FIGO System Research Articles

Positive peritoneal cytology is highly predictive of prognosis and relapse patterns in stage III (FIGO 2009) endometrial cancer

ObjectivesAccording to the updated FIGO system, positive peritoneal cytology does not affect endometrial cancer stage. This revision may reduce rates of obtaining cytology, with unclear implications in advanced disease. This study evaluates the significance of positive cytology in stage III (FIGO 2009) endometrial cancer. MethodsEligible patients received treatment for stage III endometrial cancer at a single institution and had peritoneal cytology performed. ResultsOf 196 patients, 58% were ≥60years old, 48% had deep myometrial invasion, 71% lymphovascular invasion, 25% cervical invasion, 37% adnexal involvement, 79% nodal involvement, and 46% aggressive histology. Positive cytology was present in 23% (45/196) and significantly associated with cervical stromal invasion, adnexal involvement, and aggressive histology (P≤0.03). There was no significant difference in rates of lymphadenectomy, chemotherapy, or radiation between negative and positive cytology groups. At a median follow-up of 47months, the 5-year freedom from relapse was 39% for positive cytology vs. 69% for negative, disease-specific survival 42% vs. 77%, and overall survival 34% vs. 72% (P<0.001). Positive cytology correlated with higher recurrence rates in the para-aortic nodes and peritoneum (30% vs. 9%, 23% vs. 4%; P≤0.008). When controlling for adverse features including aggressive histology, positive cytology was associated with an increased hazard for relapse (HR 2.3; P=0.002) and death (HR 2.9; P<0.001). ConclusionsIn stage III endometrial cancer, positive cytology independently predicts outcome and is associated with distinct relapse patterns. Obtaining peritoneal cytology in stage III endometrial cancer is critical.

Old versus new FIGO staging systems in predicting overall survival in patients with uterine leiomyosarcoma: A study of 86 cases

ObjectivesUterine leiomyosarcoma (uLMS) was staged using the FIGO system for endometrial cancers. The new FIGO system takes into consideration tumor size disregarding myometrial and cervical involvement. We aimed to compare the two systems and see which more accurately predicts overall survival (OS). Methods86 patients with uLMS (1984–2010) were retrospectively staged using both FIGO systems. Mean OS rates were estimated using the Kaplan–Meier method. ResultsMore patients had stage-I disease by the new FIGO system (42 versus 33). Five versus 18 and 27 versus 5 had old and new stage-II and III diseases respectively. Five and 4 patients with old stage II and III uLMS respectively were downstaged to stage I while 18 with old stage III were downstaged to stage II. Median follow-up was 23.5months with a median OS of 114 (95% CI, 61–166) months. Although patients with stage I tumors had a higher mean OS rate compared to those with higher stage disease by either system, patients with old stage II–IV disease showed similar mean OS rates, with stage III–IV patients having a slightly better mean OS and a similar trend was observed with the new system. Patients with new FIGO stage III had a higher mean OS rate than those with stage II or IV disease (37.6 versus 28.1 and 34.3months). Nonetheless, no statistical significant differences were seen in OS according to stage using either system (p=0.786 and p=0.400 respectively). ConclusionNeither FIGO staging system is ideal in classifying patients into four clinically significant stages.

994P - Malignant Ovarian Germ Cell Tumors (MOGCT) At a Tertiary Care Setting in Pakistan

ABSTRACT Introduction Malignant ovarian germ cell tumors (MOGCT) are rare neoplasms. Little is known about their behavior in the South East Asian populations. Aim of our study was to evaluate MOGCT patients treated at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. Patients and methods Of 638 females identified with ovarian cancer at our hospital from 1994 to 2007, 66 presenting with MOGCT were reviewed retrospectively. Histology was based on WHO classification. Tumors were staged according to FIGO system. Data was collected on presenting age, histopathology, stage, alpha-feto protein (AFP), B-human chorionic gonadotropins (B-hCG) levels, treatment, time to recurrence (TTR) and overall survival (OS). OS was the interval between the dates of diagnosis and last visit / death and TTR was between the dates of diagnosis and first recurrence. OS was determined by the Kaplan Meier method. Seven patients were not included in survival analysis as they were lost to follow up. Results Mean presenting age: 18.1 years (6-45). Stage wise distribution (n): Stage 1 (19), II (8), III (21), IV (18). Histology (n): Dysgerminoma (22), malignant teratoma (16), yolk sac tumor (15), Mixed germ cell (12) and embryonic carcinoma in 1 patient only. AFP levels (n): elevated (29), normal (25) while unknown in 12 patients. B-hCG levels (n): elevated n = 15, normal n = 42 and unknown in 9. Median follow up time was 48 months (0.2-183). All patients underwent initial surgery, with 20 patients undergoing second look surgeries. Fertility sparing procedures were performed in 57 % of patients. Thirty four patients (57 %) achieved a complete remission at the end of treatment; while 18 (27.2%) patients did not show a response to any chemotherapy and had progressive disease. Seven patients relapsed, all within the first 3 years. The TTR was 11.2-32.5 months. Cumulative overall survival: 60 months. 16 (88 %) of stage 1 patients while only 4 (26.6 %) of stage IV patients were alive at median follow up. Conclusions The prognosis of MOGCT appears to be good and results are similar to what has been seen in the west. Fertility sparing surgery was possible in majority of cases and its feasibility should be explored in this young population of patients. Disclosure All authors have declared no conflicts of interest.

Nonepithelial ovarian cancer: Outcomes after aggressive treatment with surgery and platinum-based chemotherapy.

e15548 Background: Nonepithelial ovarian malignancies account for approximately 10% of all ovarian cancers. Germ cell tumors (GCTs) represent 5% of all ovarian neoplasms and sex cord stromal tumors (SCSTs) are rare neoplasms that account for 3%–5% of them. The aim of this study was to review treatment outcomes in patients (pts) with malignant nonepithelial ovarian cancer in a single institution. Methods: Data from all pts with nonepithelial ovarian cancer sequentially diagnosed and treated at Instituto do Câncer do Estado de São Paulo (ICESP) from 1992 to 2006 were retrospectively reviewed. Results: 38 pts were identified. Median age was 52 y (22-82) for SCTCs and 20 y (12-49) for GCTs. Twelve pts (31.6%) had granulosa cell tumors, 8 (21.1%) immature teratomas, 7 (18.4%) dysgerminomas, 4 (10.5%) endodermal sinus tumors, 3 (7.9%) Sertoli–Leydig cell tumors and 1 (2.6%) embryonal carcinoma. Pts were staged according to FIGO system and 17 (54.8%) were classified as stage I, 3 (9.7%) stage II, 9 (29%) stage III, and 2 (6.5%) stage IV. Surgery was performed in all pts: pan-hysterectomy in 51.5% (17 pts) and unilateral salpingo-oophorectomy or oophorectomy for fertility preservation in 7 (21.2%) and 8 pts (24.2%), respectively; omentectomy in 19 pts (63.3%) and lymphadenectomy in 8 pts (27.6%). Considered as having a high recurrence risk, 37 pts (97.4%) received platinum-based chemotherapy: 17 GCT pts and 14 SCTC pts with adjuvant (n = 31, 83.8%) and 6 pts with palliative intent (n = 6, 16.2%). Twenty-eight pts (75.7%) received BEP regimen and 8 pts (21.6%) were treated with carboplatin and etoposide. At a median follow-up of 4.2 y, 7 pts (18.4%) experienced disease recurrence (3 GCTs and 4 SCTCs) and 24 pts (94.7%) remained alive. One death was observed among GCT pts. The 5-year overall survival rate was 95%. Conclusions: In this high-recurrence-risk group of nonepithelial ovarian cancers, aggressive treatment with surgery and platinum- based chemotherapy resulted in excellent survival outcomes. No significant financial relationships to disclose.

Predictive value of FIGO and AJCC staging systems in patients with uterine leiomyosarcoma

Background Cancer staging systems aim to identify patient cohorts with different outcomes based on clinically relevant prognostic factors. Uterine leiomyosarcoma (ULMS) is classified using the FIGO staging system developed for epithelial malignancies; other sarcomas use the AJCC staging system. Neither has been validated in ULMS. We critically evaluated both systems to determine if either identified patient groups with distinct outcomes. Methods We staged 230 ULMS patients by the FIGO and AJCC systems. Progression-free survival (PFS) and overall survival (OS) rates were calculated; statistical pairwise comparisons were performed. Results The number of stages I and III patients varied by staging system. There were few stage II patients by either system. Using the FIGO system, PFS was better in stage I patients versus stage III or IV patients, and OS was better in stage I patients versus stage IV patients. Using the AJCC system, PFS and OS were better in stage I patients (low grade) versus stage II, III or IV patients, and OS was better in stage III patients versus stage IV patients. Prognosis of patients with serosal involvement (FIGO III) was similar to that of patients with metastases (FIGO IV). Conclusion Neither system classifies ULMS patients into four clinically meaningful, non-overlapping stages predictive of PFS and OS. This analysis highlights the relevance of certain factors (low grade, serosal involvement) and rarity of others (FIGO stage II, cervical invasion). Once identified, prognostic factors relevant to this malignancy should be incorporated into a new staging system in an effort to identify appropriate cohorts for different treatments.

Primary Female Genital Lymphoma: Prognostic and Therapeutic Considerations

Primary Female Genital Lymphoma (PFGL) is very rare, representing 1.5% of all Non-Hodgkin's Lymphomas (NHLs) and 0.5% of female genital malignant tumours; uterus is the main commonly genital site involved by NHL. Most PFGLs are B-cell lymphomas; usually they occur in 5th decade of life. Because of PFGL rarity, a standard treatment has not been identified yet. This is a retrospective study on 20 women with PFGL, treated at European Institute of Oncology. The median age was 52 yrs (range 30–79 yrs); at diagnosis 6 pts were asymptomatic, 11 reported pelvic symptoms and 3 B symptoms. According to the International Prognostic Index, 7 pts had low, 6 intermediate, 6 high risk and one pt not known. Eleven pts had uterine involvement, with a concomitant extension to vagina in 5 of them, ovary NHL was recognised in 4 pts, vaginal NHL in 4 pts and vulvar NHL in one pt. Diffuse large B-cell NHL (DLBCL) was diagnosed in 14 pts, marginal extranodal NHL in 3 pts and follicular in 3 pts. According to Ann Arbor staging system: 8 pts were in early stage (IE–IIE) and 12 pts in stage IVE; considering FIGO system: 11 pts were in early stage (I–II), 6 pts in stage III for regional lymph node involvement and 3 in stage IV for concomitant non-genital extranodal localization; 12 pts presented with bulky disease. At diagnosis no pts had bone marrow involvement. The diagnostic biopsy was performed by endoscopy in 13 pts and by ultrasound-guided in 2 pts, whereas 5 pts underwent laparotomy. One pt with vulva-limited marginal NHL did not receive any treatment until disease progression (PD) and transformation to DLBCL. Five pts underwent laparotomy and adjuvant chemotherapy (CT) alone (n=4) or in combination with radiotherapy (RT) (n=1); 14 pts received CT alone (n=8) or in combination with RT (n=6) as first line therapy.Anthracycline-containing CT was delivered to all pts with DLBCL (n=14) and to one pt with high grade follicular NHL, 12 of them received concurrent immunotherapy anti-CD20 (Rituximab). Central nervous system (CNS) chemo-prophylaxis with i.v. high dose methotrexate was delivered to 3 pts because of advanced or bulky disease. Two pts with follicular and 2 with marginal subtype received alkylating-containing CT alone (n=2) or with Rituximab (n=2). The Overall Response Rate (ORR) to first line therapy was 80%; the response did not improve by the addition of local treatment to CT. Three pts did not response to first line therapy: one with marginal NHL in stable disease did not receive any additional treatment because of asymptomatic disease; two with DLBCL in PD underwent salvage treatment with high dose CT and died in PD, concurrent intrathecal therapy was mandatory in one pt because of CNS relapse. Three pts with follicular NHL, in response to first line therapy, relapsed: one went on to receive maintenance Rituximab, one resulted refractory to different rescue CT regimens and died in PD, one underwent autologous bone marrow transplantation obtaining CR. After a median follow up of 51 months (range 11–164 months), 17 pts are still alive: 10 in CR and 7 in PR, 3 pts died in PD. The Overall Survival (OS) at 3 and 14 yrs was 84.8% and 42.4% respectively. According to the literature the most common histological subtype of PFGL occurred in our population was DLBCL and the most frequent genital site involved was uterus (55% of cases) [Lagoo et al. 2006]. An additional local treatment did not seem to give an advantage in terms of ORR, PFS and OS in comparison with systemic therapy alone, as stated by the literature [Signorelli et al. 2006]. Concerning the pts treated with anthracycline-containing CT with or without Rituximab (n=15), 8 pts (53%) and 5 pts (33%) achieved CR and PR respectively, 2 pts (13%) had a PD during treatment, only one pt in CR relapsed after 65 months from the first line therapy. After a median follow up of 27 months 12 pts (80%) are alive, 3 (20%) died in PD. The Response Rate and OS in the subgroup of pts that received anthracycline-containing CT resulted similar to those reported in the literature [Coiffier 2002]; therefore female genital involvement by NHL doesn't seem to represent a negative prognostic factor.

Dynamic staging and risk factor scoring for gestational trophoblastic disease

It is proposed that a dynamic staging and risk factor scoring system is introduced for the classification of gestational trophoblastic disease as a logical development of the system presently used by the FIGO. Modern computer technology permits such change as the disease changes and particularly if it progresses. By allowing a change of both stage and risk factor score for each patient reported, a dynamic scoring system results. Moreover, such a system allows the introduction of more clinical detail than is permitted by the present FIGO system. FIGO combining its anatomic staging, first devised by Professor Song of Beijing, with the World Health Organization risk factor scoring, first devised by Professor Kenneth Bagshawe of Charing Cross Hospital, London, in 2002 was a significant progress. The most important change of the FIGO 2002 modification was that criteria were defined for the diagnosis of postmolar gestational trophoblastic neoplasia. However, hydatidiform mole still has no place in that classification. Also, the time when the staging occurs is not mandated. The present FIGO classification allows for no change in the status of the patient. A dynamic staging and risk factor scoring system would allow such changes to be recorded and, therefore, permit a more precise account of the patient's disease. A third issue is whether invasive mole should be included in the classification, as the Japanese Gynecologic Cancer Society insists is necessary. This problem may also be solved by the use of a dynamic risk factor scoring system.

Why Cancer Staging?

The major task faced by a clinician having made a diagnosis of cancer is to determine the most effective therapy and formulate a prognosis for the patient. In order to optimally manage a cancer, both the extent of the disease and the knowledge of its biology are essential. The extent of the disease is generally expressed in terms of its stage. The major purpose of staging that has been agreed upon internationally is to offer a classification of a cancer’s extent so as to provide a method of conveying ones clinical experience to others for the comparison of treatment methods without confusion or ambiguity. Cancer staging is central to the modern management of cancer patients. Cancer is also a biologic continuum and a dynamic process, which is artificially compartmentalized by staging systems. It is clear, however, that the phases or sub-stages must have clinical relevance. Cancer staging systems should also be evidence-based and they should be user friendly. Staging systems need to be based on the best available knowledge at hand and this implies that the changes will occur over time based upon the development or the acquisition of new knowledge. It also follows that the acquisition of this knowledge is facilitated by the use of staging system insofar as staging will help with knowledge creation by facilitating clinical research, producing new data on similar groups of patients and also by integrating this new data about similar patients from diverse sources. Staging also helps knowledge dissemination by providing a common international language for information sharing and facilitates the teaching of both new and established health care workers. Gynecologists have a long and proud tradition of using staging systems for female cancers, dating back to the League of Nations staging system for cervical cancer, first published in 1920. In 1954 FIGO assumed the patronage of the Annual Report on the Treatment of Gynecological Cancer. With it also came the responsibility for overseeing the staging of gynecological cancers, which were at the heart of the Annual Report data and information system. Since that time the FIGO Oncology Committee has made several modifications to the various staging systems for gynecological cancer, most notably those for cervix and endometrial cancer. 1954 also saw the UICC set up a committee on clinical stage classification and applied statistics, which had as its aim the extension of the general technique of classification of cancer at all sites by anatomical extent of the disease using the TNM system. The FIGO system of classification was originally based on clinical examination, essentially of the anatomical extent of disease. Over the years all staging systems for gynecological cancers, with the exception of cervical cancer and gestational trophoblastic neoplasia, have moved from a clinical basis to one of a surgical pathological nature. The classification system and stage grouping, once established, must remain unchanged in medical records. Clinical stage is essential to select and evaluate therapy, while the pathological stage provides the most precise data to estimate prognosis and calculate end results. The FIGO and TNM classifications are virtually identical. The TNM Prognostic Factor Project Committee has graciously agreed to defer to all questions regarding staging of gynecological cancer to the FIGO Committee on Gynecologic Oncology. In conclusion, any good staging system must have three basic characteristics. It must be valid, reliable, and above all, it must be practical. Validity means that the staging system must allow for the creation of groups of cases, that experience similar outcomes at the same time reflecting a full range of possible presentations for each type of cancer. Also over time, the system in order to retain its validity must be flexible so that it can adapt to important changes in medical care. A reliable staging system should ensure that identical cases would always be assigned to the same stage category. It should be unambiguous; it should be based as far as possible on measurement quantities that have been evaluated objectively. The system should also not be subject to frequent changes until sufficient data and information is obtained to warrant such changes. Finally, a practical staging system must be suitable for day to day use in a wide range of clinical environments and must not require diagnostic procedures that are not readily available to most practitioners or extraordinary expertise or knowledge regarding a particular malignancy. The staging classification is reported at the beginning of each tumor site section, along with rules and recommendations.

Endometrial carcinoma metastatic to the vulva: A case report and review of the literature

In this paper, we report a new case of metastatic endometrial carcinoma to the vulva and describe the clinical and pathological features. We reviewed the literature to determine the frequency and to evaluate the prognostic significance of this rare disease. Moreover, we discuss the criteria for the differential diagnosis of endometrial carcinoma metastatic to the vulva, the primary vulvar adenocarcinomas, and other metastatic adenocarcinomas. The patient, previously diagnosed to have endometrial adenocarcinoma with squamous differentiation at III C stage (according to the FIGO system) and T2N1M0 stage (according to the TNM system), presented with a small plaque on the vulvar mucosa 8 months after endometrial primary carcinoma had been diagnosed. The histological evaluation of excisional vulvar biopsy revealed a neoplasm with pathological features of endometrial carcinoma. Thus, the final diagnosis was metastatic endometrial carcinoma to the vulva. A total body computed tomography scan (CT) and an echotomography with contrast medium revealed a second metastatic lesion at the 8th segment of the liver. No other metastatic lesions developed, nor was a reduction in the size of liver metastasis observed after 3 months of hormonic treatment with progesterone. Fourteen months after the diagnosis of primary endometrial carcinoma, the patient died of disseminated metastatic lesions. In conclusion, metastatic endometrial carcinoma to the vulva, although rare, might develop and could appear within a few months after the diagnosis of primary tumor. Moreover, in the presence of metastatic endometrial carcinoma to the vulva, it is necessary to verify if other visceral metastases are present.

Immunohistochemical analysis of c-myc, c-jun and estrogen receptor in normal, hyperplastic and neoplastic endometrium

To evaluate the role of c-jun and c-myc proto-oncogenes in normal, hyperplastic and neoplastic endometrium in relation to estrogen receptor (ER) status and to investigate whether these genes can be related to other histopathological features of endometrial carcinoma, 32 endometrial carcinomas, 38 endometrial hyperplasias and 22 cyclic endometria (10 proliferative and 12 secretory) were evaluated histologically. Endometrial hyperplasia cases were classified as simple and complex hyperplasia without atypia, and atypical hyperplasia. Endometrial carcinoma cases were subtyped according to the International Society of Gynecological Pathologists. Modified FIGO system was used for both grading and staging. Immunohistochemical examination was performed using antibodies to ER-alpha, c-myc and c-jun with streptavidin-biotin-peroxidase technique. The mean percentage of ER-alpha positive cells changed cyclically during the menstrual cycle, and it was the highest (96%) and the lowest (31.6%) in proliferative and carcinomatous endometrium, respectively. There was a statistically significant difference between proliferative and secretory phases and proliferative and carcinomatous endometrium in relation to ER-alpha staining (p<0.05). There was also a statistically significant difference with respect to ERalpha reactivity between secretory phase and each hyperplastic group, as well as between the carcinoma group and each hyperplastic group (p<0.05). Although not significant, the mean percentage of c-myc expressing cells in the carcinoma group was higher (15.3%) than that of proliferative phase and hyperplastic groups. The mean percentage of c-jun positive cells in proliferative endometrium was slightly higher than in secretory endometrium, and it was the highest in atypical hyperplastic endometrium (28.3%), but there was no statistically significant difference between the groups. In carcinoma cases, a positive correlation was observed between c-jun positivity and tumor grade (p=0.027, r=0.3908), but such a correlation with c-myc was not found. A positive correlation was detected between ER-alpha and c-myc expression (p=0.038, r=0.3686). A progressive loss of ER seems to be correlated with increasing malignant transformation. C-myc expression might play a role in the development of endometrial carcinoma via ER. The association between c-jun and ER appears to be lost in endometrial carcinoma. The relationship between c-myc, c-jun and ER appears to be altered in endometrial carcinoma compared to that of menstrual endometrium.

Comparison of the interobserver variability and prognostic significance of two grading systems for endometrial carcinoma in the pathology review of the randomized portec trial

Purpose/Objective: For endometrial carcinoma the most widely used histological grading system is the three-tiered FIGO system. Recently, Lax et al have proposed a new binary grading system, discriminating between high and low grade tumors, based on the amount of solid growth, the pattern of myometrial invasion and the presence of necrosis. The FIGO grading system is based primarily on the amount of nonsquamous solid growth and on the degree of nuclear atypia. The aim of our study was to compare the interobserver variability and prognostic significance of both grading systems in endometrial carcinomas included in the multicenter randomized PORTEC-trial.

Cervical cancer staging.

The "International Classification of the Stages of Carcinoma of the Uterine Cervix" dates back to 1950; since then, seven changes have been made to the staging system for cervical cancer (almost all were made to Stage I), the most recent being in 1995. The FIGO system of classification of cervical cancer is originally based on the results of clinical examination, essentially of the anatomical extent of disease, and is determined at the time of primary diagnosis. Only if the rules for clinical staging are strictly observed is it possible to compare results using different modalities of treatment. Cervical cancer remains a clinically staged malignancy according to the FIGO staging system. Surgical-pathologic staging would not be feasible for advanced-stage disease or in early-stage patients treated primarily with radiation, especially in nations that do not routinely offer surgical extirpation due to different or limited health care resources. However, surgical and pathological data are important for precise analysis of survival and prognostic risk factors.

Gestational trophoblastic tumors in Norway, 1968-1997: patient characteristics, treatment, and prognosis.

The aim of this study was to give an overview of the Norwegian population of gestational trophoblastic tumors (GTT), diagnosed during 1968-1997 and treated with chemotherapy at the Norwegian Radium Hospital (NRH), with regard to patient characteristics, treatment, and prognosis. The cases were grouped according to a modified version of the WHO scoring system. Staging was performed retrospectively according to the systems adopted by FIGO. Survival estimates were calculated by the method described by Kaplan and Meier. Cox regression models were used to find the best classification system with regard to prognosis (disease-free survival). A total of 141 cases, 106 invasive moles (IM) and 35 choriocarcinomas (CC), were diagnosed in Norway and treated with chemotherapy at the NRH in the period 1968-1997. Altogether, 56% of the patients were assigned to the low-risk category, 20% to the medium-risk category, and 15% to the high-risk category. Most cases were classified into the clinical stages I (69%) and III (23%). The overall 5-year survival rate was 96%. A more favorable prognosis was seen in patients diagnosed in the 1980s and 1990s compared with those diagnosed in the 1970s (P = 0.04). Five patients had progressive disease and died from the disease. Nine patients relapsed. The prognosis (disease-free survival) was more favorable for IM compared with CC (P < 0.01). The FIGO classification system seemed to be a better predictor of disease-free survival than the WHO scoring system. This study showed that the prognosis of patients with GTT improved in the 1980s and 1990s in Norway, and that the FIGO system might be the best predictor of disease-free survival.

To the Editor

Abstract Objective. Because there is no universally accepted grading system for ovarian epithelial carcinoma, we attempted to compare the prognostic utility of the individual components used in some systems—both architectural and cytologic features, as well as mitotic activity and histologic tumor type—to determine which of these components fit best with survival. Methods. We studied 461 patients with invasive ovarian carcinoma who had uniform treatment, complete clinical data including staging and follow-up, and slides available for review. Each tumor was assigned a histologic subtype, architectural grade (based on whether the predominant pattern was glandular, papillary or solid), nuclear grade, mitotic count, and FIGO grade (based on the system for endometrial carcinoma). These features were compared with each other and with tumor stage and survival. Results. The architectural grade, nuclear grade, and mitotic count were independent variables both in stage I/II and stage III/IV disease. Each of them correlated with survival for most combinations of histologic type and stage. By multivariate analysis, in stage I/II cancer, nuclear grade and architectural grade were significantly correlated with survival, mitotic count showed only a trend, and FIGO grade did not correlate. In stage III/IV disease, nuclear grade, architectural grade 3, and mitotic count were significant, and FIGO grade was not. Conclusion. The new architectural grading system proposed worked better than the FIGO system in this study. Furthermore, it could be applied to all histologic subtypes of carcinoma. The nuclear grade and mitotic count were also independent of each other, correlated with survival, and could be utilized for all histologic types. These data support the development of a grading system which combines these architectural, nuclear, and mitotic features and can be applied regardless of the histologic type of carcinoma, modeled after the Nottingham system for grading of breast carcinoma.

Management and Prognosis of Primary Fallopian Tube Carcinoma

We retrospectively analyzed 143 women treated in 28 departments from 1980 to 1995, to study the impact of prognostic factors in primary carcinoma of the fallopian tube. Further aims of the study were to evaluate the treatment of fallopian tube carcinoma in Austria. Staging of disease was done according to the modified FIGO system, and grading according to the criteria suggested by Hu et al. The mean age of the patients was 62.5 years. Sixty (42%) tumors were found to be in stage I, 28 (19%) in stage II, 38 (27%) in stage III, and 17 (12%) in stage IV. Radical resection was achieved in 102 (71%) patients. In 122 (85%) women surgery involved removal of the uterus, the adnexa, and/or the omentum or lymph nodes. Postoperatively patients underwent adjuvant therapy consisting of either irradiation (n = 40; 28%) or chemotherapy (n = 70; 49%); 33 women (23%) did not receive any treatment after surgery. The 5-year survival rate for all stages of disease was 43%. The 5-year survival rate was 59% for stages I and II and 19% for stages III and IV. FIGO stage, histologic grading and residual tumor showed an independent prognostic impact in multivariate analysis.

Primary ovarian mucinous cystadenocarcinomas: a clinicopathologic study of 49 cases with long-term follow-up.

Prognostic data for ovarian mucinous carcinoma are limited and difficult to interpret because of differing diagnostic criteria and inclusion of secondary tumors. To better characterize these neoplasms, 49 primary ovarian mucinous tumors diagnosed as carcinoma by the Hart and Norris criteria and staged by the FIGO system were studied. Forty-four tumors (90%) were stage I, four were stage III and one was unstaged. Sixteen tumors (33%) were classified as intraglandular ("noninvasive") carcinoma; all were stage I and all patients were alive without tumor after 4-216 months (mean, 74 months); two patients had received adjuvant chemotherapy. Stromal invasion was present in the remaining 33 cases (67%), including 19 tumors with extensive invasion and 14 with one or more discrete foci of microinvasion (each focus < or = 1 mm). The microinvasive tumors were reclassified into intraglandular carcinoma with microinvasion (nine cases) and borderline (low malignant potential) tumor with microinvasion (five cases). All microinvasive tumors were stage I and none recurred after postoperative intervals of 9-176 months (mean, 71 months) for the microinvasive carcinomas and 33-117 months (mean, 60 months) for the microinvasive borderline tumors; only 1 of the 14 patients received adjuvant chemotherapy. All 19 extensively invasive carcinomas also had intraglandular carcinoma. Fourteen were stage I, four were stage III, and one was unstaged. Eleven (79%) of the stage I patients were alive without tumor after 10-220 months (mean, 110 months), including six who received chemotherapy; one was dead without tumor and two developed progressive disease (one had received adjuvant chemotherapy). The four extensively invasive stage III carcinomas were fatal after 1-59 months. The unstaged patient received adjuvant chemotherapy and was alive without recurrence at 98 months. Conclusions of this study are as follows: (1) primary mucinous carcinomas are very uncommon tumors, after rigorous exclusion of metastatic carcinomas and tumors associated with pseudomyxoma peritonei; (2) bilaterality is not a feature of primary mucinous carcinomas; (3) FIGO stage is the single most important prognostic factor, with stage I carcinomas having a very favorable prognosis; (4) stage I carcinomas that metastasize have extensive stromal invasion; (5) extensive stromal invasion is found only in tumors with a component of intraglandular carcinoma; (6) high-stage carcinomas invariably contain extensively invasive carcinoma and have a very poor prognosis; and (7) stromal microinvasion with individual foci not exceeding 1 mm does not appear to be an adverse factor in either carcinomas or borderline tumors of stage I.

Toward the Development of a Universal Grading System for Ovarian Epithelial Carcinoma: I. Prognostic Significance of Histopathologic Features—Problems Involved in the Architectural Grading System

Objective.Because there is no universally accepted grading system for ovarian epithelial carcinoma, we attempted to compare the prognostic utility of the individual components used in some systems—both architectural and cytologic features, as well as mitotic activity and histologic tumor type—to determine which of these components fit best with survival.Methods.We studied 461 patients with invasive ovarian carcinoma who had uniform treatment, complete clinical data including staging and follow-up, and slides available for review. Each tumor was assigned a histologic subtype, architectural grade (based on whether the predominant pattern was glandular, papillary or solid), nuclear grade, mitotic count, and FIGO grade (based on the system for endometrial carcinoma). These features were compared with each other and with tumor stage and survival.Results.The architectural grade, nuclear grade, and mitotic count were independent variables both in stage I/II and stage III/IV disease. Each of them correlated with survival for most combinations of histologic type and stage. By multivariate analysis, in stage I/II cancer, nuclear grade and architectural grade were significantly correlated with survival, mitotic count showed only a trend, and FIGO grade did not correlate. In stage III/IV disease, nuclear grade, architectural grade 3, and mitotic count were significant, and FIGO grade was not.Conclusion.The new architectural grading system proposed worked better than the FIGO system in this study. Furthermore, it could be applied to all histologic subtypes of carcinoma. The nuclear grade and mitotic count were also independent of each other, correlated with survival, and could be utilized for all histologic types. These data support the development of a grading system which combines these architectural, nuclear, and mitotic features and can be applied regardless of the histologic type of carcinoma, modeled after the Nottingham system for grading of breast carcinoma.

The Prognostic Value of Semiquantitative Nuclear Grading in Endometrial Carcinomas

The objective of this study was to evaluate the prognostic value of a convenient nuclear grading system based on only the proportion of nuclei measuring more than 10 μm in length at the shortest axis in endometrial carcinomas. Of the 235 cases reviewed, 9 serous and 5 clear cell adenocarcinomas and 2 small cell carcinomas were eliminated, resulting in a study population of 219 cases of endometrial adenocarcinoma. The architectural grade was determined by the FIGO system. The criteria for nuclear grade were as follows: grade 1, no nucleus measuring more than 10 μm in length at the shortest axis; grade 2, nuclei measuring more than 10 μm in length at the shortest axis seen in percentages ranging between 0 and 10% of tumor cells in active areas; and grade 3, more than 10% of tumor cells in active areas with nuclei measuring more than 10 μm in length at the shortest axis. The criteria for combined grades were as follows: the tumors were graded according to the architectural grade, but high-grade nuclear abnormalities increased the grade by one for architectural grade 1 and 2 tumors. The cumulative 10-year survival rates for architectural grades 1, 2, and 3 were 92.4, 82.6, and 65.2%, respectively (χ2= 17.9,P= 0.001). The survival rates for nuclear grades 1, 2, and 3 were 96.2, 76.1, and 70.1%, respectively (χ2= 21.6,P< 0.001), while for combined grades 1, 2, and 3 the survival rates were 98.3, 83.2, and 65.2%, respectively (χ2= 26.9,P< 0.001). Even when the cases were limited to the 147 stage I endometrial carcinomas examined, the prognostic value of the combined grading system was still found to be superior to that of the architectural grading system. Our observations therefore supported the FIGO recommendation for nuclear grade not only in stage I endometrial carcinomas, but also in all stages of endometrial carcinomas.

Survival Rates and Prognosis Factors of Endometrial Cancer Stage I

Background: Since the introduction of the new FIGO classification for endometrial cancer, there have been few studies evaluating the prognosis of endometrial cancer on the basis of this new classification. Materials and Methods: For a total of 514 patients with endometrial cancer stage I who had been treated from January 1, 1980 to December 31, 1991 and followed up until January 7,1993, a reclassification on the basis of the new FIGO system was undertaken and a multivariate analysis carried out to identify prognosis factors on the basis of the Cox Proportional Hazard Model. Results: The 5-year survival rate at FIGO stage la is 92.4%, at FIGO stage lb 96.7%, and at FIGO stage Ic 88.2%. According to the FIGO classification, 14.6% belonged to stage la, 44.6% to stage lb, and 40.8% to stage Ic. In spite of the large number of investigated cases, the FIGO subclassification Ia––Ic showed in a multivariate analysis no statistical difference between stage la and lb concerning prognosis. On the other hand, grading (odds ratio 3.3), type of therapy (odds ratio 2.2), and age at diagnosis proved to be highly significant prognosis factors. Conclusions: The evaluation of 514 endometrial cancers shows that the subclassification at FIGO stage I using the Cox Proportional Hazard Model cannot be identified as a significant prognosis factor except stage Ic. The study shows that despite of the large number of documented cases, the prognostic differences between stages la and lb are too small to be distinguished by using the Cox Proportional Hazard Model.

Pathologic stage III endometrial carcinoma: Significance of extrauterine sites

Little information is available concerning the influence of specific extrauterine sites in patients with stage III endometrial carcinoma. To define better the prognostic factors and patterns of failure, we reviewed 105 patients with pathologic stage III disease (1988 FIGO system) who were treated between 1970 and 1990. Following hysterectomy, all patients received postoperative external beam irradiation to the pelvis alone (88 patients) or to the pelvis and paraaortic regions (17 patients) for pathologically positive paraaortic nodes. Actuarial techniques were used to analyze survival and recurrences. Range of follow-up was 7–251 months (median 83 months). Five-year disease-free survival (DFS) for all patients was 64%. Multivariate analysis revealed clear cell/papillary serous histology and histologic grade to be significant predictors of DFS. Based on our analysis, four prognostic groups are described for the purpose of predicting outcome and patterns of disease recurrence. Patients who have a single extrauterine site of involvement and histologic grade 1 tumors have an excellent prognosis. Patients with a single extrauterine site of involvement and grade 2 or 3 tumors have a lower DFS rate, as do patients with two or more sites of extrauterine involvement. However, patterns of disease recurrence for these groups are different, and these are discussed. Radiat Oncol Invest 1996;4:122–128. © 1996 Wiley-Liss, Inc.