical stage I endometrial adenocarcinoma were treated over an 11-year period at Madigan Army Medical Center and Brooke Army Medical Center. Following surgical staging, 44 selected patients were placed on oral estrogen replacement for a median duration of 64 months. In the estrogen user group, there were no recurrent endometrial cancer and no intercurrent death. Of the 99 nonestrogen users, there were 8 recurrences (8%) and 8 intercurrent deaths. Patients placed on estrogen replacement had low-risk factors for recurrence, namely, low tumor grade (grades 1 and 2), less than 1/2 myometrial invasion, and no metastases to lymph nodes or other organs. Postoperative estrogen replacement appears to be safe in selected low-risk patients.     

子宫内膜样腺癌术后辅助放化疗的临床观察

目的评价有高危因素的子宫内膜样腺癌术后辅助放化疗的价值。方法选择宫颈侵犯、G3级、深肌层浸润、淋巴脉管侵犯、腹水细胞学阳性等高危因素的子宫内膜样腺癌268例,140例接受术后放疗,128例接受术后放化疗,比较两组的5年生存率。结果术后辅助放疗和术后辅助放化疗的5年生存率分别为92．14％和92．19％,两者比较,差异无统计学意义（P〉0．05）。而两组的毒性反应比较,术后辅助放化疗组的毒性反应明显增加（P〈0．05）。结论术后辅助盆腔放疗加化疗不能提高具有高危因素的子宫内膜样腺癌的5年生存率,且毒性反应明显增加。     

Magnetic resonance imaging in stage I endometrial carcinoma

A prospective study was conducted on 50 consecutive patients with stage I endometrial cancer who had primary surgical treatment. The purpose of the study was to assess the value of magnetic resonance imaging (MRI) for accurate staging of early disease and determination of myometrial invasion. Features identified by MRI were correlated with surgical pathology. Preliminary MRI results provided additional valuable information. All but one of 18 patients with histologically proven deep myometrial invasion were predicted preoperatively by MRI. Of 17 patients with detached fragments of malignant tissue in the endocervical curettage (ECC) but with results inconclusive for actual cervical invasion, MRI revealed all three patients with true cervical tissue involvement. Magnetic resonance imaging detected all six patients with gross extrauterine spread and also precisely measured uterine enlargement by myomata. The extent and location of tumor growth in the uterus could be mapped out in the majority of cases. Based on these findings, a pretreatment MRI scan of the pelvis in presumably stage I endometrial carcinoma resulted in an advance in staging in 18% of the patients, and accurately predicted deep myometrial invasion in 94% of the cases. Inclusion of MRI in the routine work-up in stage I endometrial carcinoma should be considered for proper clinical staging, particularly in patients with a positive but nondiagnostic ECC, uterine papillary serous carcinoma, or grade 3 tumor.     

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.     

Surgery without radiotherapy for primary treatment of endometrial cancer

Objective: To analyze the role of surgery alone, including pelvic and para-aortic lymphadenectomy, in patients with endometrial cancer who did not receive radiotherapy.Methods: Between August 1987 and January 1997, 225 women with disease clinically confined to the uterus were staged surgically by a standard protocol that included pelvic and para-aortic lymphadenectomy in women with high risk factors. No radiation was administered before or after surgery.Results: The combination of preoperative endometrial biopsy grade and gross depth of myometrial invasion identified 123 (55%) high-risk patients who had lymphadenectomy and 102 (45%) low-risk patients who did not. Eighteen (15%) high-risk patients had lymph node metastases and received postoperative systemic therapy. Three low-risk, eight high-risk-node-negative, and no high-risk-node-positive patients were diagnosed with recurrent cancer, corresponding to 5-year recurrence-free proportions of 0.95, 0.89, and 1.00, respectively. Although sample sizes and limited follow-up limit conclusions, the experience to date suggests a high rate of survival in all three groups.Conclusion: Our preliminary experience indicates that even high-risk patients have an excellent prognosis when treated with surgery, including pelvic and para-aortic lymphadenectomy, without radiotherapy.     

Individualization of indications for postoperative irradiation in stage I endometrial cancer

The results of the treatment of 550 Stages I-III endometrial cancer patients are analysed. The postoperative radiation therapy was employed in 311 (56.5 +/- 2.8%) patients. In the pathological Stage I 235 (50.5 +/- 3.2%) out of 465 women were irradiated postoperatively, but the distant irradiation was used in only 93 (20.6%), the others began prophylactic irradiation of vagina. With the aim of regression the nonparametric Cox model it was stated, that some factors, such as hormonosensitivity of the tumor, pathogenic type, histology, stage and mode of operation have a significant influence on survival, and the postoperative irradiation has not. The comparison of the results of treatment in Stage I revealed a slight tendency to increased survival in prognostically unfavourable subgroups with the aim of postoperative irradiation. The 5-year survival in Stage I 90.3%. The individualized indications for postoperative radiation therapy in Stage I endometrial cancer are elaborated deep myometrial invasion, lowering of differentiation of the tumors, hormonoresistence.     

Surgical pathologic staging in apparent stage I endometrial carcinoma

A multicenter trial on apparent stage I endometrial carcinoma was performed to establish an intensive surgical staging, to formulate a treatment on the basis of the pathological extent of the disease and to determine the effectiveness of adjuvant medroxyprogesterone acetate therapy. The results of the first objective on 1,055 patients are herein reported. All patients had total abdominal hysterectomy, bilateral salpingo-oophorectomy, colpectomy of the superior third, and biopsy of lymph nodes positive or doubtful at radiological imaging or on surgical inspection. On the basis of the pathologic extent of the disease, patients were classified into five categories: disease outside the uterine corpus (RE); disease limited to endometrium (RO); disease with inner myometrial invasion and high or moderate grade (R1); disease with deep myometrial invasion or poor differentiation (R2); disease with positive retroperitoneal nodes (R3). One hundred and forty-six patients were RE, 163 RO, 382 R1, 341 R2 and 23 R3. The results showed a clinical understaging in 16% of the cases. According to the new FIGO classification, the relapse-free survival at 84 months was 96% for patients at stage IA, 92% for patients with stage IB-C, 86% for stage IIA-B, 76% for stage IIIA-B and 74% for patients at stage IIIC. These data confirm the importance of an intensive surgical staging in apparent stage I endometrial carcinoma.     

Adjuvant chemotherapy in stage I uterine endometrial carcinoma.

OBJECTIVE: We have assessed prognostic factors and the efficacy of adjuvant chemotherapy in stage I uterine endometrial carcinoma. METHODS: 251 primary surgically treated stage I patients were studied. Prognostic factors were evaluated and 5-year and 10-year survival rates were compared in patients with lymph-vascular space invasion to investigate whether adjuvant chemotherapy improves survival. RESULTS: The overall 5-year and 10-year survival rates were 94% and 93%. Multivariate analysis indicates that lymph-vascular space invasion is the most significant prognostic factor in both 5- and 10-year survival rates (P<0.001 at both times) and stage/depth of invasion is significant for the 10-year survival rate (P=0.04). Of 54 patients with lymph-vascular space invasion, statistically significant differences were observed in 10-year survival rate (P=0.02) between patients who had surgery followed by adjuvant chemotherapy (n=23) and patients who had surgery alone (n=31). Toxicities were mild to moderate (30%). CONCLUSIONS: The clinical importance of lymph-vascular space invasion and the efficacy of adjuvant chemotherapy were confirmed. This observation warrants a larger comparative study with adjuvant chemotherapy.     

Flow cytometric DNA analysis of stage I endometrial carcinoma

Flow cytometric DNA analysis was performed on 203 paraffin-embedded archival specimens obtained from patients with surgical stage I endometrial carcinoma. Primary therapy for those patients (1979-1983) had been definitive extirpation with adjuvant therapy determined by histologic grade, histologic subtype, myometrial invasion, and peritoneal cytologic findings. Diploid DNA patterns were identified in 171 (84%) specimens and nondiploid characteristics were observed in the remaining 32 (25 DNA aneuploid, 7 DNA tetraploid). Although DNA nondiploid specimens accounted for only 16% of all stage I patients, they accounted for 50% of all relapses. Regardless of treatment or other pathologic features, progression-free 5-year Kaplan-Meier survival estimates were 92 and 63% for patients with DNA diploid and DNA non-diploid patterns, respectively (P less than 0.001). Overall 5-year progression-free survival for patients with grade 1 or 2 lesions was 90%; stratification by DNA diploid and DNA nondiploid patterns revealed progression-free survivals of 94 and 64%, respectively (P less than 0.001). Peritoneal cytologic study was positive in seven patients; none of the five with a DNA diploid pattern had a relapse and both with the DNA nondiploid pattern had relapses. These studies suggest that DNA ploidy status may be an objective prognostic determinant for patients with stage I endometrial carcinoma.     

Experience with pelvic washings in stage I and II endometrial carcinoma

Pelvic washings for cytologic analysis have become an accepted diagnostic procedure in the management of endometrial carcinoma. A retrospective study was performed in 163 consecutive patients with FIGO Stage I and II endometrial carcinoma to assess the significance and value of the washings. Abnormal results were obtained in 5.5% of patients. Patients with FIGO grade 3 lesions were significantly most likely to have abnormal washings (P less than 0.05). Significant association was not observed with stage, depth of myometrial invasion, extrauterine spread, histologic subtype, prior hormone usage, or hormone receptor status. Multivariant analysis indicated that, for Stages I and II combined and for Stage I alone, FIGO grade 3 was most predictive of poor survival (P less than 0.01). The postoperative therapy of only 2 patients (1.2%) was altered by the results of the pelvic washings and only one of these patients has survived. No patients have had recurrent disease (median follow-up 31 months) in the peritoneal cavity with negative washings unless two or more other adverse prognostic factors were present. It is concluded that pelvic washings have a limited role in the clinical management of Stage I and II endometrial carcinoma.     

Ovarian metastasis in women with clinical stage I endometrial carcinoma

BACKGROUND: The incidence of ovarian metastasis in women with clinical stage I endometrial carcinoma is generally reported to be 5%, leading to the practice of removing the ovaries at surgery even in young patients. METHODS: A retrospective study of 84 patients with clinical stage I endometrial cancer was carried out. Patients were excluded if the pathologic study revealed any evidence of extrauterine, apart from adnexal, spread or if the peritoneal cytology was positive. Patients with serous papillary or clear cell tumor histology were also excluded. RESULTS: Sixty-seven patients fulfilled the inclusion criteria. Only three (4%) patients were found to be in surgical stage IIIA, all three had grade 3 tumors. Of these patients, two had uterine serosal involvement and one had a microscopic tumor implant in a fallopian tube; none had ovarian metastasis. CONCLUSIONS: The risk of ovarian metastasis in women with well to moderately differentiated endometrial cancer, myometrial invasion limited to less than one half of the myometrium, negative peritoneal cytology and no evidence of metastatic lymph node spread is negligible. Young patients with a preoperative histological diagnosis of well to moderately differentiated endometrial carcinoma may be surgically staged, leaving the final decision regarding removal of the ovaries pending a thorough pathological review of the surgical specimens.     

Adjuvant high dose rate vaginal brachytherapy as treatment of stage I and II endometrial carcinoma

OBJECTIVE: To evaluate the efficacy of high dose rate vaginal brachytherapy in the treatment of International Federation of Gynecology and Obstetrics stage IB, IC, and II endometrial carcinoma after surgical staging and complete lymphadenectomy. METHODS: All patients with stage IB, IC, or II adenocarcinoma or adenosquamous carcinoma of the endometrium who received postoperative high dose rate vaginal brachytherapy at our institution between June 1, 1989, and June 1, 1999, were eligible. High dose rate vaginal brachytherapy was delivered in three fractions of 700 cGy. Retrospective chart review was performed. Kaplan-Meier estimates were calculated for disease-free and overall survival. RESULTS: One hundred sixty-four women were identified. Fifty-six percent had stage IB disease, 30% had stage IC disease, and 14% had stage II disease. Approximately one third of patients had high-grade lesions and nearly 40% had deep myometrial invasion. Median follow-up was 65 months (range 6-142 months). To date, 14 patients have had recurrence; 2 at the vaginal apex, 9 at distant sites, 1 at the pelvic sidewall, 1 simultaneously in the pelvis and at a distant site, and 1 at an unknown site. Both patients with vaginal apex recurrences had salvage therapy and are now free of disease. The overall 5-year survival and disease-free survival rates were 87% and 90%, respectively. There were no Radiation Therapy Oncology Group grade 3 or 4 toxicities. High dose rate vaginal brachytherapy was approximately $1,000 less expensive than external-beam whole-pelvic radiation. CONCLUSIONS: Adjuvant high dose rate vaginal brachytherapy in thoroughly staged patients with intermediate-risk endometrial carcinoma provides excellent overall and disease-free survival with less toxicity and at less cost compared with whole-pelvic radiation.     

Pelvic lymphadenectomy as alternative to postoperative radiotherapy in high risk early stage endometrial cancer

Objective: The purpose of the study is to evaluate whether surgery followed by radiotherapy in high-risk patients of early stage endometrial cancer can be replaced by formal surgical staging. Cancer-related survival and recurrence-free survival (RFS) were the endpoints of the analysis. Study design: One hundred and eighteen patients with endometrioid endometrial adenocarcinoma between 1996–2003 were reviewed. Patients with incomplete follow-up and extrauterine spread excluded, leaving 78 women in the final analysis. Low-risk patients (n=37) (Grade 1, myometrial infiltration <1/2 or Grade2, <1/3), treated by standard surgical procedure including total abdominal hysterectomy, bilateral salpingo-oophorectomy and peritoneal washing, while staging lymphadenectomy (n=24) or postoperative irradiation (n=17) was added in the high-risk group (Grade 1, >1/2 or Grade 2, >1/3 or Grade3). Results: The median age of patients was 65 years (range, 35–80 years) and the median follow-up 38 months (range, 9–98 months). The recurrence rate in low-risk patients was 2.7%, the cancer-related survival 97.5% and RFS 97%, while in the high-risk patients 12%, 93% and 88%, respectively. Comparing the therapeutic modalities (staging lymphadenectomy vs. postoperative irradiation) in the high-risk group the cancer-related survival and RFS was not differed (P=0.70, P=0.90, respectively). The high grade of the tumor was significantly correlated with RFS, while age, stage and myometrial infiltration were not. No moderate or severe complications developed after lymphadenectomy, while two moderate gastrointestinal complications occurred after adjuvant radiotherapy. Conclusion: According our results the low-risk patients of early stage endometrial adenocarcinoma had excellent survival with minimal intervention. The cancer-related survival and RFS in high-risk patients concerning the therapeutic modalities were comparable. Poor tumor differentiation was the most unfavorable prognostic factor related with RFS. Moderate complications developed only after postoperative radiotherapy.