The prognostic significance of age in surgically staged patients with Type II endometrial carcinoma

Objective

Many studies have examined the impact of older age on tumor recurrence and survival after hysterectomy for patients with endometrioid carcinoma. However, there is paucity of data examining the prognostic significance of age in patients with Type II endometrial carcinoma. The study was conducted to determine the prognostic impact of age in this patient population.

Materials and methods

In this Institutional Review Board (IRB)-approved study, our prospectively-maintained database of 1305 patients with endometrial cancer was reviewed. Seventy-two consecutive patients with serous and clear carcinoma 2009 FIGO stages I-II were identified with at least one year follow-up after surgical staging. Patients with mixed histology and those who received preoperative therapy were excluded. All the patients underwent surgical staging from 1989 to 2009. Their medical records were reviewed. The study cohort was divided into two groups based on their age at hysterectomy (≤ 65 vs. > 65). Patient's demographics, pathologic features and treatment-related factors were compared. The impact of age on recurrence-free survival (RFS), disease-specific survival (DSS) and overall survival (OS) were calculated. Following univariate analysis, multivariate modeling was done using step-wise Cox proportional hazards analysis to assess the impact of age on clinical outcomes after adjusting for various clinical variables.

Results

Median follow-up for the study cohort was 45 months (range 13-246). Fifty percent of patients received adjuvant platinum-based chemotherapy and/or adjuvant radiation treatment (RT). Thirty-five patients were older than 65 years (49%) and 37 were ≤ 65 (51%). There were no significant differences between the two groups in regard to race (African American vs Caucasian), FIGO stage, number of lymph nodes dissected, lymphovascular space involvement (LVSI), or adjuvant therapy received. There were more clear cell histology in the younger age group (p = 0.035). Patients > 65 years old developed more recurrences with a 5-year RFS of 59% compared to 84% for younger patients (p = 0.036). The five-year DSS was not statistically different between the two groups (68% vs. 79%, respectively with p = 0.313). 5-year OS was significantly shorter in the elderly patients (58% vs. 78% with p = 0.014). On multivariate analysis, the presence of LVSI, not receiving RT and age > 65 were independent predictors of worse RFS (p = < 0.001, 0.005, and 0.040 respectively).

Conclusion

In this study for surgically staged FIGO I-II patients with Type II endometrial carcinoma, age more than 65 years is a significant adverse prognostic factor for tumor recurrence.     

Efficacy and prognostic implications of administering adjuvant chemotherapy to patients with endometrial cancer that is confined to the uterus

OBJECTIVE: The purpose of this study was to determine the value of prognostic factors and to assess the efficacy of adjuvant chemotherapy in patients with endometrial cancer confined to the uterus. STUDY DESIGN: Patients surgically stage IB, IC and II endometrial cancer according to the International Federation of Gynecology and Obstetrics were enrolled in this study. Stage IIIA tumors with positive peritoneal cytology, in the absence of other evidence of extra uterine disease, were also included. RESULTS: One hundred and sixty-seven patients fulfilled the eligibility criteria and 58 patients (34.7%) underwent combination chemotherapy. Disease recurrence occurred in 10 patients within a median time of 17 months. Histologic grade 3 was an independent prognostic factor for both disease-free and overall survival rates. Fourteen of 23 patients with histologic grade 3 tumors received adjuvant chemotherapy consisting of cyclophosphamide (or etoposide), epirubicin and cisplatin (in 1989-1999) or paclitaxel, pirarubicin and carboplatin (in 2000-2002). The 5-year disease-free and overall survival rates for these individuals was 92.3%, a value significantly higher than those in patients who had not undergone chemotherapy (50.0%). CONCLUSIONS: Histologic grade of 3 is an independent prognostic marker in patients with endometrial cancer confined to the uterus and adjuvant chemotherapy might improve the survival rates in these patients.     

Stage IC adenocarcinoma of the endometrium: survival comparisons of surgically staged patients with and without adjuvant radiation therapy

OBJECTIVE: The goal of this study was to determine the outcomes of stage IC endometrial carcinoma patients who are managed with and without adjuvant radiation therapy after comprehensive surgical staging. METHODS: Patients with FIGO stage IC adenocarcinoma of the endometrium diagnosed from 1988 to 1999 were identified from tumor registry databases at four institutions. A retrospective chart review identified 220 women who underwent comprehensive surgical staging including a total hysterectomy, bilateral salpingo-oophorectomy, pelvic/paraaortic lymphadenectomy, and peritoneal cytology. RESULTS: Of the 220 stage IC patients, 56 (25%) patients received adjuvant brachytherapy (BT), 19 (9%) received whole-pelvis radiation (WPRT), and 24 (11%) received both WPRT and BT. One hundred twenty-one patients (55%) did not receive adjuvant radiation. There were 6 recurrences (6%) in the radiated group and 14 (12%) in the observation group (P = 0.20). Seven of fourteen recurrences in the observation group were local, and all local recurrences were salvaged with radiation therapy. Two of seven distant recurrences in this group were also salvaged with surgery and chemotherapy. The overall salvage rate for the observation group was 64%. There was a statistical difference in 5-year disease-free survival between the radiated and observation groups (93% vs 75%, P = 0.013). However, the 5-year overall survival was similar in the two groups (92% vs 90%, P = 0.717). CONCLUSION: Adjuvant radiation therapy improves disease-free survival in surgical stage IC patients; however, overall survival is not improved with adjuvant radiation therapy since the majority of local recurrences in conservatively managed patients can be salvaged with radiation therapy.     

Recurrence patterns and prognostic factors in lymphovascular space invasion-positive endometrioid endometrial cancer surgically confined to the uterus

Objective

The purpose of this study was to determine the patterns of failure and prognostic factors for lymphovascular space invasion (LVSI)-positive endometrioid endometrial cancer (EC) patients in the setting of negative lymph nodes (LNs).

Prognostic significance of serous and clear cell adenocarcinoma in surgically staged endometrial carcinoma

BACKGROUND: The serous adenocarcinoma (SA) and clear cell adenocarcinoma (CCA) of endometrium have been shown to be associated with high relapse rate and poor survival. It is not clear whether prognostic significance of these specific cell types of tumor is independent of retroperitoneal lymph node metastasis and other histopathologic prognostic factors in endometrial carcinoma. METHODS: We examined 240 consecutive patients with clinical stage I to stage III endometrial carcinoma who were treated prospectively with radical surgery and/or platinum-based chemotherapy. Surgery included extended hysterectomy, bilateral salpingo-oophorectomy, and systematic pelvic and paraaortic lymph node dissection. Prognostic significance of various histopathologic factors was determined by Cox regression analysis. RESULTS: SA/CCA were more frequently associated with deep myometrial invasion, high nuclear grade (G3), lymph-vascular space invasion (LVSI), and pelvic lymph node metastasis when compared to endometrioid adenocarcinoma (EMA). Of 216 clinically staged stage I or II disease, seven of 12 cases of SA/CCA had extrauterine disease. This incidence was much higher than that for EMA (46/204) (p<0.01). A multivariate Cox regression analysis revealed that cell type, grade, LVSI, and paraaortic node metastasis (PANM) were independent prognosticators. CONCLUSIONS: Prognosis of patients with endometrial carcinoma depends on cell type, grade, LVSI, and PANM. Poor prognosis for patients with SA/CCA is independent of lymph node metastasis and other histopathologic prognostic factors. The SA/CCA should be strictly discriminated from EMA.     

Outcomes of patients with low-risk endometrial cancer surgically staged without lymphadenectomy based on intra-operative evaluation

Objective

The objective of the study was to evaluate clinical outcomes in patients with stage I endometrial cancer undergoing surgical management without lymphadenectomy based on intra-operative assessment for low-risk disease.

Methods

Between 2000 and 2009, a total of 179 patients were surgically staged without lymphadenectomy for low-risk stage I endometrial cancer. Low-risk cancer was defined by intra-operative criteria based on both gross and frozen tissue microscopic evaluation: 1) G1 or G2 endometrioid histology; 2) myoinvasion < 50%; 3) no cervical disease, and 4) no intra-abdominal metastasis. Records were reviewed for postoperative complications, pathological diagnoses, adjuvant radiation treatment, cancer recurrence, and mortality.

Results

Morbidity, cancer recurrence, and disease-specific mortality were low. Postoperative complications occurred in 5 patients (2.8%). Nine patients (5.0%) were offered adjuvant radiation for higher risk disease diagnosed on final pathology. Radiation morbidity was minimal: grade 1 vaginal toxicity in 2 patients. Three patients (1.7%) experienced recurrent cancer with mean time to recurrence of 43.7 months. Five year overall survival was 95.8%. The five year probability of disease-specific death was 1.1%.

Conclusion

In an institution with reliable capability of pathological frozen tissue diagnosis, omission of lymph node dissection is a reasonable option in the surgical management of those patients with low-risk disease diagnosed by intra-operative factors.     

Retrospective analysis of prognostic variables and clinical outcomes in surgically staged intermediate risk endometrial carcinoma

Objective

To identify independent prognostic variables for surgically staged intermediate risk endometrial carcinoma as defined by the Gynecologic Oncology Group 99 (GOG99) criteria.

Study design

Retrospective study of 239 patients with FIGO stage IB-occult IIB endometrioid type endometrial cancer, who were primarily treated with comprehensive staging surgery. Data were collected on clinicopathological variables, extent of primary surgery, postoperative adjuvant treatment, and patterns of recurrences. Kaplan–Meier survival curves were used to estimate disease free survival (DFS) and overall survival (OS), and multivariate Cox regression models were used to identify independent prognostic variables. The median follow-up time was 67 months (range, 12–183 months).

Results

The 5-year DFS and OS were 91.0% and 93.0%, respectively. On univariate Kaplan–Meier analysis, age > 60 years, deep myometrial invasion (MI), presence of lymph vascular invasion (LVSI), and negative progesterone receptor (PR) status were significantly associated with diminished 5-year DFS and OS. The univariate analysis on patterns of failures demonstrated that patients with older age or positive LVSI were more inclined to develop locoregional recurrence, while PR status and the depth of MI had a statistically significant impact on distant failure. On multivariate analysis, PR status, age, and the depth of MI were independent prognostic variables for 5-year DFS, and age was the only independent prognostic variable for 5-year OS. LVSI and age were independent prognostic variables for locoregional recurrence, while PR status and depth of MI were independent prognostic variables for distant recurrence.

Conclusions

Age, depth of MI, PR status and presence of LVSI are of independent prognostic value for intermediate risk endometrial cancer. The presence of these variables warrants consideration when deciding upon treatment strategies.     

The prognostic significance of lower uterine segment involvement in surgically staged endometrial cancer patients with negative nodes

OBJECTIVES: Endometrial cancer is the most common female genital malignancy in the United States. Stage is the most important prognostic factor. Other factors include grade, lymph-vascular space invasion (LVI), and myometrial invasion. Tumor location in the lower uterine segment (LUS) may also be important. LUS involvement correlates with nodal involvement, and nodal involvement is an important prognostic indicator. This study investigates the importance of LUS involvement in patients with pathologically negative nodes. METHODS: This was an IRB approved retrospective study. Data were collected for patients diagnosed with endometrial cancer from June 1999 to September 2004. Patients who underwent nodal evaluation with no evidence of nodal disease were eligible for analysis. The primary endpoint was progression-free survival. Secondary endpoints included recurrence rate and overall survival. Analysis was performed with the JMP5.1 statistical program. RESULTS: 285 patients were identified. 85 were excluded because they received postoperative care elsewhere. 3 charts were missing, and 15 pathology reports did not mention LUS. 147 of the remaining 182 subjects had negative nodes and formed the study population. 57% of these subjects had LUS involvement. Follow-up was similar for those with and without LUS involvement at 74 vs. 73 months respectively. PFS was similar at 70 and 63 months in those with and without LUS involvement (p=0.2). Recurrence correlated with LUS involvement on univariate analysis, however, not on multivariate analysis. CONCLUSIONS: In endometrial cancer patients with negative nodes, disease within the lower uterine segment does not imply a worse prognosis. The previously described implications of LUS involvement are likely due to the strong association of LUS disease with lymph node spread.     

子宫内膜癌的放射治疗

放射治疗(放疗)是子宫内膜癌的重要治疗方式。对于有高危因素的术后患者,辅助性放疗可明显改善肿瘤的局部控制率;对于不能手术的患者,根治性放疗是重要的替代治疗手段。放疗方式主要包括腔内照射和体外照射两种。     

Pure lipoma of the uterus in association with endometrial carcinoma

Pure lipoma of the uterus is a very rare entity, with few cases described in the English literature. We report the case of a 71-year-old woman, with pure lipoma of the uterus and coexistent endometrial carcinoma and discuss the possible relationship between these pathologic entities.     

The outcome of stage I-II clinically and surgically staged papillary serous and clear cell endometrial cancers when compared with endometrioid carcinoma

PURPOSE: The aim of this study was to compare survival and recurrence in clinical and surgical stage I-II papillary serous (PS), clear cell (CC), and endometrioid (EM) cancers of the endometrium and examine the prognostic utility of myometrial invasion. METHODS: Clinical, surgicopathologic, and survival data were retrospectively collected on 574 clinical stage I-II endometrial cancer patients, including 53 PS and 18 CC (based on postoperative histology), undergoing hysterectomy at Duke University Medical Center between 1967 and 1990. All staging material was available and reexamined prior to this analysis, and FIGO surgical staging was retrospectively assigned. Prognostic variables examined included age, stage, grade, myometrial invasion, lymph-vascular space invasion (LVSI), and histology. PS and CC histologic subtypes were compared as both common category and discrete categories versus EM, EM grade 1 (EM1), EM grade 2 (EM2), and EM grade 3 (EM3). Statistical analyses were performed using chi(2), Fisher's exact, and Wilcoxon rank sum tests, Cox regression analysis, and Kaplan-Meier survival analysis. RESULTS: PS tumors accounted for 9%, CC for 3%, and EM for 88% of cases. Recurrences were more frequent among PS (38%) and CC (22%) compared with EM (9%) (P < 0.001 and 0.08, respectively), and PS recurred more frequently than EM3 alone (20%) (P = 0.06). Among PS, CC, and EM3 patients with recurrences there were no statistical differences in the proportion that received preoperative or postoperative radiotherapy or chemotherapy. Prognostic factors for shorter survival included age >=60, surgical stage III+IV, presence of LVSI, histology (PS, CC, or EM3), and >=50% myometrial invasion. The estimated 5-year survival of PS+CC patients with <2 mm myometrial invasion is 0.56 compared to 0.93 for EM patients (P < 0. 001). PS + CC tumors confined to the endometrium had a 5-year survival of 0.60 compared to 0.98 and 1.00 for EM and EM3, respectively. The 5-year survival for surgically staged IA patients (0.57) was not different from stages IB and IC combined (0.53) (P = 0.72). The 5-year survival for surgical stage I + II PS + CC patients (0.56) was comparable to that for clinical stage I + II PS + CC patients (0.46) and remained significantly smaller than that for EM patients (0.86) (P < 0.001). CONCLUSION: Recurrences are more frequent among PS and CC tumors compared with EM and among PS compared with EM3. When controlled for surgical stage I-II tumors, 5-year survival for PS + CC patients remains comparable to that of clinical stage I-II patients and below that of EM. Prognostic factors for survival in PS and CC patients include age, stage, and LVSI. PS, CC, and EM3 subtypes together are predictors of poor survival. Thorough extended surgical staging is indicated in PS and CC tumors, and prospective trials of aggressive adjuvant therapies for surgical stage I-II tumors are needed to improve outcome in PS and CC patients.     

Prognostic significance of Bcl-2, p53 overexpression,and lymph node metastasis in surgically staged endometrial carcinoma

OBJECTIVE: The purpose of this study was to clarify whether Bcl-2 and p53 have prognostic significance that is independent of lymph node metastasis and other conventional histopathologic factors in endometrial carcinoma. STUDY DESIGN: Immunohistochemistry for Bcl-2 and p53 expression was performed on the frozen sections of 102 cases that were treated with surgery, including pelvic and para-aortic lymphadenectomy. Cox regression analysis was used to determine the prognostic significance. RESULTS: By univariate analysis, both loss of Bcl-2 expression and p53 overexpression were related to patient survival. Lymph node metastasis, p53 overexpression, and nuclear grade were found to be independent prognostic factors (determined by multivariate analysis). The estimated 5-year survival rate of patients with stage III/IV disease without p53 overexpression was 75.7%; the estimated 5-year survival rate for patients with p53 overexpression was only 40.4%. The difference was highly significant (P =.0053). CONCLUSION: Lymph node metastasis, p53 overexpression, and nuclear grade are independent prognostic factors for endometrial carcinoma. Bcl-2 may have little importance in the progression of endometrial carcinoma and is a less potent prognostic factor than is p53. A new treatment strategy is necessary for advanced stage endometrial carcinoma with p53 overexpression.     

Adjuvant therapy in stage III endometrial cancer confined to the pelvis

Objective

To review outcomes of patients with stage III endometrial cancer confined to the pelvis treated with adjuvant pelvic radiotherapy (RT) or sequential chemoradiotherapy (CRT).