Pathologic stage III endometrial cancer treated with adjuvant radiation therapy

Gerszten K, Faul C, Huang Q. Pathologic stage III endometrial cancer treated with adjuvant radiation therapy. Int J Gynecol Cancer 1999; 9: 243–246.
This study was undertaken to evaluate the outcome of pathologic stage III endometrial carcinoma treated with adjuvant radiation therapy (RT). A retrospective review was performed on 32 patients receiving adjuvant RT following abdominal hysterectomy for stage III endometrial carcinoma (19 IIIA, 2 IIIB, 11 IIIC) between 1980 and 1996. Papillary-serous and clear cell adenocarcinomas were excluded. Pathologic nodal sampling was performed on 25 patients (78%). All patients received postoperative external beam RT to the pelvis and 25 of 32 received an additional brachytherapy boost to the vaginal apex. Three patients with involved para-aortic nodes received extended field RT. Mean follow up was 70 mos. Twenty-four patients remain disease-free at mean follow-up of 68 mos. Distant recurrence (DR) occurred in 7 patients at mean of 38 mo. Two local failures were associated with DR. Six patients died of disease after recurrence despite salvage systemic therapy. One patient developed isolated local failure (vaginal apex) and remains disease-free 37 mo after surgical/chemotherapeutic salvage. 5 of 8 (45%) stage IIIC patients developed recurrence vs. only 2 of 19 (10%) stage IIIA cases. 2 of 3 patients treated with extended field RT for positive para-aortic nodal disease remain disease-free at 128 and 56 mo. Long-term survival can be achieved in stage III endometrial carcinoma. Few patients with either adnexal metastases or positive cytology alone develop recurrence. However, patients with stage IIIC disease fare poorly with local therapy alone .     

Potential therapeutic role of para-aortic lymphadenectomy in node-positive endometrial cancer

OBJECTIVE: The aim of this study was to assess the potential therapeutic role of para-aortic lymphadenectomy (PAL) in high-risk patients with endometrial cancer. METHODS: We studied two groups of patients with endometrial cancer who underwent operation at Mayo Clinic (Rochester, MN) during the interval 1984 to 1993: (1) 137 patients at high risk for para-aortic lymph node involvement (myometrial invasion >50%, palpable positive pelvic nodes, or positive adnexae), excluding stage IV disease, and (2) 51 patients with positive nodes (pelvic or para-aortic), excluding stage IV disease. By our definition, PAL required removal of five or more para-aortic nodes. RESULTS: In both groups, no significant difference existed between patients who had PAL (PAL+) and those who did not (PAL-) in regard to clinical or pathologic variables, percentage irradiated, or surgical or radiation complications. Among the 137 high-risk patients, the 5-year progression-free survival was 62% and the 5-year overall survival was 71% for the PAL- group compared with 77 and 85%, respectively, for the PAL+ group (P = 0.12 and 0.06, respectively). For the 51 patients with positive nodes, the 5-year progression-free survival and 5-year overall survival for the PAL- group were 36 and 42% compared with 76 and 77% for the PAL+ group (P = 0.02 and 0.05, respectively). Lymph node recurrences were detected in 37% of the PAL- patients but in none of the PAL+ patients (P = 0.01). Multivariate analysis suggested that submission to PAL was a cogent predictor of progression-free survival (odds ratio = 0.25; P = 0.01) and overall survival (odds ratio = 0.23; P = 0.006). CONCLUSIONS: These results suggest a potential therapeutic role for formal PAL in endometrial cancer.     

A validation study of the new revised FIGO staging system to estimate prognosis for patients with stage IIIC endometrial cancer

Objective

The aim of this study was to validate the role of the new FIGO staging system for estimating prognosis for patients with stage IIIC endometrial cancer.

Methods

A total of 93 cases with stage IIIC were entered in this study and classified into three groups: one group of patients who underwent pelvic lymphadenectomy (PLX) and para-aortic lymphadenectomy (PALX) and who were for positive for pelvic node metastasis (PLNM) and negative for para-aortic node metastasis (PANM) (Group 1), one group of patients who underwent PLX alone and were positive for PLNM (Group 2) and one group of patients who underwent PLX and PALX and were positive for PANM (Group 3). Information on clinicopathologic findings and treatments was obtained from medical charts. Cox regression analysis was used to select prognostic factors.

Results

The 5-years survival rates were 89.3% in Group 1, 46.5% in Group 2 and 59.9% in Group 3. The overall survival rate in Group 1 was significantly better than that in Group 2 (p = 0.0001) and Group 3 (p = 0.0016). No significant difference in overall survival was found between Group 2 and Group 3. Age, number of metastatic lymph nodes, type of lymphadenectomy and type of adjuvant therapy were significantly and independently related to overall survival. Only when patients received PALX, PANM was a prognostic risk factor.

Conclusion

Sub-classification of stage IIIC would be functional for estimating prognosis in the revised FIGO staging system. Systematic lymphadenectomy including PALX has therapeutic significance for patients with stage IIIC endometrial cancer. Prognosis of patients with stage IIIC endometrial cancer would depend much more on application of lymphadenectomy including PALX than nodal status.     

Correlation between clinical and histopathologic risk factors and lymph node metastases in early endometrial cancer (a multivariate analysis of 183 cases)

This study includes 183 patients with clinical stage I endometrial cancer subjected to peritoneal cytology, total abdominal hysterectomy, bilateral salpingo-oophorectomy, bilateral pelvic and para-aortic lymphadenectomy and omental biopsy during a 12-year period in a single institution. The factors analyzed were age, menopausal state, cell type, grade, mitotic activity, myometrial invasion, lymphovascular space invasion, cervical involvement, microscopic vaginal metastases, adnexal metastases, peritoneal cytology, presence of concomitant endometrial hyperplasia and lymph node status. The overall incidences of pelvic and para-aortic lymph node metastases were found to be 15.3% (28/183) and 9.3% (17/183), respectively. In five of 17 patients (29.4%) with para-aortic nodal metastases, pelvic nodes were free of tumor. The most significant prognostic factors for positive pelvic and/or para-aortic nodes were found to be the depth of myometrial invasion, grade of tumor and age.     

Significance of Lymph Node Sampling in Epithelial Carcinoma of the Ovary

From 1979 to 1984, 127 patients operated on for ovarian cancer underwent pelvic, para-aortic, or pelvic and para-aortic lymph node sampling. Forty-seven patients proved to be stage I (14 IA and 33 IC), 14 were stage II (3 IIA, 8 IIB, and 3 IIC), 58 were stage III (7 IIIA, 13 IIIB, and 38 IIIC), and 8 were stage IV. Positive lymph nodes were found in 4.2% of patients at stage I, 35.7% at stage II, 41.3% at stage III, and 87.5% at stage IV. With regard to grading, positive lymph nodes were found in 4.4% of G1, in 21.6% of G2, and in 49.1% of G3. A significant increase in survival (P= 0.04) was found for patients classified as stage IIIC only according to lymph node involvement compared to patients in peritoneal stage IIIC with positive lymph nodes (3-year survival: 46% vs 12%). A small increase in survival was observed for N− patients compared to N+ patients, at both stage III and IV, even with same residual tumor size, but the difference is not statistically significant. All other things being equal, because the prevalence of lymph node positivity depends closely on the number of lymph nodes removed and examined (OR = 3.9 for >10 lymph nodes removed compared to 1–5 lymph nodes removed), lymph node sampling does not seem to be a reliable method for evaluating the retroperitoneal status. With regard to the therapeutic role of systematic lymphadenectomy, few data in literature are available and, most important, are not derived from experimental studies. Probably, only randomized studies with a large number of patients will provide useful answers.     

Ⅱb~Ⅲ期宫颈癌264例疗效及预后因素分析

目的探讨Ⅱb~Ⅲ期宫颈癌患者的疗效及预后相关因素。方法分析2007年3月至2008年10月辽宁省肿瘤医院收治的264例宫颈癌患者的临床资料。结果 264例患者的中位随访时间75个月,2、5年总生存率(overall survival,OS)分别为77.7%、65.5%。2、5年肿瘤特异性生存率(disease-specific survival,DSS)分别为78.1%、66.5%。2、5年无病生存率(disease-free survival,DFS)分别为72.7%、64.2%。单因素分析显示,影响OS、DSS、DFS的因素有临床分期(Ⅱb期与Ⅲ期,P0.01),肿瘤大小(4 cm、4~6 cm、6 cm,P0.01)、病理类型(鳞癌与腺癌,P0.01)、阴道受侵范围(无、上1/3、中1/3、下1/3,P0.01)、淋巴结情况(盆腔腹主阴性、仅盆腔阳性、盆腔腹主阳性、未做CT,P0.01)、最低血红蛋白(110 g/L、95~110 g/L、75~95 g/L、52~75 g/L,P0.01)。入院血红蛋白是DFS的影响因素。多因素分析显示,临床分期、病理类型、淋巴结情况、治疗方式、最低血红蛋白为宫颈癌OS、DSS和DFS的独立预后因素。结论Ⅲ期、腺癌、淋巴结阳性、单纯放疗以及最低血红蛋白75 g/L的宫颈癌患者预后不良。     

Stage II adenocarcinoma of the endometrium treated by two standard regimens of combined preoperative irradiation and surgery

We retrospectively analyzed 77 patients with stage II endometrial carcinoma treated with standard regimens of preoperative radiotherapy (RT) and surgery (S). The age range was 31–74 years with a median of 56.3 years. Thirty-three patients received 40 Gy whole pelvis RT followed by either radical or modified radical hysterectomy. Forty-four patients received 50 Gy whole pelvis RT and sequential intrauterine and intravaginal cesium-137 brachytherapy followed by a simple hysterectomy. Median follow-up was 111 months. No patient was lost to follow-up. The overall 5-year actuarial survival was 78%. There was no significant difference between the two treatment groups. Several prognostic variables were analyzed. Those with histologic grade I and II had 5-year survival of 89% and 83%, respectively, compared to 62% for grade III ( P =0.045). The 5-year survival for microscopic cervical involvement was 87% compared to 59% for gross involvement ( P = 0.008). Patients with negative or microscopic residual tumor in the surgical specimen and those with negative lymph nodes had less risk of treatment failure. Local failure occurred in only 9%. Major complications (3%) were seen only in the radical surgery group. Combined preoperative RT and S provide high cure rates with minimal complications for patients with stage II endometrial carcinoma. Patients with adverse prognostic factors are candidates for trials of more aggressive local and systemic therapy.     

Para-aortic node biopsy in cervical and endometrial cancers: does it affect survival?

Two hundred ten patients with endometrial and cervical carcinoma had para-aortic node biopsies. Nineteen of the 210 patients (9.0%) had positive para-aortic nodes. These 19 patients received pelvic irradiation, and 18 patients received para-aortic irradiation. The incidence of para-aortic nodal involvement in cervical carcinoma was directly related to the stage of the disease. Eleven of the 12 patients with cervical carcinoma and positive para-aortic nodes received both pelvic and para-aortic irradiation. Three of these patients are alive without disease, resulting in a survival rate of 25%. These patients are surviving for 16, 30, and 41 months. The incidence of positive para-aortic nodes in endometrial adenocarcinoma was related to the uterine length and the histologic grade. The survival rate for patients with endometrial adenocarcinoma and positive para-aortic nodes in this study was 57.1%. Four patients have survived for 1, 30, 60, and 71 months. There were no surgical deaths or radiation therapy complications directly attributable to para-aortic biopsy or irradiation.     

Evaluating the significance of location of lymph node metastasis and extranodal disease in women with stage IIIC endometrial cancer

Objective

To determine the prognostic significance of location of lymph node metastasis and extranodal disease for women with stage IIIC endometrial cancer.

Methods

Data were extracted from the Surveillance, Epidemiology, and End Results database between 1988 and 2005. Statistical analysis used Chi-square test, Kaplan–Meier method, and Cox proportional hazards model.

Results

A total of 2559 women were identified; 1453 stage IIIC1, and with 906 stage IIIC2 tumors. Compared to stage IIIC1; more stage IIIC2 patients demonstrated high-risk factors such as grade III disease (p < 0.001), unfavorable histologic types (p = 0.01), concurrent disease at other extrauterine sites (p < 0.001), and greater than two positive lymph nodes (p < 0.001). While the 5-year disease specific survival was comparable (p > 0.05) among node positive patients found to have positive peritoneal cytology (44.0%), adnexal/serosal metastasis (42.9%), and vaginal/parametrial involvement (41.8%); it differed individually in all three categories from those with nodal metastasis alone (67.0%, p < 0.001). Among women with extranodal disease, the location of nodal metastasis had no effect on survival (HR = 0.92; 95% CI, 0.74–1.14). For women with node only stage IIIC tumors, those patients with positive para-aortic nodes were more likely to die from their tumors (HR = 1.40; 95% CI, 1.12–1.75).

Conclusion(s)

Location of lymph node metastasis is prognostic in patients with nodal disease alone, and not in those with extranodal disease. Extranodal disease is associated with a poor prognosis and should be regarded in conjunction with location of lymph node metastasis for risk-stratification in stage IIIC endometrial cancer.     

Radiotherapy in the adjuvant setting of cervical carcinoma: treatment, results, and prognostic factors

To evaluate the efficacy of postoperative radiotherapy and to investigate prognostic factors for early-stage cervical cancer patients. From December 1993 to December 2001, 141 patients with stage I-II cervical cancer without para-aortic lymph node (LN) metastases and treated by surgery and postoperative radiotherapy (RT) were included in this study. Indications for postoperative external RT were based on pathologic findings, including LN metastasis, positive surgical margins, parametrial involvement, pT2 tumor, and presence of any two minor risk factors like lymphvascular space involvement, deep stromal invasion, and tumor diameter between 2-4 cm. Sixty-six (47%) patients received RT alone, whereas 59 (42%) were treated with RT and concomitant chemotherapy (CT), and 16 received neoadjuvant CT. Patients with positive vaginal margins also received 27.5 Gy high-dose rate vaginal cuff brachytherapy in five fractions. Median follow-up time was 55 months. The actuarial 5-year overall (OS), disease-free (DFS), locoregional recurrence-free (LRFS), and distant metastases-free (DMFS) survival rates are 70%, 68%, 77%, and 88%, respectively. Univariate and multivariate analyses revealed that level and number of metastatic LNs and concomitant CT were unique significant prognostic factors for OS, DFS, and LRFS. Endometrial involvement, on the other hand, was proven to be significant for DFS and DMFS. Patients with less than three LN metastases or having only obturator LN involvement showed similar prognosis with their counterparts having no LN metastases. On the other hand, patients with either common iliac LN or more than three LN metastases had significantly worse outcome. Our results indicate that level and number of metastatic LNs are the most important prognostic factors determining the survival rates, and patients with upper lymphatic involvement or more than three metastatic LNs seem to need more effective treatment approaches.     

Analysis of clinicopathologic factors predicting para-aortic lymph node metastasis in endometrial cancer

The purposes of this study were to compare the relationships between para-aortic lymph node metastasis and various clinicopathologic factors to evaluate whether para-aortic lymph node dissection is necessary when treating endometrial cancer. A retrospective study was performed on 841 patients with endometrial cancer, who underwent the initial surgery at the Keio University Hospital. Clinicopathologic factors related to para-aortic lymph node metastasis significant on a univariate analysis were analyzed in a multivariate fashion using a logistic model. According to the multivariate analysis, the clinicopathologic factor most strongly related to the existence of para-aortic lymph node metastasis was positive pelvic lymph node metastasis (P < 0.01). Among the 155 patients who underwent pelvic and para-aortic lymph node dissection, the difference of 5-year overall survival by the presence of retroperitoneal lymph node metastasis was examined by Kaplan-Meier method. The prognosis was poor even if para-aortic lymph node dissection was performed in cases of positive para-aortic lymph node metastasis. In conclusion, when deciding whether to perform para-aortic lymph node dissection in patients with endometrial cancer, it is necessary to consider the pelvic lymph nodal status. If there is no pelvic lymph node metastasis, it could not be necessary to perform para-aortic lymph node dissection.     

The prognostic factors for patients with early cervical cancer treated by radical hysterectomy and postoperative radiotherapy

PURPOSE: This study was undertaken to evaluate the efficacy of postoperative radiotherapy (post-OP RT) and to investigate the prognostic factors for early-stage cervical cancer patients who were treated by radical surgery, and the pathological findings suggested a relatively high risk of relapse with surgery alone. MATERIALS AND METHODS: From January 1990 to December 1995, 222 patients with stage IB-IIA cervical cancer, treated by radical surgery and a full course of post-OP RT, were included in this study. The indications for post-OP RT were based on pathological findings, including lymph node metastasis, positive surgical margins, parametrial extension, lymphovascular permeation, and invasion of more than two-thirds of the cervical wall thickness. The radiation dose of external beam was 44-45 Gy to the whole pelvis and 50-54 Gy to the true pelvis. One hundred seventy-two patients also received intravaginal brachytherapy as a local boost. The minimal follow-up period was 2 years. RESULTS: The actuarial 5-year overall and disease-specific survival rates for all patients were 76 and 82%, respectively. The tumor control rate within the pelvis reached 94%, and distant metastasis was the major cause of treatment failure. Univariate analysis of clinical and pathological parameters revealed that clinical stage, bulky tumor size, positive lymph nodes, parametrial extension, and histologic type were significant prognostic factors. After multivariate analysis, only positive lymph nodes (P = 0.01), bulky tumor size (P = 0.02), and parametrial extension (P = 0.05) independently influenced the disease-specific survival (DSS). For patients with lymph node metastasis, the number and location of the nodal involvement significantly affected the prognosis. The 5-year DSS for patients with no, one, and more than one lymph node metastasis were 87, 84, and 61% (P = 0.0001), respectively. Patients with upper pelvic lymph node metastasis had a higher incidence of distant metastasis (50% vs 16% in lower pelvic node group, P = 0.03). In the subgroup of single lower pelvic nodal metastasis, the prognosis was similar to that of patients without lymph node involvement (5-year DSS 85% vs 87%, P = 0.71). CONCLUSION: Our results indicate that post-OP RT can achieve very good local control in stage IB-IIA cervical cancer patients whose pathological findings show risk features for relapse after radical surgery. The prognostic factors for treatment failure identified in this study can be used as selection criteria for clinical trials to test the effects of other adjuvant treatments, such as chemotherapy. Patients with a single lower pelvic lymph node metastasis have a relatively good prognosis and may not need adjuvant treatment beyond radiation therapy.     

Resection of bulky positive lymph nodes in patients with cervical carcinoma

From January 1987 to April 1992, 34 patients had resection of bulky positive lymph nodes, detected either at the time of radical hysterectomy ( n = 23) or by computed tomographic (CT) scan of the pelvis and abdomen prior to radiation therapy for more advanced cervical cancer ( n = 11). Following nodal resection, 33 patients received pelvic external beam radiation, 28 received pelvic and para-aortic radiation, and 23 received four cycles of cisplatin chemotherapy. The median number of resected positive nodes was 4, with a range of 1–44. All macroscopic nodal metastases could be resected in each patient and morbidity was acceptably low. Positive nodes were confined to the pelvis in 17 patients, involved the common iliac group in nine patients, and involved the para-aortic area in eight patients. With a mean follow-up of 36 months, 23 patients (67.6%) were alive, of whom 20 were free of disease. For patients having a radical hysterectomy, actuarial 5-year survival was 80% for patients with disease involving pelvic and common iliac lymph nodes, and 48% for those with positive para-aortic nodes. Survival for patients with completely resected bulky pelvic and common iliac nodes was comparable to that for patients with micrometastases. This study suggests that every effort should be made to identify patients with cervical cancer who have bulky positive lymph node metastases, and to remove these nodes surgically prior to radiation therapy.     

Laparoscopic Debulking of Enlarged Pelvic Nodes during Surgical Para-aortic Staging in Locally Advanced Cervical Cancer: A Retrospective Comparative Cohort Study

Study ObjectiveTo evaluate laparoscopic pelvic lymph node debulking during extraperitoneal aortic lymphadenectomy in diagnosis, therapeutic planning, and prognosis of patients with locally advanced cervical cancer and enlarged lymph nodes on imaging before chemoradiotherapy.DesignRetrospective, multicenter, comparative cohort study.SettingThe study was carried out at 11 hospitals with specialized gynecologic oncology units in Spain.PatientsTotal of 381 women with locally advanced cervical cancer and International Federation of Gynecology and Obstetrics 2018 stage IIIC 1r (radiologic) and higher who received primary treatment with chemoradiotherapy.InterventionsPatients underwent pelvic lymph node debulking and para-aortic lymphadenectomy (group 1), only para-aortic lymphadenectomy (group 2), or no lymph node surgical staging (group 3). On the basis of pelvic node histology, group 1 was subdivided as negative (group 1A) or positive (group 1B).Measurements and Main ResultsFalse positives and negatives of imaging tests, disease-free survival, overall survival, and postoperative complications were evaluated.In group 1, pelvic lymph node involvement was 43.3% (71 of 164), and aortic involvement was 24.4% (40 of 164). In group 2, aortic nodes were positive in 29.7% (33 of 111). Disease-free survival and overall survival were similar in the 3 groups (p = .95) and in groups 1A and 1B (p = .25). No differences were found between groups 1 and 2 in intraoperative (3.7% vs 2.7%, p = .744), early postoperative (8.0% vs 6.3%, p = .776), or late postoperative complications (6.1% vs 2.7%, p = .252). Fewer early and late complications were attributed to radiotherapy in group 1A than in the others (p = .022).ConclusionLaparoscopic pelvic lymph node debulking during para-aortic staging surgery in patients with locally advanced cervical cancer with suspicious nodes allows for the confirmation of metastatic lymph nodes without affecting survival or increasing surgical complications. This information improves the selection of patients requiring boost irradiation, thus avoiding overtreatment of patients with negative nodes.     

Prognostic factors and failure pattern in lymph node-negative stage IB and II cervical carcinoma treated with radical hysterectomy and postoperative irradiation

The aim was to determine the prognostic factors and recurrence pattern in stages IB and II cervical carcinoma patients with negative pelvic lymph nodes. 224 patients with stages IB and II cervical carcinoma underwent radical hysterectomy (RH) from 1982 through 1995. Of 161 patients with negative lymph nodes, 65 patients received postoperative irradiation (RT) and 96 patients were given no further therapy according to surgical pathological findings. The overall 5-year disease-free survival was 94.1%. Two of 96 RH patients (2%) and 10 of 65 RH + RT patients (15%) had recurrence in pelvic and distant sites almost equally. Multivariate analysis revealed deep cervical invasion as the only independent prognostic factor. The 5-year disease-free survival was 98.8% for patients with shallow invasion and 85.8% for patients with deep invasion (p < 0.0001). It is worthwhile to develop new strategies for the lymph node-negative patients with deep stromal invasion.     

Significance of pathologic patterns of pelvic lymph node metastases in endometrial cancer

OBJECTIVE: The aim of this study was to correlate the pathologic characteristics of pelvic lymph node metastases with survival, recurrence, and patterns of recurrence in endometrial cancer. METHODS: Sixty patients with epithelial endometrial cancer and pelvic node metastasis were managed surgically between 1984 and 1993 at the Mayo Clinic. The mean number of nodes harvested was 16.7 and the mean number of nodes positive was 3.0. Mean follow-up was 45.5 months. The pathologic patterns of lymph node metastases were characterized. RESULTS: Outcome was related to pathologic patterns of pelvic node metastasis. Both diameter of lymph node metastasis (P < 0.01) and capsular integrity (P < or = 0.01) influenced 5-year disease-related survival and 5-year progression-free survival. The percentage of biopsied pelvic lymph nodes harboring metastatic disease and the proportion of the involved lymph nodes occupied by tumor significantly influenced death rates and recurrence rates (P < 0.05). The immune response and the absolute number of positive pelvic nodes did not impact recurrence or survival. The above characteristics of pelvic node metastasis correlated also with patterns of recurrence. Regression analysis indicated that capsular integrity (RR = 2.97; P = 0.005) and proportion of positive pelvic nodes biopsied (RR = 3.84; P = 0.01) were significant predictors of recurrence, whereas diameter of metastasis (RR = 3.68; P = 0.02) and proportion of positive pelvic nodes biopsied (RR = 4.04; P = 0.02) were most predictive of survival. CONCLUSIONS: The pathologic patterns of pelvic node metastasis appear to be significantly related to survival, recurrence, and patterns of recurrence.     

Lymph-vascular space invasion and number of positive para-aortic node groups predict survival in node-positive patients with endometrial cancer

OBJECTIVE: The aim of this study was to determine pathologic variables associated with disease-specific survival of node-positive patients with endometrial carcinoma treated with combination of surgery including pelvic and para-aortic lymphadenectomy and adjuvant chemotherapy. METHODS: Survival of 55 node-positive endometrial carcinoma patients prospectively treated with surgery and adjuvant chemotherapy between 1982 and 2002 at Hokkaido University Hospital was compared to various histopathologic variables. All patients underwent primary surgical treatment including pelvic and para-aortic lymphadenectomy followed by adjuvant chemotherapy consisting of intravenous cisplatin, doxorubicin, and cyclophosphamide. Survival analyses were performed by the Kaplan-Meier curves and the log-rank test. Independent prognostic factors were determined by multivariate Cox regression analysis using a forward stepwise selection. RESULTS: Among 303 consecutive endometrial cancer patients treated during the period of this study, 55 patients (18.2%), including 44 without peritoneal metastasis (FIGO stage IIIc) and 11 with peritoneal metastasis (FIGO stage IV), were found to have retroperitoneal lymph node metastasis. Multivariate Cox regression analysis revealed that peritoneal metastasis and lymph-vascular space invasion (LVSI) were independently related to poor survival in node-positive endometrial carcinoma. The estimated 5-year survival rate of stage IIIc patients with or without moderate/prominent LVSI was 50.9% and 93.3%, respectively with statistically significant difference (P=0.0024). The estimated 5-year survival rate of stage IV patients was 20.0%. Prognosis of stage IIIc patients could be stratified into three groups by the number of positive para-aortic node (PAN) with an estimated 5-year survival rate of 86.4% for no positive PAN (n = 23), 60.4% for one positive PAN (n = 13), and 20.0% for > or = 2 positive PAN (n = 8). The difference of survival rate between no or one positive PAN and > or = 2 positive PAN was statistically significant (P = 0.0007 for no positive PAN vs > or = 2 positive PAN, P = 0.0319 for one positive PAN vs > or = 2 positive PAN). Multivariate analysis including number of positive PAN groups showed that LVSI, number of positive PAN groups were independent prognostic factors for survival. Survival of patients with stage IIIc disease could be stratified into three groups by combination of LVSI and number of positive PAN groups with an estimated 5-year survival rate of 93.3% for no or one positive PAN group with nil or minimal LVSI, 62.6% for no or one positive PAN group with intermediate or prominent LVSI, and 20.0% for > or = 2 positive PAN groups irrespective of LVSI (P = 0.0002 for no or one positive PAN group with nil or minimal LVSI vs > or = 2 positive PAN groups, P = 0.0223 for no or one positive PAN group with nil or minimal LVSI vs no or one positive PAN group with intermediate or prominent LVSI, P = 0.0388 for no or one positive PAN group with intermediate or prominent LVSI vs > or = 2 positive PAN groups). CONCLUSIONS: LVSI and number of positive PAN groups were independent prognostic factors for stage IIIc endometrial cancer patients. Postoperative therapy and follow-up modality need to be individualized according to LVSI and the number of positive PAN for stage IIIc patients. New molecular markers to predict the prognosis of endometrial cancer patients preoperatively should be found for individualization of treatment. New chemotherapy regimen including taxane needs to be considered as an adjuvant therapy for patients with node-positive endometrial cancer.     

Efficacy of systematic lymphadenectomy and adjuvant radiotherapy in node-positive endometrial cancer patients

OBJECTIVE: To assess the efficacy of systematic lymphadenectomy and adjuvant radiotherapy in minimizing pelvic sidewall and para-aortic failures. METHODS: Between January 1984 and December 2001, a total of 146 patients with stage III and IV endometrial cancer and lymph node metastases were treated at our institution. Adequate pelvic lymphadenectomy was defined as the removal of more than 10 pelvic lymph nodes, and adequate para-aortic lymphadenectomy was defined as removal of 5 or more para-aortic lymph nodes. The 24 patients who received adjuvant chemotherapy were excluded. We assessed the ability of adequate pelvic and para-aortic lymphadenectomy, together with radiotherapy, to prevent pelvic and para-aortic recurrences. RESULTS: Of the 122 patients studied, 94 (77%) had adequate pelvic lymphadenectomy and 47 (39%) had adequate para-aortic lymphadenectomy. Pelvic radiotherapy was administered to 78% and para-aortic radiotherapy to 29% of patients. Median follow-up of censored patients was 56 months. Twenty-five percent of patients had pelvic sidewall failure at 5 years. Pelvic sidewall failures at 5 years occurred in 57% of patients who had inadequate node dissection and/or no radiotherapy, compared with 10% for those having both adequate lymphadenectomy and radiotherapy (P < 0.001). After risk factor assessment in a regression model, only treatment with adequate lymphadenectomy and radiotherapy was a significant independent predictor of pelvic control (P = 0.03). The performance of definitive pelvic lymphadenectomy may have increased treatment-related morbidity in the subgroup of patients who had postoperative radiotherapy. For the 41 patients with positive para-aortic lymph nodes, the 5-year para-aortic failure rate was 34% after adequate lymphadenectomy but without adjuvant para-aortic radiotherapy. Likewise, 69% failed in the para-aortic area when adjuvant para-aortic radiotherapy was administered to patients not having adequate para-aortic lymphadenectomy; however, none of the 11 patients failed in the para-aortic area after adequate lymphadenectomy and para-aortic radiotherapy (P = 0.08). CONCLUSIONS: Adequate (pelvic and para-aortic) lymphadenectomy and adjuvant radiotherapy appear complementary in reducing failures in both the pelvis and para-aortic areas in patients with node-positive endometrial cancer.     

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.     

盆腹腔淋巴取样术在子宫内膜癌手术中的临床意义

目的探讨盆腹腔淋巴取样术在子宫内膜癌的临床意义。方法分析2000年1月-2007年12月上海同济大学附属第一妇婴保健院手术治疗的213例子宫内膜癌患者,其中,86例行盆腹腔淋巴取样术,127例行淋巴结切除术。手术方式根据手术切除淋巴结的情况分为两组。①取样组：淋巴取样术,筋膜外全子宫双附件切除/次广泛子宫切除术＋盆腔/腹主动脉旁淋巴结取样术86例;②切除组：次广泛/广泛子宫切除术＋盆腔淋巴结切除/腹主动脉旁淋巴结切除术127例。结果取样组：切除淋巴结中位数18枚,淋巴结的转移10例。切除组：切除淋巴结中位数32枚,淋巴结转移11例。5年生存率分别为94.2%和94.5%。取样组无病发症发生,淋巴结切除组中有9例,分别是1例术中大出血（〉2000ml）,淋巴囊肿感染6例,淋巴漏2例。结论在子宫内膜癌中淋巴结取样术可准确了解淋巴结的转移情况,适宜手术分期,并不影响生存率,是避免过度手术减少并发症发生的有效方法。