Prevention of vaginal recurrence of stage I endometrial adenocarcinoma with postoperative vaginal radiation

From 1975 to 1982 a prospective study was conducted at Roswell Park in 68 patients (group 1) for surgical stage I endometrial cancer, grade 1 or 2, and less than 50% myometrial invasion. These patients were treated by total abdominal hysterectomy, bilateral salpingo-oophorectomy, and postoperative vaginal radium. With median follow-up of 4.8 years, there has not been a single vaginal recurrence. This treatment plan was based on a prospective study at the same institute from 1958 to 1967, which compared patients with stage I endometrial cancer treated by hysterectomy alone, preoperative radium followed by hysterectomy, and hysterectomy followed by postoperative radium. In addition, 19 patients (group 2) were evaluated as to their initial treatment after their referral to Roswell Park with vaginal recurrence after surgical treatment for stage I endometrial cancer. None of these patients were treated initially with postoperative vaginal radium after hysterectomy. Based on the zero incidence of vaginal recurrence in 117 patients with FIGO stage I endometrial cancer, the estimated five-year survival rate of 97.2% for the group 1 patients, and the actuarial five-year survival of 95% in the 1958 to 1967 prospective study, it is concluded that primary surgery should be followed by postoperative vaginal radium (cesium) in those patients with stage I endometrial cancer, grade 1 or 2, with less than 50% myometrial invasion.     

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.     

New treatment procedure for stage I endometrial adenocarcinoma

A series of 80 Stage I adenocarcinomas of the endometrium is described. Treatment is based on a more frequent use of surgery and there is greater individualization of the treatment procedure, which combines vaginal or uterovaginal Curie therapy and surgery. Overall 5 year survival rates are 82%, compared with 91.5% for patients having been treated with Curie therapy plus surgery. The patient's age and the size of the uterus were found to be significant from the prognostic standpoint. However, other factors, such as histological type and grade, penetration into the myometrium, and lymph node involvement did not seem especially important. Treatment described here appears to give better results than that used previously; survival rates are higher and complications of treatment are negligible.     

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.     

Surgical therapy in high-risk patients with endometrial adenocarcinoma

Personal experience with 100 cases of endometrial adenocarcinoma surgically treated in 1983-87 revealed a significant link between grading, myometrial infiltration and lymph node involvement. This finding forms the basis for the creation of a special classification system used in selecting the therapeutic approach, the aim being to avoid radical surgery in those patients considered "high risk" due to their poor cardiovascular or metabolic condition or obesity, while ensuring that the appropriate treatment is given.     

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.     

Accuracy of intraoperative frozen-section diagnosis in stage I endometrial adenocarcinoma

The purpose of our study was to determine if frozen-section diagnosis accurately identified patients suffering from endometrial adenocarcinoma FIGO stage I for surgical staging consisting of total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal cytology, and complete bilateral pelvic lymphadenectomy in moderately differentiated tumors with myometrial invasion. In all poorly differentiated tumors, and in all tumors with deep myometrial invasion (more than 50%) surgical staging included additional para-aortic lymphadenectomy. We performed a retrospective study including 70 patients. Frozen-section diagnosis of myometrial invasion and tumor grade was compared with permanent-section diagnosis. The accuracy rates were determined, and compared with accuracy rates of frozen-section diagnosis in the literature, and a total accuracy rate for 624 patients suffering from stage I endometrial adenocarcinoma was evaluated. In our patient collective, the overall accuracy rate of frozen-section diagnosis for myometrial invasion and tumor grade was 80 and 84%, respectively. In the five comparable studies, the mean accuracy rate for myometrial invasion and tumor grade was 89 and 84%, respectively. In combination with the five comparable studies our recent study produced an accuracy rate of frozen-section diagnosis for myometrial invasion and tumor grade of 88 and 84% in 624 patients, respectively. Despite an accuracy level of frozen-section diagnosis for myometrial invasion of 80 and 84% for tumor grade in our patient collective, all patients who required surgical staging were accurately identified.     

Prognostic significance of squamous differentiation in stage I endometrial adenocarcinoma

The prognostic implication of benign and malignant squamous differentiation was examined in 267 consecutive patients with stage I endometrial carcinoma. Patients with adenosquamous carcinoma had a significantly poorer ten-year survival rate (54.7%) than patients with adenocarcinoma (70.5%) or adenoacanthoma (87.4%). This was related to a tendency for adenosquamous carcinoma to be associated with poorly differentiated glandular elements and to deeply invade the myometrium. The mean depth of myometrial penetration was 57% for adenosquamous carcinoma compared with 24% for adenocarcinoma and 19% for adenoacanthoma. To examine the prognostic significance of malignant squamous differentiation independently of the grade of the associated glandular component, the subgroup of patients with well-differentiated adenocarcinoma was compared. Patients with well-differentiated adenosquamous carcinoma persisted in having a worse prognosis (58.3% ten-year survival rate), compared with adenocarcinoma (84.3% ten-year survival rate), which was explained by the propensity of adenosquamous carcinoma to deeply invade the myometrium.     

Pelvic and paraaortic lymph node metastasis in clinical stage I endometrial adenocarcinoma: an analysis of 58 consecutive cases

OBJECTIVE: The aim of this study was to evaluate the importance of complete surgical-pathologic staging in clinical Stage I endometrial adenocarcinomas. METHODS: 58 consecutive women with clinical Stage I endometrial adenocarcinomas were investigated. RESULTS: Isolated paraaortic lymph node invasion was found in one patient without pelvic node invasion (5%). CONCLUSIONS: We recommend a complete lymphadenectomy instead of selective lymphadenectomy. With this practice the real stages of the cases can be determined and over treatment can be avoided.     

Significance of lower uterine segment involvement in women with stage I endometrial adenocarcinoma

OBJECTIVE: To determine whether lower uterine segment involvement (LUSI) correlates with recurrence and survival in women with stage I endometrial adenocarcinoma who do not receive postoperative radiotherapy on the basis of this histologic criterion. STUDY DESIGN: Eighty patients with endometrial adenocarcinoma stage I who underwent surgery between 1989 and 2002 were divided into 2 groups according to the presence of LUSI. Group 1 consisted of 25 patients with LUSI; group 2 consisted of 55 patients without LUSI. The 2 groups were compared with regard to prognostic factors and outcome measures. RESULTS: There were no statistically significant differences between the 2 groups with regard to the following parameters: age and proportion of patients who underwent complete surgical staging and postoperative adjuvant radiotherapy. Pathologic parameters of the 2 groups, such as histologic type, grade and deep myometrial invasion, were comparable. A greater proportion of patients with LUSI had capillary space-like involvement. The patients were followed for a median of 48 months (range, 11-168) from the date of surgery. The overall 5-year recurrence-free survival, disease-specific survival and overall survival rates were 91% (SE .04), 94% (SE .03) and 77% (SE .06), respectively. There was no significant difference between the two groups with regards to these measures (P < .05). CONCLUSION: In patients with state I endometrial cancer, the presence of lower uterine segment involvement does not correlate with their outcome.     

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.     

Intraoperative evaluation of depth of myometrial invasion in stage I endometrial adenocarcinoma

In patients with stage I endometrial adenocarcinoma, the incidence of pelvic and para-aortic lymph node metastasis is related to the grade of the tumor and the depth of myometrial invasion. Although the grade of the tumor may be predicted preoperatively by endometrial sampling, the depth of myometrial invasion cannot be determined until after the uterus has been removed. Although complications have been attributed to lymph node sampling, failure to perform the procedure in patients at risk for nodal metastasis may result in underdiagnosis of extrauterine disease, leading to inadequate therapy. Gross visual examination of the cut surface of the tumor at the time of hysterectomy accurately determined the depth of myometrial invasion in 135 of 148 prospectively studied patients (91%) (P less than .001). The sensitivity of the test was 0.71, the specificity was 0.96, and the positive predictive value was 0.80. Intraoperative assessment of the depth of myometrial invasion is a simple, inexpensive, and useful technique for selecting those patients with stage I endometrial adenocarcinoma who might benefit from selective para-aortic lymphadenectomy.     

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.     

Doxorubicin as an adjuvant following surgery and radiation therapy in patients with high-risk endometrial carcinoma, stage I and occult stage II: a Gynecologic Oncology Group Study

The Gynecologic Oncology Group studied the use of adjuvant doxorubicin after surgery and radiation therapy for endometrial carcinoma in a randomized, prospective manner. The study population consisted of patients clinically stage I or II (occult) who, after surgical-pathologic evaluation, had one or more risk factors for recurrence: greater than 50% myometrial invasion, pelvic or aortic node metastasis, cervical involvement, or adnexal metastases. All patients without aortic node metastasis received 5000 rads to the whole pelvis at 160-180 rads per day. If aortic node metastasis was documented, aortic field radiation to the top of T12 was offered. The aortic target dose was 4500 rads at 150 rads per day. After completion of radiation therapy, the patients were randomized to receive doxorubicin bolus therapy (60 mg/m2 starting dose) to a maximum cumulative dose of 500 mg/m2. Between November 1977 and July 1986, 92 patients were entered into the doxorubicin (DOX) treatment arm, and 89 patients entered the no-DOX arm. There was no statistically significant difference in survival or progression-free interval of the two arms. The 5-year survival rates for patients with deep myometrial invasion, cervical involvement, and pelvic node metastases were similar (63-70%), whereas the rate for patients with aortic node metastases was 26%. There was no significant difference in the recurrence pattern between the two treatment arms. There were no cases of grade 3 or 4 cardiac toxicity. Twelve patients (6.9%) developed small bowel obstruction after radiation therapy. There were three treatment-related deaths in the DOX arm and two in the radiation therapy-only arm. We conclude that, because of protocol violations, small sample size, and the number of patients lost to follow-up, this study was unable to determine what effect use of doxorubicin as adjuvant therapy had on recurrence, progression, and survival of the endometrial cancer study population. The combination of surgical staging and postoperative radiation as used in this study appears to increase the risk of bowel complications.     

Adjuvant radiotherapy for stage I, grade 2 endometrial adenocarcinoma and adenoacanthoma with limited myometrial invasion

All cases of endometrial adenocarcinoma from January 1970 to December 1980 treated at the Geisinger Medical Center were reviewed retrospectively. One hundred eighty-eight cases of stage I grade 2 adenocarcinoma of favorable histologic subtype (adenocarcinoma, adenoacanthoma) and limited myometrial invasion (less than one-third of the myometrium) were identified. Surgery and adjuvant radiotherapy was used in 136 cases, and 52 cases were treated with surgery alone. There was no statistically significant difference between the two groups in menopausal status, parity, exogenous estrogen, obesity, hypertension, diabetes, or uterine size. Five-year survival for the surgery and radiotherapy group was 94% (128 of 136), and the recurrence rate was 2.2% (three of 136). The five-year survival for the surgery-alone group was 98% (51 of 52), and the recurrence rate was 1.9% (one of 52). There was no statistically significant difference in five-year survival or recurrence between the two groups. This study suggests that surgery alone is adequate treatment for stage I grade 2 adenocarcinoma of favorable histologic subtype and limited myometrial invasion. This study also shows a possible benefit in the combined use of histologic subtype, grade, and myometrial invasion as prognostic indicators and as guides for adjuvant radiotherapy.     

Reliability of frozen section examination in identifying poor prognostic indicators in stage I endometrial adenocarcinoma

Management of Stage I adenocarcinoma of the uterus includes hysterectomy, bilateral salpingo-oophorectomy, and selective paraaortic and pelvic lymphadenectomy. Postoperative radiation therapy (RT) is selectively employed in patients with histologically defined poor prognostic indicators. We attempted to identify these poor prognostic indicators by frozen section (FS) at primary surgery in 55 patients with Stage I endometrial adenocarcinoma; we found an excellent correlation between the results obtained on gross examination of the uterus with selected FS and the results after extensive sampling and microscopic examination of permanent section (PS). The depth of myometrial invasion was accurately predicted in 96.5%, and histologic grade in 94.5% of these patients. Sixty-six percent of patients with occult invasion of the cervix on PS were identified on FS. Using the above criteria, we identified by FS all patients (15/55) who required adjuvant RT obviating the need for pelvic lymph node dissection. On the basis of our preliminary data, we recommend the use of careful gross examination and selective FS to identify patients requiring selective pelvic and paraaortic lymphadenectomy and adjuvant therapy, thereby eliminating the need for staging lymph node dissection with its associated morbidity and complications.