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.     

The use of adjuvant radiation therapy by members of the Society of Gynecologic Oncologists.

OBJECTIVES. The aim of this study was to determine the attitudes of the members of the Society of Gynecologic Oncologists with respect to the use of adjuvant radiation therapy in women with endometrial cancer. METHODS: An anonymous survey concerning the use of adjuvant radiation therapy in endometrial cancer was mailed to all members of the Society of Gynecologic Oncologists listed in the 1998 directory. RESULTS: Of the 767 listed members, 325 (42%) returned completed surveys. Less than 20% of respondents recommended adjuvant radiation therapy in stage IA grade 1 or 2 and stage IB grade 1 endometrial cancer. Adjuvant radiation is recommended by 40 to 50% of respondents in women with stage IA grade 3 and IB grade 2 tumors. Most recommend adjuvant radiation for all women with >50% myometrial invasion or grade 3 tumors with any myometrial invasion. Lymph node sampling is attempted in all cases by 48% of respondents. For those familiar with Gynecologic Oncology Group (GOG) Study No. 99, 20% stated that they were more likely to recommend adjuvant radiation and 27% stated that they were less likely to recommend adjuvant radiation based on the preliminary results. Except in stage IA grade 1 tumors, the chance of recommending further therapy in women with all stages and grades was significantly less if a complete staging procedure including lymph node dissection had been performed. CONCLUSIONS: Complete staging appears to decrease the chance that postoperative therapy will be recommended. The use of adjuvant radiation therapy seem to have declined slightly as a result of GOG Study No. 99. Future studies in women with endometrial cancer that do not require lymph node sampling should evaluate the frequency of adjuvant therapy in the absence of complete staging.     

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.     

Patterns of practice and outcomes in intermediate- and high-risk stage I and II endometrial cancer: a population-based study

To evaluate patterns of practice and outcomes in intermediate- and high-risk stage I and II endometrial cancer in the province of Ontario, Canada. This was a retrospective population-based study of women diagnosed with stage I and II endometrial cancer in Ontario from 1996 to 2000. After excluding low-risk (stages IA and IB, grades 1 and 2) and nonendometrioid histologies, the population was stratified into two risk groups: intermediate risk (stages IA and IB, grade 3; stages IC and IIA, grades 1 and 2; stage IIA, grade 3 if <50% myometrial invasion) and high risk (stage IC, grade 3; stage IIA, grade 3 if >50% myometrial invasion, and all stage IIB). Patterns of practice were assessed in each risk group, including use of surgical staging and adjuvant pelvic radiotherapy (APRT). Cox proportional hazards models determined effects of prognostic factors on 5-year overall survival (OS), including age, income, comorbidities, lymphvascular space invasion (LVSI), surgical staging, and APRT. There were 995 women in this study: 748 intermediate risk (75.2%) and 247 high risk (24.8%). Only 69 (9.2%) and 40 (16.2%) women underwent surgical staging in the intermediate- and high-risk groups, respectively. Surgical staging did not reduce rates of APRT. Determinants of survival included age >60 and comorbidities in the intermediate-risk group, and age >60, income, and LVSI in the high-risk group. In this population-based study, there were variable patterns of practice for intermediate- and high-risk stage I and II endometrial cancer. Surgical staging and APRT did not affect OS.     

Outcome and Management of Pathological Stage I Endometrial Carcinoma Patients with Involvement of the Lower Uterine Segment

OBJECTIVE: The objective was to evaluate the clinicopathologic characteristics and outcome of pathologic stage I endometrial carcinoma patients with lower uterine segment (LUS) involvement. METHODS: We retrospectively reviewed the characteristics and outcomes of pathologic stage I endometrial carcinoma patients treated with primary surgery at our institution between 1988 and 1998. The significance of LUS involvement was examined with univariate and multivariate analyses. Median patient follow-up was 37.3 months. RESULTS: Of the 98 cases reviewed, 41 (42%) had LUS involvement. No differences were seen in the clinicopathologic features, extent of surgical staging, or adjuvant therapies between patients with and without LUS involvement. Univariate analysis revealed that grade, lymphovascular invasion (LVI), myometrial invasion (MI), and histology were correlated with recurrence. While the 5-year actuarial disease-free survival was worse in women with LUS involvement (80.3 vs 94.0%) compared to those without, this difference did not reach statistical significance (P = 0.14). Moreover, after controlling for pathologic features in a multivariate model, LUS involvement was not correlated with patient outcome (P = 0.98; hazard rate 0.97; 95% confidence interval 0.24, 4.0). LUS was also not correlated with pelvic recurrence. Of 25 low-risk patients (superficial MI and grade 1-2 disease) with LUS involvement, none recurred in the pelvis following surgery alone. In contrast, pelvic recurrence was common (5/12 or 41.6%) in high-risk patients (deep MI and/or grade 3 tumors) following surgery alone regardless of LUS involvement. CONCLUSION: LUS involvement is common in pathologic stage I endometrial carcinoma but is not correlated with a worse outcome. Moreover, in the absence of adverse pathologic features, LUS involvement is not associated with an increased risk of pelvic recurrence and should not be used as an indication for adjuvant radiation therapy.     

Pelvic radiation in stage I endometrial adenocarcinoma with high-risk attributes

From 1977 to 1987, 45 patients with FIGO stage I endometrial adenocarcinoma with high-risk attributes and disease confined to the pelvis were prospectively treated with postoperative pelvic radiation. By study design, all patients underwent staging laparotomy with pelvic and paraaortic lymphadenectomy. All patients had either grade 1 or 2 adenocarcinoma and greater than 50% myometrial invasion or grade 3 adenocarcinoma with less than or greater than 50% myometrial invasion. The estimated 5-year survival for all 45 patients was 77% and the 5-year disease-free interval was 82%. Regional control was achieved in 89% of all patients, with 4% recurring at distant sites. When patients were stratified according to surgical-pathologic findings, 33 patients with disease confined to the uterus or uterus and pelvic nodes (surgical stage I) had estimated 5-year survival and disease-free interval of 88%. Of these 33 patients, 10 with grade 1 or 2 adenocarcinoma and deep myometrial invasion had 5-year disease-free intervals of 100%, while 23 patients with grade 3 adenocarcinoma with less than or greater than 50% myometrial invasion had disease-free intervals of 79 and 91%, respectively. From these results, it was concluded that patients with high-risk attributes demonstrated to have disease confined to the uterus or uterus and pelvic nodes can achieve excellent survival following surgical staging and postoperative pelvic radiation.     

Tumor size,depth of invasion,and histologic grade as prognostic factors of lymph node involvement in endometrial cancer: A SEER analysis

Objectives

The objective of this investigation was to evaluate the risk of nodal metastasis in patients with endometrial cancer, using the Mayo criteria, in a population-based analysis.

Materials and methods

Data from the SEER registry was reviewed for endometrial cancer cases diagnosed between 1988 and 2010. Patients were considered at low-risk for nodal metastasis if their tumors were histologic grade 1 or 2, myometrial invasion was less than 50%, and tumor size equal to or less than 2 cm. Patients not meeting these criteria were considered at high-risk for nodal involvement.

Results

The final study group consisted of 19,329 women with surgically staged endometrial cancer. Of these, 1035 (5.3%) had lymph node involvement. Based on Mayo criteria, 4095 (21.1%) patients were found to be at low-risk and 15,234 (78.9%) at high-risk for nodal metastasis. Low-risk features were associated with a 1.4% risk for lymph node metastasis, compared to 6.4% in patients with high-risk features (p < 0.001). When myometrial invasion was removed from the analysis, low-risk pathologic features were associated with a 2.4% risk of lymph node metastasis, compared to 10.4% in patients with high-risk features (p < 0.001).

Conclusions

In a population-based analysis, women with low-risk endometrial cancer, as defined by the Mayo criteria, have a low rate of lymph node metastasis.     

Surgical staging for patients presenting with grade 1 endometrial carcinoma

OBJECTIVE: To examine the impact of surgical staging of patients presenting with grade 1 endometrial cancer. METHODS: The charts of all patients who presented for surgery for endometrial cancer between March 1997 and July 2003 were analyzed for demographic data, final tumor histology, grade, stage, and complications. RESULTS: A total of 349 patients underwent surgical management for endometrial cancer. Preoperatively, 181 (52%) were identified with grade 1 disease, with a mean age of 61 years (range 27-89). Surgical staging (pelvic +/- para-aortic lymphadenectomy) was performed in 82% of cases and was omitted only in cases when disease was apparently confined to the endometrium and surgical risk was high. In staged patients, 3.2% had severe surgical complications. There were 2 perioperative mortalities (1 pulmonary emboli and 1 myocardial infarct). In comparison of pre- and postoperative histology, 19% of patients were upgraded, with 15% grade 2, 0.5% grade 3, 2.5% serous or clear cell, and 1% mixed mesodermal tumor. Lymph node metastases were found in 3.9% of patients presenting with grade 1 endometrial cancer, and 10.5% had extrauterine spread (> IIb). High-risk uterine features, including myometrial invasion more than 1/2, grade 3 lesions, high-risk histologic variants, and/or cervical involvement, were found in 26% of the patients. No patients with stage Ia-IIb endometrioid cancer received adjuvant teletherapy or chemotherapy. Four patients with low-risk uterine features were found to have extrauterine disease. Twelve percent of patients received adjuvant therapy, and 17% avoided teletherapy and/or chemotherapy based on surgical staging. CONCLUSION: Surgical staging in patients presenting with grade 1 endometrial cancer significantly impacted postoperative treatment decisions in 29% of patients. Omitting lymphadenectomy in patients presenting with grade 1 endometrial cancer may lead to inappropriate postoperative management.     

Role of lymphadenectomy and pelvic radiotherapy in patients with clinical FIGO stage I endometrial adenocarcinoma: an analysis of 208 patients

Two hundred and eight patients with a clinical stage I endometrial carcinoma were studied (164 fulfilled the inclusion criteria). High risk was defined as nonendometrioid, or endometrioid tumors grade 3 (G3), or G2 with any or G1 with deep (>1/2) myometrial infiltration. The low-risk group consisted of the remaining patients. Surgical staging in the high-risk group included pelvic lymphadenectomy with para-aortic lymphadenectomy in selected cases. Twelve percent of the high-risk patients had nodal metastasis. Patients with low-risk (group A, n = 85) and high-risk disease confined to the uterus (group B, n = 57) did not receive adjuvant radiotherapy. Patients with nodal metastases (group C, n = 10) received postoperative irradiation. The total recurrence rate of the entire population was 12.5%, and the actuarial overall survival, disease-specific survival, and disease-free survival were 90%, 94%, and 88%, respectively. All patients with only vaginal relapse (n = 9) were cured locally with salvage radiotherapy until the date of analysis. The pelvic relapse rate was low as only one patient of group B recurred in the pelvis. In conclusion, lymphadenectomy remains indicated to better select patients at high risk of pelvic recurrence that may benefit from postoperative radiotherapy.     

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.     

Endometrial adenocarcinoma: therapeutic impact of preoperative histopathologic examination of endometrial tissue

Adenocarcinoma of the endometrium is diagnosed by the histologic evaluation of endometrial tissue. In stage I disease, five-year survival depends upon a number of prognostic factors. Histologic grade and type of carcinoma are most important. The need for pelvic and para-aortic lymphadenectomy is often based on the preoperative histologic grade and type of tumor. The purpose of this study was: 1) to compare preoperative histology of endometrial carcinoma to that found at hysterectomy, 2) to determine if preoperative histology can accurately predict depth of myometrial invasion or extra-uterine spread, 3) to determine whether para-aortic lymphadenectomy could be deleted based only on the preoperative finding of well differentiated carcinoma. In 19 (28%) of the 68 patients studied, the histologic grade or pattern at hysterectomy was different from that found preoperatively. In seven (13%) of the 52 "good prognosis" patients with grades 1 and 2 preoperative histology, hysterectomy revealed a more serious histologic type. Three of the seven (43%) had extrauterine spread. In the 16 "poor prognosis" patients with preoperative grade 3 or papillary serous/clear cell carcinoma, 14 (88%) had a similar histologic pattern at hysterectomy. Three of these patients had metastatic disease. Depth of myometrial invasion could not be predicted by preoperative histology even though the data suggested that extrauterine spread could. Clinical stage I endometrial carcinoma, grade 1 or 2, should not be treated without para-aortic nodal sampling based only on a supposedly favorable preoperative histologic pattern. Confirmed para-aortic nodal disease will alter the fields of post-operative radiation therapy should that become necessary. In these patients, however, pelvic lymphadenectomy is not justified.2 +     

Is there a survival benefit to adjuvant radiotherapy in high-risk surgical stage I endometrial cancer?

OBJECTIVE: The aim of this study was to examine the effects of therapeutic modalities on survival of stage I endometrial cancer and also to evaluate the surgical morbidity and the prognostic importance of surgicopathological variables. METHODS: A hundred and ninety-six stage I endometrial cancer patients treated at Hacettepe University Hospital between 1982 and 1997 were included. After initial diagnosis all patients underwent surgical procedures including peritoneal cytology, infracolic omentectomy, total abdominal hysterectomy, bilateral salphingoopherectomy, and complete pelvic-paraaortic lymphadenectomy. The mean age at initial diagnosis was 56 years (SD = 9.9 years) and the patients were followed 3-18 years (median, 8 years). All patients had endometrioid carcinoma. Stage IC and/or grade 3 tumors were considered high-risk factors and by this definition 147 (75%) patients were low risk and 49 (25%) patients were high risk. Forty-nine percent of high-risk patients received adjuvant radiotherapy compared with 3.5% of patients in the low-risk group. RESULTS: The 10-year disease-free and overall survival rates of the entire group were 97 and 98%, respectively. Ten-year overall survival rate for the low-risk group was 100% compared with 94% for patients with high-risk features (P = 0.002). The 10-year disease-free survival rate in the high-risk group was 96% for 24 patients who received adjuvant radiotherapy versus 92% for 25 patients who did not receive adjuvant therapy (P = 0.53). Only high grade was a significant predictor of poor survival (P = 0.0004). Overall surgical morbidity rate was 8.1% without mortality related to surgery. CONCLUSIONS: Surgical staging achieved excellent survival for stage I endometrial cancer patients without incurring untoward morbidity and mortality. No survival advantage of adjuvant radiotherapy was detected even for high-risk patients, so we suggest the use of radiotherapy may be reserved for relapse.     

Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study

Between June 20, 1977 and February 5, 1983, the Gynecologic Oncology Group entered 1180 women with clinical stage I or II (occult) endometrial carcinoma into a surgical-pathological staging study. Eight hundred ninety-five patients with endometrioid or adenosquamous carcinoma were evaluable for this study which relates surgical-pathological parameters and postoperative treatment to recurrence-free interval and recurrence site. Proportional hazards modeling of time to recurrence was performed. For patients without metastasis determined by surgical-pathological staging the greatest determinant of recurrence was grade 3 histology adenocarcinoma grade 3, relative risk (RR) = 15; adenosquamous carcinoma grade 3, RR = 8.1; all adenocanthomas, RR = 1.0). Of 48 patients with histologically documented aortic node metastases, 47 had one or more of the following features: (1) grossly positive pelvic nodes, (2) grossly positive adnexal metastasis, or (3) outer one-third myometrial invasion. Pelvic radiation was administered to 48.0% and vaginal brachytherapy alone to 10.2% of patients postoperatively; 41.8% received no adjuvant radiation therapy. None of three recurrences in the vaginal implant group were vaginal or pelvic; 7.4% (7 of 95) of recurrences in the pelvic radiation therapy (RT) group were vaginal and 16.8% were pelvic; 18.2% (8 of 44) of recurrences in the no adjuvant radiation group were vaginal and 31.8% pelvic. Because of the high degree of selection bias no valid comparisons can be made of recurrence-free interval in these groups. The 5-year recurrence-free interval for patients with negative surgical-pathological risk factors (other than grade and myoinvasion) was 92.7%; involvement of the isthmus/cervix 69.8%; positive pelvic cytology 56.0%; vascular space invasion 55.0%; pelvic node or adnexal metastases 57.8%; and aortic node metastases or gross laparotomy findings 41.2%. It is not clear that cervix invasion per se diminishes survival, because it is more often associated with poor tumor differentiation (34.7% versus 24.0%, grade 3) and deep myoinvasion (47.0 vs 18.6%) than cases without cervix invasion. The relapse rate among cervix-positive and -negative cases with grade 3 lesions and deep myoinvasion is not dramatically different (48.8% vs 39.8%). The proportion of failures which were vaginal/pelvic (34.6% for the surgery only group compared to 12.5% of the RT group) appears to favor the use of adjuvant radiation for patients with more than one-third myoinvasion and grade 2 or 3 tumor. There were 97 patients in the study group with malignant cytology of which 29.1% had regional/distant failure, which compares to 10.5% of the cytology-negative patients.(ABSTRACT TRUNCATED AT 400 WORDS)     

Management of endometrial cancer with suspected cervical involvement

The 1989 International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer cells for operative assessment of the extent of uterine disease, grade, and sites of metastasis before assigning a stage to the cancer. In the current study, 70 endometrial cancer patients with suspected cervical involvement based on a positive endocervical curettage or punch biopsy were treated with initial surgery followed by tailored radiation or chemotherapy. Only 37% of the patients had operative findings consistent with the preoperative suspicion of stage II disease. Postoperative therapy was determined by the extent of cervical involvement, depth of myometrial invasion, cell type, tumor grade, and the presence and location of extra-uterine disease. Based upon these parameters, 21 patients were believed to have low risk for pelvic recurrence and received no adjuvant therapy (90% 5-year survival); 38 patients received postoperative pelvic radiation because of high-risk factors for pelvic recurrence or pelvic nodal involvement (65% 5-year survival); and 11 patients received chemotherapy and/or extended radiation because of extrapelvic disease (no 5-year survivors). The approach outlined supports initial surgery for cases of endometrial cancer with suspected cervical involvement. This approach permits accurate surgical staging under the new FIGO system, avoids radiotherapy in many patients whose disease is less extensive than suspected preoperatively, and can accomplish good local control with limited morbidity.     

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.     

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.     

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.     

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.     

Intraoperative assessment of depth of myometrial invasion in endometrial carcinoma.

OBJECTIVE: To evaluate the adequacy of intraoperative assessment of depth of myometrial invasion in patients with endometrial adenocarcinoma. METHODS: Of the 58 evaluable cases, depth of myometrial invasion was estimated by gross examination of fresh tissue by an experienced surgeon and a pathologist and on the frozen section by the same pathologist. This was compared with the depth of invasion on the final microscopic examination performed by another pathologist. RESULTS: The depth of invasion was accurately predicted by the surgeon in 89.7% of the patients, while the pathologist's accurate prediction rates on fresh tissue and frozen section were 86.2% and 91.4%, respectively. The accurate prediction rate gradually diminished for both the surgeon and the pathologist as the histologic grade increased. Frozen section examination was reliable in grade I cancer (100%), while gross examination of the surgeon and the pathologist had a significant error rate in predicting accurate depth of invasion (7.6%-33%). CONCLUSION: If frozen section shows that myometrial invasion in patients with grade 1 endometrial carcinoma is less than 1/3, lymphadenectomy may be omitted. In all other cases radical surgery and surgical staging is mandatory to avoid undertreatment.     

Accuracy of preoperative endometrial sampling diagnosis of FIGO grade 1 endometrial adenocarcinoma

ObjectiveTo evaluate the ability of a preoperative diagnosis of FIGO grade 1 endometrial adenocarcinoma and intraoperative depth of myoinvasion (DOI) to predict low-risk (LR) and high-risk (HR) final uterine pathology.MethodsWe reviewed 1423 consecutive cases of endometrial cancer treated at our institution between 1/1/93 and 5/31/06 to identify cases with a preoperative endometrial biopsy demonstrating FIGO grade 1 endometrial adenocarcinoma. All cases were pathologically reviewed at our institution and underwent surgical therapy at our institution. We excluded equivocal preoperative biopsies as well as those with serous or clear cell histology. Final uterine pathologic findings were grouped into low- and high-risk. Chi-square and Fisher-exact tests were used as appropriate.ResultsWe identified 490 cases with a median age of 60 years (range 29–90 years). In 482 cases in which final pathologic grade was assessable, FIGO grade was greater in 71 (14.7%) cases; (66 [13.7%] were grade 2, and 5 [1%] were grades 2–3/3). Serous or clear cell histology was diagnosed in 6 (1.2%) additional cases. HR final uterine pathology was seen in 86 (18.5%) cases. Frozen section assessment of DOI, when performed, was associated with HR pathology (p < 0.001). HR pathology was present in 3 (3.6%) of 84 cases with either no tumor or myoinvasion identified on frozen section. Lymph node metastasis was identified in 9 (4.4%) of 205 patients that underwent nodal evaluation.ConclusionsPreoperative FIGO grade 1 diagnosis correlates with final post-hysterectomy grade in 85% of cases. The rate of HR uterine pathology based on preoperative grade 1 alone is 18.5%. Frozen section may help further stratify for the risk of final HR uterine pathology but is not entirely accurate. The rate of HR uterine pathology is 4% if no cancer or myoinvasion is identified on frozen section and 18% if myoinvasion up to 50% is identified.