High-dose rate brachytherapy for Stage I/II papillary serous or clear cell endometrial cancer

OBJECTIVE: To determine the efficacy of high-dose rate brachytherapy as adjuvant treatment for Stage I/II papillary serous or clear cell endometrial cancer. METHODS: A retrospective study of all patients with Stage I/II papillary serous or clear cell endometrial cancer treated with high-dose rate brachytherapy between 1995 and 2001 was performed. Following surgical staging, which included hysterectomy with pelvic and aortic lymphadenectomy, all patients without extrauterine disease were treated with high-dose rate brachytherapy and followed for recurrence. The locations of recurrences were noted and were classified as local or distant. RESULTS: Three (13%) recurrences occurred among 24 patients with Stage I/II papillary serous or clear cell carcinoma. The risk of recurrence was similar for papillary serous and clear cell cancer (12% vs. 12%). Local control was achieved in 96%. The risk of recurrence for those with no myometrial invasion, less than 1/2, or more than 1/2 myometrial invasion was 0%, 10%, and 50%, respectively (P < 0.04). Two of the three recurrences were distant and all patients with recurrence died despite additional treatment. CONCLUSIONS: High-dose rate brachytherapy (HDR) as the sole adjuvant treatment of Stage I/II papillary serous or clear cell carcinoma is associated with a 13% risk of recurrence. Although local control with HDR is excellent, the risk of distant recurrence is increased with deep myometrial invasion. High-dose rate brachytherapy is adequate for Stage IA cases, but more aggressive treatment combining chemotherapy with HDR should be evaluated for more advanced Stage I/II cases.     

Improved survival in surgical stage I patients with uterine papillary serous carcinoma (UPSC) treated with adjuvant platinum-based chemotherapy

OBJECTIVE: Uterine papillary serous carcinoma (UPSC) is an aggressive form of endometrial cancer characterized by a high recurrence rate and a poor prognosis. Prior studies evaluating treatment of UPSC have been limited by small numbers of patients and inclusion of partially staged patients. The purpose of this study was to evaluate the efficacy of adjuvant platinum-based chemotherapy and vaginal cuff radiation in a large cohort of surgical stage I UPSC patients. METHODS: We retrospectively reviewed 74 stage I patients with UPSC who underwent complete surgical staging at our institution between 1987 and 2004. RESULTS: Stage IA patients were divided into two groups: patients with no cancer in the hysterectomy specimen (defined as no residual uterine disease) and patients with cancer in the hysterectomy specimen (defined as residual uterine disease). Stage IA patients with no residual uterine disease had no recurrences, regardless of adjuvant therapy (n = 12). Stage IA patients with residual uterine disease who were treated with platinum-based chemotherapy had no recurrences (n = 7). However, 6 of 14 (43%) stage IA patients with residual uterine disease who did not receive chemotherapy recurred. The 15 patients with stage IB UPSC who received platinum-based chemotherapy had no recurrences but 10 of the 13 (77%) stage IB patients who did not receive chemotherapy recurred. One of the 7 patients with stage IC UPSC who received platinum-based chemotherapy recurred and 4 of the 5 (80%) stage IC patients who did not receive chemotherapy recurred. Overall platinum-based chemotherapy was associated with improved disease-free survival (P < 0.01) and improved overall survival (P < 0.05) in patients with stage I UPSC. None of the 43 patients who received radiation to the vaginal cuff recurred locally, but 6 of the 31 (19%) patients who were not treated with vaginal radiation recurred at the cuff. CONCLUSIONS: Platinum-based chemotherapy improves the disease-free and overall survival of patients with stage I UPSC and vaginal cuff radiation provides local control. Stage IA UPSC patients with no residual uterine disease can be observed but concomitant platinum-based chemotherapy and vaginal cuff radiation (referred to as chemoradiation) should be offered to all other stage I UPSC patients.     

Salvage of isolated vaginal recurrences in women with surgical stage I endometrial cancer: a multiinstitutional experience

The objective of this study was to evaluate the treatment outcomes and risk factors of women with surgical stage I endometrial adenocarcinoma who were initially treated with surgery alone and subsequently developed isolated vaginal recurrences. Patients with surgical stage I endometrial adenocarcinoma diagnosed from 1975 to 2002 were identified from tumor registry databases at seven institutions. All patients were treated with surgery alone including a total hysterectomy, bilateral salpingo-oophorectomy, pelvic (+/- para-aortic) lymph node dissection, and peritoneal cytology and did not receive postoperative radiation therapy. Vaginal recurrences were documented histologically. Metastatic disease in the chest and abdomen was excluded by radiologic studies. Overall survival was calculated by the Kaplan-Meier method. Sixty-nine women with surgical stage I endometrial cancer with isolated vaginal recurrences were identified. Of the 69 patients, 10 (15%) were diagnosed with stage IA disease, 43 (62%) were diagnosed with stage IB disease, and 16 (23%) were diagnosed with stage IC disease. Patients diagnosed with grade 1 disease were 22 (32%), grade 2 disease were 26 (38%), and grade 3 disease were 21 (30%). Among women, 81% with isolated vaginal recurrences were salvaged with radiation therapy. The mean time to recurrence was 24 months, and the mean follow-up was 63 months. Among women, 18% died from subsequent recurrent disease. The 5-year overall survival was 75%. The majority of isolated vaginal recurrences in women with surgical stage I endometrial cancer can be successfully salvaged with radiation therapy, further questioning the role of adjuvant therapy for patients with uterine-confined endometrial cancer at the time of initial diagnosis.     

Treatment of adenocarcinoma of the endometrium at Memorial-James Ewing Hospitals, 1949-1965.

This retrospective study of patients receiving initial therapy for endometrial adenocarcinoma at Memorial-James Ewing Hospitals from 1949-1965 confirmed that the most important factor related to survival was extent of disease at presentation. Those patients with spread beyond the corpus had a much poorer prognosis regardless of method of therapy. Within Stage I, histologic grade and depth of myometrial penetration were of much greater prognostic significance than uterine size. Advanced age was associated with a higher incidence of poorly differentiated tumors. Apparently for Stage I, simple hysterectomy alone was not as effective as simple hysterectomy combined with preoperative radium or radical hysterectomy with or without node dissection. There was a 6% incidence of positive nodes when node dissection was performed in Stage I patients who had no spread of disease to the cervix confirmed at operation. Pure vaginal recurrence rate was low for all methods of therapy in Stage I. Eradication of recurrences by any means was relatively ineffective.     

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.     

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.     

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.     

Interstitial Brachytherapy for Vaginal Recurrences of Endometrial Carcinoma

OBJECTIVE: The aim of this study was to evaluate the efficacy of interstitial brachytherapy in the management of vaginal recurrences of endometrial carcinoma. METHODS: Thirty patients received interstitial irradiation, with or without external beam radiotherapy. They were followed for a minimum of 5 years or until death. RESULTS: The median age was 66 years at initial diagnosis of endometrial cancer. FIGO stages included Stage I (n = 18), Stage II (n = 7), and Stage III (n = 5). All patients were treated originally by total abdominal hysterectomy and bilateral salpingo-oophorectomy, with or without lymphadenectomy, and 13 (43%) also received postoperative adjuvant whole pelvis radiotherapy as part of their primary treatment. Vaginal recurrences were diagnosed at a mean interval of 29 months after hysterectomy (range, 3-119 months). No patient had clinical evidence of pelvic sidewall extension or of distant metastatic disease. All patients were treated with interstitial brachytherapy; each implant delivered a mean maximal tumor dose of 25.5 Gy. Eighteen patients (60%) also received external beam radiotherapy (mean dose, 48 Gy) as part of their treatment for vaginal recurrence. Twenty-eight patients (93%) experienced a complete clinical response. Ten patients relapsed in the vagina (n = 5) or at distant sites (n = 5). Eleven patients are dead of disease. From the time of vaginal recurrence, the median overall survival was 60 months and the cause of death adjusted 5-year survival rate was 65%. Major morbidity included radiation proctitis (n = 2), fistula (n = 2), and radiation stricture (n = 1). CONCLUSION: Interstitial irradiation resulted in favorable local control as well as a 5-year survival rate and morbidity comparable to that reported previously for conventional brachytherapy.     

Laparoscopic treatment of endometrial cancer: five-year recurrence and survival rates

PURPOSE: To evaluate the 5-year recurrence and survival of patients with clinical Stage I endometrial cancer treated by the laparoscopic approach. METHODS: Retrospective review of 56 patients with clinical Stage I endometrial cancer treated laparoscopically. The mean follow-up was 6.4 (4.8-9.6) years. The International Federation of Obstetricians and Gynecologists (FIGO) surgical staging was: I, 45 (80.4%); II, three (5.4%); III, six (10.7%); and IV, two (3.6%). RESULTS: For patients with surgical Stage I (n = 45), the 5-year recurrence rate was 4.9% and the 5-year cause-specific survival was 94.7%. Factors univariately associated with survival were grade (p = .017), depth of myometrial invasion (p = .018), node metastasis (p = .013), and surgical stage according to FIGO (p = .097). CONCLUSION: The laparoscopic approach provided 5-year survival and recurrence rates similar to those previously attained by laparotomy in our institution.     

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

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

Is levonorgestrel intrauterine system effective for treatment of early endometrial cancer? Report of four cases and review of the literature

BACKGROUND: Intrauterine progesterone therapy potentially provides a simple alternative treatment for women with Stage I Grade I endometrial cancers who are at high risk for surgery. The case histories of four women with early endometrial cancer primarily treated with levonorgestrel intrauterine system (Mirena) are reported and the literature reviewed. CASES: Four women had Stage I grade 1 endometrial adenocarcinoma with positive progesterone receptor. All were assessed to be in American Society of anaesthesiologists risk class IV. After insertion of mirena intrauterine system, one woman (25%) had complete histological regression of disease within 6 months. One of three women who did not respond to treatment subsequently had a vaginal hysterectomy, which showed endometrial cancer with superficial myometrial invasion. CONCLUSION: This report raises doubts about the effectiveness of intrauterine progesterone therapy as a definitive alternative for the treatment of early endometrial cancer.     

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.     

A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study

BACKGROUND: Despite their low risk for recurrence, many women with endometrial adenocarcinoma receive postoperative radiation therapy (RT). This study was developed to determine if adjunctive external beam irradiation lowers the risk of recurrence and death in women with endometrial cancer International Federation of Gynaecology and Obstetrics (FIGO) stages IB, IC, and II (occult disease). METHODS: Four hundred forty-eight consenting patients with "intermediate risk" endometrial adenocarcinoma were randomized after surgery to either no additional therapy (NAT) or whole pelvic radiation therapy (RT). They were followed to determine toxicity, date and location of recurrence, and overall survival. A high intermediate risk (HIR) subgroup of patients was defined as those with (1) moderate to poorly differentiated tumor, presence of lymphovascular invasion, and outer third myometrial invasion; (2) age 50 or greater with any two risk factors listed above; or (3) age of at least 70 with any risk factor listed above. All other eligible participants were considered to be in a low intermediate risk (LIR) subgroup. RESULTS: Three hundred ninety-two women met all eligibility requirements (202 NAT, 190 RT). Median follow-up was 69 months. In the entire study population, there were 44 recurrences and 66 deaths (32 disease or treatment-related deaths), and the estimated 2-year cumulative incidence of recurrence (CIR) was 12% in the NAT arm and 3% in the RT arm (relative hazard (RH): 0.42; P=0.007). The treatment difference was particularly evident among the HIR subgroup (2-year CIR in NAT versus RT: 26% versus 6%; RH=0.42). Overall, radiation had a substantial impact on pelvic and vaginal recurrences (18 in NAT and 3 in RT). The estimated 4-year survival was 86% in the NAT arm and 92% for the RT arm, not significantly different (RH: 0.86; P=0.557). CONCLUSIONS: Adjunctive RT in early stage intermediate risk endometrial carcinoma decreases the risk of recurrence, but should be limited to patients whose risk factors fit a high intermediate risk definition.     

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.     

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.     

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.     

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.     

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.     

Brachytherapy for early endometrial carcinoma: a comparative study with long-term follow-up

The current study was undertaken to evaluate the effect of preoperative uterine or postoperative vaginal brachytherapy compared to no adjuvant therapy on the disease-free interval, sites of recurrence, and survival in favorable stage IB endometrial carcinoma.
One hundred and forty-six patients with FIGO grade 1 and 2 endometrial carcinoma and 1–33% myometrial invasion treated between 1974 and 1992 were retrospectively studied. The use of brachytherapy varied among the treating physicians during the study period. A Kaplan-Meier survival analysis was used to estimate disease-free survival and differences between treatment groups were evaluated with the Mantel-Cox statistic.
Recurrent disease occurred in 7 patients (5.3%). Vaginal recurrences accounted for 6 of the 7 sites of recurrences. Recurrences occurred in 1.3% of grade 1 vs. 8.7% of grade 2 tumors ( P = 0.04). Among 69 grade 2 tumors, recurrences occurred in 7.5% of those treated with brachytherapy vs. 10.3% of those not treated ( P = 0.68). Brachytherapy did not affect the disease-free or overall survival. No serious complications directly related to therapy occurred.
Vaginal recurrences occur even in early endometrial carcinoma. This study demonstrates no apparent benefit to brachytherapy. A larger study would be required to see a recurrence or survival difference.     

Conservative management of stage I endometrial carcinoma after surgical staging.

OBJECTIVE: The aim of this study was to determine the outcomes of Stage I endometrial carcinoma patients who are managed without adjuvant radiation after comprehensive surgical staging. METHODS: A computerized hospital database identified women diagnosed with adenocarcinoma of the endometrium from 1993 to 1998. A chart review identified 864 women as having primary surgery for adenocarcinoma of the endometrium. A total of 670 of 864 patients (78%) underwent comprehensive surgical staging with total hysterectomy, bilateral salpingo-oophorectomy, pelvic/para-aortic lymphadenectomy, and peritoneal cytology. After 57 patients with high-risk histologic subtypes were excluded, 613 patients remained for analysis. RESULTS: A total of 321 of 325 Stage IB patients (99%) did not receive adjuvant radiation. Fifteen of 321 patients (5%) recurred; 9 recurred in the pelvis or vagina. All 9 local recurrences were salvaged with whole pelvic radiation (XRT) and brachytherapy (BT). Seventy-seven patients were diagnosed with Stage IC disease; 53 (69%) received no adjuvant therapy. Four patients (8%) recurred, of which 2 recurred in the vagina. Three of 4 patients (75%) were salvaged, 2 with XRT/BT and 1 with surgery and chemotherapy. For all Stage I patients, the 5-year disease-free survival was 93% and the 5-year overall survival was 98%. CONCLUSIONS: Surgically staged patients with endometrial carcinoma confined to the uterine corpus have a small risk of recurrence and the majority of these recurrences can be salvaged with radiation therapy. Conservative management of Stage I endometrial carcinoma patients is an effective treatment strategy.