Resection of lymph node metastases influences survival in stage IIIC endometrial cancer

OBJECTIVE: Surgical staging of endometrial cancer identifies those patients with microscopic metastatic disease most likely to benefit from adjuvant therapy and may also confer therapeutic benefit. Our objective was to compare survival of patients who underwent resection of grossly positive lymph nodes (LN) to those with microscopically positive LN. METHODS: Patients had stage IIIC endometrial cancer with pelvic and/or aortic LN metastases and underwent surgery between 1973 and 2002. Exclusion criteria included pre-surgical radiation and second primary cancer. Survival was analyzed using Kaplan-Meier method and Cox proportional hazards model. RESULTS: Mean age of 96 patients with stage IIIC endometrial cancer was 64. There were 45 cases with microscopic LN involvement and 51 with grossly enlarged LN. Overall, 41% had disease in aortic LN, which in 18% represented isolated aortic LN metastasis. Adjuvant therapies were given to 92% of patients (85% radiotherapy, 10% chemotherapy, 10% progestins). Among those with grossly involved LN, 86% were completely resected. Five-year disease-specific survival (DSS) was 63% in 45 patients with microscopic metastatic disease compared to 50% in 44 patients with grossly positive LN completely resected and 43% in 7 with residual macroscopic disease. In multivariable analyses, gross nodal disease not debulked (HR=6.85, P=0.009), serosal/adnexal involvement (HR=2.24, P=0.036), diagnosis prior to 1989 (HR=4.33, P<0.001), older age (HR=1.09, P<0.001), and >2 positive lymph nodes (HR=3.12, P=0.007) were associated with lower DSS. CONCLUSION: Grossly involved LN can often be completely resected in patients with stage IIIC endometrial cancer. These retrospective data provide evidence suggestive of a therapeutic benefit for lymphadenectomy in endometrial cancer.     

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

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

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.     

Treatment for early endometrial cancer. Cost-effectiveness analysis.

OBJECTIVE: To evaluate the cost-effectiveness of treatment for early endometrial cancer. STUDY DESIGN: Cost-minimization type of cost-effectiveness analysis with payer costs based on CPT (physician's current procedural terminology) and DRG (disease related group) codes. The six principles of cost-effectiveness analysis were evaluated. We compared the standard treatment protocol of selected lymphadenectomy/selective teletherapy (lymphadenectomy and postoperative teletherapy administered for high-risk tumors) as performed by the majority of gynecologic oncologists vs. an alternate treatment protocol of lymphadenectomy/selective brachytherapy (lymphadenectomy for all tumors, brachytherapy for high-risk tumors and teletherapy reserved for nodal metastasis) as performed by 10-12% of gynecologic oncologists. RESULTS: In cost-minimization analysis, lymphadenectomy/selective brachytherapy was 12% less expensive than the standard treatment protocol of selective lymphadenectomy/teletherapy. CONCLUSION: Although only 10-12% of gynecologic oncologists perform lymphadenectomy on all patients, deliver brachytherapy for high-risk tumors and reserve teletherapy for lymph node metastasis, it is a cost-effective treatment strategy for early endometrial cancer.     

Chemotherapy and Extended-Field Radiation Therapy to Para-aortic Area in Patients with Histologically Proven Metastatic Cervical Cancer to Para-aortic Nodes: A Phase II Pilot Study

From November 1983 to October 1992, 22 patients with invasive cervical cancer stage IB through stage IIIB with metastasis to para-aortic nodes were entered in this study. Five patients were excluded. Of 17 remaining evaluable patients, 5 (29%) were stage IB, 6 (35%) were stage lIB, and 6 (35%) were stage IIIB. Four (24%) had grade 1, 5 (29%) had grade 2, and 8 (47%) had grade 3 tumor. Lymph node metastases were microscopic in 8 (47%) and macroscopic in 9 (53%) patients. All patients received 2 courses of chemotherapy concomitant with radiation as a sensitizer. They were randomized to receive either cisplatin (regimen A) or combination of cisplatin with 5-FU infusion (regimen B). This was followed by maintenance chemotherapy with cisplatin for a maximum of 10 additional courses. Of 17 patients, 7 (41%) received 4-6 courses, 4 (24%) received 6-8 courses, and 6 (35%) received 8-10 courses of maintenance chemotherapy. For extended-field radiation, a panhandle technique was used. External radiation therapy was delivered via 10 or 18 MeV linear accelerator photons, followed by 1 or 2 intracavitary cesium applications. Patients were followed up 8-103 months (median 21 months). Progression-free interval (PFI) for all patients was 5-103 months (median 18 months). Patients with microscopic metastasis to para-aortic nodes had median PFI of 26.5 months compared to 14 months in those with macroscopic nodal metastasis. Seven of 17 patients (41%) are alive from 17 to 103 months with median survival of 32 months. Overall survival for the entire group was 8-103 months (median 21 months). Median survival for patients with microscopic and macroscopic nodal metastasis was 30 and 21 months, respectively. Two- and five-year survival for the entire group was 35 and 12%, respectively. The survival with microscopic metastasis to para-aortic nodes was 50 and 12% compared to survival of 22% at 2 years and 11% at 5 years respectively in those with macroscopic nodal metastasis. There was no significant difference between regimen A and B for local disease control. Maintenance chemotherapy with cisplatin did not appear to significantly improve the 5-year survival. Distant metastases were the predominant sites of failure.     

Is aortic lymphadenectomy necessary in the management of endometrial carcinoma?

OBJECTIVE: To evaluate the role of aortic lymphadenectomy in the management of endometrial carcinoma. METHODS: Clinical notes of 163 patients with endometrial carcinoma were reviewed. All patients had peritoneal cytology, total abdominal hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy with or without aortic lymphadenectomy. RESULTS: Seventy-five (46.0%) patients had pelvic lymphadenectomy alone whereas 88 (54.0%) had both pelvic and aortic lymphadenectomy. Thirty-five (21.5%) patients had nodal metastases with positive pelvic and aortic nodes in 26 (16.0%) and 24 (27.3%) patients, respectively. Isolated aortic metastases were found in 17 cases (19.3%). Among 35 patients with nodal metastases, recurrence developed in 15 (42.9%) patients and all except one died within five to 50 months. The remaining patients had a median disease-free period of 55 months (13-93 months). The recurrence rate was higher (63.6%) among patients with upper aortic lymph node metastases, and all those who recurred died of disease within seven to 28 months. CONCLUSIONS: Our data suggest that aortic lymphadenectomy provides both diagnostic and therapeutic value in the management of endometrial carcinoma with high metastatic risk. After surgical removal and adjuvant radiotherapy, patients with nodal metastases achieved a better survival chance.     

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.     

Pelvic and aortic lymph node metastasis in epithelial ovarian cancer

OBJECTIVE: The appropriate management of advanced ovarian cancer has been controversial in recent years. There are no adequate data about the importance of lymphadenectomy and the appropriate sites for lymph node assessment. We sought to evaluate the distribution, size, and number of pelvic and aortic lymph node metastases in patients with epithelial ovarian carcinoma. METHODS: Retrospective chart review of 116 patients with stage IIIC or IV epithelial ovarian carcinoma treated at Mayo Clinic who underwent systematic bilateral pelvic and aortic lymphadenectomy between 1996 and 2000. RESULTS: Eighty-six (78%) of 110 patients who underwent pelvic lymphadenectomy were found to have nodal metastases in 422 (16%) of 2705 pelvic nodes that were removed. Eighty-four (84%) of 100 patients had documented aortic lymph node metastases in 456 (35%) of 1313 aortic nodes that were removed. Fifty-five (59%) of 94 patients had bilateral metastatic pelvic and aortic lymph nodes and bilateral aortic lymphadenectomy was conducted in 53 (72%) of 74 patients. The most representative group for detection of nodal metastases was the aortic group (83%) followed by the external iliac group (59%) and the obturator nodes (53%). There was no significant difference between the mean size of positive (1.8 cm) and negative nodes (1.6 cm). Thirty-seven patients had unilateral tumor, and 1 patient (7%) had contralateral node metastasis. CONCLUSION: The incidence of positive nodes bilaterally and positive high aortic nodes indicates the need for bilateral pelvic and aortic node dissection (extending above the inferior mesenteric artery) in all patients regardless of laterality of the primary tumor.     

Stage IIIC endometrioid corpus cancer includes distinct subgroups

OBJECTIVE: Because stage IIIC corpus cancer is a heterogeneous substage, the outcomes of patients with stage IIIC disease were assessed according to the extent of extrauterine disease. METHODS: From 1984 through 1993, 51 patients with surgical stage IIIC corpus cancer were treated at our institution; 5 patients had tumors with nonendometrioid histologic features and were excluded from the analyses. Of the 46 patients with endometrioid carcinoma, 22 had lymph nodes as the only site of extrauterine disease (stage IIIC(0)) and 24 also had peritoneal cytologic, uterine serosal, adnexal, or vaginal involvement or a combination of these (stage IIIC(ab)). The mean number of lymph nodes removed was 18 pelvic and 8 aortic nodes. Median follow-up for surviving patients was 84 months. RESULTS: Patients with stage IIIC(0) cancer had a 5-year cause-specific survival (CSS) of 72% and a 5-year recurrence-free survival (RFS) of 68%, and those with stage IIIC(ab) had a CSS of 33% and an RFS of 25% (P < 0.01). Of the 22 patients with stage IIIC(0) endometrioid cancer, 21 had adjuvant radiotherapy (1 also received chemotherapy) and 1 was not treated. Relapse occurred in 7 (32%) patients, with only 1 having an initial failure component outside the node-bearing areas (lung). Of the 24 patients with stage IIIC(ab) cancer, 16 received adjuvant radiotherapy (1 had concomitant chemotherapy), 2 had chemotherapy, 4 had hormonal therapy, and 2 were not treated. We observed 16 recurrences (67%). Of the 14 patients with known initial sites of failure, 9 had an extranodal failure component. CONCLUSION: Assessment of CSS, RFS, and sites of relapse suggests that FIGO surgical stage IIIC endometrioid corpus cancer includes two distinct and readily separable subgroups: (1) stage IIIC(0), nodal involvement only, and (2) stage IIIC(ab), nodal plus cytologic, uterine serosal, adnexal, or vaginal involvement, or a combination of these. Our results also suggest that different treatment strategies are needed for these subgroups.     

Surgical stage III endometrial cancer: analysis of treatment outcomes,prognostic factors and failure patterns

OBJECTIVE: The purpose of this study was to evaluate the survival estimates of stage III endometrial cancer patients, and also to detect the prognostic factors and failure patterns. MATERIALS AND METHODS: Sixty-eight surgical Stage III endometrial cancer patients treated at Hacettepe University Hospital were included. All patients underwent surgical staging procedures consisting of peritoneal cytology, infracolic omentectomy, total abdominal hysterectomy, bilateral salpingo-oophorectomy and complete pelvic-paraaortic lymphadenectomy. By surgical staging 26 (38%) patients had Stage IIIA and 42 (62%) patients had Stage IIIC disease. The mean resected lymph node number was 26 (median, 25; range, 15-58). RESULTS: The median age was 60 years (range, 38-77), and the median follow-up period was 62 months (range, 36-90 months). The 5-year disease free survival rate was 58% and the 5-year overall survival rate was 64%. These figures for Stage IIIA were 60% and 68%, respectively; and for Stage IIIC they were 57% and 62%, respectively. No significant survival difference was detected between Stage IIIA and IIIC (p = 0.60 for disease-free survival and p = 0.48 for overall survival). High grade and positive peritoneal cytology predicted poor survival in both univariate (p = 0.004 and p = 0.006, respectively) and multivariate (p = 0.05 and p = 0.04, respectively) analysis. Twenty-eight patients (41%) had recurrence with a median time of 23 months (range, 10-54 months). Nine patients (13%) had only local, 13 patients (19%) had only distant and six patients (9%) had both local and distant relapse. CONCLUSION: Surgical staging is important in the management of Stage III endometrial cancer, and the main problem is still distant failure. In multivariate analysis high grade and positive peritoneal cytology predicted poor survival significantly.     

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.     

盆腔淋巴清扫术对子宫内膜癌预后的影响

目的　探讨子宫内膜癌盆腔淋巴转移的相关因素及盆腔淋巴清扫术对子宫内膜癌预后的影响。方法　选择 1981年 1月至 2 0 0 2年 12月行子宫内膜癌盆腔淋巴清扫术患者 90例 ,淋巴结取样活检术患者 12例 ,分析这 10 2例患者淋巴转移与各临床病理指标的关系。随机选取同期未行淋巴清扫术的 90例患者作为对照与行淋巴清扫术的 90例患者进行比较 ,寿命表法计算两者的生存率。结果　 10 2例患者中 ,低分化、深肌层浸润、宫颈浸润、腹腔冲洗液细胞学检查阳性、附件浸润、远处转移者 ,盆腔淋巴转移的发生率升高 ,分别为 46%、42 %、44%、52 %、75%、10 0 %。盆腔淋巴转移患者的 5年累计生存率 (3 7% )低于无淋巴转移者 (89% ,P <0 0 1)。 90例行盆腔淋巴清扫术患者与对照者的 5年累计生存率分别为 78%和 72 % ,两者比较 ,差异无显著性 (P >0 0 5)。COX逐步回归分析显示 ,盆腔淋巴清扫术不是影响患者预后的独立因素。结论　低分化、深肌层浸润、宫颈浸润、腹腔冲洗液细胞学检查阳性、附件浸润、远处转移是子宫内膜癌盆腔淋巴转移的高危因素 ,有盆腔淋巴转移的患者预后差 ,但盆腔淋巴清扫术并不改善患者预后     

The incidence of isolated para-aortic nodal metastasis in completely staged endometrial cancer patients

Objective

To describe and review the incidence of para-aortic (PA) nodal metastasis in completely staged endometrial cancer patients who are negative for pelvic nodal metastasis.

Methods

Using an institutionally maintained database, we identified all patients with endometrial cancer from 2002 to 2006 who had both pelvic and aortic nodal dissections and determined the rate of isolated para-aortic nodal metastasis in non-malignant (i.e. negative) pelvic nodes.

Results

201 endometrial cancer patients were surgically treated at our institution from 2002 to 2006. 171 patients had both pelvic and PA nodes removed during surgery, and specimens examined by a pathologist. Only 2 (1.2%) had PA nodes that tested positive for malignance (i.e. positive PA nodes) with pelvic nodes that tested negative for malignance (i.e. negative pelvic nodes). The final International Federation of Gynecology and Obstetrics (FIGO) grade for the endometrial tumor cells in the two patients was “G1” with endometrioid adenocarcinoma and “G3” with endometrioid adenocarcinoma and mucinous differentiation, respectively.

Conclusion

Based on the very low incidence of patients inflicted with endometrial cancer that have positive para-aortic lymph nodes (PALNs) with negative pelvic nodes found both in our literature review (1.5%) and in our own study (1.2%), the addition of PA lymphadenectomy in all patients was found to have minimal diagnostic and therapeutic value. At the present, the role of complete PA lymphadenectomy in all patients with endometrial cancer should be re-examined. Individualized algorithms should be developed based on risk factors and status of pelvic nodes.     

Effectiveness of postoperative chemotherapy for para-aortic lymph node metastasis of endometrial cancer

OBJECTIVE: To examine the effectiveness of postoperative chemotherapy for para-aortic lymph node (PAN) metastasis in patients with endometrial cancer. METHODS: Among 350 clinical stage I-II endometrial cancer patients who underwent systemic pelvic and para-aortic lymphadenectomy during the period 1995 through 2002, 26 patients were identified with PAN metastasis. Of these patients, nine had only one positive PAN and 17 had two or more positive PANs (mean 4.9, range 1-22). All patients were treated postoperatively with a single chemotherapy regimen consisting of ifosfamide, epiadriamycin, and cisplatin scheduled for 5 cycles. Median (range) follow-up for surviving patients was 85 (38-119) months. Treatment outcome, including disease-free survival relative to the number of positive PANs, was investigated. RESULTS: Among the 26 patients with PAN involvement, four developed recurrence. Three of the four patients had 10 or more positive PANs. Estimated 5-year disease-free survival rates were 89% for patients with one positive PAN, 82% for those with two or more positive PANs, and 85% for all patients. No significant difference was identified between the first two groups (P = 0.6543). CONCLUSIONS: Postoperative chemotherapy can yield a favorable outcome in endometrial cancer patients with PAN metastasis, even those with multiple positive nodes.     

Ⅰ期子宫内膜癌盆腔淋巴清扫术的意义

目的:探讨Ⅰ期子宫内膜癌患者预后的相关因素及盆腔淋巴清扫术对其预后可能的影响。方法:收集1997年8月至2005年3月浙江大学医学院附属妇产科医院临床Ⅰ期子宫内膜癌患者202例,分析影响预后的各项临床病理指标,寿命表法计算生存率,比较盆腔淋巴清扫组与平行淋巴结清扫组的复发率,并发症。结果:Ⅰ期子宫内膜癌盆腔淋巴转移率1·53%。病理类型、腹腔细胞学、盆腔淋巴转移、手术-病理分期、肌层浸润及CA125值是影响预后的独立因素。Ⅰ期低危患者,盆腔淋巴清扫术无助于提高生存率(P>0.05),其复发率也无明显差异(P>0.05),手术并发症率明显增高(P<0.05);Ⅰ期高危患者,盆腔淋巴清扫术未能延长其生存期(P>0·05),但可减少复发的例数,并发症率无明显增多(P>0.05)。结论:特殊病理类型,腹腔细胞学阳性,手术-病理分期高,盆腔淋巴转移,深肌层浸润及CA125>100U/ml的患者预后较差(P<0.05)。Ⅰ期高危子宫内膜癌患者盆腔淋巴清扫术具有一定的临床意义。     

Endometrial cancer: what's new?

OBJECTIVES: New and much debated data of the endometrial cancer concerning the preoperative assessment of myometrial invasion, the surgical staging, and the adjuvant treatment. PATIENTS AND METHODS: Medline (1998-2002): searching for "endometrial carcinoma". RESULTS: The pap smears are useful when it is difficult to have a transvaginal ultrasonography or an MRI. We can perform the pap smears and the endometrial biopsy in the clinic. If a patient has pap smears with malignant cells or elevated preoperative CA 125, it probably is a cancer with poor prognostic factors. Surgical staging with abdominal and node evaluation is necessary. The MRI seems to be the best preoperative imaging because we have information about adnexal and abdominal metastases, pelvic or aortic nodes and the invasion of the myometrium. So it gives us information on the surgical route, and provides indication for a lymphadenectomy. The surgical staging is a part of the treatment of the endometrial cancer: an exploration of the peritoneal cavity, a pelvic lymphadenectomy, a para-aortic lymphadenectomy if the pelvic nodes are positive or if there are factors of bad prognosis (deep stage IC, grade 3, adnexal or abdominal involvement, serous carcinoma of the endometrium). It can be performed if technical conditions are correct. The adjuvant teletherapy in the documented stage IpN0 (surgical staging with pelvic lymphadenectomy) does not seem to be necessary. But we can perform an adjuvant brachytherapy (high-dose rate if it is possible) in patients with a high local recurrence (stage IC, stage I with grade 3, stage IB grade 2). CONCLUSION: The preoperative MRI is useful choosing the surgical approach, and the depth of the myometrial invasion, which can be an indication for a pelvic lymphadenectomy. The surgical staging must be a part of the treatment of the endometrial cancer. So the adjuvant teletherapy in patients with stage IpN0 documented should not be used.     

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 .     

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.     

Endometriumkarzinom im Stadium IB

The role of surgical lymph node dissection and adjuvant radiation therapy (RT) in early stage endometrial cancer is no longer clearly defined. The increased appreciation of lymphadenectomy and the absence of survival advantage from adjuvant RT have given rise to controversies over how patients should adequately be treated in stage IB endometrial cancer. Based on the available data in the literature, for stage IB grade 1 or 2, the risk of pelvic relapse is considered too low to justify pelvic RT. However, intravaginal RT (IVRT) should be recommended for those ≥ 60 years old or with lymphovascular invasion (LVI). For patients with stage IB grade 3 (and IC all grades), the treatment recommendation is mainly based on whether surgical lymph node staging was performed. These patients have—without surgical lymph node staging—a high risk of pelvic recurrence and should therefore primarily undergo relaparotomy for lymphadenectomy or pelvic RT as second choice. If these patients had a surgical lymph node staging, then IVRT alone is a reasonable alternative to pelvic RT. Overall survival may not be the only ideal endpoint for stage IB endometrial cancer since causes of death are mostly other than endometrial cancer. Conventional pelvic RT may be overtreatment in some patients, in particular in those patients with a large number of negative lymph nodes after lymphadenectomy. However, negative surgical staging should not be understood to mean that adjuvant RT can be omitted in all patients.     

Randomized study comparing two techniques of conization: cold knife versus loop excision

OBJECTIVE: The aim of this study was to analyze the prognostic significance of DNA ploidy in patients with endometrial cancer. METHODS: Between October 1988 and January 1997, DNA ploidy was determined prospectively in 208 women who were staged surgically by a standard protocol that included pelvic and para-aortic lymphadenectomy. Median follow-up was 48 months. RESULTS: Diploid tumors were identified in 154 (74%) patients and aneuploid tumors in 54 (26%). Patients with aneuploid tumors had a significantly higher prevalence of metastases to the cervix, adnexa, and omentum, malignant pelvic cytology, and advanced surgical stage. Patients with aneuploid tumors had a 4.5 times higher prevalence of pelvic lymph node metastases and a 5.8 times higher prevalence of para-aortic lymph node metastases. A significantly higher proportion of patients with aneuploid tumors was diagnosed with recurrent or progressive endometrial cancer (22.2 versus 6.5%, P = 0.002). Patients with aneuploid tumors had a significantly lower rate of survival from cancer death (P = 0.038) with 83% versus 94% surviving 5 years. CONCLUSION: Patients with aneuploid tumors are at high risk for lymph node metastases and should be surgically staged, including pelvic and para-aortic lymphadenectomy. Aneuploidy confers a risk for endometrial cancer death and these patients should be candidates for clinical trials evaluating treatment following surgery.