Influence of grade, histologic subtype, and timing of radiotherapy on outcome among patients with stage II carcinoma of the endometrium

In 1988, the Federation of International Gynecologic Oncologists (FIGO) adopted a new staging system mandating preradiotherapy surgical staging in endometrial cancer. To evaluate the potential impact of this recommendation on patients with cervical involvement (stage II), an analysis of 184 consecutive patients with clinical or pathologic stage II carcinoma of the endometrium treated with definitive intent at three institutions was performed. Median follow-up time was 5.7 years. Treatment consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy with preoperative radiation therapy (RT) (54%), postoperative RT (37%), or both (1%); definitive RT (7%); or radical hysterectomy (1%). The median total RT dose for combined intracavitary and external beam or either alone was 70.6 Gy with a range of 32.4-105.0 Gy. The overall 5-year survival rate and disease-free survival (DFS) rate at 5 years were 70 and 79%, respectively. Of patients treated with surgery and adjuvant radiation, 13% (22/168) had infield pelvic failure (PF) and 18% (31/168) had distant metastases (DM). Patterns of failure in patients receiving preoperative and postoperative radiotherapy are presented. Univariate analysis of pretreatment and treatment factors, including histology, grade, clinical stage, extent of cervical involvement, and timing of adjuvant radiation, revealed histology and grade to be significant predictors of DFS, PF, and DM. Clinical stage was a significant predictor of DFS only in univariate analysis. Multivariate analysis found only histology (P less than 0.001) and grade (P = 0.002) to be predictors of DFS. From this review, we conclude that histology and grade are independent predictors of DFS, and more aggressive treatment should be directed at patients with stage II endometrial cancer found to have high grade adenocarcinoma or papillary serous/clear cell histologic variants. The timing of radiotherapy was not an independent predictor of outcome; therefore, preradiotherapy surgical staging should not impact on DFS and should provide surgicopathologic information to tailor treatment and predict prognosis. The FIGO clinical staging system used in this analysis was not an independent predictor of outcome, and future multivariate analyses will be necessary to test the predictive value on outcome of the new 1988 FIGO surgical staging.     

The impact of pre-therapy extraperitoneal surgical staging on the evaluation and treatment of patients with locally advanced cervical cancer.

OBJECTIVE: The use of extraperitoneal surgical staging prior to treatment in patients with bulky or locally advanced cervical cancer allows the detection and treatment of disease beyond the standard pelvic radiation fields. This study was conducted to evaluate the impact of extraperitoneal surgical staging in the treatment and outcome of patients with locally advanced cervical cancer. METHODS: 51 patients with locally advanced cervical cancer treated between 1985 and 1998 were retrospectively reviewed. Information on morbidity, usefulness, and results of surgery and patterns of disease recurrence were obtained. Survival distributions were calculated by the Kaplan-Meier product limit method and compared with the log-rank test. RESULTS: All 51 women were surgically staged by an extra-peritoneal approach. Preoperative CT scans (n=27) when compared with surgical findings showed sensitivity for pelvic and para-aortic lymph node metastasis of 39%, specificity of 88%, positive predictive value of 39% and negative predictive value of 88%. Lymph node metastases were found in 30/51 patients (59%). There were no significant treatment delays or surgical morbidity as a result of extra-peritoneal surgical staging. In 21 patients (41%), the highest level of involved nodes was in the pelvis and they were treated with pelvic radiation. The para-aortic nodes were involved in nine patients (18%) and were treated with extended field radiation. All patients also received concurrent radiosensitization with chemotherapy. The estimated survival for the entire group was 60% at 5 years. For node negative patients, estimated 5-year survival was 67% while it was 54% for all node positive patients (p=0.17). Analysis according to anatomic site of involved nodes showed that the estimated 2-year and 5-year survival for those with pelvic nodal involvement was 81% and 64%, respectively. However, in the group of nine patients with para-aortic nodal disease, the estimated 2-year survival was 44%. Five (56%) were dead of disease with a median time to death of 16.0 months and four patients (44%) were alive with a median duration of follow up of 16.1 months. There was a statistically significant difference in survival for the group of patients with positive pelvic nodes only compared to the group with positive para-aortic nodes (p=0.03). The estimated 5-year survival by FIGO stage was 80%, 70% and 51% for stages Ib, II, III, disease, respectively. Factors that did not significantly affect survival included age, histology and type of chemotherapy. CONCLUSIONS: Pre-therapy extra-peritoneal surgical staging resulted in treatment modification in 18% of patients with locally advanced cervical cancer. The morbidity from surgery and subsequent radiation therapy was acceptable. The procedure is recommended to allow for individualization of treatment in patients with local-regional cervical cancer.     

Therapeutic approaches to uterine papillary serous carcinoma: a preliminary report

Uterine papillary serous carcinoma (UPSC) is a recently identified and characterized unique histopathologic subtype of endometrial cancer. Unlike the more common types of endometrial cancer, UPSC has a high likelihood of transperitoneal seeding and upper abdominal recurrence. Since our initial report of 26 patients with UPSC, an additional 10 patients with FIGO stage I disease have been diagnosed, operatively staged, and managed by an individualized approach. Operative staging revealed 5 of the 10 patients to have more advanced disease than had been determined clinically. Adjuvant postoperative abdominopelvic radiation was administered to 6 patients, 4 of whom remain free of disease within the treated area. Two patients received adjunctive hormonal and chemotherapy; neither has recurred. Two patients received no adjunctive therapy. One of these failed initially in the vagina with subsequent recurrence in the lungs and supraclavicular nodes. The value of operative staging and selection of appropriate adjunctive therapy awaits additional patient accrual and follow-up.     

Carcinoma of the cervix, FIGO Stage IB: treatment failures

All patients with carcinoma of the cervix, FIGO Stage IB, treated at the University of Minnesota Hospitals during a 10-year period were reviewed. Of the 220 patients 31 (14.0%) developed recurrent disease and did not survive. Thirteen patients had pelvic wall recurrences, with concurrent cervical involvement. No patient had a resectable pelvic recurrence. Hysterectomy was subsequently performed on 10 of the 172 patients who received radiation therapy. Carcinoma was not present in any of the operative specimens although two patients with adenocarcinoma later died of metastatic cancer. Median time of recurrence was 9 months, with median survival following recurrence of 6 months. Cervical cytology was not of value in the early diagnosis of recurrent disease. The 5-year adjusted actuarial survival rate for patients with adenosquamous carcinoma was significantly lower than that for patients with squamous cell carcinoma. The median age of patients not surviving with adenosquamous carcinoma was significantly lower than that for patients not surviving with squamous cell carcinoma. Patients with invasive carcinoma presumably confined to the cervix may have disseminated disease. It is essential such selected patients receive primary treatment that includes systemic therapy.     

Prognostic significance of the extent of cervical involvement by endometrial cancer

The prognostic significance of the extent of cervical involvement by endometrial cancer is impossible to determine from the literature because previous reports have included fractional dilatation and curettage for staging, preoperative radiotherapy, and surgical stage III and IV disease. Therefore, we reviewed and restaged according to the new FIGO system all patients with endometrial cancer from January 1981 to December 1989. Of 180 patients undergoing hysterectomy for endometrial cancer, 20 had surgical stage II disease. No patient received preoperative radiotherapy. None of 12 patients (0%) with stage IIA disease developed recurrence, while 5 of 8 (63%) with stage IIB disease recurred (P less than 0.01). All 5 recurrences were in extrapelvic sites. Endocervical stroma invasion appears to import a statistically significant worse prognosis than endometrial glandular involvement.     

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.     

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.     

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.     

Outcome of endometrial carcinoma patients with involvement of the uterine serosa

OBJECTIVE: The goal of this work was to evaluate the outcome of endometrial carcinoma patients undergoing primary surgery who have serosal involvement (SI). METHODS: Between 1980 and 1998, 562 women underwent primary surgery for endometrial cancer at the University of Chicago. Thirty-nine were noted to have SI. FIGO stages were IIIA (19), IIIB (1), IIIC (7), and IV (12). Of the 19 IIIA patients, 15 had solitary SI. Twenty-six patients received pelvic radiation therapy (RT) with or without vaginal brachytherapy (VB). One patient received whole-abdomen radiation therapy, and 13, adjuvant chemotherapy. Solitary SI patients received pelvic RT with or without VB as their sole adjuvant therapy. Disease-free survivals (DFSs) were estimated using the method of Kaplan and Meier and prognostic factors were analyzed by the log-rank test. RESULTS: With a median follow-up of 30.3 months, the 5-year actuarial DFS of the entire group was 28.9%. Factors correlated with disease recurrence included tumor stage (P = 0.003) and lymph node involvement (P = 0.04). In addition, patients with solitary SI had a better 5-year DFS (41.5% vs 20%, P = 0.04) than patients with SI plus other extrauterine sites. Relapse occurred in 23 women overall and in 7 of 15 solitary SI patients. The most common site of disease recurrence was distant both in the entire group and in the solitary SI patients. While abdominal recurrences were common in the entire group, they were infrequent in solitary SI patients. CONCLUSION: Endometrial carcinoma patients with SI have a high rate of relapse and a poor outcome. Even when patients have extrauterine disease limited to SI, the outcome is relatively unfavorable. Nonetheless, our results demonstrate the need to distinguish patients with solitary SI and those with SI plus other extrauterine disease sites.     

早期高危子宫内膜癌“夹心模式”序贯放化疗的疗效分析

目的评估“化疗-放疗-化疗”的“夹心模式”序贯放化疗在早期高危子宫内膜癌患者中疗效及可行性。方法回顾性分析2004年1月至2015年12月于北京大学人民医院行分期手术,分期(FIGO 2009)Ⅰ~Ⅱ期,且术后行“夹心疗法”的内膜癌患者,分析其临床病理特征,复发、生存及副反应。结果40例纳入研究,平均年龄(57±7)岁;随访51~182个月,仅1例术后66个月发生远处复发,其余均无瘤生存;5年总生存率及无疾病生存率均100%;无疾病生存期(178.7±3.3)m(95%CI:172.3~185.1);16例出现化疗副反应,仅1例发生Ⅲ度骨髓抑制;8例出现放疗副反应,其中1例发生左侧输尿管狭窄,其余为Ⅰ~Ⅱ度副反应。结论“夹心疗法”应用于早期高危内膜癌具有较好疗效,副反应可耐受。因病例数有限,有待积累病例,进一步总结。     

Impact of Surgical Staging in Women with Locally Advanced Cervical Cancer

OBJECTIVE: The aim of this study was to evaluate the impact of surgical staging in the treatment and outcome of women with locally advanced cervical cancer. METHODS: Ninety-eight women with locally advanced cervical cancer treated between 1993 and 1997 were retrospectively reviewed. Survival probabilities were calculated by the Kaplan-Meier product limit method and compared with the log-rank test. RESULTS: Of the 98 women treated over the 5-year period, 86 were surgically staged: 61 by a retroperitoneal approach, 18 by laparoscopy, and 7 by laparotomy. Median blood loss was 120 cc and median length of hospitalization was 3 days. Preoperative CT scans (n = 55), when compared with surgical findings, missed macroscopic nodal disease in 20% and microscopic disease in 15% and overcalled disease in 10% of cases. Lymph node metastases were found in 45/86 patients (52%): 12 microscopic and 33 macroscopic. The highest level of nodes found to be involved was pelvic in 23, common iliac nodes in 3, para-aortic nodes in 14, and scalene nodes in 5 cases. Of the 86 patients, 49 received pelvic radiation, 27 received extended field radiation, and 10 were identified for palliative treatment only (5 scalene node metastasis, 5 extensive intraperitoneal disease). For node-negative patients, 5-year survival was 74%; for microscopic nodal involvement it was 58%; and for macroscopic involvement it was 39% (P = 0.007). Five-year survival for women with para-aortic node involvement was 52%. Number of nodes involved was a significant prognostic variable (P = 0.008). Patients who received chemotherapy had a 5-year survival of 68% compared to 35% for those who did not (P = 0.06). Factors which did not affect survival included age, histology, type of surgery, stage, and type of radiation (pelvic vs extended). CONCLUSION: Surgical staging of women with locally advanced cervical cancer can be performed with acceptable morbidity and it provided more accurate information than CT scans and resulted in a modification of the standard pelvic radiation field for 43% of our patients. The information obtained from surgical staging allows better individualization of therapy, which may improve overall clinical outcome.     

Thrombospondin-1 expression in epithelial ovarian carcinoma: association with p53 status, tumor angiogenesis, and survival in platinum-treated patients

OBJECTIVE: The aim of this study was to analyze FIGO Stage IIIc endometrial cancer (EC) patients to better define clinicopathologic associations, patterns of failure, and survival. METHODS: Charts were abstracted from EC patients with lymph node metastasis from 1989 to 1998. Data on clinicopathologic variables, adjuvant treatment, site of first recurrence, and survival were collected. Associations between variables were tested by chi(2) and Wilcoxon rank sums. Survival analyses were performed by the Kaplan-Meier method, and multiple regression analysis was done by the Cox proportional hazards model. RESULTS: From 607 EC patients evaluated, 47 (8%) were identified with FIGO Stage IIIc disease. All 47 underwent hysterectomy and pelvic lymph node (PLN) sampling, and 42/47 had para-aortic lymph node (PALN) sampling. Stage IIIc disease was defined by positive PLN alone in 38%, positive PLN and PALN in 41%, and positive PALN alone in 17%. Twelve of 47 also had positive peritoneal cytology and/or adnexal metastases. Grade III tumors were present in 56% and >50% myometrial invasion in 61%. No association between depth of invasion (DOI) and grade was seen, however. Nearly 1/3 of cases had papillary serous or clear cell histology. Postoperative adjuvant treatment included whole abdominal radiation (36%), pelvic radiation with (19%) and without (17%) extended field, chemotherapy (17%), and oral progestins (11%). The 3-year and 5-year survival estimates for all patients were 77 and 65%, respectively. At a median follow-up of 37 months, 5 patients are alive with disease, and 10 are dead of disease. A distant site of first recurrence was most common (21%), followed by pelvic failure (9%). Only 1 patient has had an abdominal recurrence. Univariate predictors of survival included age, DOI, and extranodal disease, but not grade, histology, or PALN involvement. For the 12 patients with nodal disease and positive cytology and/or adnexa, 3-year survival was 39% versus 93% for those patients without evidence of extranodal disease. In a multivariate analysis only DOI was an independent predictor of survival (P = 0.03). CONCLUSIONS: Once lymph node involvement occurs, the importance of additional extranodal disease increases. Consideration of substaging Stage IIIc patients based on positive adnexa or cytology is supported by the data. The extent which adjuvant treatments contributed to the 77% 3-year survival remains to be defined. The patterns of failure suggest a possible role for combined modalities in future treatments.     

Survival of nonsurgically staged patients with negative lymphangiograms who had Stage IIB carcinoma of the cervix treated by pelvic radiation plus hydroxyurea

Twenty patients with Stage IIB carcinoma of the cervix who did not undergo pretherapy para-aortic lymphadenectomy, but who had negative preradiation therapy lymphangiograms, were treated with pelvic radiation plus hydroxyurea. Patients received a median of 5020 rads of pelvic radiation plus 4000 rads of radium to point A. During radiation therapy and for a total of 12 weeks, patients received hydroxyurea administered at a dose of 80 mg/kg of body weight every 3 days if the white blood cell count was greater than or equal to 2,500/mm3 and platelets were greater than or equal to 75,000/mm3. The median follow-up time was 28 months (6 to 83 months). The estimated 5-year survival rate was 92%. Seventeen patients are alive with no evidence of disease (median, 28 months); one died of intercurrent disease with no evidence of disease (17 months); one is alive with no evidence of disease after recurrence (18 months); and one died of cervical cancer (22 months). The survival rate of patients with nonsurgically staged negative pretherapy lymphangiograms who had Stage IIB cervical cancer treated by pelvic radiation therapy plus hydroxyurea approximated the improved survival rate reported for patients with negative pretherapy para-aortic lymphadenectomy who were treated with pelvic radiation therapy plus hydroxyurea. Both studies would suggest that pelvic radiation plus hydroxyurea improves the rate of survival in patients with Stage IIB cervical cancer.     

Evaluation of patients after extraperitoneal lymph node dissection for cervical cancer

OBJECTIVE: The presence of nodal metastases is an important prognostic factor in patients with cervical cancer. To adjust our therapy to the anatomic extent of the disease, we performed a surgical staging with extraperitoneal lymph node dissection (EPLND). The goal of our study was to evaluate the clinical outcome and side effects of the combined treatment approach of EPLND and either radical hysterectomy in case of early stage cervical cancer (FIGO Ia/b and IIa) and negative nodes, or pelvic radiotherapy/extended field radiotherapy with concomitant chemotherapy in case of positive nodes or advanced stage cervical cancer (FIGO IIb, III, and IVa). PATIENTS AND METHODS: Fifty-nine patients with primarily diagnosed invasive cervical cancer underwent EPLND. The value of this procedure as a diagnostic tool for evaluating the extent of disease was determined. Additionally, treatment-related complications and clinical outcomes were monitored. RESULTS: A total of 983 lymph nodes were removed during EPLND (mean 16.7). According to the results of EPLND, radical hysterectomy was abandoned due to histopathologically confirmed lymph node involvement by frozen section in 11 out of 36 patients with early stage cervical cancer (31%). The most common adverse effects directly related to surgery in general (EPLND or combined EPLND and radical hysterectomy) were lymph cysts in seven patients (12%). Only in the group of patients who received EPLND followed by radical hysterectomy, 2 out of 25 patients (8%) developed a severe ileus postoperatively (WHO Grade 3 toxicity). The treatment approach of combined EPLND followed by radio- and chemotherapy was without major complications (WHO Grade 3 or 4 toxicity). After a mean follow up of 28 months (range 6-60), 44 out of 58 patients (one patient lost to follow up) are without evidence of disease (76%), 2 patients have progressive disease (3%), and 12 patients died of their disease (21%). Using Kaplan-Meier analysis, the estimated 5-year overall survival rate for all patients is 64% (SD +/- 9%). Performing the Cox proportional regression analysis, in contrast to clinical FIGO staging (P = 0.24; ns), lymph node involvement was the only significant independent predictor for overall survival (P = 0.04). CONCLUSION: Our data support the approach of pretherapeutic surgical staging by performing EPLND as a diagnostic tool with a low complication rate. This allows an individualized treatment for cervical cancer patients.     

Risk factors and prognosis in stage II endometrial cancer

Ninety-seven patients with Stage II endometrial cancer were analyzed by life table analysis for survival as a function of patient age, cell type, grade of tumor, depth of invasion, treatment, surgical stage, and extent of cervical involvement. The corrected 5-and 10-year survival was 65.9% and 57.9%, respectively. Cumulative 5-year survival of patients treated with radiation was 77.0%, with surgery 66.1%, and with combined therapy 58.5%. The extent of tumor, including depth of invasion, degree of cervical involvement, and presence of occult distant metastases, was most important in assessing prognosis. Of 36 patients without preoperative radiation, all those with superficial tumors lived at least 5 years, as compared with 57.9% of patients with deeply invasive tumors. These factors were less valuable in patients treated initially with radiation therapy where 30% of patients without residual tumor in the uterus died with recurrence within 5 years. The accuracy of endocervical curettage in determining cervical extension from an endometrial cancer and the patterns of recurrence were also analyzed. Less than half of patients with a normal-appearing cervix and positive endocervical curettage had tumor found in the nonirradiated hysterectomy specimen. There was poor correlation between the stage of disease and the extent of tumor found at operation. Agreement between the stage and operative findings was found in only half the patients treated initially with surgery.     

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.     

Survival of women with surgical stage II endometrial cancer.

OBJECTIVE: The aim of this study was to report survival and determine prognostic factors and results of therapy in women with surgical stage II endometrial cancer. METHODS: Forty-eight consecutive women with surgical stage II endometrial cancer treated at the University of Vermont between March 1984 and March 1998 were reviewed. Patients' characteristics, surgical procedure, postoperative treatment and its complications, and tumor recurrence and its treatment were recorded. In addition, a formal review of their pathological material for confirmation of the diagnosis was performed. RESULTS: The median duration of follow-up was 6.2 years. Three patients (6.3%) had tumor recurrence and two (4.2%) died of their disease. The estimated 5-year overall survival and disease-free survivals were 92.1% (SE = 5.5%, 95% confidence interval: 81.3, 100%) and 89.9% (SE = 5.8%, 95% confidence interval: 78.5%, 100%), respectively. None of the patients treated by total abdominal hysterectomy followed by both whole pelvic and vaginal cuff radiation therapy (the main line of treatment for patients in whom cervical involvement was diagnosed following hysterectomy, n = 20) or by radical hysterectomy (the main line of treatment for patients in whom cervical involvement was known before hysterectomy, n = 11) had tumor recurrence. Three of 17 (17.6%) patients treated with total abdominal hysterectomy followed by either whole pelvic (n = 13) or vaginal cuff (n = 4) radiation therapy had tumor recurrence. The difference between those two groups was statistically significant (0/31 versus 3/17, P = 0.02). There was no difference in survival among women with stage IIA and IIB or women who underwent radical abdominal hysterectomy and those who underwent total abdominal hysterectomy with postoperative pelvic and vaginal cuff radiation. Morbidity secondary to therapy was mild. Age, depth of myometrial invasion, tumor histology, and grade were not significantly related to recurrence. CONCLUSIONS: Survival of women with surgical stage II endometrial cancer is excellent especially among those treated with total abdominal hysterectomy followed by both pelvic and vaginal cuff radiotherapy or by radical abdominal hysterectomy.     

Neoadjuvant Chemotherapy with Vincristine and Cisplatin Followed by Radical Hysterectomy and Pelvic Lymphadenectomy for FIGO Stage IB Bulky Cervical Cancer: A Gynecologic Oncology Group Pilot Study

Thirty-five patients with bulky (designated as 4 cm size) International Federation of Gynaecology and Obstetrics (FIGO) Stage IB cervical cancer were treated with cisplatin, 50 mg/m², and vincristine, 1 mg/m², administered intravenously at 10-day intervals for a total of three courses before planned radical hysterectomy. One patient died of unrelated cause following one course of chemotherapy and was not evaluated for response. Of the 34 evaluable patients who completed chemotherapy, a complete clinical response was noted in two patients (6%) and a partial response in 26 patients (76%). Five patients (15%) had stable disease and one patient (3%) had disease progression. All chemotherapy was completed within 4 weeks (range 17-28 days). There was no grade 4 toxicity noted. Only one case each of reversible grade 3 granulo-cytopenia and stomatitis and two cases of reversible grade 3 peripheral neuropathy were noted. Of the 34 patients who received chemotherapy, the only patient with disease progression received standard pelvic radiation therapy in lieu of radical surgery. A second patient with stable disease had unresectable pelvic lymph node metastases and underwent confirmatory lymph node biopsy only and received standard radiation therapy postoperatively. The remaining 32 patients underwent radical hysterectomy and pelvic lymphadenectomy from 12 to 49 days following chemotherapy. Surgery was performed without significant difficulty. Eight of these patients (25%) had pelvic node metastases and received postoperative pelvic radiation therapy. Twenty-four months following initiation of treatment, 25 (74%) were alive and presumed free of disease, 4 had died of cancer (12%), 1 was alive with recurrence (3%), and 4 patients (12%) were lost to follow-up. A prospective randomized study is needed to assess the value of this approach compared with standard management.     

FIGO stage IIIC endometrial carcinoma with metastases confined to pelvic lymph nodes: analysis of treatment outcomes, prognostic variables, and failure patterns following adjuvant radiation therapy.

OBJECTIVES: This study was undertaken to evaluate the prognostic significance of isolated positive pelvic lymph nodes on survival and to analyze other prognostic variables, overall survival, and failure patterns in surgically staged endometrial carcinoma patients with positive pelvic lymph nodes and negative para-aortic lymph nodes following radiation therapy (RT). METHODS: Between January 1, 1987, and December 31, 1997, 782 women underwent primary treatment for uterine cancer at Indiana University Medical Center. Through a review of the medical records, we identified 58 patients with pathologic stage IIIA, 27 patients with pathologic stage IIIB, and 77 patients with pathologic stage IIIC endometrial carcinoma. Patients with pathologically positive or unsampled para-aortic lymph nodes and patients who received preoperative radiation therapy were excluded, leaving a study group of 17 patients with nodal metastases confined to pelvic lymph nodes. Thirteen patients received adjuvant pelvic RT using AP-PA or four-field technique. A median dose of 5040 cGy was delivered. Four patients received whole abdominal irradiation (WAI) delivering a median dose of 3000 cGy. Two patients received vaginal cuff boosts of 1000 and 3560 cGy to 0.5 cm from the vaginal surface mucosa via Cs-137 brachytherapy. Two patients also received adjuvant chemotherapy (cis-platinum and doxorubicin) and/or hormonal therapy (megestrol acetate). Disease-free and overall survivals were estimated using the Kaplan-Meier method of statistical analysis and prognostic variables were analyzed using the log-rank test. RESULTS: With a median follow-up of 51 months the actuarial 5-year disease-free survival was 81% and the actuarial 2-year and 5-year overall survival rates were 81 and 72%, respectively. Univariate analysis revealed that positive peritoneal cytology in conjunction with positive pelvic lymph nodes imparts a greater risk of recurrence and decreased overall survival. There were no pelvic and/or upper abdominal failures, but there were recurrences in the para-aortic lymph nodes (two patients) and distantly (two patients). CONCLUSION: Surgery followed by postoperative pelvic RT is a viable treatment option for pathologically staged stage IIIC endometrial carcinoma with disease confined to the pelvic lymph nodes. Failures in the para-aortic region suggest a possible role for extended-field RT. Patients with positive peritoneal cytology in conjunction with nodal metastasis fared poorly with pelvic RT. Studies evaluating the efficacy of WAI are ongoing. Finally, substages within FIGO stage IIIC are recommended in an effort to better understand and define treatment strategies which might be appropriate for these patients.     

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.