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.     

Extended surgical staging for uterine papillary serous carcinoma: survival outcome of locoregional (Stage I-III) disease

OBJECTIVE: The aim of this study was to evaluate survival outcome in patients with locoregional uterine papillary serous carcinoma (UPSC) after extended surgical staging (ESS). METHODS: All patients diagnosed with FIGO Stage I-III UPSC undergoing ESS (vertical incision, peritoneal cytology, TAH/BSO, omental biopsy, lymph node sampling, peritoneal biopsy) between 1/1/89 and 12/31/98 were identified retrospectively from the tumor registry database. Pathologic features predictive of regional extrauterine spread were evaluated using the log-rank test. The Kaplan-Meier method was used to generate survival curves, and median survival determinations were compared using the log-rank test or the proportional hazards regression model. RESULTS: Twenty-six patients with locoregional UPSC were identified: FIGO Stage I (n = 11), Stage II (n = 7), and Stage III (n = 8). The median age at diagnosis was 66 years. Preoperative endometrial pathology correctly identified the presence of UPSC in 76.9% of cases. The only pathologic feature found to be predictive of regional extrauterine spread (Stage III) was myometrial invasion > or =50% (P = 0.028). Adjuvant radiation therapy (RT) was administered to 6/18 patients with Stage I/II disease and 5/8 patients with Stage III disease. Platinum-based chemotherapy was administered to 5 patients with Stage III disease. All recurrences of Stage I/II disease were located within the pelvis (16.7%). For Stage III disease, all recurrences occurred at distant sites (42.9%). The median follow-up time for surviving patients was 39.0 months (mean = 45.0 months). For all patients, the overall 5-year survival rate was 61.2%. According to FIGO stage, the overall 5-year survival rates were Stage I, 81.8%; Stage II, 64.3%; and Stage III, 31.3%. No significant differences were detected in the risk of death by stage, although there was a trend toward worse survival with Stage III disease: Stage I hazard ratio [HR] = 1.00, Stage II HR = 1.68, 95% confidence interval [CI] = 0.23-12.03, Stage III HR = 3.63, 95% CI = 0.65-20.12. CONCLUSIONS: Patients with locoregional UPSC following ESS have a more favorable prognosis than previously thought. The additional information provided by ESS facilitates the selection of adjuvant therapy. Whole pelvic RT is recommended for patients with Stage I/II disease. Pathologic Stage III disease portends a significant risk of distant recurrence. For these patients, administration of adjuvant chemotherapy should be considered in addition to directed RT.     

Postoperative radiotherapy in endometrial carcinoma: analysis of prognostic factors in 440 cases

PURPOSE: The aim of this study was to determine the prognostic factors influencing overall, disease-free and local recurrence-free survival in patients treated postoperatively with adjuvant radiotherapy for endometrial carcinoma. METHODS: The records of 440 patients with endometrial carcinoma treated by postoperative radiotherapy between January 1985 and June 1997 were reviewed retrospectively. All patients received postoperative external radiotherapy with 1.8-2.0 Gy daily fractions up to 36-68 Gy (median 54 Gy). Intracavitary brachytherapy was applied to 61.8% of the cases. Survival analysis was performed using the Kaplan-Meier method. The log-rank test was used for univariate analysis and the Cox regression model for multivariate analysis. RESULTS: Median age of the patients was 57 (range: 35-83). Histologically 80.2% were adenocarcinoma, 5.7% adenosquamous carcinoma, 5.2% clear-cell carcinoma and 4.3% serous papillary carcinoma. The distribution by stages were: 62.2% Stage I, 20.0% Stage II, 14.9% Stage III, 2.8% Stage IV. Median follow-up time was 53 months (7-173 months). Total failure rate was 15.2% with 2.7% of patients having only local failure, 2.0% local and distant failure and 10.5% distant failure only. Five-year overall, disease-free and local recurrence-free survival rates were 81.6%, 80.7% and 94.6%, respectively. According to univariate analysis prognostic factors influencing disease-free survival were histologic type (p=0.0067), histologic grade (p=0.0015), stage (p<0.0001), myometrial invasion (p<0.0001), peritoneal cytology (p=0.0013) and cervical involvement (p=0.0106) while the prognostic factors affecting local recurrence-free survival were stage (p=0.0277), myometrial invasion (p=0.0054), peritoneal cytology (p=0.0427). According to multivariate analysis prognostic factors influencing disease-free survival were histologic type (p=0.0194), myometrial invasion (p=0.0021), and histologic grade (p=0.0303) while the only prognostic factor influencing local recurrence-free survival was myometrial invasion (p=0.0241). CONCLUSION: Radiotherapy is a highly effective adjuvant treatment providing an excellent locoregional control rate and it should be continued for patients with unfavorable prognostic factors.     

The impact of age on long-term outcome in patients with endometrial cancer treated with postoperative radiation

PURPOSE: Endometrial cancer is the most commonly diagnosed gynecologic malignancy in the United States. Age has been associated with worse outcome in univariate analysis. However, the patterns of failure and associated risk factors in older patients remain unclear. We reviewed our institution's experience to assess the effect of age in a population of endometrial cancer patients treated with surgery and adjuvant radiation therapy. METHODS: From 1992-2002, 243 endometrial cancer patients underwent a total abdominal hysterectomy and adjuvant radiation. Forty-nine patients with stage I-II (occult) endometrial adenocarcinoma (no clear cell or serous papillary) were treated postoperatively with vaginal intracavitary high-dose rate (HDR) brachytherapy alone using Iridium-192 (median dose 30 Gy) to a median length of 4 cm. Forty-eight patients with stage I-III endometrial adenocarcinoma (no clear cell or papillary serous) were treated with postoperative pelvic RT (median dose 45 Gy) and intracavitary HDR brachytherapy (median dose 20 Gy). One hundred forty-six patients underwent postoperative whole abdomino-pelvic irradiation (WAPI) secondary to unfavorable histology (clear cell or serous papillary) or two of the following: deep myometrial invasion, grade 3, or FIGO stage III. Age was analyzed as a continuous and a categorical variable. The age of 63 year split the age group using various statistical analyses. RESULTS: Median follow-up of all patients was 4.2 years. Patients grouped by age of < or =63 years or older had similar FIGO stage (P = 0.5), grade (P = 0.09), treatment modality (P = 0.7), and lymphovascular space invasion (LVSI) (P = 0.6). Twenty-five percent (60/243) of patients developed recurrence. Of these failures, 15% (15/102) were age < or =63 years and 32% (45/141) were age >63 years at diagnosis (P = 0.02). For all patients, the 5-year event-free survival (EFS), cause specific survival (CSS), and overall survival (OS) were 64%, 82%, and 72%, respectively. Five-year EFS for patients age < or =63 years and >63 years was 76% vs. 55% (P < 0.001). Five-year OS for age < or =63 years and >63 years was 85% vs. 63% (P < 0.001). Five-year CSS for age < or =63 years and >63 years was 91% vs. 75% (P = 0.003). Various factors were analyzed to determine an association with age. Older patients with stage III-IVA had significantly more failures than patients less than age 63 (P = 0.002). Older patients (>63 years) were found to have serous papillary histology (28%) more often than younger patients (15%) (P = 0.02). Greater depth of invasion was associated with older age (P = 0.01). On univariate analysis, older age (P = 0.003), LVSI (P = 0.002), FIGO stage (P < 0.001), grade (P < 0.001), and depth of invasion (P = 0.03) predicted for failure. On Cox multivariate analysis, older age (P = 0.006, HR 2.83), higher FIGO stage (P = 0.001, HR 1.96), and higher grade (P = 0.002, HR 2.66) were significant prognostic factors for recurrence. No difference was seen between the two age groups from date of surgery and start of radiation. The duration of therapy was not different between the two groups. CONCLUSIONS: Older endometrial cancer (age >63 years) patients have a significantly decreased overall survival, cause-specific survival, and greater risk of recurrence following postoperative RT independent of other prognostic factors and/or treatment technique. The impact of treatment-related variables did not alter the age-related outcome.     

Population-based treatment and outcomes of Stage I uterine serous carcinoma

Objective

Uterine serous carcinoma (USC) is a rare type of endometrial cancer that often recurs in patients with Stage I disease. Our objective was to evaluate treatment and outcomes in Stage I USC in the context of a population-based study.

Methods

This was a population-based retrospective cohort study of all patients with Stage I USC in British Columbia, Canada from 2004 to 2012. The British Columbia Cancer Agency (BCCA) recommends three cycles of paclitaxel and carboplatin chemotherapy followed by pelvic radiotherapy for all women with Stage I USC and any myometrial invasion (Stage IA MI −). If no myometrial invasion (Stage IA MI −), no postoperative treatment is given. Patient and disease characteristics, surgery, adjuvant therapy, recurrence rates and sites, and 5-year disease-free survival rates were evaluated.

Results

Of the 127 patients with Stage I USC, 41 were Stage IA MI −, 56 Stage IA MI +, and 30 Stage IB. Median follow-up was 25 months (2–98 months). Five year disease-free survival rates were 80.7%, 74.4%, and 48.5% for Stages IA MI −, IA MI +, and IB, respectively, and recurrence rates according to BCCA guidelines were 10%, 2.9% and 30%, respectively. Of the 18 with recurrences, 13 had a distant component (72.2%). There were no pelvic recurrences among those receiving adjuvant radiotherapy.

Conclusion

Our current protocol of observation alone postoperatively for Stage IA MI − and chemoradiotherapy for Stage IA MI + is associated with a low recurrence rate. In contrast, those with Stage IB USC have a higher recurrence rate despite chemoradiotherapy, and likely require alternate treatment strategies.     

Management of aggressive histologic variants of endometrial carcinoma at the Tom Baker Cancer Centre between 1984 and 1994

OBJECTIVE: The aim of this study was to determine the patient characteristics and outcome of patients with aggressive histologic variants (AV) of endometrial carcinoma, including uterine papillary serous carcinoma (UPSC), uterine clear cell carcinoma (UCCC), and mixed type. METHODS AND MATERIALS: All cases with AV histological type of endometrial carcinoma from January 1984 to December 1994 at the Tom Baker Cancer Centre were identified using the Alberta Cancer Registry. Relevant data from the charts of these patients were entered into a study database (Microsoft Excel) and analyzed for presentation, demography, treatment parameters, and outcome of treatment. All pathology was reviewed at the time of diagnosis. Statistical analysis was performed using the S-plus statistics computer program. Univariate and multivariate analyses were used to assess independent prognostic factors using the Cox proportional hazards model. RESULTS: A total of 103 patients with AV histological type were identified and analyzed; there were 61, 31, and 11 cases of UPSC, CCC, and mixed tumors, respectively. Sixty-three patients had Stage I, 11 had Stage II, 15 had Stage III, and 14 had Stage IV disease. The median age of patients was 67 years with a range of 36 to 86 years. Median follow-up was 60 months with a range of 36 to 156 months. The Cox proportional hazards model showed that lymphvascular space invasion and stage are the two independent prognostic factors affecting recurrence and survival. Forty six percent of all cases underwent surgery alone, 39% underwent treatment which included pelvic RT, and 17% underwent treatment which included chemotherapy. Pelvic recurrence was reduced significantly by radiotherapy in Stages I, II, and III (19% recurrence with no RT vs 7% recurrence with RT, P < 0.005). Chemotherapy improved overall survival, but made little difference in distant relapse rates. CONCLUSIONS: Stage Ia cases treated by surgery alone have a low risk of relapse and need not be offered adjuvant systemic therapy or pelvic radiation. Patients with Ib, Ic, II, and III have significantly lower pelvic failure rates if treated with pelvic radiation, but still have a high distant failure rate. Systemic therapy did not significantly improve distant relapse-free survival, but did extend overall survival. Stage IV patients usually died within 6 months with a few responding to systemic chemotherapy. These results suggest that there is a need for randomized trials for these patients.     

Adenocarcinoma of the endometrium: Analysis of 256 cases with carcinoma limited to the uterine corpus: Pathology review and analysis of prognostic variables

Histologic specimens of all patients undergoing hysterectomy for clinical Stage I adenocarcinoma of the endometrium at Stanford University Hospital between 1959 and 1975 were reexamined. From this group 256 acceptable cases of adenocarcinoma confined to the uterine corpus (Pathologic Stage I) were identified. In patients treated with initial surgery, relapse rate was highly correlated with depth of myometrial invasion (P = 0.0001) and also with the histologic grade of the uterine adenocarcinoma (P = 0.008). Twenty-six patients (10%) had lesions with papillary architecture and anaplastic cytology similar to papillary serous carcinoma of the ovary. These women with uterine papillary serous carcinoma (UPSC) had a 50% relapse rate and accounted for one-half the treatment failures ( ) in the entire study group. Six of the seven upper abdominal relapses in this study were in patients with UPSC, suggesting that this histologic variant may behave more like ovarian serous carcinoma than the usual endometrial adenocarcinoma. Twenty-one patients (9%) had endometrial carcinomas with extensive mucinous differentiation (mucinous carcinoma), while 38% of all the cases of endometrial carcinoma showed at least some focal mucin production. Twenty percent showed focal squamous differentiation. Neither mucinous nor squamous differentiation, as we have applied these designations, were significantly correlated with relapse rate. Among the patients undergoing hysterectomy for clinical Stage I adenocarcinoma, 99 patients were found on review to have lesions which fell short of our current criteria for diagnosis of carcinoma in the uterine corpus and were reinterpreted as metaplasia and/or hyperplasia. None of these patients subsequently developed clinical relapse. The results of this study suggest a need for modification in the FIGO grading system for endometrial cancer and also support a definition of well-differentiated endometrial carcinoma more restrictive than that commonly employed.     

Potential benefit of lymphadenectomy for the treatment of node-negative locally advanced uterine cancers

OBJECTIVE: The aim of this study was to examine the outcomes in patients with high-risk Stage I endometrial cancers surgically staged by complete pelvic and para-aortic lymphadenectomy, with negative nodes, and treated with postoperative brachytherapy. METHODS: From the database of patients treated for Stage I endometrial cancer, 23 patients were identified with either >50% myometrial invasion or grade 3 histology treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic and para-aortic lymphadenectomy. All patients had no pathologic evidence of disease in the lymph nodes. These patients were then treated with brachytherapy and followed for treatment and cost outcomes. A comparison was made of the cost of treatment between brachytherapy and external beam radiation. RESULTS: All 23 patients with either grade 3 tumor or greater than 50% myometrial invasion were treated with total abdominal hysterectomy with lymphadenectomy followed by brachytherapy for lesions that did not extend outside the uterine specimen. For all patients in this series, there were no recurrences in the follow-up period (median 25 months). This regimen is more cost efficient and spares the patient from possible complications related to whole pelvic radiation, at an average cost savings of $4100. CONCLUSION: Women undergoing hysterectomy for endometrial adenocarcinoma with high-risk node-negative disease confined to the uterus can be safely treated with brachytherapy, at a substantial cost savings, without compromising survival.     

Treatment results in women with clinical stage I and pathologic stage II endometrial carcinoma

Abstract. Jobsen JJ, Schutter EMJ, Meerwaldt JH, van der Palen J, van der Sijde R, Naudin ten Cate L. Treatment results in women with clinical stage I and pathologic stage II endometrial carcinoma.
The aim of this study is to report survival and results of therapy and possible prognostic factors in women with pathologic stage II endometrial carcinoma. Forty-two patients with pathologic stage II endometrial carcinoma were treated at the department of Radiation Oncology of the Medisch Spectrum Twente between 1987 and 1998. All patients received external radiotherapy following standard surgical procedures and no adjuvant systemic therapy was given. From the 42 patients 21 had a pathologic stage IIA and 21 stage IIB. The median follow-up was 62 months. The overall recurrence rate was 21.5% (9/42). Seven patients had distant metastasis, of which three also had locoregional recurrence, vaginal vault and/or pelvic. The presence of myometrial invasion (> ½) and/or lymph-angioinvasion showed a significant relation with distant metastasis ( P = 0.017). Stage IIB showed more recurrences, 33% (7/21). There was a significant different 5-year disease specific survival for stage IIA and IIB, respectively, 95% and 74% ( P = 0.0311). Patients with a differentiation grade 3 and stage IIB showed a significantly poorer ( P = 0.003) 5-year survival of 48.6% ( P = 0.003). Results obtained in the present series of patients are in accordance with the literature. The present treatment policy seems justified, except for patients with pathologic stage IIB and grade 3, in which a more aggressive treatment should be considered.     

Uterine papillary serous carcinoma: A study on 108 cases with emphasis on the prognostic significance of associated endometrioid carcinoma, absence of invasion, and concomitant ovarian carcinoma

One hundred eight cases of uterine papillary serous carcinoma (UPSC) were analyzed to characterize its histologic features and biologic behavior. Special situations that could conceivably modify the behavior and therapeutic approaches were considered: (1) the occurrence of areas of endometrioid carcinoma in otherwise typical UPSC; (2) the confinement of UPSC to an otherwise benign endometrial polyp or the endometrial mucosa or absence of residual tumor at the time of hysterectomy; and (3) the coexistence of a superficial UPSC and a serous ovarian carcinoma. There was coexistence of endometrioid and UPSC in 22 cases, and tumor was confined to an endometrial polyp or endometrium in 19 cases. There was simultaneous pathologic stage I UPSC and papillary serous ovarian carcinoma in 10 cases. In patients with pathologic stages I and II UPSC the presence of areas of endometrioid carcinoma intermixed with the UPSC did not improve survival. Patients with stage I disease and no residual tumor or tumor confined to an endometrial polyp/endometrial mucosa and without vascular invasion had a survival not statistically different from those with stage I disease but with myometrial and/or vascular invasion. Patients with stage I UPSC with concomitant ovarian serous surface papillary carcinoma had survival not statistically different from patients with stage IV UPSC.     

Cost-effectiveness analysis of the treatment for intermediate risk endometrial cancer: postoperative brachytherapy vs. observation

OBJECTIVE: To compare the survival, morbidity, and cost of treating women with intermediate risk endometrial cancer with postoperative vaginal cuff brachytherapy versus observation followed by treatment for vaginal recurrence. METHODS: A cost-effectiveness analysis was performed comparing two treatment strategies for intermediate risk endometrial cancer (Stage IC, IG3, II-tumors limited to the uterus with greater than 50% myometrial invasion or poor differentiation or cervical metastasis). All patients undergo hysterectomy, oophorectomy, and lymphadenectomy: strategy 1-postoperative vaginal cuff brachytherapy, strategy 2-observation. Strategy 2 patients who develop vaginal recurrence undergo diagnostic work-up followed by teletherapy and brachytherapy. All six principles of cost-effectiveness analysis were employed. Importantly, actual payer costs were evaluated, not charges. RESULTS: Although the treatment for vaginal cuff recurrence is expensive, since only 8% of patients develop a vaginal recurrence, there was a 31% decreased cost by not treating patients with postoperative low-dose rate brachytherapy (strategy 2). Also, although the complication rate for teletherapy is greater than brachytherapy, since only 8% of patients develop a vaginal recurrence and require teletherapy, projected complication rates for the two strategies are similar. Survival would be decreased 3% by withholding postoperative brachytherapy (strategy 2). With postoperative high-dose rate brachytherapy (strategy 1), the cost per life saved would be 38,764 US dollars. CONCLUSION: Using a cost-effectiveness analysis, we have shown that withholding postoperative brachytherapy for patients with intermediate risk endometrial cancer results in a 31% decrease in cost, has a similar radiation complication rate, and results in a 3% decrease in survival.     

Long-term survival of intermediate risk endometrial cancer (stage IG3, IC, II) treated with full lymphadenectomy and brachytherapy without teletherapy

OBJECTIVES: The aim of this study was to determine long-term survival and late complications of intermediate risk endometrial cancer (Stage IG3, IC, and II) treated with full lymphadenectomy and brachytherapy without teletherapy. METHODS: Two-hundred sixty-five consecutive patients underwent surgical staging for endometrial cancer consisting of hysterectomy, oophorectomy, and bilateral pelvic and periaortic lymphadenectomy. Sixty-six patients had intermediate risk endometrial cancer (Stage IG3, IC, and II) and received postoperative brachytherapy without teletherapy. Mean age was 68 years and mean weight was 188 lb. Seventy-seven percent had associated medical illness. RESULTS: At a mean follow-up of 4.4 years, Kaplan-Meier estimated 5-year progression free survival is 97%. Two patients (3%) developed distant recurrence (abdomen, lungs) with no vaginal or pelvic recurrence. Major complications occurred in 6% of patients. CONCLUSIONS: Complete lymphadenectomy with brachytherapy without teletherapy for intermediate risk endometrial cancer results in excellent progression-free survival and minimal major morbidity.     

Malignant endometrial pathology.

This review discusses recent papers on endometrial carcinoma variants, immunohistochemical studies, and prognostic indicators. The aggressive nature of uterine papillary serous carcinoma is confirmed, even in the absence of myometrial or vascular invasion, with a comprehensive review of the histology, clinical presentation, and proposed treatment protocols. The possible etiologic role of radiation in the development of uterine papillary serous carcinoma is alluded to. The virulence of endometrial carcinomas with trophoblastic differentiation, endometrial carcinomas with a malignant giant cell component, and clear cell carcinomas of the endometrium is documented. A series of immunohistochemical studies is presented suggesting that uterine carcinosarcomas are metaplastic carcinomas derived from a common stem cell and that a shared histogenesis of endometrial stromal tumors and uterine mesoderm exists. Immunohistochemical techniques may clarify diagnostic problems of uterine tumors and their metastases and differentiate mucinous tumors of endometrium from endocervical origin. Staining of both carcinoembryonic antigen and ferritin in neoplastic endometria may be helpful in their differentiation from hyperplasias in curettage specimens. Significant prognosticators in endometrial carcinoma are depth of myometrial invasion and lymphovascular space involvement with greatest prognostic information provided by the depth of myometrial invasion above DNA index.     

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.     

National patterns of care and cancer-specific outcomes of adjuvant treatment in patients with serous and clear cell endometrial carcinoma

ObjectivesTo investigate outcomes of adjuvant therapy for serous and clear cell endometrial carcinoma, as prior studies are limited by sample size and/or patient heterogeneity. National guidelines permit substantial variations in treatment, suggesting the need for additional data.MethodsPatients with FIGO stages I–III serous or clear cell uterine carcinoma who underwent at least total hysterectomy were identified in SEER-Medicare. Adjuvant external beam radiation, brachytherapy, and chemotherapy were determined using SEER fields and Medicare claims. The primary outcome was death from endometrial cancer (cancer-specific mortality [CSM]) evaluated using Gray's test (univariable analysis, UVA) and Fine-Gray regression (multivariable analysis, MVA).ResultsA total of 1789 patients (1437 serous, 352 clear cell) were identified. In stages I–II patients (n = 1188), brachytherapy was significant for survival in UVA (P = 0.03) and MVA (P = 0.02). Additionally, in the subset with serous histology (n = 947), chemotherapy was also significant in UVA (P = 0.002) and approached significance in MVA (P = 0.05). The 4-year CSM for stages I–II serous cancers was 25% without brachytherapy or chemotherapy, 15% with one, and 9% with both (P ≤ 0.05 for all pairwise comparisons). In stage III patients (n = 601), chemotherapy was significant in UVA (P = 0.002) and MVA (P = 0.006). Most (81%) patients underwent lymph node dissection, which predicted lower CSM in stage III (P = 0.001) but not stages I–II patients.ConclusionsOur results suggest brachytherapy benefits stages I–II serous/clear cell cancers, chemotherapy benefits stage III serous/clear cell cancers, and both chemotherapy and brachytherapy benefit stages I–II serous cancers.     

Final analysis of RTOG 9708: adjuvant postoperative irradiation combined with cisplatin/paclitaxel chemotherapy following surgery for patients with high-risk endometrial cancer

PURPOSE: A phase II study was completed by the RTOG to assess the feasibility, safety, toxicity, and patterns of recurrence and survival when chemotherapy was combined with adjuvant radiation for patients with high-risk endometrial cancer. MATERIALS AND METHODS: Pathologic requirements included grade 2 or 3 endometrial adenocarcinoma with either >50% myometrial invasion, cervical stromal invasion, or pelvic-confined extrauterine disease. Radiation included 45 Gy in 25 fractions to the pelvis along with cisplatin (50 mg/m(2)) on days 1 and 28. Vaginal brachytherapy was performed after the external beam radiation. Four courses of cisplatin (50 mg/m(2)) and paclitaxel (175 mg/m(2)) were given at 4-week intervals following completion of radiotherapy. RESULTS: Forty-six patients were entered between 10/97 and 4/99. Follow-up times range from 6.8 to 72 months with a median of 4.3 years. Maximum late toxicity was grade 1 in 16%, grade 2 in 41%, grade 3 in 16%, and grade 4 in 5%. At 4 years pelvic, regional and distant recurrence rates are 2%, 2%, and 19%, respectively. Overall survival and disease-free survival (DFS) rates at 4 years are 85% and 81%, respectively. Four-year rates for survival and DFS for Stage III patients are 77% and 72%, respectively. There have been no recurrences for patients with stage IC, IIA, or IIB. CONCLUSION: Local-regional control is excellent following combined modality treatment in all patients suggesting additive effects of chemotherapy and radiation. Distant metastases continue to occur in more advanced staged patients. This regimen appears reasonable to be tested for efficacy in randomized studies.     

Preoperative radiation therapy in clinical stage II endometrial carcinoma.

From 1980 to 1987, 30 patients with FIGO clinical Stage II carcinoma of the endometrium were treated with 5000 cGy preoperative pelvic radiation therapy at Thomas Jefferson University Hospital. Patients with gross cervical disease received additional intracavitary irradiation with a tandem and ovoids for a combined total dose of 7000 cGy to point A. All patients then underwent exploratory laparotomy, total abdominal hysterectomy, and bilateral salpingo-oophorectomy (TAH/BSO). The 5-year actuarial survival for the entire group was 69%. The 5-year actuarial survival for the 8 patients with papillary serous, clear cell, and undifferentiated small cell carcinoma was 38%, with most patients failing in the upper abdomen. The 5-year actuarial survival for the remaining 22 patients was 82%. The only local failure occurred in the patient with an undifferentiated small cell carcinoma. Although preoperative pelvic radiation therapy together with TAH/BSO appears to offer excellent local control in all patients with Stage II endometrial carcinoma, additional treatment options should be considered for patients with papillary serous and clear cell histologies because of the poor survival and high failure rate in the upper abdomen.     

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)     

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.     

Magnetic resonance (MR) in endometrial carcinoma preoperative evaluation

BACKGROUND: Myometrial invasion of endometrial carcinoma is an important prognostic factor because the degree of myometrial invasion is correlated with the rate of lymphnode metastases and of recurrences. The aim of the study was a preoperative evaluation of endometrial carcinoma by Magnetic Resonance (MR). METHODS: The authors present a prospective study performed on 54 cases of endometrial carcinoma collected at the Department of Gynecology and Obstetrics of the University of Trieste (Italy). All the patients were considered as Stage I after hysteroscopy and endocervical curettage. Prior to surgery all the patients underwent MR at the Department of Radiology of the University of Trieste (Italy) in order to evaluate the depth of myometrial invasion. The surgical procedure included total abdominal hysterectomy, bilateral salpingo-oophorectomy and pelvic and lomboaortic lymphadenectomy in high risk cases. Statistical evaluation was performed by Fischer's exact test. RESULTS: Statistically significant positive correlation was found (p<0.001) between MR staging and surgical staging. The sensitivity reported in our series for distinguishing between superficial disease (Stage IA and IB) and deep myometrial invasion (Stage IC) was 92%. CONCLUSIONS: Preoperative MR is helpful in selecting patients at high risk of nodal involvement and it is suggested that, although MR is considered an expensive examination, its use should be always considered before surgical treatment of patients with high surgical risk.