PROGNOSTIC FACTORS IN

ADVANSED OVARIAN CANCER

Dr. Hisham Rahahle Gynecologist, MD, Ph.D

Subspecialty in Gynecological Oncology

E-mail: hisham_re@yahoo.com

mailto:hisham_re@yahoo.com

Abstract:

This study includes (68) patient diagnosed with advanced epithelial ovarian cancer in the years (1990-1995).

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%.

Introduction

Incidence:

In the US approximately 25 000 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 60 – 65.

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)

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

CONT..

Investigations:

-Complete blood analysis

-Urine analysis

-Coagulation profile

-Tumor markers CA-125

-chest X-ray

-ECG

-Extension studies

-Abdominal ultrasound

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) .

Staging of advanced epithelial ovarian

cancers according to FIGO(12) .

Stage

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 Tumor grossly limited to the true pelvis with negative lymph nodes but

with histological confirmed microscopic seeding of abdominal peritoneal

surfaces.

Stage IIIb Tumor of one or both ovaries with histologically confirmed implants of

abdominal peritoneal surfaces, non exceeding 2cm in diameter. Nodes are

negative.

Stage IIIc Abdominal implants greater than 2cm in diameter and/or positive

retroperitoneal or inguinal lymph nodes.

Stage IV 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.

Stage IVa Parenchymal liver metastases equals stage IVa.

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

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.

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%.

Table 1:

Distribution according to Age, Parity and Abortion

STAGE III AND IV CA OVRAY DISTRIBUTION OF AGE AND PARITY

Max 75 Min 34 56 Years Age

0% 23% Nullipara Parity

0% 76% Multipara

0% 61% Nulligravida Abortion

0% 24% With abortion

Table 2: Initial surgical treatment of ovarian cancer Stage III & IV.

STAGE III,IV CA OVARY INITIAL

SURGICAL TREATMENT

% N=68 Type of surgery

45.7% 31 Biopsy

17.6% 12 Cytoreductive

36.7% 25 Complete surgery

Table 3:

Second look laparotomy among cancer group

STAGE III, IV CA OAVARY TREATED

WITH CHEMOTHERAPY

% N=68

26.47 18 Second-look

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.

R e s u l t:

DISTRIBUTION ACCORDING TO AGE

Age (years) N=68 %

31-40 3 4.410

41-50 12 17.65

51-60 30 44.12

61-70 17 25.00

71-80 6 8.820

Table 6: Parity among the

malignant groups

Distribution according to parity in stage III and IV

ovarian cancer

Parity N=68 %

Nulliparous 16 23.53%

Primipara 4 5.88%

Multipara 41 60.30%

Unknown 7 10.29%

Table 7:Distribution according to the presence

of ascitis in ovarian cancer stage III and IV

Ascitis N = 68 %

With 54 79.5

Without 14 20.5

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

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%

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%

Table 11: Distribution according to the types in the

malignant groups

Histological type n=68 %

Serous

adenocarcinoma

40 58.80%

Muscinous

adenocarcinoma

5 7.35%

Endometroids 8 11.76%

Undifferentiated 7 10.00%

Mixed 3 4.41%

Clear cell carcinoma 5 7.35%

Table 12: Distribution according to the

histological grades after treatment in Stage III,

IV ovarian cancer

Stage III, IV Ca ovary

Classification of histological grade

Histological

grade

N=68 %

GI highly date 12 17.60%

GII mild date 11 16.70%

GIII poorly 38 55.80%

Unknown 7 10.30%

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

51 75.00%

Cisplatinum,Adriamycin

and Clorambucil

2 2.94%

Intraperitoneal,

Cisplatinum

14 20.59%

Cisplatinum +

Intraperitoneal

Bleomycin

1 1.47%

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 20 29.41%

More than 5

cycles

28 41.17%

Table 15: Number of patients who had a

second-look laparotomy after chemotherapy

Second-look n=68 %

Done 18 26.47%

Not done 50 73.53%

Table 17 :distribution according to the

evolution of the patient with advanced

epithelial ovarian cancer

Situation N=68 %

Persistent 32 47.06 %

Complete

response

13 19.12 %

Metastases 8 11.76%

Recurrence 12 17.64 %

Un known 3 4.42 %

Stage III and IV ovarian cancer

Evolution

Stage III and IV ovarian cancer

Evolution

Situation n=68 %

Alive without

disease

13 19

Died due to tumor 51 75

Died due to another

cause

1 1.4

Don’t know 3 4.7

Study of the survival rates among our patients

in stage III and IV epithelial ovarian cancer.

Figure 1: Survival rates for all groups of Patients

Global Survival rate

0

20

40

60

80

100

120

0 3 5 7 11 13 14 17 19 22 25 29 39 75

Months

Survival

Figure 2: Distribution According to histological

types, Grades among the malignant groups

Survival according histological

type

0

20

40

60

80

100

120

0 3 6 9 10 12 15 18 19 24 28 39 75

Months

serous

mucinous

mixed

Undife.

Endometroide

Clear cell

Figure 3: Survival rates according to the

histological grades among the malignant

groups

Survival rates according to histological grades

0

20

40

60

80

100

120

0 5 6 7 12 15 18 19 24 28 63 92

Months

Mildly

Poorly

highly

Figure 4: Survival rates according to the stage

of the tumor.

Survival rates according to the stage

0

20

40

60

80

100

120

0 4 5 6 8 12 13 15 17 19 22 25 28 29 64 91

Months

Stage 3

Stage 4

Figure 5: Actual calculation of survival rates

according to the route of administration of

chemotherapy.

0

20

40

60

80

100

120

0 4 5 7 8 11 13 15 17 18 24 27 29 39 75

Months

Intraperitoneal

Systemic

Survival rates according to the route of administration of chemotherapy

Figure 6: Survival rates according to the

second - look laparotomy among the malignant

group.

0

0,2

0,4

0,6

0,8

1

1,2

SL neg.

SL post.

According to the second – look laparotomy

Discussion

The 5-year survival rate for stage III ovarian carcinoma was found to

be 42.88 % 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).

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)

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)

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.