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Table of Contents
ORIGINAL ARTICLE: REAL WORLD DATA
Year : 2021  |  Volume : 4  |  Issue : 3  |  Page : 486-491

Clinicopathological features and outcomes of choriocarcinoma: A retrospective analysis from an Indian tertiary cancer center


1 Department of Medical Oncology, Tata Medical Center, Kolkata, West Bengal, India
2 Department of Gynaecologic Oncology, Tata Medical Center, Kolkata, West Bengal, India

Date of Submission29-May-2021
Date of Decision02-Sep-2021
Date of Acceptance05-Sep-2021
Date of Web Publication08-Oct-2021

Correspondence Address:
Joydeep Ghosh
Department of Medical Oncology, Tata Medical Center, Kolkata, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/crst.crst_124_21

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  Abstract 


Background: Choriocarcinoma is the most common form of gestational trophoblastic neoplasia seen by medical oncologists. It is a rare condition and data related to its long-term outcomes from the Indian subcontinent are sparse.
Objectives: The primary objective of this study was to assess the clinicopathological characteristics and clinical outcomes of patients with of choriocarcinoma; the secondary objective was to assess the correlation of outcomes with risk stratification.
Materials and Methods: This single-center retrospective study was conducted at the Tata Medical Center, a tertiary cancer center in West Bengal, India. We identified all the cases of choriocarcinoma treated at our hospital from the electronic medical records and noted their baseline characteristics, treatment details, and clinical outcomes. Descriptive statistics were used for baseline characteristics, and the Kaplan–Meier method was used for the survival analysis.
Results: A total of 24 patients were included in the study. The median age of the patients was 29 years (interquartile range, 25.9–39.5). The median time interval from the last pregnancy was 5 months (range, 0 months to 11 years). The World Health Organization risk score was low in 8 (33.3%) and high in 16 (66.7%) patients. There were 6 (25%) patients who received single-agent chemotherapy, 14 (66.7%) received the EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine) regimen, and 1 (4.7%) received the VIP (etoposide, ifosfamide, and cisplatin) regimen, with the latter 2 being given only to high-risk patients. The median follow-up was 10.9 months (95% confidence interval [CI], 4.2–28.5). The median progression-free survival was not reached (NR) (95% CI, 7.2–NR). Similarly, the median overall survival was NR (95% CI, 10.56–NR).
Conclusion: Our study provides real-world data for this rare malignancy and reinforces the fact that choriocarcinoma is a highly curable disease. Despite the clinicopathological variations in the different parts of the country, the long-term outcomes are favorable.

Keywords: Choriocarcinoma, India, outcome, real world


How to cite this article:
Ghosh J, Dey S, Mandal D, Ganguly S, Biswas B, Dabkara D, Ghosh A, Chakraborty B, Roy A, Rai S, Mathai S, Bhaumik J. Clinicopathological features and outcomes of choriocarcinoma: A retrospective analysis from an Indian tertiary cancer center. Cancer Res Stat Treat 2021;4:486-91

How to cite this URL:
Ghosh J, Dey S, Mandal D, Ganguly S, Biswas B, Dabkara D, Ghosh A, Chakraborty B, Roy A, Rai S, Mathai S, Bhaumik J. Clinicopathological features and outcomes of choriocarcinoma: A retrospective analysis from an Indian tertiary cancer center. Cancer Res Stat Treat [serial online] 2021 [cited 2021 Dec 9];4:486-91. Available from: https://www.crstonline.com/text.asp?2021/4/3/486/327756




  Introduction Top


Choriocarcinoma is a malignant form of gestational trophoblastic neoplasia. Its incidence in the United States of America ranges from 1 per 19,000 to 1 per 24,000 persons.[1] The incidence increases with increasing maternal age.[1] Moreover, there are significant ethnic differences, with a higher incidence noted in Asians than non-Asians and in African Americans compared to Caucasians.[1],[2] The 5-year survival for choriocarcinoma has been reported to be around 90%.[2] The survival is lower among African − Americans and those who are older and have advanced disease.[2] There are two types of staging systems used for choriocarcinoma prognostication: The International Federation of Gynecology and Obstetrics (FIGO) staging system and the other more commonly used World Health Organization (WHO) risk stratification.[3] The WHO classification considers the probability of drug resistance and classifies patients into low risk (score <7) and high risk (score ≥7) groups. Low-risk patients are treated with single-agent regimens like actinomycin D or methotrexate.[4] Methotrexate has been associated with significantly more treatment failure than actinomycin D (relative risk, 3.81; 95% confidence interval [CI], 1.64–8.86). On the contrary, high-risk cases are best treated with multi-agent chemotherapy like EMA-CO (etoposide, methotrexate, actinomycin D-cyclophosphamide, and vincristine), and EMA-EP (etoposide, methotrexate, actinomycin D–etoposide, and cisplatin).[5] With multi-agent chemotherapy regimens, the 5-year survival has been reported to be 86%.[6]

Few studies have reported on the outcomes of choriocarcinoma in Indian patients. Bafna et al. reported their findings from a retrospective analysis of 128 patients with choriocarcinoma, but there were no patients with long-term survival.[7] Another study by Gulia et al. showed that overall survival (OS) in the low- and high-risk groups were 100% and 88.8%, respectively, at a median follow-up of 16.6 months.[8] However, another retrospective study by Hussain et al. reported the clinicopathological features but not the survival data of patients with choriocarcinoma.[9]

Due to the rarity of the disease, most of the evidence is based on retrospective data. Moreover, there are no data available on choriocarcinoma from the eastern part of India. Hence, we present our institutional experience and survival outcomes for patients with choriocarcinoma from Eastern India.


  Materials and Methods Top


General study details

This retrospective study was conducted at the Tata Medical Center, a tertiary care hospital in West Bengal in East India. All patients diagnosed with choriocarcinoma and who received treatment at our center from May 2011 to December 2019 were included. As this was a retrospective study, as per our institutional protocol, a waiver for obtaining informed consent was granted. The study was conducted according to the ethical guidelines outlined in the Declaration of Helsinki, Good Clinical Practice guidelines, and the Indian Council of Medical Research guidelines.

Participants

All patients aged between 18 and 70 years who were diagnosed with choriocarcinoma (either with the combination of clinical features, radiological picture, serum beta human chorionic gonadotropin [HCG] levels, or on histopathological diagnosis) were included in the study. Patients who visited the hospital only for an opinion but did not get treatment were excluded. Patients who did not have follow-up data for more than 3 months post-therapy were also excluded from the study.

Variables

The primary aim of the study was to assess the clinicopathological profiles and outcomes of patients with choriocarcinoma. The secondary objective was to assess the correlation between outcomes and the individual risk groups.

Definitions

The patients were classified into high- and low-risk groups according to the WHO risk stratification[4] based on their age, antecedent pregnancy interval in months, pre-treatment serum hCG, largest tumor dimension in centimeters, sites and number of metastases, and number of prior failed lines of chemotherapy. Those with a score of 0–6 were considered to have a low risk for resistance to single-agent chemotherapy. Those with a score ≥7 were considered to be at high risk for resistance to single-agent chemotherapy, and hence, were given combination chemotherapy. Complete normalization of beta(β)-hCG was considered as complete response. Rising level of β-hCG in two or more consecutive samples was considered progressive disease. The progression-free survival (PFS) was defined as the time from the start of chemotherapy to disease progression, and OS was defined as the time from the start of chemotherapy to death due to any cause.

Study methodology

All consecutive patients who were diagnosed with choriocarcinoma either at our institution or were referred to our institution from other centers after initial treatment were included in the study. Radiological imaging was performed, and serum β-hCG level and other routine organ function parameters were investigated for all patients. Patients were divided into low- and high-risk groups based on the WHO risk stratification score. Patients in the low-risk group were treated with either methotrexate or actinomycin D, while those in the high-risk group were treated with either EMA-CO, EMA-EP, or VIP (etoposide, ifosfamide, and cisplatin) regimen. Surgery was considered, if clinically indicated. The data related to the patients' clinicopathological characteristics, treatment received, and outcomes were obtained from the hospital electronic medical records. The baseline demographic data including the age, site and number of metastases, baseline β-hCG level, treatment interval since the last pregnancy, type of last pregnancy, type and line of chemotherapy regimen received, clinical and serological response, date of progression and death (in case of an event), and the status at the last follow-up were also recorded.

Statistics

As this was a retrospective analysis, all patients fulfilling the eligibility criteria within the time frame of the study were included. No sample size calculation was performed for the study. Descriptive statistics were used for demographics and clinical characteristics. Absolute numbers and percentages were used for baseline demographics, clinical characteristics, and treatment variables. Pearson's correlation coefficient was used to analyze the degree of correlation between variables. P <0.05 was considered statistically significant. STATA (version 14.1, StataCorp, 4905 Lakeway Dr College Station, TX 77845, USA) statistical software was used for the statistical analysis.


  Results Top


Baseline characteristics

A total of 24 patients were included in the analysis [Figure 1]. The median age of the patients was 29 (range 19–53) years. The presenting symptoms are described in [Table 1]. Magnetic resonance imaging of the brain was performed in those who had headache at baseline. Histopathological diagnosis was made in 16 (66.5%) patients. The majority of the antecedent pregnancies were abortions, as recorded in 12 (50%) patients, followed by molar and term pregnancies recorded in 8 (33.3%) and 4 (16.7%) patients, respectively. The median β-hCG level at presentation was 101030.5 IU/L (range, 5.67–1431800). Distant metastasis was present in 17 (70.8%) patients. The median number of metastases was 3 (range, 0–13). The most common site of metastasis was the lung in 14 (82%) patients, followed by the brain in 5 (29.4%). A total of 8 (33.3%) patients had received chemotherapy before they came to our institution. According to the WHO risk stratification score, 16 (66.67%) patients were considered high risk. At our center, 6 (25%) patients received single-agent chemotherapy, 14 (66.7%) received the EMA-CO regimen, and 1 (4.7%) patient received the VIP regimen as the second-line treatment. A dose intensity of 100% was maintained in 19 (90.5%) patients.
Figure 1: Scheme of the inclusion of patients with choriocarcinoma in the study (EMR=Electronic medical records)

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Table 1: The baseline characteristics and treatment details of all included patients with choriocarcinoma

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Toxicities

The most commonly reported toxicity was Grade 3 neutropenia in 6 (28.5%) patients [Table 1]. There were no treatment-related deaths.

Efficacy

All patients in the low-risk group achieved a complete response, while 10 (66.6%) out of 15 who were treated in the high-risk group achieved complete remission. None of the patients underwent any cancer-directed surgery after they came to our center.

Survival data were available for 20 patients. The median follow-up was 10.9 months (95% CI, 4.2–28.5). The median PFS was not reached (NR, 95% CI, 7.2–NR) [Figure 2]. Similarly, the median OS was NR (95% CI, 10.56–NR) [Figure 3]. The PFS of the low-risk group was numerically better than that of the high-risk group (P = 0.14) [Figure 4]. Similarly, the OS of the low-risk group was numerically better than that of the high-risk group (P = 0.29) [Figure 5].
Figure 2: Progression-free survival in the overall population

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Figure 3: Overall survival of all patients

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Figure 4: Progression-free survival based on risk categories

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Figure 5: Overall survival based on risk categories

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  Discussion Top


In our study, nearly 70% of the patients with choriocarcinoma were in the high-risk group. The β-hCG level of our patients at baseline was higher than that reported in other studies. All low-risk patients in our study achieved a complete remission. The median survival, both PFS and OS were not achieved in our study at a median follow-up of 10.9 months. The toxicity rates with chemotherapy were comparable to those reported in the published literature.

Choriocarcinoma is a rare disease, and most of the available data have been obtained from retrospective analyses. The largest study on choriocarcinoma from India was conducted by Gulia et al.;[8] this study included 70 patients. In this study, nearly 70% of the patients were low-risk, and 30% were high-risk. In our study, the proportion of low- and high-risk patients was reversed. This could be attributed to the differences in the referral patterns of the two hospitals, with our center receiving more patients with advanced disease and pretreated cases. The median baseline β- hCG level in Gulia et al's study was 50000 IU/L, but it was higher (around 100000 IU/ml) in our study. This is likely because of a higher proportion of high-risk cases in our study. In our study, the lung was the most common (82%) site of metastasis. This has also been reported in other studies.[8],[9],[10] The most common antecedent pregnancy event in our study was abortion. This is different from that observed in other studies, where molar pregnancy was the most common event.[10] We are uncertain what the reason for this difference was. The median time interval from the last pregnancy of 5 months was similar to that reported in other studies.[8],[9],[10]

In the low-risk group, all patients had a complete remission. A formal comparison between those who received actinomycin D and methotrexate could not be made due to the absence of progressive disease and low number of events. Other larger studies have shown response rates of approximately 80% with single-agent chemotherapy. A high rate of complete response was observed in our study. In the high-risk group, 14 patients received the EMA-CO regimen, of which 11 (81%) achieved a complete remission. One of the high-risk patients received the VIP regimen as she had received prior treatment with the EMA-CO and EMA-EP regimens. Fortunately, she responded to the treatment. The response rate noted in our patients to EMA-CO was similar to that reported in other studies at around 80%.[6],[8],[10],[11],[12]

The median follow-up duration of our study was 10.9 months. We acknowledge that this is a short follow-up for a study on choriocarcinoma, but in most cases, recurrence occurs at a median duration of 9 months.[13] The median PFS and OS were not reached because of the high complete response rates in both the groups. Although there was an obvious numeric difference in the PFS and OS between the high- and low-risk groups, the difference did not reach statistical significance because of the low number of events and small sample size.

Out toxicity rates were comparable to those observed in other published studies. Although Grade 3 neutropenia was observed in 30% of patients who received multi-agent chemotherapy (EMA-CO), none of the patients developed febrile neutropenia. The other common toxicities such as mucositis and diarrhea were observed in <10% of the patients. The high rate of Grade 3 neutropenia could be easily mitigated with primary growth factor prophylaxis in susceptible patients.

There are a few limitations to our study. First, this was a single-center retrospective analysis. Second, our sample size was small. However, most of the published retrospective studies on choriocarcinoma have small sample sizes because of the rarity of these tumors. Third, due to the retrospective nature of the analysis, we did not have long-term data for a few patients. Finally, we could not capture the precise details of toxicities for all the patients.

Overall, our study highlights the fact that our outcomes are similar to those reported in the published literature. Our study adds to the knowledge base about the outcomes of this rare disease from the eastern part of India. For a rare disease like choriocarcinoma, most of the knowledge about the disease comes from retrospective audits. This makes our analysis important. However, in future, well-designed prospective studies are warranted, including multi-centric conglomerate data sharing.

The take home points for this study are the fact that choriocarcinoma is a very treatable condition with very high cure rates. Our patients present with a high disease burden and they should undergo accurate risk stratification. Newer agents that may offer some hope for the treatment of refractory cases include pembrolizumab and cell-based antibody targets.[14]


  Conclusion Top


Our results reinforce the fact that choriocarcinoma is a highly curable disease. Despite the clinicopathological variations in the country, the long-term outcomes are favorable.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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You B, Harvey R, Henin E, Mitchell H, Golfier F, Savage PM, et al. Early prediction of treatment resistance in low-risk gestational trophoblastic neoplasia using population kinetic modelling of hCG measurements. Br J Cancer 2013;108:1810-6.  Back to cited text no. 13
    
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Kim GS, Hwang KA, Choi KC. A promising therapeutic strategy for metastatic gestational trophoblastic disease: Engineered anticancer gene-expressing stem cells to selectively target choriocarcinoma. Oncol Lett 2019;17:2576-82.  Back to cited text no. 14
    


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