PROGNOSTIC FACTORS IN ADVANSED OVARIAN CANCER

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1 PROGNOSTIC FACTORS IN ADVANSED OVARIAN CANCER Dr. Hisham Rahahle Gynecologist, MD, Ph.D Subspecialty in Gynecological Oncology

2 Abstract: This study includes (68) patient diagnosed with advanced epithelial ovarian cancer in the years ( ). The aim of this study was to evaluate the effect on the survival rate in relation to the following factors: age, parity, number of abortions, surgically removable tumors, surgical findings, staging, histological types and grades of tumors, size of the residual tumors, chemotherapy, a second look operation, recurrence, metastasis and treatment. According to FIGO staging of epithelial ovarian cancer, the results were: 56% had stage III, 44 % had stage IV. All patients received adjuvant cytotoxic (I.V) cisplatin polychemotherapy after primary cytoreduction then a second-look laparotomy was performed. Overall survival rate at five years was 26.15%. Overall survival rate at ten years was 18%.

3 Introduction Incidence: In the US approximately new cases are diagnosed annually. Epithelial ovarian cancer is the 5th cause of death indicating that 1 in 70 women will develop ovarian cancer in her life time. Age and Parity: The highest incidence of ovarian cancers was in menopausal women between ages Parity: nulliparous rather than multiparous were more affected. Breast Feeding: Is a protective factor against ovarian cancer. Menopause: More common in late menopause and early menarche (Hildreth,cols,1981)(5)

4 Clinical picture: History: Signs and symptoms: -Abdominal distension. -Abdominal discomfort. -Flatulence. -Change in the bowel motion. On physical examination: -A Pelvic mass was palpated -Ascites was found -Pleural effusion

5 CONT.. Investigations: -Complete blood analysis -Urine analysis -Coagulation profile -Tumor markers CA-125 -chest X-ray -ECG -Extension studies -Abdominal ultrasound

6 Metastasis: - Direct spread transcodomic through peritoneal surface, - Lymphatic metastasis mainly in advance stage.(12,15) - Hematogenous spread: Metastasis to lung, liver, kidney and bone (Dauplat and cols 1987) (16,17,18).

7 Stage Staging of advanced epithelial ovarian cancers according to FIGO (12). Criteria Stage III Tumors involving one or both ovaries with peritoneal implants outside the pelvis and/or positive retroperitoneal or inguinal lymph nodes. Superficial metastases equals stage III. Tumor is limited to the true pelvis but with histological proven malignant extension to small bowel or omentum. Stage IIIa Stage IIIb Stage IIIc Stage IV Stage IVa Tumor grossly limited to the true pelvis with negative lymph nodes but with histological confirmed microscopic seeding of abdominal peritoneal surfaces. Tumor of one or both ovaries with histologically confirmed implants of abdominal peritoneal surfaces, non exceeding 2cm in diameter. Nodes are negative. Abdominal implants greater than 2cm in diameter and/or positive retroperitoneal or inguinal lymph nodes. Growth involving one or both ovaries with distant metastases. If pleural effusion is present there must be positive cytology to allot a case to stage IV. Parenchymal liver metastases equals stage IVa.

8 The Surgical procedure: The goal of our surgical treatment is removal of the tumor as much as possible.(21,22) Big supraumbilical vertical incision - Peritoneal washing if no ascitis. - Exploration of the whole abdominal cavity - Biopsies were taken from : - greater omentum - Adhesion areas - Pouch of Douglas - Round ligaments Surgical interventions, which consists of: - Total abdominal hysterectomy and bilateral salpingoopherectomy. - Debulking of all the tumor mass. - Omentectomy and appendectomy. - Multiple biopsies. - Para aortic and iliac lymphadenectomy

9 CONT.. Chemotherapy: Combined chemotherapy protocol consisting of Taxol and Carboplatin(27) Second look laparatomy: Laparotomy according to the technique of Lippman (23) - Peritoneal washing for cytology. - Multiple biopsies were taken.

10 Material & Methods Our study involved a total number of 68 patients diagnosed with stage III and IV ovarian cancer (according to the FIGO classification) during the time period between January 1990 and December 1995 with a minimal follow up period of 5 years. The mean patients age was 56 years (range:34-78 Years). Parity: Nulliparous 24%, Multiparous 76%.

11 Table 1: Distribution according to Age, Parity and Abortion STAGE III AND IV CA OVRAY DISTRIBUTION OF AGE AND PARITY Age 56 Years Min 34 Max 75 Parity Nullipara 23% 0% Multipara 76% 0% Abortion Nulligravida 61% 0% With abortion 24% 0%

12 Table 2: Initial surgical treatment of ovarian cancer Stage III & IV. STAGE III,IV CA OVARY INITIAL SURGICAL TREATMENT Type of surgery N=68 % Biopsy Cytoreductive Complete surgery % 17.6% 36.7%

13 Table 3: Second look laparotomy among cancer group STAGE III, IV CA OAVARY TREATED WITH CHEMOTHERAPY N=68 % Second-look

14 Chemotherapy: Five regimens were instituted in our patients: Cisplatinum, Adriamycin, and Cyclophosfamide. Intra-peritoneal cisplatinum. Cisplatinum, Adriamycin, and clorambucil Intraperitoneal Cisplatinum and bleomycin. Cisplatinum, Adriamycin and Genoxal Method of administration of intraperitoneal chemotherapy 2 L of normal saline was injected intraabdominal through a catheter followed by the administration of 200 mg/m2 of cisplatinum and sodium thiosulphate.

15 R e s u l t: DISTRIBUTION ACCORDING TO AGE Age (years) N=68 %

16 Table 6: Parity among the malignant groups Distribution according to parity in stage III and IV ovarian cancer Parity N=68 % Nulliparous % Primipara % Multipara % Unknown %

17 Table 7:Distribution according to the presence of ascitis in ovarian cancer stage III and IV Ascitis N = 68 % With Without

18 Table 8: Distribution according to the peritoneal washing results in ovarian cancer stage III and IV Peritoneal wash Cases Positive 4 cases Negative 1 cases Not done 9 cases

19 Table 9: Distribution according to residual tumor after salvage surgery among the cancer groups Residual mass Cases (n=22) % No Residual Tumor 7 cases 10% Tumor < 2cm 5 cases 7% Tumor > 2cm 10 cases 14.71%

20 Table 10: Distribution of different stages of the disease Stage No. of patients % Stage IIIa 4 5% Stage IIIb 2 2% Stage IIIc 32 47% Stage IV 30 44%

21 Table 11: Distribution according to the types in the malignant groups Histological type n=68 % Serous adenocarcinoma Muscinous adenocarcinoma % % Endometroids % Undifferentiated % Mixed % Clear cell carcinoma %

22 Table 12: Distribution according to the histological grades after treatment in Stage III, IV ovarian cancer Histological grade Stage III, IV Ca ovary Classification of histological grade N=68 % GI highly date % GII mild date % GIII poorly % Unknown %

23 Table 13:Types of chemotherapy used among the malignant groups STAGE III, IV epithelial ovarian cancer adjuvant chemotherapy Poly chemotherapy N=68 % Cisplatinum, Adriamycin and cyclophosphamide Cisplatinum,Adriamycin and Clorambucil Intraperitoneal, Cisplatinum Cisplatinum + Intraperitoneal Bleomycin % % % %

24 Table 14: distribution according to number of cycles patient tolerated among the malignant groups No. of cycles No. of patients % Less than 5 cycles 17 25% 5 cycles % More than 5 cycles %

25 Table 15: Number of patients who had a second-look laparotomy after chemotherapy Second-look n=68 % Done % Not done %

26 Table 17 :distribution according to the evolution of the patient with advanced epithelial ovarian cancer Stage III and IV ovarian cancer Evolution Situation N=68 % Persistent % Complete response % Metastases % Recurrence % Un known %

27 Stage III and IV ovarian cancer Evolution Situation n=68 % Alive without disease Died due to tumor Died due to another cause Don t know 3 4.7

28 Study of the survival rates among our patients in stage III and IV epithelial ovarian cancer. Global Survival rate Survival Months Figure 1: Survival rates for all groups of Patients

29 Figure 2: Distribution According to histological types, Grades among the malignant groups 120 Survival according histological type serous mucinous mixed Undife. Endometroide Clear cell Months

30 Figure 3: Survival rates according to the histological grades among the malignant groups Survival rates according to histological grades Months Mildly Poorly highly

31 Figure 4: Survival rates according to the stage of the tumor. Survival rates according to the stage Stage 3 Stage Months

32 Figure 5: Actual calculation of survival rates according to the route of administration of chemotherapy. Survival rates according to the route of administration of chemotherapy Intraperitoneal Systemic Months

33 Figure 6: Survival rates according to the second - look laparotomy among the malignant group. 1,2 According to the second look laparotomy 1 0,8 0,6 SL neg. SL post. 0,4 0,2 0

34 Discussion The 5-year survival rate for stage III ovarian carcinoma was found to be % and for stage IV it drops to 6 %. Different authors report comparable percentage. General Characteristics: - 1- Age: The mean age of the patients was 56 years, 71 % of them were postmenopausal, which is approximately the same percentage reported internationally. Yancik, 1986(3) 2- Parity: 23 % nullipara. 76 % multipara, same result as Averette 1993(43) In contrary to most published articles, the incidence was found to be higher in nullipara.(5,6,9) 3- Presence of Ascites: Absence of ascites was found to be a good prognostic factor (P> 0.001). We are thinking as Dembo (33).

35 Discussion cont. 4- Residual tumor size: Is an important prognostic factor, widely recognized by other researchers. If residual mass < 2 cm mortality rate increases and vice versa. (24,25,28,30,33,36,37,39,40,41,42,44,46) 5- Localization of the tumor: In agreement with international sources, we found that survival rate is higher in patients with unilateral ovarian cancer. 6- FIGO staging: The earlier the stage, the higher the survival rate coinciding with other studies.(31,32) 7- Histological type: Survival rate in serous, mucinous and mixed tumors was found to be significantly higher than endometrioid and undifferentiated varieties. 8- Tumor grading: The more differentiated the tumor, the higher the survival rate (P > 0.005).(28,31,35,45,48,49)

36 Discussion cont. 9- Primary debulking surgery: Patients who underwent primary complete debulking surgery had better survival rates than those having incomplete surgery or biopsy alone. 10-1st line chemotherapy: When platinum was added to the chemotherapy regimen, survival rate was increased.(50,52) Also intraperitoneal cisplatin was more efficient than systemic cisplatin.(26,51) 11-Number of cycles: Increasing number of cycles increased the survival rate. 12- Second look laparotomy: In this study, a very important prognostic factor was the result of second-look laparotomy, patients with negative second look laparotomy had better survival rates. Frigerio(52)

37 Conclusion: 1- The use of Systemic chemotherapy in patients with minimal residual disease after a second look laparotomy proved to increase the survival rate. 2- The serous histological type has a better survival rate than other types. 3- Treatment at an early stage has a better survival rate than advanced stages. 4- The primary debulking surgery must be as complete as possible. 5- Residual mass less than 2 cm in size has a better survival rate.

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