Pattern of Care and Outcomes of Gallbladder Cancer Patients: Retrospective Study from a High Incidence Region in India

Introduction

Gallbladder cancer (GBC) is often diagnosed at advanced stage and carries dismal prognosis.12 GBC is the 20th most common cancer in India with crude incidence of 2.3 per 100,000 persons.3 However, it is among leading sites of cancer in the northern and northeast part of India.4 Surgery is the mainstay of treatment in GBC and modest outcomes is reported with systemic chemotherapy alone.56 Also, often surgery is deferred in GBC patients due to either locally advanced disease or medical inoperability secondary to poor nutrition and performance status (PS).15 GBC is an aggressive cancer and 5-year survival among resected patients is 5 to 32% while survival in unresectable/metastatic disease is less than 5%.789 To optimize the outcomes in these patients, it is imperative to identify pattern of care and limitations of treatment in real-world scenario. We present the clinical outcomes and pattern of care of GBC from high-incident area in India.

Materials and Methods

This was a retrospective audit done at Mahamana Pandit Madan Mohan Malviya Cancer Centre, Varanasi, Uttar Pradesh, India. We screened our hospital records from January to June 2021 for suspected GBC patients (patients who presented with gallbladder mass or incidentally detected GBC). Fig. 1 shows the consort diagram of the study, out of 200 screened patients, 170 GBC patients were included in the study. Treatment intent and plan of management were formulated after discussion in the multidisciplinary tumor (MDT) board. Based on imaging findings, disease was classified as early stage (node negative, liver invasion ≤ 2 cm, and no adjacent organ invasion), or locally advanced (node positive, liver invasion > 2 cm, or adjacent organ invasion).10 Patients with early stage disease was planned for upfront surgery while patients with locally advanced disease were assessed after neoadjuvant chemotherapy. Patients with metastatic/unresectable disease were planned for palliative chemotherapy. Besides, consultation with pain and palliative care team was taken for all patients with metastatic/unresectable disease.

Close

Fig. 1: Consort diagram depicting patient selection. EHCC, extrahepatic cholangiocarcinoma; GB, gallbladder; GBC, gallbladder cancer; HCC, hepatocellular carcinoma; MDT, multidisciplinary tumor board; NEC, neuroendocrine carcinoma.

Export to PPT

Electronic medical records of these patients were used to extract demographic, treatment, and outcome data. Patients were censored at last follow-up. Progression was defined as development of a new site of disease, increase in extent of baseline disease, or death due to any cause. Progression-free survival (PFS) was calculated from date of diagnosis (date of histopathology or date of registration when former was not available) to date of progression while overall survival (OS) was calculated from date of diagnosis to date of death. Demographics and treatment characteristics were reported as simple percentage and proportion. Kaplan–Meir survival statistics was used for estimating PFS and OS. Between groups, proportions were compared with chi-squared test while continuous data was compared with Mann–Whitney U test. SPSS version 24 (IBM Corp. Released 2016; IBM SPSS Statistics for Windows, Version 24.0, IBM Corp, Armonk, New York, United States) was used for statistical analysis.

Results

Outcomes

At a median follow-up of 1.7 months (95% confidence interval [CI], 1–2.4 months), disease progression and death occurred in 42 (24%) and 24 (14%) patients, respectively. Median PFS was 7.3 months (95% CI, 6.7–7.9 months) and the estimated PFS at 6 months was 60.2% (95% CI, 49–71.4). Median OS was not reached while the estimated OS at 6 months was 79% (95% CI, 70.8–87.2). After disease progression only 14 patients (33%) could receive second-line chemotherapy. Most common chemotherapy regimen in the second line was irinotecan. Figs. 2 and 3 show PFS and OS curves, respectively.

Close

Fig. 2: Progression-free survival.

Export to PPT

Close

Fig. 3: Overall survival.

Export to PPT

Discussion

India accounts for 10% of global GBC incidence and it is prevalent in the northern and northeastern part of the country.11 In our study, all patients were residents in Gangetic plains which may be partly due to proximity of our center in this region and partly a reflection of high incidence of GBC in the region.12 Majority of patients in our study were diagnosed in mid-fifties which is consistent with other studies from India.1511 GBC has female predilection as is reflected in our study with two-thirds patients being female.

Majority of the patients presented in the advanced stage in our study. The GBC often presents with vague symptoms which leads to delay in diagnosis. This was consistent with reported literature.13 In our study, less than half of the patients could undergo treatment as planned in MDT. Patients with compromised PS were less likely to come up for treatment.14 Moreover, there seems to be association of comorbid condition, metastatic disease, obstructive jaundice, and raised CA 19–9 with treatment noncompliance. Patients with metastatic disease and higher CA 19–9 often have significant disease-related symptoms which may compromise their nutrition and overall general condition. Besides, third of patients in our cohort had obstructive jaundice which led to treatment delay and further deterioration in PS. Even in patients with incidentally detected GBC, more than half were lost to follow-up and among those who received treatment majority had interim disease progression thus precluding surgery. There was high attrition after initial workup. Possible reasons were logistics of access to health care, financial constraints, and lack of awareness.15 Surgery could be performed in only 20% (n = 33) of patients due to locally advanced disease in the majority of patients.16 Poor nutrition as reflected in low baseline albumin in third of patients, also led to compromise in chemotherapy intensity with only a third of patients completing planned chemotherapy cycles.17 Most of the patients received gemcitabine-based chemotherapy (gemcitabine and cisplatin or oxaliplatin), this is consistent with reported literature and efficacy of gemcitabine-based regimen in biliary tract tumors.181920 Due to heterogeneous patient cohort (metastatic as well as nonmetastatic), analysis of prognostic variables could not be done.

In our study, around 40% (n = 66) of the patients relapsed (n = 42) or died (n = 24) within 6 months and estimated OS at 6 months was 79%. Other studies have reported median survival of 12 to 15 months and 4 to 5 months in locally advanced and metastatic GBC, respectively.12122 This reflects dismal prognosis of advanced GBC.15916 A third of patient could receive second-line treatment after relapse in our study. Frequently, post-relapse deterioration in PS precludes any cancer-directed treatment in GBC patients. Single-agent chemotherapy has shown benefit with limited toxicity in this scenario.2324

Our study reiterates the poor outcome of GBC patients. There is need to identify these patients at early stage which calls for institution of screening in high incidence area. The nutritional optimization and supportive care can improve the treatment compliance and overall outcomes. Telephonic follow-up and financial support in low-income region during the treatment may help in reducing attrition.25 Strength of our study is relatively large sample size and sample being representative of high incidence region. However, there were some limitations, follow-up duration was short, there was poor documentation of chemotherapy-related toxicity, and outcomes post-relapse and progression was not available.

In conclusion, GBC is an aggressive cancer often diagnosed in advanced stage with female predilection and carries dismal prognosis. Screening in high-risk areas, multimodality treatment in locally advanced disease, and optimization of adjuvant treatment is the need of the hour.