|Year : 2014 | Volume
| Issue : 4 | Page : 650-656
Retrospective study of epithelial ovarian cancer in the Oncology Department, Menoufia University
Khalid K Abdel Aziz, Mouhmed A Shehata, Ashraf E Abdel Ghany, Enas A Baker El Khouly MD , Reham A Abdel Aziz
Department of Oncology and Nuclear Medicine, Faculty of Medicine, Menoufia University, Shebin El-Kom, Egypt
|Date of Submission||10-Dec-2013|
|Date of Acceptance||03-Mar-2014|
|Date of Web Publication||22-Jan-2015|
Enas A Baker El Khouly
Department of Oncology and Nuclear Medicine, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia
Source of Support: None, Conflict of Interest: None
The aim of this study was to conduct clinicopathological, treatment, and survival analysis of epithelial ovarian cancer patients treated at the Clinical Oncology Department, Menoufia University.
Epithelial ovarian cancer constitutes the majority of ovarian neoplasms (about 80%). Predisposing factors may be genetic, personal history of breast or endometrial cancer, nulliparity, endometriosis, and postmenopausal estrogen. Symptoms are often vague, and until now there are no effective screening programs. Typically, treatment depends on a combination of surgery and chemotherapy in most of the patients.
Patients and methods
This study included 83 patients diagnosed with epithelial ovarian cancer presented to the Clinical Oncology Department, Menoufia University, from January 2006 until December 2011. Data were collected regarding clinicopathological characteristics, treatment modalities including surgery and chemotherapy, response to treatment, and survival analysis including progression-free survival and overall survival.
This study included 83 patients; the mean age of the patients was 55 years. Most of the patients presented at advanced stages (stages III and IV were seen in 84.3% of the patients). Serous cystadenocarcinoma was the predominant type of tumor seen in 68.7%. Surgery was the initial step in 86.7% of the patients. Paclitaxel-carboplatin was the most commonly used regimen as first-line chemotherapy. Response rate to first-line chemotherapy reached 80.2% (35% complete response).
In our study, the age incidence of ovarian cancer was 55 years. For most of the patients, typical presentation was late. Progression-free survival was nearly the same as that reported in the western literature. There was significant correlation between response and stage. There was significant correlation between overall survival, progression-free survival, and debulking type.
Keywords: Cancer, epithelial, ovarian, survival
|How to cite this article:|
Abdel Aziz KK, Shehata MA, Abdel Ghany AE, Baker El Khouly EA, Abdel Aziz RA. Retrospective study of epithelial ovarian cancer in the Oncology Department, Menoufia University. Menoufia Med J 2014;27:650-6
|How to cite this URL:|
Abdel Aziz KK, Shehata MA, Abdel Ghany AE, Baker El Khouly EA, Abdel Aziz RA. Retrospective study of epithelial ovarian cancer in the Oncology Department, Menoufia University. Menoufia Med J [serial online] 2014 [cited 2020 Sep 20];27:650-6. Available from: http://www.mmj.eg.net/text.asp?2014/27/4/650/149637
| Introduction|| |
Ovarian neoplasms consist of several histopathological entities and treatment depends on the specific tumor subtype. Epithelial ovarian cancer constitutes the majority of ovarian neoplasms (about 80%) . Ovarian cancer is the seventh most common cancer in women under the age of 65 years. A woman's risk of developing ovarian cancer by 65 years ranges from 0.36% in developing countries to 0.64% in developed countries . In Europe, only one-third of women with ovarian cancer live for 5 years after diagnosis, largely because most women with ovarian cancer are diagnosed when the cancer is already at an advanced stage . Symptoms are often vague and not specific, such as bloating, abdominal distension or urinary symptoms, and are of a short duration, and as yet there are no effective screening programs. However, initial results of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), evaluating the effectiveness of annual CA-125 or transvaginal ultrasound, or both. Screening in postmenopausal women shows promise in identifying early-stage disease, although survival data are still pending . Typically, the treatment of epithelial ovarian cancer depends on a combination of surgery and chemotherapy in most of the patients. Improvement in surgical techniques and chemotherapy agents has resulted in a modest increase in the 5-year survival over the last three decades, from 37 to 45%, although, even now, two-thirds of women die from this disease . In early-stage disease [Federation of International Gynecologists and Obstetricians (FIGO) stage I/II], radical surgery will cure most women, although a minority of women will benefit from adjuvant chemotherapy, especially those who are not adequately staged at primary surgery . Unfortunately, around 75% of women present when the disease has spread outside the pelvis (FIGO stage III/IV), when surgery alone cannot be curative. The standard treatment at these advanced stages is staging laparotomy with primary debulking surgery followed by platinum-based chemotherapy. The extent of tumor cytoreduction is considered the most important independent prognostic factor .
Surgery is recommended to be performed by a specialist gynecologic oncologist surgeon in patients who are highly suspicious for malignancy .
| Patients and methods|| |
This is a clinical audit that included 83 patients diagnosed with epithelial ovarian cancer presented to the Clinical Oncology Department, Menoufia University, from January 2006 until December 2011. Data were collected from the available files of patients regarding clinicopathological characteristics, treatment modalities, response to surgery, and survival. The clinicopathological characteristics studied in patients included the following: patient characteristics (age and median age group); and disease characteristics including pathology (serous, mucinous, and endometrioid), grade (grade I: well differentiated; grade II: moderately differentiated; and grade III: poorly differentiated), and TNM staging system of the American Joint Committee on Cancer (AJCC 2010). Treatment modalities offered to patients included: surgery [type of surgeon (general surgeon, oncosurgeon, or gynecologist), debulking surgery either optimal or suboptimal, time of surgery (initial, interval, or delayed debulking)], and chemotherapy (in this study we focused on first-line platinum-based chemotherapy either with single-agent carboplatin or with combination platinum-based chemotherapy). Response to treatment was assessed according to the revised RECIST guideline (version 1.1) as follows: complete response (CR), defined as the disappearance of all target lesions and reduction in the short axis in any pathological lymph nodes (whether target or nontarget) to less than 10 mm; partial response (PR), defined as at least 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters; progressive disease (PD), defined as at least 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum in the study (this includes the baseline sum, if that is the smallest in the study); in addition to a relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm; and stable disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameter in the study. Data analysis was performed using SPSS program (version 16; SPSS Inc., Chicago, Illinois, USA) for Windows. The Pearson c2 -test and Fisher's exact test were used in the analysis. They were used to determine the significance of associations between categorical variables and response. Progression-free survival (PFS) was analyzed using the Kaplan-Meier curves. It was calculated from the date of diagnosis to the date of progression or death (all causes), whichever occurred first; patients who did not show progression at last follow-up were censored. Differences between groups were assessed by means of the log-rank test. Two-sided P-values less than 0.05 were considered statistically significant.
| Results|| |
Clinicopathologic criteria in the studied patients
The median age of patients in the study was 55 years, and they were classified into two groups on the basis of this median age. The first group comprised patients who were 55 years or older and constituted more than half of the patients (54.2%), and the other group comprised patients who were below 55 years, which constituted 45.8% [Table 1].
Serous cystadenocarcinoma was the prominent histological type (68.7%), followed by endometrioid type (18.1%) and lastly the mucinous type (13.3%).
Most of the patients had high-grade tumors (74.7%), followed by grade I tumors, which represented 19.3%, and grade II tumors, which represented only 6%.
Most of the patients (84.3%) presented with advanced stage disease III and IV, whereas only 15.7% of patients presented with stage I and II.
Eighty-three patients were available for treatment analysis. Of them, 72 (86.7%) patients underwent debulking surgery, whereas 11 (13.3%) did not. Early debulking was carried out in 59% and other treatment modalities (interval, delayed, and no debulking) were carried out in 41%. An overall 53% of patients underwent optimal debulking, whereas 47% had suboptimal debulking. An oncosurgeon performed 38.9% of surgeries, a gynecologist performed 34.7%, a general surgeon performed 26.4%, and unfortunately no surgery was carried out by a specialist gynecologic oncologist. All patients received chemotherapy; of them, 77 patients completed six cycles and six patients died before treatment completion. Most of the patients (86.7%) received combination platinum-based chemotherapy, whereas only 13.3% received single-agent carboplatin [Table 2].
Forty patients were available for response assessment. After the first-line platinum-based chemotherapy, 35% of patients showed CR, 55% showed PR, 2.5% showed SD, and 7.5% showed disease progression [Table 3].
Progression status was assessed after the first-line platinum-based chemotherapy; 67.5% of patients showed progression, 32.5% were progression free, 61.4% were alive, and 38.6% had died [Table 4].
The median PFS was 17 months, whereas the median overall survival (OS) was 45 months.
| Discussion|| |
Ovarian cancer incidence is strongly related to age, with the highest incidence rates being in older women. In the UK, between 2008 and 2010, an average of 53% of cases were diagnosed in women aged 65 years. The mean age of the patients in this study was 53.4 years (range 18-72 years) and the median age was 55 years. Age incidence of ovarian cancer in our patients is 10 years younger than that seen in the UK .
In the Gharbia population-based cancer registry, the mean age at diagnosis was 47.2 years and the median age was 49 years . In a retrospective study evaluating clinicopathological characteristics of ovarian tumors in the state of Espirito Santo in Brazil, it was found that the mean age at diagnosis of ovarian cancer was 54.6 years . Therefore, the age incidence of ovarian cancer in our patients was 10 years younger than that seen in the UK. This could be explained by a higher median age of women in the normal population in the UK than in Egypt, but this needs to be further studied.
Among our patients, 68.7% had serous carcinomas, 13.3% had mucinous carcinomas, and 18.1% were endometrioid. In the Middle East consortium study, serous carcinomas predominate, ranging between 27.2 and 49.9%, followed by adenocarcinomas. The proportion of mucinous carcinomas among Egyptians in this study was 16.1% and among Jordanians was 11.7%, whereas in Israeli and Cypriot registries the percentage was low, ranging from 6 to 8.7% .
Paes et al.  found that 30% of the epithelial tumors were serous, whereas 13.7% were mucinous. Therefore, the incidence of serous among all ovarian cancer cases in our study was higher than that of all other mentioned studies, whereas the incidence of mucinous was nearly the same, and this could be explained by the predominance of molecular phenotype, and genotype expressing serous histology more in patients in our country.
For all patients in this study, typical presentation was late; stages III and IV were seen in 84.3% of the cases. Our results had the highest percentage among most of the studies that mentioned the issue of staging. Malik  found that 78% of the cases presented at stage III or IV. Paes et al.  found that stages III and IV accounted for only 56.2% of their cases. This could be explained by the low education standard in Menoufia resulting in late presentation after the disease has advanced.
In our study, 86.7% of patients were treated initially with surgery. In the study evaluating ovarian cancer in oriental women from Singapore, it was found that surgery was the primary treatment modality in 97% of the cases . In a university hospital in Berlin that reviewed 372 consecutive patients with advanced ovarian cancer it was found that 89% of the patients underwent surgery . In the Medicare population evaluating patients with advanced ovarian epithelial carcinoma, it was found that surgery was performed initially in 58.8% of the women, which is much lower compared with our study, as well as with the German and Singapore trials .
The slightly lower incidence of our patients' starting surgery in comparison with the German and Singapore trials could be explained by the fact that there was no established multidisciplinary team between our department and the gynecology department to evaluate every case and plan for further management.
Of those who underwent surgery, 53% of our patients had optimum cytoreduction surgery (no residual or residual <2 cm). In the study evaluating surgery in 115 patients with stages III and IV ovarian cancer in the southwest of the Netherlands, it was found that optimal surgery was performed in only 45% of the patients . A survey among gynecologists performing surgery for ovarian carcinoma in Australia and New Zealand showed that about 65% of the surgeons performed optimal debulking surgery . It is obvious from the comparison that, in our series, optimal debulking surgery was performed in the median range between two previously mentioned trials, and this can be explained by the experience of our surgeons and their awareness of their surgical fields, as 73.6% of optimal debulking was performed by gynecologists or oncosurgeons.
In our study, all patients received platinum-based chemotherapy; of them 77 patients completed six cycles of chemotherapy and six patients received only one or two cycles and died. An overall 36.1% of the patients started neoadjuvant chemotherapy. As regards the type of chemotherapy regimen, paclitaxel-carboplatin was the most frequently used regimen as first-line therapy in 86.7% of patients, followed by single-agent carboplatin in 13.3% (two patients had indications for only single-agent carboplatin, whereas in other cases it was used alone because the patients were fragile and had moderate performance status or because of a shortage of paclitaxel). Response to first-line chemotherapy (all patients had suboptimally debulked stage III or IV, either with initial, interval, or delayed debulking) after six chemotherapy cycles was seen in 90% of the patients (CR 35%); if we added cases with SD after three cycles of chemotherapy, the overall response was 92.5%; only 7.5% of the patients progressed after six cycles of first-line chemotherapy. The rates of CR varied across studies . In the GOG study protocol 47 the CR rate for the cisplatin-containing arm reached 51%. The response rate to paclitaxel followed by either cisplatin or carboplatin in the exploratory phase III study ranged between 64 and 74% , whereas the pathological CR in another phase III trial comparing paclitaxel plus cisplatin versus paclitaxel plus carboplatin was nearly similar between the two groups (46 vs. 53%) .
One of the old studies compared cisplatin-paclitaxel versus cisplatin-cyclophosphamide in patients with stage IV or suboptimally debulked stage III and found that the overall response was 73 vs. 60% and the clinical CR was 51 vs. 31% .
It is obvious after comparing our results with those of the large international studies that the response rate excluding clinical CR in our patients is closely similar to those of the international studies. The possible explanation for the difference in clinical CR between our study and the other international studies could be explained as follows: first, the number of patients in our study was small in comparison with the other studies; second, no standard chemotherapy protocol was given for patients in our study (most patients who received single-agent carboplatin had indications for combination paclitaxel and carboplatin); third, the high frequency of chemotherapy underdosage and frequent interruption of the treatment were due to limited resources and unavailability of the drugs, especially paclitaxel; and finally no surgery was performed by a specialist gynecologic oncologist.
In our study, the PFS after first-line chemotherapy was 17 months. Reviewing the PFS in different international studies, we found that it ranged between 11 and 21 months, which is highly similar to that seen in our study ,,,,.
In our study there was a statistically significant correlation between response and stage (P = 0.009) [Table 5]. All patients who underwent response evaluation were at stage III or IV due to suboptimally debulked disease in these advanced stages or no surgery because of highly advanced, metastatic disease or inoperability of the patients because of associated comorbidities.
There was a statistically significant correlation between PFS and grade, as shown in [Figure 3] (P = 0.002). The median PFS of low-grade tumors was 34.5 months and of high grade was 20.5 months. A study by Winter et al.  that included 1895 women with FIGO stage III showed that 9.5% had tumor grade 1, 37.9% had grade 2, and 52.6% had grade 3. The study showed that patients with grade 2 or 3 tumors were associated with decreased PFS and OS. The results of this study were similar to those of our study .
In our study, there was a statistically significant correlation between PFS and stage, as shown in [Figure 1] (P = 0.001). The median PFS of early-stage disease was 40.3 months and of advanced stages was 20.5 months. Many studies found that, the higher the stage, the lower will be the survival, either progression or OS. Baldwin et al. , using the Surveillance, Epidemiology and End Results 1995-2007 database for epithelial ovarian cancer, found that relative survival at 5 years was 89, 70, 36, and 17%, and at 10 years was 84, 59, 23, and 8% for stages I, II, III, and IV, respectively, and at all stages patients with nonsurgical primary treatment and those with advanced age had reduced relative survival.
|Figure 1: Correlation between progression-free survival (PFS) and stage. Kaplan-Meier curve showing statistically significant correlation between PFS and stage (P = 0.001).|
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There was a statistically significant correlation between OS and age group (P = 0.039). The median OS for patients younger than 55 years was 60 months, whereas for patients who were 55 years or older the median OS was 37.7 months. A study by Chan et al.  included younger women (range 22-45 years) with advanced-stage epithelial ovarian carcinoma, who were identified from tumor registry databases, and a comparable group of 52 women who were an average 21 years older (range 46-85 years), who served as controls. Median survival was 66 and 45 months in young and old patients, respectively, which was largely met with our results. This could be explained by the poor tolerance of elderly patients, especially those presenting with advanced disease, to standard combination chemotherapy and with associated comorbidities, which made the patient inoperable; further, patients with bulky disease also had increased risk of death from other causes .
There was a statistically significant correlation between PFS, OS, and debulking surgery, as seen in [Figure 2],[Figure 3] and [Figure 4], respectively (P = 0.036 and 0.003, respectively). The median PFS and OS for the patients with optimally debulked surgery were 27.3 and 51.5 months, respectively, whereas for suboptimally debulked patients the median PFS and OS were 22.3 and 40.8 months, respectively. A study by Winter et al.  included data from 1895 patients with FIGO stage III epithelial ovarian cancer who underwent primary surgical cytoreduction followed by six cycles of paclitaxel/platinum chemotherapy. The reported categories for residual disease were as follows: microscopic disease in 437 (23.1%) patients, of whom 15 were deemed to have had no residual disease; residual disease between 0.1 and 1 cm in 791 (41.7%) patients; and residual disease greater than 1 cm in 667 (35.2%) patients. PFS was 33.0, 16.8, and 14.1 months, respectively (P < 0.001), and OS was 71.9, 42.4, and 35.0 months, respectively (P < 0.00). These results were to a great extent similar to ours, especially as regards suboptimal debulking (residual>1 cm) .
|Figure 2: Correlation between progression-free survival (PFS) and type of debulking surgery. Kaplan-Meier curve showing statistically significant correlation between PFS and type of debulking surgery (P = 0.036).|
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|Figure 3: Correlation between progression-free survival (PFS) and grade. Kaplan-Meier curve showing statistically significant correlation between PFS and grade (P = 0.002).|
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|Figure 4: Correlation between overall survival (OS) and debulking surgery. Kaplan-Meier curve showing statistically significant correlation between OS and debulking surgery (P = 0.003).|
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There was a statistically significant correlation between OS and chemotherapy regimen (P = 0.007) [Figure 5]. The median OS for the patients who received single-agent carboplatin was 17.8 months, whereas that for patients who received combination carboplatin-based chemotherapy was 53.2 months; these results are partially similar to those of the MRC-ICON3 randomized trial including three arms, paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin. The median OS for combination paclitaxel/carboplatin was 40 months, whereas that for the single-agent arm was 35 months .
|Figure 5: Correlation between overall survival (OS) and chemotherapy regimen. Kaplan-Meier curve showing statistically significant correlation between OS and chemotherapy regimen (P = 0.007).|
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| Conclusion|| |
The age incidence of ovarian cancer in our study is 55 years, which is 8 years higher than that of other parts of Egypt, Gharbia, and Alex, and other Middle East countries and 10 years lower than that in the UK. For all patients in this study, typical presentation was late and stages III and IV predominated. The response rate to first-line chemotherapy was high and the PFS was nearly the same as that reported in the western literature.
There was significant correlation between response and stage. There was significant correlation between PFS and grade, stage, and debulking surgery. There was significant correlation between OS and median age group, type of debulking, and chemotherapy regimen.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]