PROGNOSTIC FACTORS IN

ADVANSED OVARIAN CANCER

Dr. Hisham Rahahle
Gynecologist, MD, Ph.D
Subspecialty in Gynecological Oncology
E-mail: 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) .
Criteria
Stage

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

Age 56 Years Min 34 Max 75

Parity Nullipara 23% 0%
Multipara 76% 0%
Abortion Nulligravida 61% 0%
With abortion 24% 0%
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 31 45.7%

Cytoreductive 12 17.6%

Complete surgery 25 36.7%

Table 3:
Second look laparotomy among cancer group

STAGE III, IV CA OAVARY TREATED

WITH CHEMOTHERAPY
N=68 %

Second-look 18 26.47
 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 7 cases 10%

Tumor
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 40 58.80%
adenocarcinoma
Muscinous 5 7.35%
adenocarcinoma
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 N=68 %
grade
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 51 75.00%
and
cyclophosphamide
Cisplatinum,Adriamycin 2 2.94%
and Clorambucil
Intraperitoneal, 14 20.59%
Cisplatinum
Cisplatinum + 1 1.47%
Intraperitoneal
Bleomycin
 Table 14: distribution according to number of
cycles patient tolerated among the malignant
groups
No. of cycles No. of patients %

Less than 5 17 25%

cycles
5 cycles 20 29.41%

More than 5 28 41.17%

cycles
 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
Stage III and IV ovarian cancer
Evolution
Situation N=68 %
Persistent 32 47.06 %
Complete 13 19.12 %
response
Metastases 8 11.76%
Recurrence 12 17.64 %
Un known 3 4.42 %
 Stage III and IV ovarian cancer
Evolution

Situation n=68 %

Alive without 13 19
disease
Died due to tumor 51 75

Died due to another 1 1.4

cause

Dont know 3 4.7

Study of the survival rates among our patients
in stage III and IV epithelial ovarian cancer.
Global Survival rate

120

100

80

60 Survival

40

20

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

Months

Figure 1: Survival rates for all groups of Patients

Figure 2: Distribution According to histological
types, Grades among the malignant groups

Survival according histological

type

120

100 serous
80 mucinous
mixed
60
Undife.
40
Endometroide
20 Clear cell

0
0 3 6 9 10 12 15 18 19 24 28 39 75
Months
 Figure 3: Survival rates according to the
histological grades among the malignant
groups
Survival rates according to histological grades

120

100

80

60

40

20 Mildly

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

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

120

100

80

60 Stage 3
Stage 4

40

20

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

120

100

80

60 Intraperitoneal
Systemic

40

20

0
0 4 5 7 8 11 13 15 17 18 24 27 29 39 75
Months
 Figure 6: Survival rates according to the
second - look laparotomy among the malignant
group.
According to the second look laparotomy
1,2

0,8
SL neg.
0,6 SL post.

0,4

0,2

0
 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.