Prognostic significance of positive peritoneal cytology in endometrial carcinoma

A retrospective review of 280 patients with endometrial carcinoma who had peritoneal cytologic examination done at the time of laparotomy was undertaken. A positive cytologic finding was the only manifestation of extrauterine disease in 16 patients (6%). Four (25%) of these patients had a recurrence. Only 13 (5%) of 237 patients with negative cytologic findings had a recurrence. Positive peritoneal cytology is a marker for potential recurrence.     

Prognostic factors associated with recurrence in clinical stage I adenocarcinoma of the endometrium

Two hundred sixty-four consecutive patients with clinical stage I endometrial adenocarcinoma who underwent primary surgical therapy between July 1979 and August 1988 were followed prospectively and evaluated for disease recurrence for 8-112 months (mean 51.5). Thirty-three patients (12.5%) developed recurrence or died of disease. In univariate statistical analysis, prognostic factors significantly associated with disease recurrence were as follows: age (mean 68.6 years with versus 60.3 years without recurrence; P = .0001); histology (adenocarcinoma 8.8%, adenosquamous 35.7%, papillary 25%, clear-cell 57.1%; P less than .0001); tumor grade (grade 1, 7.7%, grade 2, 10.5%, grade 3, 36.1%; P less than .0001); depth of myometrial invasion (none 9.8%, less than one-half 7.4%, one-half or greater 29.6%; P = .0001); lymph node status (negative 8.3%, positive 47.6%; P less than .0001); non-nodal extrauterine disease spread (absent 11.0%, present 50%; P = .0003); peritoneal cytology (negative 9.4%, positive 26.3%; P = .004), and tumor size (2 cm or less 7%, greater than 2 cm 17.3%; P = .05). Cervical extension and uterine size had no significant effect on recurrence. Using multivariate analysis, grade 3 tumor (P = .002), advancing age (P = .004), lymph node metastasis (P = .006), and presence of extrauterine disease spread other than lymph node metastasis (P = .038) were the only variables significantly associated with disease recurrence or death. This study supports the new International Federation of Gynecology and Obstetrics surgical staging system for endometrial cancer.(ABSTRACT TRUNCATED AT 250 WORDS)     

The clinical significance of malignant peritoneal cytology in stage I endometrial carcinoma

The prevalence of malignant peritoneal cytology in patients with International Federation of Obstetrics and Gynecology (1971) stage I endometrial carcinoma and its predictive value for recurrence of disease following hysterectomy were analyzed by numerically pooling the crude results of independent studies. Malignant cytology occurred in 8.3, 12.1 and 15.9% of patients with grade 1, 2 and 3 histology, respectively, and in 7.6% and 17.2% of patients with superficial and deep myometrial invasion, respectively. Prevalence was heterogeneous in the groups with grade 1 histology, grade 2 histology and superficial invasion, and homogeneous in the groups with grade 3 histology and deep invasion. This, together with a technical false positive rate of approximately 5% in the diagnosis of malignant cytology, suggests that the pooled values of prevalence for the low grade and superficially invasive groups may be overestimated. Malignant cytology was strongly associated with disease recurrence (pooled odds ratio of 4.7 with a 95% confidence interval of 3.5–6.3). Qualitative review of the literature suggests that this is largely due to the association of malignant cytology with other adverse prognostic factors which dominate the clinical course of the disease. In the absence of other adverse prognostic factors, the true prevalence of malignant cytology is low. This limits the clinical utility of cytology as an independent predictor of either overall recurrence or site of recurrence. Routine adjuvant treatment of patients with malignant cytology is therefore not justified.     

Prognostic significance of squamous differentiation in stage I endometrial adenocarcinoma

The prognostic implication of benign and malignant squamous differentiation was examined in 267 consecutive patients with stage I endometrial carcinoma. Patients with adenosquamous carcinoma had a significantly poorer ten-year survival rate (54.7%) than patients with adenocarcinoma (70.5%) or adenoacanthoma (87.4%). This was related to a tendency for adenosquamous carcinoma to be associated with poorly differentiated glandular elements and to deeply invade the myometrium. The mean depth of myometrial penetration was 57% for adenosquamous carcinoma compared with 24% for adenocarcinoma and 19% for adenoacanthoma. To examine the prognostic significance of malignant squamous differentiation independently of the grade of the associated glandular component, the subgroup of patients with well-differentiated adenocarcinoma was compared. Patients with well-differentiated adenosquamous carcinoma persisted in having a worse prognosis (58.3% ten-year survival rate), compared with adenocarcinoma (84.3% ten-year survival rate), which was explained by the propensity of adenosquamous carcinoma to deeply invade the myometrium.     

Prognostic value of peritoneal fluid cytology in patients with endometrial cancer stage I

With increasing depth of invasion of the endometrial adenocarcinoma in the myometrium an increasing number and percentage of patients with endometrial adenocarcinoma cells in the pouch of Douglas are found. The presence or absence of endometrial tumour cells can be used as an indicator of the depth of invasion in the myometrium. Survival is correlated with the presence of endometrial adenocarcinoma cells in cases with deep invasion; 50% recurrent disease was observed when the fluid was positive, no recurrent disease when negative. No correlation between survival and presence or absence of tumour cells in the Douglas fluid was found in cases with superficial invasion of the tumour in the myometrium.     

子宫内膜癌腹腔洗液细胞学检查与预后

目的 探讨腹腔洗液细胞学检查在评价子宫内膜癌患者预后中的价值。方法 对1992年1月～2000年1月我院收治临床分期Ⅰ-Ⅱ期的113例子宫内膜癌患者进行回顾分析及随访。结果 113例子宫内膜癌患者中,腹腔洗液细胞学检查阳性者23例(20.4％),其中4例(17.4％)死于术后复发;90例阴性的患者中,13例(12.56％)死于术后复发,Cox回归分析显示腹腔洗液细胞学检查结果与子宫内膜癌预后相关无显著性(P=0.9516);23例阳性患者中,6例(26％)为不良病理类型,9例(39％)有深肌层浸润,5例(21.7％)宫颈受累,5例(21.7％)有淋巴结转移,Logistic回归多因素分析表明与腹腔洗液细胞学检查阳性有显著相关(P<0.05)。结论 腹腔洗液细胞学检查不能独立作为评价子宫内膜癌患者预后的指标。与腹腔洗液细胞学检查阳性有关的高危因素有不良病理类型、深肌层浸润、宫颈受累和淋巴结转移。     

The prognostic significance of peritoneal cytology for stage I endometrial cancer

A retrospective study of 567 patients treated for surgical stage I endometrial cancer was undertaken to resolve the controversy over the significance of malignant peritoneal cytology findings in early-stage disease. Twenty-eight women (4.9%) had peritoneal cytology positive for malignant cells. Comparisons were made between the groups with positive and negative cytology. Subgroups used in analysis included stage according to the International Federation of Gynecology and Obstetrics, treatment regimen, histology, grade, depth of myometrial invasion, and cervical Papanicolaou smear results. Cervical smear status was the only subgroup in which a statistically significant difference was found, with the positive peritoneal cytology patients having a higher incidence of positive Papanicolaou smears (P = .01). Forty-nine women (8.6%) developed recurrent tumor, 7% of the negative-cytology group and 32% of the positive-cytology group (P = .0002). The progression-free survival rate was lowered significantly by positive peritoneal cytology (P less than .0001); patients with negative peritoneal cytology had a significantly better 5-year survival rate, 96 versus 84% (P = .0001). When multivariate analysis was performed on the 477 cases that had no missing values, peritoneal cytology remained significant for both survival rate (P = .01) and progression-free interval (P = .002). Positive peritoneal cytology is a poor prognostic factor for patients with surgical stage I endometrial cancer.     

The prognostic significance of positive peritoneal cytology in endometrial cancer

A retrospective analysis of clinical data extracted from hospital records of 145 patients who had had primary surgical treatment for endometrial cancer in Queen Mary Hospital, Hong Kong, from 1987 to 1993 was performed to study the prognostic significance of positive peritoneal cytology. Positive peritoneal cytology was found to be associated with poor prognostic factors such as deep myometrial invasion, high grade tumor, extrauterine spread and lymphovascular permeation. By univariate analysis, all the poor prognostic factors were found to be significant in affecting survival. These included age above 65, nonadenocarcinoma histology, deep myometrial invasion, positive cytology, extrauterine involvement and lymphovascular involvement. By multivariate analysis, only histology and extrauterine involvement remained significant. In patients with positive cytology, 61.1% had extrauterine involvement at initial presentation. Patients who had positive cytology and extrauterine disease had the shortest survival. The survival was independent of cytology result when the tumor was confined to the uterus.     

The prognostic significance of positive peritoneal cytology and adnexal/serosal metastasis in stage IIIA endometrial cancer

OBJECTIVE: The clinical significance and optimal management of patients with stage IIIA endometrial cancer are controversial. We sought to determine whether recurrence and survival of patients with stage IIIA endometrial cancer differ with surgical pathologic findings (positive peritoneal cytology versus positive adnexae or serosa) and adjuvant treatment. METHODS: Retrospective single institution analysis of patients surgically staged for IIIA endometrial cancer at Duke University Medical Center from 1973 to 2002. Stage IIIA patients were stratified into positive cytology alone (group IIIA1, n=37) and positive adnexae or uterine serosa (group IIIA2, n=20). Comparison was made with previously reported group of 467 patients with surgical stage I/II disease. Recurrence and survival were analyzed using Kaplan-Meier estimations and Cox proportional hazards model. RESULTS: Mean age of 57 patients with stage IIIA endometrial cancer was 63. Adjuvant therapies were administered to 89% patients (74% radiotherapy, 4% chemotherapy, 19% progestins). Five-year overall (OS) and recurrence-free disease-specific survival (RFDSS) were 64% and 76%, respectively. Survival was similar comparing IIIA1 (62%) and IIIA2 (68%, p=0.999). RFDSS by adjuvant therapy was: external beam radiotherapy 89% (n=10), intraperitoneal P32 84% (n=21), progestins 78% (n=9), none 75% (n=6). 61% recurrences included extrapelvic component. In multivariable analysis of stage I-IIIA patients (n=517), positive cytology but not adnexal/serosal metastasis was predictive of death (HR 1.70, 95% CI 1.06-2.73) and disease recurrence (HR 1.70, 95% CI 1.07-2.71). CONCLUSION: Among patients with stage IIIA endometrial cancer, metastasis to adnexae or serosa does not appear to confer worse prognosis than positive cytology alone. Positive cytology is an independent predictor of prognosis among patients with stage I-IIIA endometrial cancer. While optimal adjuvant therapy for these groups remains unclear, recurrence patterns suggest that systemic therapies are appropriate.     

The significance of peritoneal cytology in stage IB cervical cancer.

OBJECTIVE: The purpose of this study was to determine the incidence of positive peritoneal cytology and to evaluate its usefulness in the management of patients with early-stage cervical cancer. METHODS: Peritoneal cytology was studied in 273 women undergoing primary surgical exploration for International Federation of Gynecology and Obstetrics stage IB cancer of the cervix. Charts were reviewed retrospectively for clinicopathologic data concerning tumor size, cell type, lymph node status, and outcome. RESULTS: Cytology was positive in four women, three of whom had enlarged pelvic or para-aortic lymph nodes or intraperitoneal disease. There was no association between tumor histology or tumor size and peritoneal cytology. CONCLUSION: The incidence of positive peritoneal cytology in early-stage cervical cancer is low, and the prognostic significance of positive cytology is overshadowed by other risk factors more obvious at surgery. The routine collection of cytologic specimens at laparotomy should be abandoned in this setting.     

The significance of positive tubal cytology in patients with endometrial adenocarcinoma

Malignant cells in the Fallopian tubes were demonstrated in 10 (21.3%) of 47 patients with endometrial adenocarcinoma. Positive tubal cytology did not correlate with age of the patients, grade and stage of tumor at diagnosis, preoperative radiotherapy and presence of residual tumor, or myometrial invasion in the removed uterus. No effect of positive tubal cytology on 5-year survival was found. The lack of correlation of positive tubal cytology with factors affecting prognosis and with survival seems to indicate that the Fallopian tube is not a major mode of endometrial cancer spread.     

Malignant peritoneal cytology in stage I endometrial adenocarcinoma: the effect of progesterone therapy (a preliminary report)

From February 1982-June 1986, 25 consecutive patients with surgical stage I endometrial adenocarcinoma (no evidence of metastasis at surgery or occult cervical or adnexal involvement on histopathologic review) and malignant peritoneal cytologic washings were treated with progesterone therapy. Twenty-two patients have undergone a second look laparoscopy and repeat cytologic washings, one of those also underwent a third look laparoscopy. Two patients refused second look laparoscopy, and in a third patient laparoscopy was medically contraindicated; all three have no evidence of disease (NED) at 15, 46, and 64 months respectively and are off therapy. Of the 22 patients who underwent second look laparoscopy, 21 (95%) had no macroscopic evidence of recurrent endometrial carcinoma and repeat negative peritoneal cytology; 1 patient (5%) had persistent malignant peritoneal cytology but was NED at third look laparoscopy one year later. All 25 patients are off progesterone therapy and remain clinically NED from 12-64 months. Although progesterone therapy for malignant peritoneal cytology resulted in a 100% reversal of malignant peritoneal cytology to normal in the 22 patients who underwent second or third look laparoscopy and all 25 patients remain clinically NED, the true value of progesterone therapy can only be ascertained by a randomized trial of progesterone versus no therapy.     

Malignant peritoneal cytology as prognostic indicator in stage I endometrial cancer

The prognostic significance of malignant peritoneal cytology was evaluated in 93 patients with stage I endometrial cancer seen at Roswell Park Memorial Institute. Eighty-three patients (89%) had negative cytologic samples and ten (11%) had positive cytology for neoplastic cells. All patients were followed for a minimum of ten years or until dead from cancer or intercurrent disease. No patient received treatment for positive cytology. There was one recurrence in the patients with positive cytology (10%), and six recurrences in the negative group (7%). The actuarial survival rate at five and ten years for patients with negative cytology was 93.9 and 92.5%, respectively. For patients with positive cytology, the survival was 87.5% at both time intervals. No significant difference was found between the groups. Malignant peritoneal cytology does not seem to be a prognostic indicator in stage I endometrial cancer.     

Prognostic value of peritoneal cytology in endometrial carcinoma

To determine whether positive peritoneal cytology is an independent poor prognostic factor in patients with endometrial carcinoma the records of 381 patients were reviewed. Positive peritoneal cytology was found in 24 of 381 (6.3%) patients. In clinical stage I disease, 16 of 322 (5.0%) patients had positive peritoneal cytology. Patients with positive cytology were more likely to have higher-grade tumors and extrauterine disease at the time of surgery (45% vs 2.3%) than were patients with negative cytology. Five-year survival was significantly less for patients with positive cytology than negative (50% vs 81.2%). For patients with surgical stage I disease (no extrauterine spread at surgery) there was no significant difference in 5-year survival between groups with positive and negative cytology (80% vs 86.3%). The majority (70.8%) of patients with endometrial cancer and positive peritoneal cytology have extrauterine disease at the time of surgery. Although overall 5-year survival is less for patients with positive cytology, when other risk factors are controlled for, there is no difference in survival for patients with no demonstrable extrauterine disease despite positive cytology. We conclude that positive peritoneal cytology is not an independent prognostic indicator for patients with endometrial cancer.     

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.