A Histopathological Spectrum, Descriptive Epidemiology and Survival Status of Ovarian Cancer Cases from a Tertiary Cancer Centre in Northern India: A Retrospective Cohort Study

Abstract

Background: This work aims to evaluate the demographic profile, treatment patterns and survival outcomes of ovarian cancer (OC) patients at tertiary cancer centre in Bihar.

Materials and methods: A retrospective study of ovarian cancer patients who were treated at Buddha Cancer Centre (BCC), Patna, between January 2019–December 2023. Detailed clinical history, tumor pathology, treatment modalities and survival outcomes of the patients were reviewed from clinical records. Response evaluation was done using clinical examination and computed tomography (CT) scan. Overall survival (OS) and progression-free survival (PFS) were calculated from time of diagnosis to time of death and from time of diagnosis to the time of progression. The statistical analysis was performed using Microsoft Excel. Kaplan–Meier plots were presented.

Results: A total of (N = 437) histopathological confirmed OC cases data were reviewed retrospectively. Mean age ± SD (years): 55.7 ± 16.1 years (age range 18 years to over 60 years). Most cases were diagnosed at Stage III (n = 135; 30.89%) and Stage IV (n = 191; 43.71%) at the time of diagnosis. The most common histologic types were serous (52%) followed by mucinous (22%) and endometrioid (13%). The majority of patients had received chemotherapy and supportive regimen (n = 184; 42%), P value < 0.005. Mean OS ± SD (months) was 36.2 ± 31.9 and mean PFS ± SD (months) was 19.5 ± 24.5. Complete response (CR) was achieved in 19%, partial response (PR) in 16%, stable disease (SD) in 38%, and progressive disease (PD) in 43% of patients. Early-stage disease had a better survival rate (65.2%) while advanced stage had a poor outcome.

Conclusion: Most OCs recur within 1.5 years. Mortality rates were associated with late stage of the disease clinically. Surgery followed by chemotherapy was associated with improved survival outcomes.

Graphical abstract

Keywords

ovarian cancer / cytoreductive surgery / follow-up / survival outcomes

Introduction

Advanced stage ovarian cancer (OC) cases have reported worst prognosis with high mortality rates despite of therapeutic advances[1]. As per the World Cancer Research Fund, it was estimated that 324,603 new cases of ovarian cancers were reported globally in 2022. China at the top with 61,060 followed by India with 47,333 cases were reported of ovarian cancer. In the United States, it was 21,179 cases documented. Mortality rates were seen highest in India and it was 32,998 deaths reported. China ranked second in mortality rates, 32,646 deaths were reported[2]. Bihar has the only Population Based Cancer Registry (Indira Gandhi Institute of Medical Sciences, Patna) due to this continues to lack a Population Based Cancer Registry existing statistics and future data are based on Hospital Based Cancer Registry that have some intrinsic biases and limitations. There is a dearth of publications on the trends in cancer incidence in Bihar, according to the best of the author’s knowledge[3]. Ovarian cancer is considered to be the fifth commonest cause of death among females across the globe[4].

Risk factors responsible for OC are sedentary lifestyles and environmental factors, strong family history, repeated ovulation, higher age child birth, pelvic inflammatory diseases[5]. Typically, ovarian cancer patients clinically presented with early satiety, increased abdominal size, change in bowel habit, weight loss, vaginal bleeding, abdominal ascites. It is commonly believed that no symptoms are evident at earlier stage of the disease[6]. OCs are mainly divided into three types: epithelial (commonest type), germ cell and sex–cord–stromal tumours. Epithelial ovarian cancer has four main subtypes: serous, endometrioid, mucinous, and clear cell. High-grade serous ovarian carcinomas are the commonest types, representing 75%–80% of the epithelial OC subtypes, while low grade serous carcinomas are less than 5%. Furthermore, the endometrioid, mucinous, and clear cell subtypes typically make up about 10%, 3%, and 10% of the total cases, respectively[7]. The current standard and recommended approach to treat OCs mainly involves cytoreductive surgery followed by chemotherapy with platinum doublet[8].

Chemotherapy is important in recurrent cases; recurrence of platinum sensitive tumours ideally responds well to treatment with platinum-based regimens. Platinum Platinum-based regimens are advised to be the most effective chemotherapeutic modality in ovarian cancer[9]. Several other immunotherapies and targeted therapies are widely available, olaparib, pembrolizumab, rucaparib etc. The real-world data for early-stage ovarian cancer (Stage I and Stage II) 70%–80% survival rates were reported while in advanced stage it was 30%–40%[10]. In the first line setting, bevacizumab, a humanized monoclonal antibody, increases PFS in recurrent epithelial OC and PARP inhibitors in the second line setting in OC[11]. Olaparib has been recommended to be the safest and most efficacious treatment as maintenance therapy in platinum-sensitive settings[12].

The present literature also reported a poor survival outcome as the real-world literature shown. This is mostly due to absence of effective prevention and early detection strategies of OCs.

Methodology

This is a single-institution retrospective study of pathologically confirmed cases of OC, who were treated at Buddha Cancer Centre (BCC), Patna, Bihar. Patients were treated between the year January 2019–December 2023, over a period of 5 years. The clinical data were extracted from a prospectively maintained database of the Medical Record Department (MRD) of the hospital before concern authorities. All clinical data reviewed and evaluated were patients age, demography, clinical status, stage of the disease when visited our centre, comprehensive treatment details, follow-ups and survival outcomes. All cases were clinically evaluated by experienced team of gynaecologists, medical oncologists, pathologist and oncologists at the centre.

Treatment and follow-up protocol: In early-stage surgery definitely remains the mainstay and in advanced stage chemotherapy followed by surgery. Surgical interventions done in most patients with early-stage ovarian cancer that has not spread beyond ovaries. Platinum based chemotherapies in combinations such as targeted therapies shown effective results in treating any stage of ovarian cancer. The current standard chemotherapy has given 6 cycles of paclitaxel and carboplatin. The dose was calculated as per the BSA and paclitaxel 175 mg/m² over 3 h and carboplatin AUC 5.0 to 7.5 every 21 days. Follow-up was done every 3, 6, and 12 months.

Software used for data interpretation: Microsoft Excel were used to capture the patient data. Statistical analysis was done using IBM SPSS software version 24.0. P-value < 0.05 was considered as statistically significant. Categorical values were represented in the form of frequencies and percentages. Overall survival (OS) was evaluated from the time of diagnosis to death while progression-free survival (PFS) was evaluated from the time of diagnosis to the time of progression or death.

Ethics committee approval and consent to participate: BCC Institutional ethics committee (BCC–IEC) has approved this retrospective study [BCC–IEC 01-2025].

Inclusion criteria

a. The age groups of the participants were 18–85 years.

b. Voluntarily willing to sign the informed consent form during their course of treatment.

c. Histologically confirmed cases of ovarian cases were recruited in the study.

d. Eastern Cooperative Oncology Group (ECOG) performance status scale was 0–4.

e. All patients with measurable disease based on RECIST 1.1 for response evaluation.

Exclusion criteria

a. Women of childbearing who had positive on urine pregnancy test and lactating women.

b. Participants with known history of HIV, HCV, and hepatitis B.

c. Patients not willing to sign the Informed Consent Form at the time initial interventions.

Response evaluation: Response evaluation was done using clinical examination and imaging modalities. Post treatment during follow-up visits patients were advised to do CT scan. Baseline CT scan was compared with the current CT scan reports.

Response evaluation was done using RECIST 1.1 Formula i.e.

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Result

A total of (N = 437) patients were diagnosed with OC at BCC, Patna, Bihar, India from the period January 2019 to January 2023. In this study (90%; n = 391) OC had epithelial origin whereas rest had non-epithelial origin. The baseline profiles of the patients is tabulated in (Table 1). Treatment history and response of the patients in Table 2.

Mean age ± SD (years): 55.7 ± 16.1 years (age range 18 years to over 60 years). The majority of the patients were in the age groups of ≥ 60 (n = 158; 36.16%), in 30–49 age groups it was (n = 144; 32.95%) cases (Figure 1). A large number of the patients n = 329; 75.29% were coming from a rural background. A large number of the patients n = 329; 75.29% were from rural backgrounds. The majority of cancer (OC) cases (n = 87) were registered from the state capital, Patna district, followed by Purnia (n = 32), Kishanganj (n = 27), Bhojpur (n = 20), and other districts. Patients (n = 26) from neighbour state Jharkhand had also visited our centre seeking standard care of treatment (Figure 2).

The majority of the patients are clinically presented with a distended or bloated abdomen (n = 231; 54.10) it was due to peritoneal ascites or disease progression. Constipation (20.61%), frequent urination (11.01%), ascites (18.03%), pelvic pain (18.97%), and vaginal bleeding (20.84%) respectively of the total cases, (P value < 0.005). General conditions of the patients were evaluated using the ECOG performance status scale. Of 437 cases, ECOG PS 3 was reported in (n = 172; 39.36%) patients while in ECOG 4 (n = 137; 31.35%).

CT scan (n = 348; 79.63%) was done. The tumour marker CA-125 was elevated in (n = 332; 77.72%) patients with P value < 0.005. The commonest histologic subtype was the serous type (n = 224; 52.46%) of all the cases. More than 75% patients presented clinically at a late stage of the disease. Majority of the cases were in Stage III (n = 219; 51.29%) and in Stage IV (n = 103; 24.12%) (Figure 3A).

Nearly (n = 83; 19.44%) patients were advised to do BRCA 1 and BRCA 2, but due to financial constraints, only (n = 16; 3.75%) patients went through the genetic test. Better OS was achieved in middle-aged groups 50–59 years (38.4%), P < 0.05 (Figure 4).

Kaplan-Meier survival curves depicting OS for OC patients classified into high-risk (red; n = 216) and low-risk (blue; n = 225) groups. The x-axis represents follow-up time in months, and the y-axis indicates survival probability. Patients in the high-risk group show a markedly reduced OS compared to those in the low-risk group, indicating a strong association between risk stratification and patient prognosis. Median OS was 22.7 months. 1-year OS: 68.94%, 2-year OS: 46.45%, and 5-year OS: 20.61%, P < 0.05 (Figure 5).

Curative (n = 391; 89.23%) and palliative (n = 36; 10.77%) intent of therapies have been offered to the patients. Of (N = 437) patients, (n = 112; 23.63%) patients underwent different types of surgery. Primary and Interval cytoreductive surgery was performed in (n = 69; 61.6%) and (n = 43; 38.39%), respectively, and fertility sparing surgery was conducted in (n = 9; 7.14%) patients. Additional surgical interventions, such as peritoneal stripping, pelvic peritonectomy and intestinal resection, were performed in (n = 2; 1.78%), (n = 39; 34.82%), and (n = 3; 2.67%). Of (n = 112) patients, OS was achieved in (n = 103; 91.96%) cases and mortality rates were only (2.68%). OS stratified by Reguptive status, comparing immunotherapy (solid line) with other standard therapies (dashed line) followed by chemotherapy, surgery and supportive treatment surgery followed by chemotherapy showed better overall survival rates P < 0.05 (Figures 6A–D).

Immunotherapy had also achieved better OS in the early stage of the disease, in patients who were BRCA positive.

The median duration of follow-up was 20 months (95% CI, 18.0 to 21.9). Median OS for stages I, II, III, and IV was 60, 48, 36, and 20 months, and their corresponding PFS was 58, 42, 16, and 12 months (95% CI, 16.0 to 20.0). PARP inhibitor was used in BRCA 1 and 2 positive cases. Kaplan–Meier plot showing better PFS in low-risk groups, while high-risk groups had poor prognosis. The progression-free survival (PFS) was significantly different between early disease and advanced disease (P value < 0.0001). The five-year PFS was 65.2% in stage I and II, while only 19% in stage III and IV (Figure 7) Median PFS and OS in advanced OC at our centre were equivalent to global standards.

At our centre, BRCA 1 and 2 positive patients treated with PARP inhibitors. Response rates were evaluated clinically and with imaging modality CT scan. Of 437 cases, 17% patients had complete response (CR), 38% had a partial, 20% with stable disease (SD), and 24% patients had a disease progression.

Discussion

The current literature reported that more than 61% ovarian cancer patients were in the age group of 51–70 years. Gangane et al. also presented in their literature over 90% cases of OC were in the age groups of 55–64 years[13]. More than 75% of OC patients in the current study presented in the advanced stage of the disease (Stage III–IV), similar to other literature reported in India[14]. Our findings on clinical presentations were similar to other Indian and International literature. The three most frequent symptoms were increased abdominal size and bloating (54%), followed by constipation (20%) and ascites (18%). Matuso K et al. highlighted similar clinical symptomatic findings in their literature[15].

Inadequate screening programs in rural areas, delayed diagnosis and referral by primary care physicians, and late presentation of the disease in the advanced stage lead to poor outcomes[16]. The most common histology subtype was serous type (52%), followed by mucinous (22%) and endometrioid (13%) types published in other studies too[17]. Our literature finding was similar optimal cytoreduction rate was higher (66.55% vs. 33.45%) in favour of suboptimal cytoreduction (P < 0.005). Torre et al. strongly recommended that the mainstay treatment of advanced ovarian cancer is cytoreductive surgery followed by chemotherapy, resulting in better outcomes[18].

Data revealed from our study confirmed that those patients went under cytoreductive surgery had achieved significant improvement (P < 0.003). Earle CC et al. confirmed the same in their study, the ability to achieve adequate cytoreduction in ovarian cancer is strongly influenced by expert, specialised gynaecologic onco surgeons[19]. Combination chemotherapy of paclitaxel plus carboplatin and bevacizumab regimen had achieved 100% response rate, in (n = 73) patients. Dessai SB had well documented the similar results in their literature[20]. The bevacizumab and PARP inhibitors have showed better overall survival rates in advanced ovarian cancer and have been documented in many studies[21]. Decreased survival rates were seen in the late stage of the disease. Median OS was 20 months. Median OS for stages I, II, III, and IV was 60, 48, 36, and 20 months. In the Indian subcontinents median OS was much lower compared to overseas. BRCA genetic investigation was advised in a few patients, but due to financial constraints, they avoided it and relied on conventional chemotherapies[22]. The 5-year survival rates were 20.61%, P < 0.003. All treatments were planned and executed as per National Comprehensive Cancer Network, American Society of Clinical Oncology and European Society of Medical Oncology guidelines at our centre by the team of Oncologists. National Cancer Grid guidelines were incorporated, too, in Indian settings.

The prognosis of OC patients was influenced by various factors. Several important prognostic factors that impact OS included ECOG PS score, parity, histological types, well-differentiated tumours, early-stage disease, and absence of ascites[23]. But the diagnosis of early-stage OC is challenging due to its asymptomatic nature. That’s the reason the majority of cases of OC are diagnosed in the advanced stage of the disease.

We treated > 41% (n = 180) cancer patients under Ayushman Bharat Pradhanmantri Jan Arogya Yojana (AB-PMJAY). This is the largest healthcare assurance scheme in the world, aiming to provide a health cover of five lakhs per Ayushman card holder.

Conclusion

To summarise, the patterns observed in our patient group and their outcomes align with findings from many studies nationwide, highlighting the trend of late presentations and overall poor outcomes. In rural parts of Bihar, adequate cancer screening programs need to be implemented to reduce the morbidity and mortality rates of cancer (OC).

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