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.     

Should stage IIIC ovarian cancer be further stratified by intraperitoneal vs. retroperitoneal only disease?: a Gynecologic Oncology Group study

Objective

To examine whether clinical outcomes varied with intraperitoneal (IP) and/or retroperitoneal (RP) involvement in stage IIIC epithelial ovarian cancer (EOC) patients with microscopic residual disease after cytoreduction.

Methods

Retrospective review was performed for EOC patients enrolled in Gynecologic Oncology Group (GOG)-182 who underwent primary cytoreduction to microscopic residual disease. Patients were divided into 3 groups: stage IIIC by lymphadenopathy with < 2 cm IP spread (RP); > 2 cm IP spread and negative nodes (IP/RP−); and > 2 cm IP dissemination and positive lymphadenopathy (IP/RP+). Product-limit and multivariate proportional hazards modeling were used.

Results

Analyses included 417 stage IIIC women who underwent primary cytoreduction with lymphadenectomy to microscopic residual. There were 203, 123, and 91 in the RP, IP/RP−, and IP/RP+ groups, respectively. IP/RP+ and IP/RP− were associated with worse progression-free survival (PFS) (Hazard Ratio (HR) 1.68, 95% confidence interval (CI) 1.23-2.30; HR 1.38, 95% CI 1.04-1.84) vs. RP only. IP/RP+ was associated with worse overall survival (OS) (HR 1.79, 95% CI 1.24-2.57) while IP/RP− trended towards worse OS (HR 1.21, 95% CI 0.85-1.73) vs. RP only. Median PFS for IP/RP+ and IP/RP− groups was 21 and 29 months, respectively, vs. 48 months in the RP group (p = 0.0007) and median OS of 63 and 79 months vs. “not reached,” respectively (p = 0.0038).

Conclusions

Among EOC patients surgically cytoreduced to microscopic residual disease, those upstaged to IIIC by retroperitoneal involvement demonstrated significant improvement in PFS and OS compared to patients with intraperitoneal tumor, suggesting that these women may represent a unique subset of FIGO stage IIIC patients.     

Is older age a poor prognostic factor in stage I and II endometrioid endometrial adenocarcinoma?

Objective

Prior studies have shown that age ≥ 70 years is associated with more aggressive non-endometrioid histology and worse survival in endometrial cancer. The purpose of this study is to assess if age is an independent poor prognostic factor in endometrioid histologies.

Methods

Under an IRB-approved protocol, we identified patients with surgical stage I to II endometrioid endometrial adenocarcinoma from 1995 to 2008 at two institutions. Patients were divided into two groups based on age at diagnosis: Group A (age 50-69 years) and Group B (age ≥ 70 years). All patients underwent hysterectomy, bilateral salpingoophorectomy, +/−pelvic/aortic lymphadenectomy and adjuvant therapy. Prognostic factors were evaluated by univariate and multivariate analyses.

Results

We identified 338 patients with stage IA to IIB endometrioid endometrial adenocarcinoma. The median age in Group A was 59 years (range 50-69) and Group B was 75 years (range 70-92). Patients in Group B were more likely to have hypertension (51% vs. 68%, p = 0.006) and coronary artery disease (9% vs. 18%, p = 0.03). There were no differences in progression-free or disease-specific survival, however, Group B had a worse overall survival (OS) (50.1 vs. 62.6 months, p = 0.03). On univariate analysis, age (p = 0.04), grade (p = 0.006), and coronary artery disease (p = 0.01) were associated with worse OS. After adjusting for grade and coronary artery disease, age was no longer a significant variable for OS (p = 0.17).

Conclusions

After adjusting for other poor prognostic factors, age ≥ 70 years alone may not be a significant variable affecting overall survival in patients with early stage endometrioid endometrial adenocarcinoma.     

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.     

Completed versus aborted radical hysterectomy for node-positive stage IB cervical cancer in the modern era of chemoradiation therapy

Objective

Debate continues about optimal management of patients with node-positive stage I cervical cancer. Our objective was to determine if patient outcomes are affected by radical hysterectomy in the modern era of adjuvant chemoradiation.

Methods

Cervical cancer patients diagnosed from 2000 to 2008 were identified. Demographics, therapy, clinicopathologic data, progression free survival (PFS), overall survival (OS), total radiation exposure, and grade 3-4 complications were analyzed by student t, Mann-Whitney, Fisher's exact, Kaplan-Meier, and log rank tests.

Results

This single-institution review evaluated forty-one of 334 (13.4%) patients scheduled to undergo radical hysterectomy that had gross nodal disease diagnosed intraoperatively. 15 underwent aborted radical hysterectomy following lymphadenectomy; the remaining 26 underwent radical hysterectomy and lymphadenectomy. Eleven patients undergoing radical hysterectomy underwent whole pelvic radiation therapy (WPRT) while 8 (30.7%) patients underwent WPRT and postoperative vaginal brachytherapy (BT) for local treatment secondary to close margins. All patients undergoing aborted radical hysterectomy underwent WPRT and BT. With mean follow-up of 42.3 months, there were no significant differences in urinary, gastrointestinal, or hematologic complications between groups. When comparing those undergoing radical hysterectomy to aborted radical hysterectomy, there were no significant differences in local recurrence (11.5% vs 26.7%, p = 0.39) or distant recurrence (19.2% vs. 33.3%, p = 0.45), PFS (74.9 months vs 46.8 months, p = 0.106), or OS (91.8 months vs 69.4 months, p = 0.886).

Conclusions

Treatment of patients with early stage cervical cancer and nodal metastasis may be tailored intraoperatively. Completion of radical hysterectomy and lymphadenectomy decreases radiation exposure without apparently compromising safety or outcome in the era of adjuvant chemoradiation.     

Reliability of sentinel node assay in vulvar cancer: the first Croatian validation trial

Objectives

To evaluate patterns of recurrence in 1988 FIGO stage IC endometrioid endometrial adenocarcinoma.

Methods

A prospectively maintained endometrial cancer database was utilized to identify all patients with stage IC endometrioid endometrial adenocarcinoma treated between 2/93 and 6/09. Patterns of recurrence and risk factors were analyzed.

Results

One hundred thirty-four patients with stage IC endometrial cancer were identified. Median age was 66 years (range, 31-91 years). All patients were initially treated surgically, and 79% underwent comprehensive surgical staging with lymphadenectomy. Median number of lymph nodes removed was 18 (range, 1-45). Fifty-one patients (38%) had FIGO grade 1 tumors, 55 (41%) had grade 2 tumors, and 28 (21%) had grade 3 tumors. The majority of patients (91%) received adjuvant radiation therapy. With a median follow-up of 36 months (range, 0.6-141.4 months), 10 patients recurred. Of these, 2 (20%) were grade 1, 2 (20%) were grade 2, and 6 (60%) were grade 3. Nine (90%) of these recurrences had a distant component and 7 (70%) were fatal. Overall, the 3 year cumulative incidence failure rate for grade 1/2 tumors was 5.4%; for grade 3 tumors it was 28.9% (P < 0.001). Age, BMI, and lymphovascular invasion were not associated with an increased risk of recurrence.

Conclusions

Patients with stage IC, grade 3 endometrial cancer had a significantly increased risk of recurrence (28.9%). All of these recurrences had a distant component and the majority were fatal. Further investigation into the addition of adjuvant systemic therapy in these high-risk patients is warranted.     

Prognostic significance of systematic lymphadenectomy as part of primary debulking surgery in patients with advanced ovarian cancer

Objective

The objective of this study was to evaluate the impact of systematic pelvic and para-aortic lymphadenectomy on survival in patients with advanced ovarian cancer.

Methods

We retrospectively analyzed the data of 189 consecutive patients with FIGO stage IIIC ovarian cancer between 2000 and 2011, who underwent primary cytoreductive surgery followed by platinum- and taxane-based chemotherapy. All patients were classified into two groups — patients who underwent systematic pelvic and para-aortic lymphadenectomy and those who did not. Progression-free (PFS) and overall survival (OS) times were analyzed using Kaplan-Meier method and Cox proportional hazards model.

Results

Patients who underwent systematic lymphadenectomy had significantly improved PFS (22 versus 9 months, p < 0.01) and OS (66 versus 40 months, p < 0.01). In patients with no gross residual disease (NGR) or residual disease 0.1-1 cm (GR-1), the median OS time of those who had lymphadenectomy was significantly longer than those who did not (86 versus 46 months, p = 0.02). However, in patients with residual disease > 1 cm (GR-B), there was no significant difference in OS according to lymphadenectomy (39 versus 40 months, p = 0.50). Among patients with NGR, the median OS time of those who underwent systematic lymphadenectomy was significantly longer than those who did not undergo lymphadenectomy (not yet reached [> 96] and 56 months, p < 0.01). No significant difference of OS between patients with and without lymphadenectomy was observed in the subgroup of patients with GR-1 (50 versus 38 months, p = 0.44). The performance of lymphadenectomy was a statistically significant and independent predictor of improved OS in addition to the status of residual disease and the performance of radical cytoreductive procedures (hazard ratio, 0.34; [95% CI, 0.23-0.52]; p < 0.01).

Conclusions

Systematic lymphadenectomy may have a therapeutic value and be significantly associated with improved survival in stage IIIC ovarian cancer patients with grossly no visible residual disease.     

Lymph node metastasis in endometrioid adenocarcinomas of the uterine corpus with occult cervical involvement

Objective

Surgical-pathologic studies have defined the risk of lymphatic metastasis in clinical stage I endometrial cancers. However, data on the risk of lymph node metastasis in endometrial cancers involving the uterine cervix are less robust. The aim of this study was to determine the risk of lymphatic metastasis in patients with endometrial cancers with occult tumor extension to the uterine cervix.

Methods

Our institutional tumor registry identified all patients with endometrioid endometrial cancers who underwent comprehensive surgical staging. Patients with gross involvement of the cervix and patients with extra-uterine disease were excluded. The risk of lymphatic metastasis associated with cervical involvement was analyzed in the context of known uterine risk factors for lymphatic metastasis such as age, depth of invasion, grade, and lymphovascular space invasion (LVSI).

Results

We identified 169 patients who met inclusion and exclusion criteria. Univariate analyses revealed that LVSI (p < 0.01), tumor grade (p < 0.01), depth of myometrial invasion (p < 0.01), tumor free distance (p < 0.01), tumor size (p = 0.02), and cervical involvement (p < 0.01) were associated with lymphatic metastasis while age at diagnosis (p = 0.85) was not. Multivariate analyses revealed that only LVSI (p < 0.01), tumor grade (p = 0.02), and depth of myometrial invasion (p = 0.03) were independently associated with lymphatic metastasis.

Conclusion

Cervical involvement is not an independent predictor of lymphatic metastasis in endometrial cancer. In an unstaged patient, decisions regarding adjuvant treatment or additional diagnostic procedures such as lymphadenectomy should be based on uterine factors.     

The role of cytoreductive surgery for newly diagnosed advanced-stage uterine carcinosarcoma

Objectives

Uterine carcinosarcoma (CS) is a rare but aggressive malignancy frequently associated with extrauterine metastasis at the time of diagnosis. The objective of this study was to assess the role of cytoreductive surgery in patients with stage IIIC-IVB uterine CS.

Methods

We conducted a retrospective review of all patients with uterine CS treated at our institution from 1990 to 2009. Clinicopathologic factors, surgical procedures, adjuvant therapy, and survival outcomes were collected for all patients. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Factors predictive of survival outcomes were compared using the log-rank test and Cox regression analysis.

Results

An analysis of 44 patients was performed (stage IIIC, n = 14; stage IVB, n = 30). Complete gross resection was achieved in 57% of patients. PFS and OS for the entire cohort were 8.6 months and 18.5 months, respectively. Complete gross resection was associated with a median OS of 52.3 months versus 8.6 months in patients with gross residual disease (P < 0.0001). Stage IIIC disease was associated with a median OS of 52.3 months versus 17.5 months for patients with stage IVB disease. In patients who received adjuvant therapy, OS was 30.1 months versus 4.7 months in patients who did not receive adjuvant therapy (P < 0.001). On multivariate analysis, only complete gross resection and the ability to receive adjuvant therapy were independently associated with OS.

Conclusions

Cytoreductive surgery, with a goal of achieving a complete gross resection, is associated with an improvement in OS among patients with advanced uterine CS.     

Effects of pinealectomy and melatonin supplementation on endometrial explants in a rat model

Objective

To determine the effects of pinealectomy on endometrial explants in rats and evaluate the activity of superoxide dismutase (SOD) and catalase (CAT) and the levels of malondialdehyde (MDA) in the rat endometriosis model.

Study design

Rats with experimentally induced endometriosis were randomly divided into three groups after second-look laparotomies. Group 1 (pinealectomy, n = 8) and Group 2 (pinealectomy + melatonin, n = 8) underwent pinealectomies after the second-look laparotomies. Group 3 was presented as control group (vehicle solution + without pinealectomy (n = 6)). Melatonin was administered intraperitoneally for 4 weeks in Group 2, whereas an equal volume of vehicle solution was given to Groups 1 and 3. Evaluation of the volume of the endometrial explants, histopathological examination and preservation of explant epitheliums according to the scoring system were undertaken.

Results

There was a statistically significant increase in spherical explant volumes of Group 1 compared to Groups 2 and 3. In Group 1, the level of MDA was significantly higher and SOD and CAT activity was significantly lower compared to Groups 2 and 3. A statistically significant increase in the epithelial lining scores of explants was noted in Group 1 compared to Groups 2 and 3.

Conclusion

The effects of pinealectomy on the progression of endometriosis explants were reversed by melatonin.     

Clinicopathological prognostic factors and the role of cytoreduction in surgical stage IVb endometrial cancer: A retrospective multi-institutional analysis of 248 patients in Japan

Objective

To evaluate clinicopathological prognostic factors and the impact of cytoreduction in patients with surgical stage IVb endometrial cancer (EMCA).

Methods

The records of 248 patients with stage IVb EMCA who underwent primary surgery including hysterectomy at multiple institutions from 1996 to 2005 were retrospectively analyzed. Data regarding disease distribution, surgical procedures, adjuvant therapy, and survival times were collected. Univariate and multivariate analyses were performed to identify factors associated with overall survival (OS).

Results

The median OS was 24 months. The most common histological types were endometrioid (grade 1: 15%, grade 2: 20%, grade 3: 24%) and serous (17%). The most common sites of intra-abdominal metastases were pelvis (65%), ovaries (58%), omentum (58%), retroperitoneal lymph nodes (52%), and upper abdominal peritoneum (44%). In 93 patients with extra-abdominal metastases, the most common site was the lung (n = 49). Complete resection of extra-abdominal metastases was achieved in only 13 patients. Complete resection of intra-abdominal metastases was achieved in 101 patients, 52 had ≤ 1 cm residual disease, and 95 had > 1 cm residual disease; the median OS times in these groups were 48, 23, and 14 months, respectively (p < 0.0001). Multivariate analysis showed that performance status, histology/grade, adjuvant treatment, and intra-abdominal residual disease were independent prognostic factors. Intra-abdominal residual disease was an independent prognostic factor in patients with and without extra-abdominal metastases.

Conclusions

Cytoreductive surgery and adjuvant therapy may improve survival in stage IVb EMCA, particularly in patients with favorable prognostic factors, even in the presence of extra-abdominal metastases.     

A feasibility study of carboplatin and weekly paclitaxel combination chemotherapy in endometrial cancer: a Kansai Clinical Oncology Group study (KCOG0015 trial)

Objectives.

The optimal chemotherapy regimen for women with endometrial cancer has not been established. We assessed the feasibility, toxicity and clinical efficacy of combination triweekly carboplatin and weekly paclitaxel in women with endometrial cancer.

Methods.

Eligible patients had histologically confirmed primary advanced or recurrent endometrial cancer (Group A), or had localized high-risk features (Group B). All were treated with paclitaxel 80 mg/m² (days 1, 8 and 15) and carboplatin AUC 5 (day 1) each 21-day cycle. A minimum of 3 cycles was planned; if 75% or more of patients were able to receive at least 3 cycles with acceptable toxicity, the regimen was declared “feasible.”

Results.

Forty patients were enrolled and administered 163 cycles of therapy; 38 (95%) were chemo-naive. No patients received radiation previously. Group A (measurable disease) contained 15 patients (5 with recurrent disease, 7 receiving neo-adjuvant chemotherapy, and 3 treated adjuvantly following suboptimal cytoreduction). Group B (non-measurable disease) contained 25 patients (primary stage I:10, II:5, III:8, IV:1 and relapse 1). Hematological toxicities(G3/G4) were neutropenia (31%/33%) and thrombocytopenia (6%/0%). Reversible G3 hypersensitivity (5%) and G2 cardiotoxicity (3%) was uncommon. Thirty-one patients (78%) completed ≥ 3 cycles (median 4, range: 1-9). Thirteen of 15 (87%) measurable patients responded (3CR, 10PR). Eighty-seven percent of measurable patients were not progressive at 6 months. In Group A, QOL scores were significantly improved after 3 cycles of chemotherapy (p = 0.037), and at the completion of chemotherapy (p = 0.045). QOL scores in Group B did not change during therapy.

Conclusions.

This combination chemotherapy is feasible and effective for endometrial cancer patients.     

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.     

Prognostic significance of DNA ploidy in stage I endometrial cancer

Objective.

To improve the outcome for patients with endometrial cancer, a more accurate prognostic assessment is needed. The current study was undertaken to determine the role of flow cytometric DNA ploidy as an independent prognostic factor in patients with stage I endometrial cancer and to verify if ploidy is able to identify high-risk cases among the apparent ‘low-risk’ patients, defined as stage (IA), grade (1 or 2), and histologic type (endometrioid).

Methods.

This was a retrospective study. DNA ploidy was evaluated from tumor samples in 217 patients with stage I endometrial cancer who underwent definitive surgery as the first treatment between 2003 and 2009. Ploidy and other classic parameters were analyzed in relation to the length of recurrence-free survival.

Results.

Among the 217 evaluated patients, 184 (84.8%) had diploid tumors and 33 (15.2%) had aneuploid tumors. There were 12 recurrences during the median follow-up intervals of 42.7 months. Stage, grade, histologic type, lymphovascular space invasion (LVSI), and ploidy were significantly correlated with recurrence-free interval by univariate Cox analysis. Based on multivariate Cox analysis, ploidy was an independent prognostic factor, with a hazard ratio of 4.5 (95% confidence interval [CI], 1.3-15.3; P = 0.017) adjusted for stage, grade, histologic type, and LVSI. In low-risk patients (n = 156), the recurrence rate was 2.1% for diploid tumors and 12.5% for aneuploid tumors (P = 0.038).

Conclusions.

DNA aneuploidy is an independent prognostic factor in patients with endometrial cancer and can identify high-risk patients among those considered ‘low-risk’ with stage I endometrial cancer.     

The significance of surgical staging in intermediate-risk endometrial cancer

Objective

The objective was to evaluate rates of nodal disease in endometrial cancer within risk groups based on uterine factors, and to estimate the rate of potential undertreatment and impact on survival if nodal status was unknown.

Methods

This was a population-based retrospective cohort study of endometrioid-type endometrial cancer in British Columbia from 2005 to 2009. All women with a preoperative grade 2/3 cancer underwent hysterectomy, bilateral salpingo-oophorectomy (HBSO) and lymphadenectomy, and those with intermediate- or high-risk disease based on uterine factors after HBSO alone underwent secondary lymphadenectomy. We compared rates of node-positivity and potential undertreatment in each group if nodal status had been unknown (chi-square test), and estimated the survival benefit from lymphadenectomy.

Results

There were 222 women who underwent primary or secondary lymphadenectomy. Median age was 65 (range 38-86) and median number of lymph nodes was 10 (range 2-39). Of the 66 women with intermediate-risk disease (grade 1 or 2 tumor, deep myometrial invasion), 6 had nodal disease (9.1%) and received adjuvant chemotherapy. They remain disease-free after 24 months (range 8-55). They would not have qualified for chemotherapy based on uterine factors alone, and would have been undertreated compared to other risk groups (chi-square p = 0.071). A 1% survival benefit was estimated from lymphadenectomy.

Conclusion

Women with a grade 1 or 2 tumor and deep myometrial invasion have a 9% risk of nodal disease. Lymphadenectomy is significant for this subgroup as they would have been undertreated based on uterine risk factors alone, although the survival benefit is limited.     

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.     

Obesity in relation to endometrial cancer risk and disease characteristics in the Women's Health Initiative

Objective

Obesity increases endometrial cancer risk, yet its impact on disease stage and grade is unclear. We prospectively examined the effects of body mass index (BMI) and waist-to-hip ratio (WHR) on incidence, stage, and grade of endometrial cancer.

Methods

We studied 86 937 postmenopausal women enrolled in the Women's Health Initiative. Height, weight, and waist and hip circumference were measured at baseline. Endometrial cancer cases were adjudicated by trained physicians and pathology reports were used to determine stage and grade. Cox proportional hazards models generated hazard ratios (HR) for associations between BMI and WHR and risk of endometrial cancer. Logistic regression was used to evaluate associations between BMI and WHR and disease stage and grade.

Results

During a mean 7.8 (standard deviation 1.6) years of follow-up, 806 women were diagnosed with endometrial cancer. Although incidence was higher among Whites, stage and grade were similar between Whites and Blacks. Elevated BMI (HR 1.76, 95% confidence interval [CI] 1.41-2.19) and WHR (HR 1.33, 95% CI 1.04-1.70) increased endometrial cancer risk when comparing women in the highest and lowest categories. No associations were observed between BMI or WHR and disease stage or grade.

Conclusions

Obesity increases endometrial cancer risk independent of other factors but is not associated with stage or grade of disease. These findings support and validate previous reports. Future research should evaluate the impact of obesity on racial disparities in endometrial cancer survival.     

A phase II evaluation of docetaxel and carboplatin followed by tumor volume directed pelvic plus or minus paraaortic irradiation for stage III endometrial cancer

Objective

To determine the feasibility and efficacy of administering docetaxel and carboplatin chemotherapy followed by tumor directed radiation in patients with advance stage endometrial cancer.

Methods

Patients with surgical stage III or IV (confined to the pelvis) endometrial cancer were eligible. Treatment consisted of six cycles of docetaxel (75 mg/m²) and carboplatin (AUC 6) followed by irradiation to the involved field (50.4 Gy pelvis ± 43.5 Gy paraaortic) ± brachytherapy. Kaplan-Meier (KM) methods estimated overall survival (OS) and progression free survival (PFS).

Results

Forty-five patients were enrolled, 34 (76.0%) completed the prescribed therapy. Median age 63.5 (35-85 years). Stage IIIA 8 (17.8%), IIIB 1 (2.2%) and IIIC 36 (80.0%). 39/45 (86.7%) had endometroid histology. Serious grade 4 toxicities included 14 non-hematologic and 2 hematologic. Sixteen patients died following treatment, 6 from recurrent progressive cancer, with a median follow-up of 35.6 months (0.4-74.8). KM estimates and standard error (SE) for OS at 1 year were 84.5%, (5.4%), at 3 years, 65.8%, (7.2%) and at 5 years, 56.7%, (7.9%). Median overall survival was 74.5 months. Fourteen patients recurred with KM estimates and standard error (SE) for PFS at 1 year 77.8%, (6.2%) and 3 year 54.4%, (6.7%). Median progression free survival was 36.9 months.

Conclusions

Docetaxel and carboplatin followed by tumor directed irradiation for advanced stage endometrial cancer has acceptable toxicity and efficacy that allows for this regimen to be considered a viable treatment option for these patients.     

Changes in serum CA-125 can predict optimal cytoreduction to no gross residual disease in patients with advanced stage ovarian cancer treated with neoadjuvant chemotherapy

Objective

To evaluate the predictive power of serum CA-125 changes in the management of patients undergoing neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) for a new diagnosis of epithelial ovarian carcinoma (EOC).

Methods

Using the Cancer Registry databases from our institutions, a retrospective review of patients with FIGO stage IIIC and IV EOC who were treated with platinum-based NACT-IDS between January 2006 and December 2009 was conducted. Demographic data, CA-125 levels, radiographic data, chemotherapy, and surgical-pathologic information were obtained. Continuous variables were evaluated by Student's t test or Wilcoxon-Mann-Whitney test.

Results

One hundred-three patients with stage IIIC or IV EOC met study criteria. Median number of neoadjuvant cycles was 3. Ninety-nine patients (96.1%) were optimally cytoreduced. Forty-seven patients (47.5%) had resection to no residual disease (NRD). The median CA-125 at diagnosis and before interval debulking was 1749 U/mL and 161 U/mL, respectively. Comparing patients with NRD v. optimal macroscopic disease (OMD), there was no statistical difference in the mean CA-125 at diagnosis (1566 U/mL v. 2077 U/mL, p = 0.1). There was a significant difference in the mean CA-125 prior to interval debulking, 92 v. 233 U/mL (p = 0.001). In the NRD group, 38 patients (80%) had preoperative CA-125 ≤ 100 U/mL compared to 33 patients (63.4%) in the OMD group (p = 0.04).

Conclusions

Patients who undergo NACT-IDS achieve a high rate of optimal cytoreduction. In our series, after treatment with taxane and platinum-based chemotherapy, patients with a preoperative CA-125 of ≤ 100 U/mL were highly likely to be cytoreduced to no residual disease.     

The expression of hepatocyte growth factor (HGF) and c-Met in uterine serous carcinoma

Objective

The hepatocyte growth factor (HGF) receptor c-Met plays an important role in tumor dissemination by activating mitogenic signaling pathways. The goal of this study was to investigate immunohistochemical (IHC) staining patterns of HGF and c-Met in endometrioid endometrial cancer (EC) and uterine serous cancer (USC) and to correlate staining with patient outcomes.

Methods

A tissue microarray was created using tissue from patients with atrophic endometrium (AE), grade 1 EC, grade 3 EC, and USC. Immunohistochemistry was used to detect c-Met, phosphorylated c-Met (p-c-Met), and HGF expression. Differences between IHC staining intensity were calculated using t-tests. Correlations between staining and clinicopathologic variables were determined by Chi-square testing for categorical variables and t-tests for continuous variables. Kaplan-Meier curves were constructed to analyze survival in USC.

Results

Patients with cancer had more total c-Met and HGF expression than those with AE (p = 0.037, p < 0.001 respectively), but no difference in p-c-Met staining. Total c-Met and HGF staining was significantly different between groups (p = 0.042, p < 0.001 respectively). This difference was accounted for by greater c-MET expression in USC compared to AE (p = 0.027). Depth of invasion, stage, and lymph node status were not significantly related to staining intensity. Patients with strong c-Met and HGF staining had decreased overall survival compared to patients with weaker staining.

Conclusions

HGF and c-Met may play a role in the progression of endometrial cancer and should be studied further as prognostic and therapeutic tools.