Incidence of metastasis in circumflex iliac nodes distal to the external iliac nodes in intermediate- and high-risk endometrial cancer

Objective

The aim of this study was to elucidate the incidence of metastasis in circumflex iliac nodes distal to the external iliac nodes (CINDEIN), which are also called suprainguinal nodes, in intermediate- and high-risk endometrial cancer. Removal of these nodes needs to be discussed from the viewpoint of patient's quality of life because removal of CINDEIN is strongly related to lower extremity lymphedema.

Methods

A retrospective chart review was carried out for 508 patients with intermediate- and high-risk endometrial cancer who were included in this study. We identified patients with lymph node metastasis. Lymph node sites were classified into four groups: (1) CINDEIN, (2) external iliac nodes, (3) Group A consisting of circumflex iliac nodes to the distal obturator nodes, internal iliac nodes, obturator nodes, cardinal ligament nodes (including deep obturator nodes), and sacral nodes, and (4) Group B consisting of common iliac nodes and para-aortic nodes. Logistic regression analysis was used to select risk factors for CINDEIN metastasis.

Results

In an analysis of 508 patients with intermediate- and high-risk disease, CINDEIN metastasis was found in fourteen (2.8%) of the patients. Multivariate analysis confirmed that high-risk histology (OR = 5.7, 95% CI = 1.2-16.1) and Group A node metastasis (OR = 9.7, 95% CI = 2.9-31.4) were independent risk factors for CINDEIN metastasis. None of the patients with G1 endometrioid adenocarcinoma had CINDEIN metastasis. Three (2.5%) of the patients with G2 endometrioid adenocarcinoma had CINDEIN metastasis and all of these three patients had other pelvic node metastasis.

Conclusion

Removal of CINDEIN can be eliminated in patients with G1 endometrial cancer and patients with G2 endometrial cancer who have no pelvic node metastasis.     

Clinical use of laparoscopic ultrasonography in detecting nodal metastasis in advanced-stage cervical carcinoma

Objective

To assess the clinical use of a laparoscopic ultrasound scan (LUS) to identify pelvic and para-aortic node metastasis in patients with advanced-stage cervical cancer.

Methods

After examination under general anesthesia and cystoscopy, LUS was used to examine the pelvic nodes of patients with advanced-stage cervical cancer. Abnormal nodes were excised before definitive treatment to confirm the nodal status. Patients without abnormal para-aortic nodes on preoperative computer tomography/magnetic resonance imaging in the past 3 years were surgically staged via laparoscopic extraperitoneal aortic node sampling, and the findings were correlated with LUS findings. The predictive values of abnormal pelvic nodes on LUS for pelvic and aortic node metastasis were determined.

Results

A total of 119 advanced-stage cervical cancer patients underwent LUS of pelvic nodes. Abnormal pelvic nodes were found in 62 (52.1%) patients, and metastasis was confirmed by histology in 38 (31.9%) patients. Three patients had micro-metastasis in para-aortic nodes, and all of these patients had abnormal pelvic lymph nodes on LUS.

Conclusion

Abnormal pelvic nodes are commonly found on LUS in patients with advanced-stage cervical cancer, and selective excision biopsy is needed to confirm pelvic node metastasis. Surgical staging of aortic nodes might be considered for patients with abnormal pelvic nodes on LUS.     

Para-aortic lymphadenectomy for primary fallopian tube cancer

Objective

To investigate the topography of lymph node spread and the need for para-aortic lymphadenectomy in primary fallopian tube cancer (PFTC).

Methods

Twenty-six women were diagnosed with PFTC at Cheil General Hospital and Women's Healthcare Center, Seoul, Korea, between March 1992 and November 2009. Of the 26 patients, we retrospectively analyzed 15 patients who underwent complete staging surgery, including bilateral pelvic and para-aortic lymphadenectomy.

Results

The median follow-up period was 57.9 months (range, 3-185 months) and the 5-year survival rate was 86.3%. Five (33.3%) patients were diagnosed with FIGO stage I, 1 (6.7%) with stage II, and 9 (60%) with stage III cancer. The median number of lymph nodes removed was 53.8 (range, 18-106 nodes). Four (26.7%) patients had nodal involvement: 2 patients with para-aortic lymph node involvement and 2 patients with both pelvic and para-aortic lymph node involvement. None of the patients was positive for pelvic lymph nodes alone.

Conclusion

A comprehensive para-aortic lymphadenectomy was necessary for accurate staging in PFTC.     

Sentinel lymph node mapping for endometrial cancer improves the detection of metastatic disease to regional lymph nodes

Objective

To compare the incidence of metastatic cancer cells in sentinel lymph nodes (SLN) vs. non-sentinel nodes in patients who had lymphatic mapping for endometrial cancer and to determine the contribution of metastases detected on ultrastaging to the overall nodal metastasis rate.

Methods

All patients who underwent lymphatic mapping for endometrial cancer were reviewed. Cervical injection of blue dye was used in all cases. Sentinel nodes were examined by routine hematoxylin and eosin (H&E), and if negative, by standardized institutional pathology protocol that included additional sections and immunohistochemistry (IHC).

Results

Between 09/2005 and 03/2010, 266 patients with endometrial cancer underwent lymphatic mapping. Sentinel node identification was successful in 223 (84%) cases. Positive nodes were diagnosed in 32/266 (12%) patients. Of those, 8/266 patients (3%) had the metastasis detected only by additional section or IHC as part of SLN ultrastaging. Excluding the 8 cases with positive SLN on ultrastaging only, 24/801 (2.99%) SLN and 30/2698 (1.11%) non-SLN were positive for metastatic disease (p = 0.0003).

Conclusion

Using a cervical injection for mapping, metastatic cells from endometrial cancer are three times as likely to be detected in SLN than in the non-sentinel nodes. This finding strongly supports the concept of lymphatic mapping in endometrial cancer to fine tune the nodal dissection topography. By adding SLN mapping to our current surgical staging procedures we may increase the likelihood of detecting metastatic cancer cells in regional lymph nodes. An additional benefit of incorporating pathologic ultrastaging of SLN is the detection of micrometastasis, which may be the only evidence of extrauterine spread.     

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.     

Diagnostic accuracy of sentinel node in endometrial cancer by using hysteroscopic injection of radiolabeled tracer

Objective

Retrospective and perspective series have shown the feasibility of sentinel lymph-node (SLN) identification of pelvic nodes in endometrial cancer using a cervical injection of tracers. We designed a perspective study to assess the detection rate and diagnostic accuracy of the SLN procedure by means of hysteroscopic injection of a radiolabeled tracer in endometrial cancer patients.

Methods

Patients with endometrial cancer underwent hysteroscopic technetium injection. SLN assessment was performed intraoperatively. A systematic pelvic and paraaortic dissection was carried out thereafter. SLNs were examined by standard and immunochemistry methods. The primary endpoint was estimation of sensitivity and negative predictive value (NPV) of sentinel-node biopsy.

Results

From 2005 to 2010, 80 consecutive patients entered the study. No severe complications occurred during or after the injection or during surgical SLN biopsy. At least one SLN was detected in 76 of the 80 eligible patients. Fifty nine patients were evaluable according to the study protocol. Ten of these patients (17%) had node metastases. Thirty-three patients (56%) had SLN in the para-aortic area. NPV was 98% (95% CI 89.4-100) and sensitivity 90% (55.5-99.8).

Conclusions

SLN detection for endometrial cancer patients has a high sensitivity and NPV when injection is carried out by hysteroscopy. The occurrence of a 56% of sentinel node in paraaortic area may suggest a better sensitivity in this area using hysteroscopic injection compared to cervical injection.     

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.     

Accuracy of sentinel lymph node detection following intra-operative cervical injection for endometrial cancer: A prospective study

Objective

The objective of this study is to evaluate the detection rate and diagnostic accuracy of sentinel lymph node (SLN) mapping using intra-operative cervical injection of filtered 99mTc-sulfur colloid (99mTc-SC) and patent blue in patients with endometrial cancer.

Methods

Prospective evaluation of the first 100 endometrial cancer patients undergoing SLN mapping using cervical injection of patent blue combined with filtered 99mTc-SC in the operating room was done. Patients underwent robotic-assisted lymphatic mapping with frozen section, hysterectomy, BSO, and completion bilateral lymphadenectomy (including para-aortic nodes in grade 2 and 3 tumors).

Results

At least one SLN was detected in 92% of patients; in 66 of these (72%) bilateral SLN were detected, and in 15 cases the SLN was in the para-aortic area. Eleven percent of all patients had lymph node metastases, and 4 of which had pre-operative grade 1 tumor. The SLN was the only positive node in 44% of the cases with positive nodes. Sensitivity was 89% with 1 false negative result, yielding a negative predictive value of 99% (95% CI 93-100). Specificity was 100% (95% CI 94-100), and positive predictive value was 100% (95% CI 60-100). No complications or anaphylactic reactions were noted.

Conclusions

Intra-operative SLN biopsy, using cervical injection of patent blue and filtered 99mTc-SC in endometrial cancer patients is feasible and yields adequate detection rates.     

Lymphovascular space invasion is an independent risk factor for nodal disease and poor outcomes in endometrioid endometrial cancer

Objective

Adjuvant radiotherapy improves local control but not survival in women with endometrial cancer. This benefit was shown in staged patients with “high intermediate risk” (HIR) disease. Other studies have challenged the need for systematic staging including lymphadenectomy. We sought to determine whether LVSI alone or in combination with other histologic factors predicts lymph node (LN) metastasis in patients with endometrioid endometrial cancer.

Methods

A retrospective review was conducted of patients with endometrioid endometrial carcinoma who had confirmed presence/absence of LVSI and clinicopathologic data necessary to identify HIR criteria. Kaplan-Meier curves were generated and univariate and multivariate analyses performed as appropriate.

Results

We identified 757 eligible patients and 628 underwent systematic lymphadenectomy for staging purposes. In the surgically staged group, 242 (38%) patients met uterine HIR criteria and 196 (31%) had LVSI. Both HIR and LVSI were significantly associated with LN metastasis. Among the HIR positive group, 59 had LN metastasis (OR 4.46, 95% CI 2.72-7.32, P < 0.0001). Sixty-six LVSI positive patients had nodal metastasis (OR 11.04, 95% CI 6.39-19.07, P < 0.0001). The NPV of LVSI and HIR negative specimens was 95.6% and 93.4% respectively. In multivariate analysis, PFS and OS were significantly reduced in both LVSI positive (P < 0.0001) and HIR patients (P < 0.0001) when compared to patients who were LVSI and HIR negative.

Conclusions

HIR status and LVSI are highly associated with LN metastasis. These features are useful in assessing risk of metastatic disease and may serve as a surrogate for prediction of extrauterine disease.     

Feasibility of laparoscopic extraperitoneal pelvic lymphadenectomy in gynecologic malignancies

Objective

The aim of this study is to evaluate the feasibility of laparoscopic extraperitoneal pelvic lymphadenectomy (LEPL) in gynecologic malignancies.

Methods

Twenty-nine women with cervical, ovarian or endometrial cancer underwent laparoscopic extraperitoneal pelvic lymphadenectomy between July 2008 and December 2010. The operating time, nodal yield, blood loss and complications were recorded.

Results

The number of patients with cervical, ovarian and endometrial carcinoma was 14, 3 and 12, respectively. The median age of patients was 48.9 ± 12.6 years. The median body mass index was 25.6 ± 4.8. Conversion to the transperitoneal laparoscopic approach was necessary in 6 patients for peritoneal tears causing CO₂ gas leakage. Among the remaining 23 patients, the median operating time for laparoscopic extraperitoneal pelvic lymphadenectomy was 69 min (range 50-126 min), and the median estimated blood loss was 20 ml (range 5-105 ml). The median total number of resected nodes was 26 (range 14-42), and complications related to the procedure were rare.

Conclusions

Laparoscopic extraperitoneal pelvic lymphadenectomy is a feasible and safe procedure. It can be used in gynecologic malignancies.     

Robotically assisted fluorescence-guided lymph node mapping with ICG for gynecologic malignancies: a feasibility study

Objective

Traditional techniques of sentinel lymph node (SLN) mapping for endometrial and cervical cancer present challenges which may be overcome with newer technologies such as near infrared (NIR) imaging of the fluorescent dye Indocyanine green (ICG). We performed a feasibility and dose-finding study to define the dose of ICG required to identify pelvic and para-aortic sentinel lymph nodes with robotically assisted endoscopic NIR imaging after cervical injection.

Methods

20 subjects with cervical or endometrial carcinoma were prospectively enrolled for SLN mapping. ICG was injected into the cervical stroma at 3 o'clock and 9 o'clock Data was collected for the number of nodes identified, the location of SLN's, the duration of procedure and the pathology characteristics of the SLN's compared to the non-sentinel lymph nodes.

Results

20 subjects received cervical injection with at least one SLN observed in 17 subjects. 15 of the 17 subjects who received 1 mg injections of ICG mapped a SLN for an observed detection rate of 88% (95% CI is (64%,99%)). A median of 4.5 SLN's was identified per patient. Three patients had lymphatic metastases, one of whom had a positive SLN. No adverse events were identified.

Conclusions

A 1 mg cervical injection of ICG identified a SLN in 88% of patients (95% CI is (64%, 99%)). Robotically assisted fluorescence imaging is a feasible, safe, time efficient and reliable method for lymphatic mapping in early stage cervical and endometrial cancer.     

Intra-operative detection of nodal metastasis in early stage cervical cancer: a survey of the practice patterns of SGO members

Objectives

To determine the practice patterns of members of Society of Gynecologic Oncologists (SGO) in different clinical situations involving the intra-operative detection of nodal metastasis in early stage cervical cancer.

Methods

A study questionnaire was mailed to the current members of SGO (n = 874). Data were collected using an internet survey database. Frequency distributions were determined, and non parametric tests were performed.

Results

Thirty percent SGO members responded (n = 274). Only 38.6% routinely performed an intra-operative frozen section evaluation of the lymph nodes. Of these; most (79%) did not abort the radical hysterectomy (RH) for an isolated microscopically positive pelvic lymph node. The likelihood of aborting RH for microscopic nodal involvement increased however with number of positive pelvic lymph nodes (21% with 1, 40% with 2-3, and 61% with > 3 positive pelvic lymph nodes), involvement of para-aortic lymph nodes (61%), or bilaterally positive lymph nodes (54%). Similarly, a large number did not complete the RH due to gross involvement of pelvic (45%) or para-aortic lymph node/s (69%). Most (90%) completed the lymphadenectomy before aborting RH. When completing RH, the majority tailored its extent to perform a less radical resection. Variables significantly associated with the likelihood of completing RH in different clinical situations included: location of current practice (West), practice type (private), years in practice (> 15 years), and number of cases seen per year (> 10/month).

Conclusion

Practice patterns of SGO members are considerably diverse, which is reflective of the conflicting evidence available in the literature. Well designed studies are required to determine the best overall approach.     

Tracer injection sites and combinations for sentinel lymph node detection in patients with endometrial cancer

Objective

The aim of the present study was to clarify the most effective combination of injected tracer types and injection sites in order to detect sentinel lymph nodes (SLNs) in early endometrial cancer.

Patients and methods

The study included 100 consecutive patients with endometrial cancer treated at Tohoku University Hospital between June 2001 and December 2012. The procedure for SLN identification entailed either radioisotope (RI) injection into the endometrium during hysteroscopy (55 cases) or direct RI injection into the uterine cervix (45 cases). A combination of blue dye injected into the uterine cervix or uterine body intraoperatively in addition to preoperative RI injection occurred in 69 of 100 cases. All detected SLNs were recorded according to the individual tracer and the resultant staging from this method was compared to the final pathology of lymph node metastases including para-aortic nodes.

Results

SLN detection rate was highest (96%) by cervical RI injection; however, no SLNs were detected in para-aortic area. Para-aortic SLNs were detected only by hysteroscopic RI injection (56%). All cases with pelvic lymph node metastases were detected by pelvic SLN biopsy. Isolated positive para-aortic lymph nodes were detected in 3 patients. Bilateral SLN detection rate was high (96%; 26 of 27 cases) by cervical RI injection combined with dye.

Conclusion

RI injection into the uterine cervix is highly sensitive in detection of SLN metastasis in early stage endometrial cancer. It is a useful and safe modality when combined with blue dye injection into the uterine body.     

Mucinous histology is a risk factor for nodal metastases in endometrial cancer

Objectives

Mucinous adenocarcinoma of the endometrium (MUC) is a rare histological variant of endometrial carcinoma accounting for 1-9% of endometrioid tumors. Few studies have characterized its clinical behavior. This is a case-control study at a single institution comparing the risk factors and clinical course of MUC relative to endometrioid adenocarcinoma.

Methods

A case-control study was performed including patients treated for endometrial cancer between 1996 and 2006. 41 cases of mucinous adenocarcinoma were identified. Each case was matched with two controls of endometrioid histology by age and histological grade. Cases and controls were compared with regard to known risk factors for endometrial cancer and the extent of disease at diagnosis. Chi-square tests were used to compare proportions and Student's t-tests for the comparison of means. Multivariate regression was used to identify the independent predictors of lymph node metastases. Overall survival was calculated using the Kaplan-Meier method and compared with the Log-rank test. p < .05 was considered significant for all tests.

Results

Cases and controls were matched by age and FIGO grade and were found to be similar in regard to ethnicity, body mass index and medical history. No significant difference in myometrial invasion (MI) > 50% or the presence of lymph-vascular space invasion was found between cases and controls, however, 17% of patients with MUC had lymph node metastases compared to 3% of controls (p = .01). Multivariate analysis controlling for both tumor grade and depth of MI identified mucinous histology as an independent predictor of lymph node metastasis (p = .02). There was no difference in adjuvant treatment, recurrence rate or survival between the two groups.

Conclusion

Mucinous differentiation was found to be an independent predictor of lymph node metastasis in the study population. Comprehensive surgical staging including retroperitoneal node dissection should be strongly considered in all endometrial cancer patients with predominantly mucinous histology.     

Incidence of metastasis in the circumflex iliac nodes distal to the external iliac nodes in ovarian cancer

Objective

The circumflex iliac nodes distal to the external iliac nodes (CINDEINs) are included in the regional lymph nodes that are commonly dissected during systematic lymphadenectomy for ovarian cancer. Because in recent years CINDEIN dissection has been reported as a significant risk factor for postoperative lower limb lymphedema, we investigated the validity of omitting the CINDEIN dissection by evaluating the distribution pattern of positive lymph nodes in ovarian cancer, in order to improve postoperative quality of life (QOL).

Methods

We performed a retrospective chart review of 142 patients with ovarian cancer who had undergone systematic lymphadenectomy between 1995 and 2010. We assessed the distribution pattern of lymph node metastasis and the presence of CINDEIN metastasis according to the pT classification (pT1, pT2, and pT3).

Results

Of the 142 patients, 71, 21, and 50 were classified into pT1, pT2, and pT3, respectively. The lymph nodes most frequently involved were the para-aortic lymph nodes superior to the mesenteric artery (14%), followed by the obturator nodes (11%), the internal iliac nodes (9.4%), and the common iliac nodes (7.4%). Although the frequency of CINDEIN metastasis was 5.3% (6 of 114 cases with CINDEIN dissection), no metastasis to the CINDEINs was observed in pT1 patients.

Conclusions

It may be acceptable to omit CINDEIN dissection during surgery for pT1 ovarian cancer in view of postoperative QOL.     

Establishing a sentinel lymph node mapping algorithm for the treatment of early cervical cancer

Objective

To establish an algorithm that incorporates sentinel lymph node (SLN) mapping to the surgical treatment of early cervical cancer, ensuring that lymph node (LN) metastases are accurately detected but minimizing the need for complete lymphadenectomy (LND).

Methods

A prospectively maintained database of all patients who underwent SLN procedure followed by a complete bilateral pelvic LND for cervical cancer (FIGO stages IA1 with LVI to IIA) from 03/2003 to 09/2010 was analyzed. The surgical algorithm we evaluated included the following: 1. SLNs are removed and submitted to ultrastaging; 2. any suspicious LN is removed regardless of mapping; 3. if only unilateral mapping is noted, a contralateral side-specific pelvic LND is performed (including inter-iliac nodes); and 4. parametrectomy en bloc with primary tumor resection is done in all cases. We retrospectively applied the algorithm to determine how it would have performed.

Results

One hundred twenty-two patients were included. Median SLN count was 3 and median total LN count was 20. At least one SLN was identified in 93% of cases (114/122), while optimal (bilateral) mapping was achieved in 75% of cases (91/122). SLN correctly diagnosed 21 of 25 patients with nodal spread. When the algorithm was applied, all patients with LN metastasis were detected; with optimal mapping, bilateral pelvic LND could have been avoided in 75% of cases.

Conclusions

In the surgical treatment of early cervical cancer, the algorithm we propose allows for comprehensive detection of all patients with nodal disease and spares complete LND in the majority of cases.     

High-grade endometrial cancer: Revisiting the impact of tumor size and location on outcomes

Objective

Research on tumor size (TS) and intracavitary tumor location in endometrial cancer has focused primarily on low-grade tumors. Data in patients with high-grade histology are limited. Our goal is to determine if TS or lower uterine segment (LUS) involvement, is associated with nodal disease and recurrence in women with high-grade endometrial cancer.

Methods

This is an IRB-approved, multi-institutional cohort study of patients with clinically early-stage, high-grade endometrial cancer who underwent comprehensive surgical staging. Records were reviewed for demographic, pathologic, and treatment data. Nodal involvement and recurrence as a function of TS and location were estimated with odds ratios and hazard ratios.

Results

From 2005 to 2012, 208 patients were identified. Of these, 188 patients had tumor location and 183 had TS reported. There were 75 endometrioid (36.1%), 35 serous (16.8%), 12 clear cell (5.8%), and 26 carcinosarcoma (12.5%) cases, and 60 (28.8%) undifferentiated or mixed histologies. There were 55 recurrences (median follow up 17.2 mo). LUS tumors were associated with pelvic and para-aortic nodal disease (OR 3.83, 95% CI 1.70–8.60, p < 0.01, OR 5.13, 95% CI 1.96–13.45, p < 0.01). TS ≥ 2 cm was associated with pelvic nodal disease (27.4% vs. 0%, p = 0.01; OR 10.00, p = 0.01). Neither TS nor LUS location was independently associated with recurrence.

Conclusions

In high-grade endometrial cancers, tumor involvement of the LUS and TS > 2 cm was associated with pelvic nodal disease, and LUS involvement was also significantly associated with para-aortic nodal disease. There was no association between LUS involvement or TS > 2 cm and recurrence.     

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.     

Systematic pelvic and aortic lymphadenectomy in intermediate and high-risk endometrial cancer: Lymph-node mapping and identification of predictive factors for lymph-node status

Objective

To systematically assess the metastatic pattern of intermediate- and high-risk endometrial cancer in pelvic and para-aortic lymph-nodes and to evaluate risk factors for lymph-node metastases.

Study Design

Between 01/2005 and 01/2009 62 consecutive patients with intermediate- and high-risk endometrial cancer who underwent a systematic surgical staging including pelvic and para-aortic lymphadenectomy were enrolled into this study. Patients’ characteristics, histological findings, lymph-node localization and involvement, surgical morbidity and relapse data were analyzed. Univariate analysis was performed to define risk factors for lymph-node metastasis.

Results

Of the 13 patients (21%) with positive lymph-nodes (N1), 8 (61.5%) had both pelvic and para-aortic lymph-nodes affected, 2 (15.4%) only para-aortic and 3 (23%) only pelvic lymph-node metastases. Overall, 54% of the N1-patients had positive lymph-nodes above the inferior mesenteric artery (IMA) to the level of the renal veins. Univariate analysis revealed lymph vascular space invasion (p-value: <0.001), vascular-space-invasion (p-value: <0.001) and incomplete tumor resection (p-value: 0.008) as significant risk factors for N1-status. Overall and progression-free survival was not significantly different between N1- and N0-patients.

Conclusions

Since the proportion of N1-endometrial cancer patients with positive para-aortic lymph-nodes is, at 76%, considerably high, and more than half of them have affected lymph-nodes above the IMA-level, lymphadenectomy for endometrial cancer should be extended up to the renal veins, when indicated. The therapeutic impact of systematic lymphadenectomy on overall and progression-free survival has still to be evaluated in future prospective randomized studies.     

A novel low dose fractionation regimen for adjuvant vaginal brachytherapy in early stage endometrioid endometrial cancer

Purpose

To evaluate local control, survival and toxicity in patients with early-stage endometrioid adenocarcinoma of the uterus treated with adjuvant high-dose-rate (HDR) vaginal brachytherapy (VB) alone using a novel low dose regimen.

Methods

We reviewed records of 414 patients with stage IA to stage II endometrial adenocarcinoma treated with VB alone from 2005 to 2011. Of these, 157 patients with endometrioid histology received 24 Gy in 6 fractions of HDR vaginal cylinder brachytherapy and constitute the study population. Dose was prescribed at the cylinder surface and delivered twice weekly in the post-operative setting. Local control and survival rates were calculated by the Kaplan-Meier method.

Results

All 157 patients completed the prescribed course of VB. Median follow-up time was 22.8 months (range, 1.5-76.5). Two patients developed vaginal recurrence, one in the periurethral region below the field and one in the fornix after treatment with a 2.5-cm cylinder. Three patients developed regional recurrence in the para-aortic region. Two patients developed distant metastasis (lung and carcinomatosis). The 2-year rate of vaginal control was 98.6%, locoregional control was 97.9% and disease-free survival was 96.8%. The 2-year overall survival rate was 98.7%. No Grade 2 or higher vaginal, gastrointestinal, genitourinary or skin long-term toxicity was reported for any patient.

Conclusion

Vaginal brachytherapy alone in early-stage endometrial cancer provides excellent results in terms of locoregional control and disease-free survival. The fractionation scheme of 24 Gy in 6 fractions prescribed to the cylinder surface was well-tolerated with minimal late toxicity.