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.     

卵巢癌腹主动脉旁淋巴结清除术与生存率的关系

目的:探讨上皮性卵巢癌患者行腹主动脉旁淋巴结清除术与其生存预后的关系。方法:回顾分析卵巢癌肿瘤细胞减灭术的80例患者,将其中行腹主动脉旁淋巴结(PAN)+盆腔淋巴结(PLN)清除术分为A组(30例),仅行PLN清除术者分为B组(50例),分析PAN清除与患者生存预后的相关性。结果:行卵巢肿瘤细胞减灭术的80例患者中,32例(40.0%)发生淋巴结转移。A组中19例发生淋巴结转移,其中仅PAN阳性7例,仅PLN阳性3例,PAN和PLN均阳性9例;B组中13例发生PLN转移。A与B组患者的淋巴结转移与临床分期、肿瘤细胞分化程度和组织学类型显著相关(P0.05)。A组中淋巴结转移部位以PAN最多16例,其余依次为髂内、闭孔、髂总、腹股沟及髂外淋巴结。A组患者的3年、5年生存率分别为77.9%和46.7%,均高于B组(69.0%和39.2%),但无显著差异(P0.05)。A与B组患者中转移至PLN者的3年生存率分别是68.5%和41.4%,5年生存率是49.7%和26.4%,两组比较差异显著(P=0.044)。A组患者中淋巴结阳性与阴性患者3年生存率分别为43.5%和72.7%,5年生存率是27.2%和58.5%,差异显著(P=0.048)。Cox模型单因素分析提示,淋巴结状态对患者的生存率有影响(P0.01),而且是死亡风险因素。结论:腹主动脉旁淋巴结的清除对改善卵巢癌患者预后起着重要作用。     

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.     

Initial failure site according to primary treatment with or without para-aortic lymphadenectomy in endometrial cancer

Objective

The objective of this study was to compare the initial failure sites in patients with endometrial cancer who underwent surgical treatment including pelvic lymphadenectomy with or without para-aortic lymphadenectomy.

Methods

A retrospective chart review was carried out for 657 endometrial cancer patients with no residual disease after initial treatments including lymphadenectomy at two tertiary centers between 1987 and 2004. Surgical treatment at one institute included pelvic lymphadenectomy (PLX) without para-aortic lymphadenectomy (PALX), while surgical treatment including PLX + PALX was routinely performed at the other institute. We identified patients with recurrence and evaluated initial failure sites. Rates of recurrence in the respective sites were compared according to the type of lymphadenectomy.

Results

Of the 657 patients, 103 (15.7%) suffered recurrence. There was no significant difference between the rate of intrapelvic recurrence in the PLX alone group and that in the PLX + PALX group (4.7% vs. 2.9%, p = 0.22). The rate of extrapelvic recurrence in the PLX alone group was significantly higher than that in the PLX + PALX group (16.1% vs. 6.2%, p < 0.0001), and the rate of para-aortic node (PAN) recurrence in the PLX alone group was also significantly higher than that in the PLX + PALX group (5.1% vs. 0.6%, p = 0.0004). In the analysis of patients who received adjuvant chemotherapy, the rate of PAN recurrence in the PLX alone group was significantly higher than that in the PLX + PALX group (9.5% vs. 1.3%, p = 0.0036).

Conclusion

PAN recurrence was a failure pattern peculiar to the PLX alone group. Adjuvant chemotherapy might not be able to replace surgical removal as a treatment for metastatic lymph nodes.     

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.     

An unusual case of recurrent endometrial cancer presented with isolated cervical lymph node metastasis

Endometrial cancer (EC) is the most common malignancy of the female genital tract. Lymph node involvement is one of the major prognostic factors. Therefore, pelvic and paraaortic lymph nodes dissection is a part of the surgical management of these patients. Isolated peripheral lymph node metastasis has not been previously reported as a finding of recurrence in EC. We report a 67-year-old woman with recurrent EC presented with an isolated cervical lymph node metastasis (ICLM). Following the combination chemotherapy of doxorubicin, cisplatin and cyclophosphamide, her cervical lymph node was completely regressed. To our knowledge, this is the first case of recurrent EC presented with ICLM. We suggest that for women with EC who had isolated peripheral lymphadenopathies, peripheral lymph node metastasis should be considered as the finding of recurrence in patient with EC.     

Sentinel lymph node biopsy in endometrial cancer: meta-analysis of 26 studies

Objective

The validity of the sentinel lymph node (SLN) procedure for the assessment of nodal status in patients with endometrial cancer is unclear. We aimed to assess the diagnostic performance of this procedure.

Methods

We searched the PubMed and Embase databases for studies published before June 1, 2011. Eligible studies had a sample size of at least 10 patients, and reported the detection rate and/or sensitivity of the SLN biopsy.

Results

We identified 26 eligible studies, which included 1101 SLN procedures. The overall weighted-mean number of harvested SLNs was 2.6. The detection rate and the sensitivity were 78% (95% confidence interval [CI] = 73%-84%) and 93% (95% CI = 87%-100%), respectively. Significant between-study heterogeneity was observed in the analysis of the detection rate (I-squared statistic, 80%). The use of pericervical injection was correlated with the increase of the detection rate (P = 0.031). The hysteroscopic injection technique was associated with the decrease of the detection rate (P = 0.045) and the subserosal injection technique was associated with the decrease of the sensitivity (P = 0.049), if they were not combined with other injection techniques. For the detection rate, significant small-study effects were noted (P < 0.001).

Conclusions

Although SLN biopsy has shown good diagnostic performance in endometrial cancer, such performance should be interpreted with caution because of significant small study effects. Current evidence is not yet sufficient to establish the true performance of SLN biopsy in endometrial cancer.     

Contemporary analysis of pelvic and para-aortic metastasis in endometrial cancer using the SEER registry

Objective

To determine the incidence of regional lymph node involvement for early-stage endometrial cancer by using the Surveillance, Epidemiology, and End Results (SEER) registry.

Methods

In a retrospective study, data were analyzed from patients who were diagnosed with stage IA–IIB endometrioid adenocarcinoma and were treated between 1998 and 2003. The incidence of pelvic and para-aortic lymph node involvement was determined.

Results

Data were analyzed from 4052 patients. Incidences of pelvic and para-aortic lymph node metastases were: 1% and 0% in stage IA, grade 1 disease; 2% and 0% in IA, grade 2; 2% and 1% in IA, grade 3; 2% and 0% in IB, grade 1; 3% and 1% in IB, grade 2; 3% and 2% in IB, grade 3; 7% and 3% in IC, grade 1; 8% and 5% in IC, grade 2; 12% and 8% in IC, grade 3; 7% and 3% in IIA, grade 1; 10% and 4% in IIA, grade 2; 10% and 5% in IIA, grade 3; 8% and 4% in IIB, grade 1; 13% and 8% in IIB, grade 2; and 19% and 12% in IIB, grade 3.

Conclusion

Incidences of pelvic and para-aortic metastases were lower than previously reported. Patients at higher stages and grades had a 10% or higher risk of lymph node involvement and might benefit from aggressive therapy.     

Extended experience in the use of laparoscopic ultrasound to detect pelvic nodal metastasis in patients with cervical carcinoma

OBJECTIVE: To evaluate the use of laparoscopic ultrasound (USG) to detect pelvic nodal metastasis in patients with early stage cervical carcinoma. METHODS: Laparoscopic USG was used to search for pelvic lymph node metastasis in stage Ia2 to IIa cervical carcinoma patients before radical hysterectomy. Suspicious lymph nodes identified by laparoscopic USG were removed laparoscopically for pathological confirmation by frozen section. If nodal metastasis was diagnosed, radical hysterectomy would be cancelled but enlarged lymph nodes were removed preferably by laparoscopic approach before closing the abdomen. These patients were treated with radiotherapy after recovering from the surgery. By comparing the laparoscopic USG and pathological findings of lymph nodes removed with or without radical hysterectomy, diagnostic accuracy of laparoscopic USG was determined. RESULTS: Ninety-three patients were recruited and the final analysis included 90 patients. Laparoscopic USG found suspicious lymph nodes in 17 patients and nodal metastases were confirmed pathologically in 14 of them. Three patients with macroscopic and five patients with microscopic pelvic nodal metastases were missed by laparoscopic USG. The accuracy, sensitivity, specificity, positive and negative predictive value of laparoscopic USG in detecting pelvic lymph node metastasis were 87.8%, 63.6%, 95.6%, 82.4%, and 89%, respectively. Macroscopic metastatic nodes were successfully removed laparoscopically in 11 out of 14 patients and laparotomy was required for the other three patients. CONCLUSIONS: Laparoscopic USG can be performed with no major morbidity. This technique is sensitive in detecting macroscopic but not microscopic metastatic pelvic lymph nodes. Removal of macroscopic metastatic nodes identified via laparoscopic USG via laparoscopic approach could be accomplished in majority of patients.     

Prospective assessment of the prevalence of pelvic,paraaortic and high paraaortic lymph node metastasis in endometrial cancer

Objective

To prospectively define the prevalence of lymph node metastasis (LNM) in at risk endometrial cancer (EC).

Methods

From 2004 to 2008, frozen section based Mayo Criteria prospectively identified patients “not at-risk” of LNM (30% EC population; grade I/II, < 50% myometrial invasion and tumor diameter ≤ 2 cm) where lymphadenectomy was not recommended. The remaining 70% EC cohort was considered “at-risk” of LNM; where a systematic pelvic and infrarenal paraaortic lymphadenectomy was recommended. Patients were prospectively followed. The area between renal vein and inferior mesenteric artery (IMA) was labeled as high paraaortic area. For calculating the prevalence of LNM in high paraaortic area, the denominator was the population with known anatomic location of nodal tissue in relation to the IMA.

Results

Of the 742 patients, 514 were at risk; of which 89% underwent recommended lymphadenectomy. A mean (± standard deviation) of 36 (± 14) pelvic and 18 (± 9) paraaortic nodes were harvested. The prevalence of pelvic and paraaortic LNM was 17% and 12%, respectively. In presence of pelvic LNM, 51% had paraaortic LNM. In absence of pelvic LNM, 3% had paraaortic LNM; of which 67% was located exclusively in high paraaortic area. Among patients with paraaortic LNM, 88% had high paraaortic LNM; and 35% had only high paraaortic LNM. The cases of paraaortic LNM with negative pelvic nodes seemed to cluster in moderate to high grade endometrioid EC with ≥ 50% myometrial invasion.

Conclusion

We present reference data for the prevalence of LNM in at-risk EC patients to guide lymphadenectomy decisions for clinical and research purposes.     

Sentinel lymph node mapping with pathologic ultrastaging: A valuable tool for assessing nodal metastasis in low-grade endometrial cancer with superficial myoinvasion

Objective

To report the incidence of nodal metastases in patients presenting with presumed low-grade endometrioid adenocarcinomas using a sentinel lymph node (SLN) mapping protocol including pathologic ultrastaging.

Methods

All patients from 9/2005 to 12/2011 who underwent endometrial cancer staging surgery with attempted SLN mapping for preoperative grade 1 (G1) or grade 2 (G2) tumors with < 50% invasion on final pathology, were included. All lymph nodes were examined with hematoxylin and eosin (H&E). Negative SLNs were further examined using an ultrastaging protocol to detect micrometastases and isolated tumor cells.

Results

Of 425 patients, lymph node metastasis was found in 25 patients (5.9%) on final pathology—13 cases on routine H&E, 12 cases after ultrastaging. Patients whose tumors had a DMI < 50% were more likely to have positive SLNs on routine H&E (p < 0.005) or after ultrastaging (p = 0.01) compared to those without myoinvasion.

Conclusions

Applying a standardized SLN mapping algorithm with ultrastaging allows for the detection of nodal disease in a presumably low-risk group of patients who in some practices may not undergo any nodal evaluation. Ultrastaging of SLNs can likely be eliminated in endometrioid adenocarcinoma with no myoinvasion. The long-term clinical significance of ultrastage-detected nodal disease requires further investigation as recurrences were noted in some of these cases.     

Magnetic resonance imaging to identify risk of lymph node metastasis in patients with endometrial cancer

Objective

To assess the value of magnetic resonance imaging (MRI) to identify endometrial cancer patients at risk of lymph node metastasis.

Methods

Retrospective review of data from 108 patients with clinical stage I endometrial cancer who underwent preoperative MRI and were treated surgically. Patients at risk of lymph node metastasis were defined as those who had more than 50% myometrial infiltration or cervical invasion. Preoperative MRI reports were compared with final pathologic results.

Results

The mean age of the patients was 69.5 years and most patients had endometrioid cancer. On final pathologic analysis, 59 patients had deep myometrial infiltration or cervical invasion. For diagnosis of deep myometrial infiltration, cervical invasion, or both, MRI sensitivity and specificity were 56% and 85%; 47% and 83%; and 67% and 77%, respectively.

Conclusion

MRI has limited value in identifying patients with endometrial cancer who are at risk of lymph node metastasis. Minimally invasive laparoscopic lymph node staging should be undertaken when it is feasible.     

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.     

Intra-operative frozen section results reliably predict final pathology in endometrial cancer

Objectives

Typically, complete surgical staging is necessary for patients with high-risk endometrial cancer. However, patients with low-risk disease may be able to avoid lymphadenectomy and its associated morbidity. We sought to evaluate the agreement rates between the intra-operative frozen sections (FSs) and the final paraffin sections (PSs) at our institution, and to determine if this was a reliable method for guiding our intra-operative decision-making with regard to the necessity of lymphadenectomy.

Materials and methods

116 patients with a pre-operative diagnosis of endometrioid adenocarcinoma of the uterus or complex atypical hyperplasia (CAH) underwent surgery at our institution. Demographic data, as well as information on stage, grade, histology and depth of invasion determined at FS and on PS were collected. Cohen's kappa statistic was used to assess the agreement rate between FS and final PS with regard to depth of invasion, grade, and histology.

Results

Our correlation rate between FS and final PS for histologic subtype, grade, and depth of myometrial invasion was 97.5%, 88%, and 98.2% respectively. Seven cases identified as complex atypical hyperplasia on FS were later determined to be cancerous on final PS, resulting in two patients being undertreated.

Conclusions

Our results support the use of FS analysis as a means to guide intra-operative decisions regarding lymphadenectomy. Determination of histologic subtype, depth of invasion and grade is reliable at our institution, and demonstrates high concordance rates between FS and PS. These factors should be used to guide intra-operative decision-making regarding the necessity of a lymphadenectomy in patients with endometrial cancer.     

子宫内膜癌腹膜后淋巴结转移相关因素分析

目的:探讨预测子宫内膜癌腹膜后淋巴结转移的指标,以期为确定子宫内膜癌手术范围提供参考。方法:回顾分析1997年1月至2006年12月初治为手术治疗的641例子宫内膜癌患者的临床与病理资料,单因素分析用χ2检验和Fish确切概率法,多因素分析用Logistic回归模型。结果:经多因素分析显示,病理分级G3、深肌层浸润、附件转移对预测子宫内膜癌盆腔淋巴结(pelvic lymph node,PLN)转移具有统计学意义;盆腔淋巴结转移与腹主动脉旁淋巴结(para-aortic lymph node,PALN)转移显著相关。结论:病理分级G3、深肌层浸润、附件转移是子宫内膜癌盆腔淋巴结转移的重要预测因素;盆腔淋巴结转移对预测腹主动脉旁淋巴结转移具有重要意义。病理分级G3、深肌层浸润、附件转移的子宫内膜癌患者应行盆腔淋巴结清扫术,并根据术中患者的盆腔淋巴结状况决定是否行腹主动脉旁淋巴结清扫术。     

Prediction model for para-aortic lymph node metastasis in patients with locally advanced cervical cancer

Objective

Concurrent chemoradiotherapy is usually administered to patients with locally advanced cervical cancer (LACC). Extended-field chemoradiotherapy is required if para-aortic lymph node (PALN) metastasis is detected. This study aimed to construct a prediction model for PALN metastasis in patients with LACC before definitive treatment.