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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 6  |  Issue : 1  |  Page : 21-25

Retrospective analysis of clinico-pathological characteristics of ovarian cancer and audit of cytoreductive surgery done at tertiary care center in Eastern India


1 Ex-Senior Resident, Gynecological Oncology, IGIMS, India
2 Professor & Head, Hematology, IGIMS, India
3 Professor & Head, Gynecological Oncology, IGIMS, India
4 Assistant Professor, IGIMS, India
5 Senior Resident, Gynecological Oncology, IGIMS, India

Date of Submission07-Oct-2019
Date of Acceptance16-Jan-2020
Date of Web Publication16-Nov-2020

Correspondence Address:
Sangeeta Pankaj
Prof. & Head Gynecological Oncology, SCI, IGIMS, Patna
India
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Source of Support: None, Conflict of Interest: None


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  Abstract 


Ovarian malignancy is a common and highly morbid cancer of females. Advanced stage ovarian cancer warrants extensive surgery to achieve the goal of optimal cytoreduction i.e. no residual macroscopic disease, which is an independent prognostic factor contributing to survival of these patients population.
The aim of index study is to describe the incidence, pattern and management of ovarian cancer at a tertiary care center in eastern India and also audit the surgeon’s performance in treating these patients surgically and the improvements if any, over a period of 7 years. No such studies focusing on analysis of pattern of ovarian cancer presentation and the optimal surgery rates alongwith outcomes have yet been published from this region.
Method: A retrospective analysis of all operated cases of histologically proven ovarian cancer at our institute from December 2009 to March 2016 was carried out.
Results: Ovarian cancer was the predominant cohort undergoing surgery for gynecological malignancies. The most common variant was epithelial ovarian cancer and 30 to 50 years was the commonest age group afflicted. The rate of surgery has been increasing consistently over the years and the rate of achieving optimal cytoreduction has improved significantly. The operability was better in the patients receiving neoadjuvant chemotherapy but the primary surgery arm has also seen improvement in achieving optimal cytoreduction. The probability of achieving R Zero has improved from 0.5 in 2009 to 0.95 in 2016.
Conclusion: The operative outcome and quality of life of patients has shown considerable improvement in hand of surgeon dealing with such cases at a high volume tertiary care center. This emphasizes upon the significance and need for well equipped, sophisticated, multi-disciplinary tertiary care center catering to population with a high propensity and prevalence of Gynaecological malignancies.

Keywords: Ovarian cancer, Optimal cytoreduction, Surgical audit,


How to cite this article:
Kumari A, Choudhary V, Pankaj S, Kumari A, Kumari J, Kumari S, Nazneen S, Rani J, Kumari P, Abhilashi K, Kumari S. Retrospective analysis of clinico-pathological characteristics of ovarian cancer and audit of cytoreductive surgery done at tertiary care center in Eastern India. J Indira Gandhi Inst Med Sci 2020;6:21-5

How to cite this URL:
Kumari A, Choudhary V, Pankaj S, Kumari A, Kumari J, Kumari S, Nazneen S, Rani J, Kumari P, Abhilashi K, Kumari S. Retrospective analysis of clinico-pathological characteristics of ovarian cancer and audit of cytoreductive surgery done at tertiary care center in Eastern India. J Indira Gandhi Inst Med Sci [serial online] 2020 [cited 2020 Nov 29];6:21-5. Available from: http://www.jigims.co.in/text.asp?2020/6/1/21/300733




  Introduction: Top


Ovarian cancer is the fourth most common cause of cancer deaths among females worldwide and is the commonest cause of death among all gynecological cancers. The very high case-fatality rate for ovarian cancer is partly because patients usually presents in advanced stage of the disease as there is no effective screening method for early detection of the disease till date. A report by the International Federation of Gynecology and Obstetrics (FIGO) has found that the preponderant age of ovarian cancer is skewing towards younger population, even though the majority of patients with epithelial cancer were more than 50 years of age.[1] The reason for the increased occurrence of epithelial ovarian cancer in younger women is not without arguments and controversies and has been attributed to an increase in ovulation induction rates during assisted reproduction techniques, nulliparity and late onset of childbearing age.[2],[3] Off late, there is illustration of ovarian cancer now being commoner in developing then developed nations.[4]

The regimentarían management of Ovarian cancer has seen a paradigm shift over the years. Even the definition of optimal cytoreduction has undergone serial refinement and revision. The management of advanced stage carcinoma ovary remains a challenge with a reported median survival ranging between 22 to 30 months.[5],[6] Though, surgery remains the mainstay of treatment, the significance and safety of its extent i.e ultra radical versus radical is not defined.[7] Primary cytoreductive surgery is now being challenged by interval debulking surgery following neoadjuvant chemotherapy (NACT) to achieve improved surgical outcome in selected cases.

In the setting of primary cytoreductive surgery, retrospective data are in abundance on the significance of achieving an optimal cytoreduction through maximal resection.[8],[9]

The aim of this study was therefore, to describe the incidence, pattern and management of ovarian cancer at this major tertiary referral center in Eastern India. We did our surgical audit and surgeon’s performance audit to nook in to the merits of the improved regimen and our pitfalls, if any.


  Materials and Methods Top


This is a retrospective, in depth review and analysis of histologically proven cases of ovarian cancer operated from December 2009 to March 2016 in the department of Gynecological Oncology, Regional Cancer Center, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India. After obtaining approval from the institutional ethics committee, records of the patients diagnosed with ovarian cancer were retrieved from the medical record section, operation theatre and the department of Pathology. A list of all operated cases of ovarian cancer was obtained from the operation theatre. Using this list as a template, the histological diagnosis of these cases was retrieved from the Department of Pathology of the hospital. Cases of primary ovarian cancer were selected. The case notes of these selected cases were then retrieved from the Medical Records Department. For missing records, efforts were made to obtain the patients’ data by contacting them over telephone. In our study, we did consider optimal debulking as no visible macroscopic disease at the end of surgery. 145 cases of ovarian cancer were operated during this period and their data was secured, scrutinized and analyzed.


  Results and Analysis Top


In the time period of 2009 to 2016, a total of 256 cases of female genital tract malignancies were operated upon in our department. Of these patient population, ovarian cancer cohorts were predominant in number (56.64%), followed subsequently by cancer cervix (31.64%) and cancer endometrium (9.7%) as shown in [Table 1], [Figure 1].
Table 1: Number distribution of female genital malignancies.

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Figure 1: Pie chart distribution depicts genital tract malignancies.

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The trend of number of cases operated for cancer ovary has seen a gradual increasing trend at our institute as depicted in [Figure 2], [Table 2].
Figure 2: Year wise distribution of cases of cancer ovary.

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Table 2: Distribution of patient demographic and clinicopathologic characteristics.

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The demographic characteristics of patients are shown in [Table 2]. Maximum number of cases were in the age group of 31-40 year and closely followed by the age group of 4150 year. Epithelial ovarian cancers were most common, accounting for 92.41% of the total cases. Most cases were diagnosed and treated in late stage (stage III and IV).

Histopathology

Type:-

[INLINE:2]

All patients were clinically examined, adequately and appropriately investigated preoperatively including tumor markers assay and CT Scan. Factors like tumor marker and primary tumor burden, either alone or in combination were not taken as criteria for NACT and decision on primary surgery or neoadjuvant chemotherapy (NACT) was made considering age, operability of tumor decided by clinical examination as well CT/MRI scan assessment. Patients having ECOG-PS 2 or above, having pleural effusion or gross ascites, liver or lung metastasis, metastatic deposits at porta hepatis and mesenteric root, or extensive peritoneal carcinomatosis were considered more favorable for NACT followed by surgery.

Surgical trends

Nearly 62% patients underwent primary cytoreduction and 38% underwent cytoreduction after receiving neo adjuvant chemotherapy [Figure 3]. The rates of optimal cytoreduction was greater in the neoadjuvant chemotherapy group but the optimal rates following primary surgery has seen an increasing trend [Figure 4]. In primary cytoreductive surgery group, the optimal debulking rate increased from 50% to 87.5% and in the NACT group, this approached to 100%.
Figure 3: Mode of primary treatment: Surgery/ NACT

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Figure 4: Rates of achieving optimal cytoreduction.

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The probability of achieving optimal cytoreduction has improved from 0.5 in 2009 to 0.95 in the year 2016 as depicted in [Figure 5].
Figure 5: Probibility of achieving optimal cytoreduction.

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Of the 40 suboptimally debulked patients, the common sites of metastatic deposits that made debulking difficult or less probable was extensive peritoneal disease, involvement of small bowel mesentry and porta hepati’s, unresectable paraaortic nodes and unresectable diaphragmatic spread.

It was on record that patients undergoing primary surgery had longer operative time and blood loss. No significant difference in post operative complications such as ileus, post operative infections, intensive care unit stay and hospital stay were noted in the two groups.

Follow up

Patients were followed up 3 monthly for two years, then 6 monthly for 3 years and then yearly. Out of 145 patients, 14 patients were lost to follow up. The mean follow up time was 25 months with minimum period of 4 months and maximum of 80 months. 20 patients expired due to disease. Recurrence was noted in 51 patients and 60 were disease free till their last visit. (Table: 3) Table 3 :- Disease status of patients at their last follow up


  Discussion: Top


Very few hospitals in the state of Bihar offer focused cancer treatment and patients need to travel long distance to Delhi or Mumbai for treatment of the same. The department of Gynecological Oncology was started at Indira Gandhi Institute of Medical sciences, Patna, Bihar in the year 2008. Since its inception, 256 patients of female genital tract malignancies have been operated till 2016. of these 56.64% (145) cases were of ovarian malignancy, 31.64% (81) of cervical cancer and 9.7% (25) cases were endometrial carcinoma. 3 cases of cancer vulva, 1 case of choriocarcinoma and 1 case of fallopian tube cancer were also operated. The department has observed an increasing incidence of patients undergoing surgery for ovarian cancer. This rise can be partly attributed to increased awareness among patients population about the treatment being offered at our center provided through increased exposure of mass media and improved communication.

In general, the variation in trends of cancer incidence may be attributed to variety of factors such as initiation of screening program, changes in the diagnostic methods, reliability& completeness of data, changing profile of risk factors in the population, or as a consequence of better health awareness. The incidence of ovarian cancer is increasing in India and this has been speculated to be due to increasing population and improved life expectancy.

There are studies stating the shift of incidence of ovarian cancer to a younger population and the possible influence of environmental and /or life-style factors in all the age groups. It has been suggested that India is rapidly stepping towards industrialization and thus urbanization resulting in change of life style factors, particularly increased age of marriage, increasing incidence of elderly prmi and subsequent reduction in parity and improved socioeconomic conditions might have plausibly contributed to gradual increase in the incidence of ovarian cancer in India. In index study, most patients were in the age group of 31 to 40 years followed by 41 to 50 years group whereas an American study has reported that the incidence of ovarian cancer increases with age and most commonly presents in the sixth and seventh decades of life.[10],[11],[12]

Treatment of Ovarian cancer and the definition of optimal cytoreduction has been improved and revised over the years. The outcome and survival of patients has improved greatly by the availability of newer drugs. The definition of optimal cytoreduction for advanced epithelial ovarian carcinoma has been changed from the past Gynecologic Oncology Group threshold of < or =1 cm residual disease to no gross residual disease owing to improved survival of patients with no macroscopic disease. Patients with macroscopically complete resection had statistically significant improved outcome and also that patients with residual disease of 0.1-1 cm and patients with residual tumor of >1 cm showed similar outcome.[13]

Surgeon’s skill has improved significantly over years owing to increased exposure. We observed an increasing trend in the number of patients being operated at our center with the numbers going up from 4 patients in 2009 to 41 patients in 2016. The rate of optimal cytoreduction has also gone up from 60% in 2010 to 95.12% in 2016. Henceforth, with experience the surgical outcome has improved proving that such surgeries done at high volume centers and by trained surgeons have a higher probability of achieving optimal goal of surgery. In a study from California it was concluded that in patients of advanced-stage ovarian cancer, the provider combination of HVH (High Volume Hospitals) and HVP (High Volume Physicians) was an independent favorable predictor of improved disease- specific survival.14 In another more recent study investigating the median ovarian cancer-specific survivals according to hospital type were : National Cancer Institute Comprehensive Cancer Center (NCI-CCC) 77.9 (95% CI 61.4 to 92.9) months, HVH 51.9 (95% CI 49.2 to 55.7) months, and LVH 43.4 (95% CI 39.9 to 47.2) months (p < 0.0001). National Cancer Institute Comprehensive Cancer Center status (hazard ratio [HR] 1.00) was a statistically significant and independent predictor of improved survival compared with HVH (HR 1.18, 95% CI 1.04 to 1.33) and LVH (HR 1.30, 95% CI 1.15 to 1.47).[15]

The debate of primary surgery versus interval debulking following neoadjuvant chemotherapy (NACT) is an unsettled one. Various authors have investigated the beneficial role of NACT in achieving optimal cytoreduction.[16],[17] In one such study, survival with primary chemotherapy was found to be non-inferior to primary surgery in women with stage III or IV ovarian cancer,. In this study population, giving primary chemotherapy before surgery was an acceptable standard of care for women with advanced ovarian cancer.[18]

Contrary to this opinion some authors have found that in primary surgery, perioperative visual estimation of tumor spread showed 98% sensitivity, 76% specificity and 95% accuracy compared to histopathology. The corresponding figures after NACT were 86%, 76% and 84%, respectively. The difference in sensitivity and accuracy in primary and interval debulking operations was statistically significant (p < 0.001).[19]


  Conclusion Top


From this study we conclude that the complex surgery required for achieving optimal cytoreduction for ovarian malignancy definitely has a learning curve and with increased experience, the outcomes improve significantly. The development of specialized gynecological oncology department and gynecological oncologists can further improve the treatment. The cytoreduction rates were better in the group receiving neoadjuvant chemotherapy but the rates have improved gradually in the primary debulking surgery arm as well. In index study, Most patients were found to be in the age group of 30 to 50 year which needs to be investigated further to determine any local or demographic contributing factors.

Conflict of interest: Nil



 
  References Top

1.
International Federation of Gynaecology and Obstetrics (FIGO). 26th Annual report on the results of treatment in gynaecological cancer. Int J Gynaecol Obstet. 2006;95(Suppl 1):S161-91.  Back to cited text no. 1
    
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Webb PM. Fertility drugs and ovarian cancer. BMJ. 2009;338:a3075.  Back to cited text no. 2
    
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Dorigo O, Baker VV. Premalignant and malignant disorders of the ovaries and oviducts. In: DeCherney AH, Nathan L, editors. Current Obstetric and Gynecologic Diagnosis and Treatment. 10th ed. New York: Lange Medical Books/McGraw Hill; 2007. pp. 933-46.  Back to cited text no. 3
    
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London: The Economist; 2009. The Economist Intelligence Unit. Breakaway: The global burden of cancer-challenges and opportunities.  Back to cited text no. 4
    
5.
Vergote I, Trope CG, Amant F, Kristensen GB, Ehlen T, Johnson N, et al. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med 2010;363:943?53.  Back to cited text no. 5
    
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Kehoe S, Hook J, Nankivell M, Jayson GC, Kitchener HC, Lopes T, et al. Chemotherapy or upfront surgery for newly diagnosed advanced ovarian cancer: Results from the MRC CHORUS trial. Am SocClinOncol Meet Abstr 2013;31 15 suppl: 5500.  Back to cited text no. 6
    
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Ang C, Chan KK, Bryant A, Naik R, Dickinson HO. Ultra?radical (extensive) surgery versus standard surgery for the primary cytoreduction of advanced epithelial ovarian cancer. Cochrane Database Syst Rev 2011 ;Apr 13; (4):CD007697.  Back to cited text no. 7
    
8.
Elattar A, Bryant A, Winter?Roach BA, Hatem M, Naik R. Optimal primary surgical treatment for advanced epithelial ovarian cancer. Cochrane Database Syst Rev 2011 ; Aug 10;(8):CD007565.  Back to cited text no. 8
    
9.
Luyckx M, Leblanc E, Filleron T, Morice P, Darai E, Classe JM, et al. Maximal cytoreduction in patients with FIGO stage IIIC to stage IV ovarian,fallopian, and peritoneal cancer in day?to?day practice: A retrospectiveFrenchmulticentric study. Int J Gynecol Cancer 2012;22:1337?43.  Back to cited text no. 9
    
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Jelovac D1, Armstrong DK. Recent progress in the diagnosis and treatment of ovarian cancer.CA Cancer J Clin. 2011 May- Jun;61(3):183-203.  Back to cited text no. 10
    
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Siegel RL1, Miller KD2, Jemal A3. Cancer statistics, 2016. CA Cancer J Clin. 2016 Jan-Feb;66(1):7-30.  Back to cited text no. 11
    
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Howlander N, Noone AM, Krapcho M, et al. SEER Cancer Stastics Review, 1975-2-13, based on November 2015 SEER data submission, posted to the SEER website, April 2016. Bethesda, MD: National Cancer Institute;2016.  Back to cited text no. 12
    
13.
Wimberger P, Wehling M, Lehmann N, Kimmig R, Schmalfeldt B, Burges A et al.Influence of residual tumor on outcome in ovarian cancer patients with FIGO stage IV disease: an exploratory analysis of the AGO-OVAR (ArbeitsgemeinschaftGynaekologischeOnkologie Ovarian Cancer Study Group).Ann SurgOncol. 2010 Jun;17(6):1642- 8.  Back to cited text no. 13
    
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Bristow RE, Chang J, Ziogas A et al. Highvolume ovarian cancer care: Survival impact and disparities in access for advanced-stage disease. GynecolOncol 2014;132:403-410.  Back to cited text no. 14
    
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Bristow RE, Chang J, ZiogasA et al. Impact of national cancer institute comprehensive cancer centers on ovarian cancer treatment and survival. J Am CollSurg 2015;220:940-950.  Back to cited text no. 15
    
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Shimoji K, Ito K, Tashima L, Tsuruta T, Nakagawa M, Kagawa Y et al.Comparison between Primary Debulking Surgery and Neo- Adjuvant Chemotherapy Followed by Interval Debulking Surgery for Patients with Stage III-IV Ovarian Cancer.GanTo Kagaku Ryoho. 2017 Aug;44(8):675-679.  Back to cited text no. 16
    
17.
Nicklin JL, McGrath S, Tripcony L, Garrett A, Land R, Tang A et al. The shift toward neo-adjuvant chemotherapy and interval debulking surgery for management of advanced ovarian and related cancers in a population-based settng: Impact on clinical outcomes.Aust N Z J ObstetGynaecol. 2017 Jul.  Back to cited text no. 17
    
18.
Kehoe S, Hook J, Nankivell M et al. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): An open-label, randomised, controlled, non-inferiority trial. Lancet 2015;386:249-257.  Back to cited text no. 18
    
19.
Hynninen J, Lavonius M, Oksa S et al. Is perioperative visual estimation of intra-abdominal tumor spread reliable in ovarian cancer surgery after neo adjuvantchemotherapy? GynecolOncol 2013;128: 229-232.  Back to cited text no. 19
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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