Text Box: UNIVERSITE DE GENEVE FACULTE DE MEDECINE Text Box: THE VALUE OF PERITONEAL CYTOLOGY IN EARLY STAGE ENDOMETRIAL CANCER Text Box: PM Tebeu(1,3), Y Popowski(2), H M Verkooijen(3), C Bouchardy(3), F Ludicke(4), M Usel(3), A L Major(1,4) 1) Department of Gynecology, Geneva University Hospital,2) Division of Radio-Oncology, Geneva University Hospitals, 3) Geneva Cancer Registry, Institute for Social and Preventive Medicine, University of Geneva,   4) Fondations pour Recherches Médicale, University of Geneva  
 
                     
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
Text Box: Background and objective: According to FIGO classification, early stage endometrial cancers with positive peritoneal cytology are classified as stage IIIA,  like patients with histological invasion of the serous or adnexa. In a recent study, including endometrial cancer patients treated with surgery and radiotherapy, we showed that patients classified as stage IIIA because of positive peritoneal cytology had the same survival as stage I endometrial cancer patients 1. In order to examine the prognostic importance of peritoneal cytology, independently from radiation therapy, we extended our previous study population to non-irradiated patients, using population-based data. 
 
              Text Box: Figure 1  Endometrial cancer specific survival curves according to stage and use of adjuvant therapy Text Box: Panel A      All patients
 
       
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
Text Box: Patients and methods: All 278 stage I and 53 stage IIIA (without cervical involvement) endometrial cancer patients  operated between 1980-1996, recorded at the Geneva Cancer registry, were included. Stage lllA cancers were re-categorised into ‘cytological‘ stage lllA (positive peritoneal cytology alone, n=33) and ‘histological’ stage lllA (serosal or adnexal infiltration, n=20). Survival rates were analysed by Kaplan Meier method and compared using log-rank test. The prognostic importance of cytology was analysed using a Cox model, accounting for other prognostic factors.   
 
                       
                         
                         
                         
                         
                         
                         
                         
                         
                         
Text Box:   Text Box: Results Patient and tumour characteristics are described in Table 1. Compared to stage I patients, women with histological or cytological stage IIIA cancer have less well differentiated tumours and more often deeper myometrial invasion. Overall, 171 (52%) women underwent adjuvant radiotherapy. Forty-six percent (n=129) of stage I patients had radiotherapy compared to 83% (n=27) of cytological stage IIIA and 75% (n=15) of histological stage IIIA patients. Figure 1 presents the five-year disease specific survival curves according to stage. For all patients combined (with and without adjuvant radiotherapy), survival for stage I endometrial cancer (92.3%) was comparable to that of cytological stage IIIA endometrial cancer (90.9%) (Figure 1, panel A) . In contrast, patients with histological stage IIIA cancer had a significantly worse survival (49.5%, p<0.001). When separately analysing patients with and without adjuvant radiotherapy, similar results were observed (Figure 1,  panels B and C). Table 2 presents the five-year disease specific survival rates and the adjusted risks (Hazard Ratio) of dying from endometrial cancer according to stage. After adjustment for factors significantly linked to disease prognosis (i.e., age, tumour differentiation, myometrial invasion and use of adjuvant radiotherapy), cytological stage IIIA patients were not at an increased risk to die from endometrial cancer compared to patients with stage I disease (HR 0.7, 95%CI 0.2-2.3). Histological stage IIIA patients however had a 4-fold increased risk to die from their disease (HR 4, 95%CI 1.7-10.3). Text Box: Panel B      Patients with radiotherapy Text Box:   Text Box:   Text Box: Panel C     Patients without radiotherapy Text Box: Discussion Previous studies 2,3 pointed out the importance of peritoneal cytology by showing that patients with early stage endometrial cancer with positive peritoneal cytology had worse survival rates than those with negative peritoneal cytology. As these studies classified patients according to the clinical staging system, other important prognostic factors like myometrial invasion were not taken into account. Other publications which used the new FIGO surgical staging system did not confirmed these results 4,5. In the current study, we eliminated many shortcomings of other studies and found that, based on positive peritoneal cytology alone, there is no survival difference between patients with stage I and IIIA endometrial cancer, even after adjusting for other prognostic factors, including use of  radiotherapy. We concluded that positive peritoneal cytology is not an independent prognostic factor in patients with endometrial cancer and that FIGO might consider reviewing it's classification.   Text Box: References  1.  Tebeu PM, Popowski GY, Verkooijen HM,  et al. : Impact of peritoneal cytology on survival of endometrial cancer patients treated with surgery and radiotherapy. Br J Cancer 89:2023-2026, 2003 2.  Morrow CP, Bundy BN, Kurman RJ, et al: Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study. Gynecol Oncol 40:55-65, 1991  3.  Obermair A, Geramou M, Tripcony L, et al: Peritoneal cytology: impact on disease-free survival in clinical stage I endometrioid adenocarcinoma of the uterus. Cancer Lett 164:105-110, 2001 4. Kadar N, Homesley HD, Malfetano JH, Positive peritoneal cytology is an adverse factor in endometrial carcinoma only if there is other evidence of extrauterine disease. Gynecol Oncol 46:145-149, 1992 5.  Kasamatsu T, Onda T, Katsumata N, et al: Prognostic significance of positive peritoneal cytology in endometrial carcinoma confined to the uterus. Br J Cancer 88:245-250, 2003    
 
                       
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                         
                        Text Box: For contact: pmtebeu@yahoo.fr
 
Text Box: The Scientific Association of Swiss Radiation Oncology. 8th Annual meeting,  Lucerne March 2004