Introduction

Esophageal carcinoma has the poor prognosis in spite of the advancement in treatment modalities. The incidence of newly diagnosed cases of carcinoma of the esophagus worldwide per year is 572,034, while the mortality is 508,585. The corresponding figures of India are 52,396 and 46,504, respectively.1 The treatment has evolved from single modality to multimodality approach over the past few decades. Conventionally, esophagectomy has been the main choice of treatment for resectable middle and lower-third esophageal cancers. The trimodality approaches involving neoadjuvant chemoradiotherapy (NACRT) followed by surgery for resectable middle and lower-third esophageal cancer have been studied.2 The feasibility of this combination treatment needs to be evaluated in developing countries, especially in the rural background. Here, we present an audit of the retrospective analysis of prospectively maintained data of such combination treatment practiced in a single rural cancer center in Western India.

Materials and Methods

This is a retrospective study of 157 consecutive patients diagnosed with nonmetastatic carcinoma of the esophagus, and who were treated in a single cancer institute in rural Western India from March 2013 to March 2017. All case records and electronic data were retrieved and analyzed. All patients underwent endoscopic evaluation of the upper gastrointestinal tract (GIT). The disease was documented, and biopsies were collected. Patients underwent staging investigations with contrast-enhanced computed tomography (CT) scan of the neck, thorax and upper abdomen, and hematological counts for determining fitness for chemotherapy. All histology proven, treatment naïve cases of carcinoma of the middle and lower-third esophagus were included in the study. Histology other than squamous carcinoma and adenocarcinoma were excluded from the study. Patients with only localized disease with or without regional nodes were included. Patients with performance status 0, 1, and 2 and who would complete the intended neoadjuvant treatment were included for the treatment. All the patients carried out discussions with the surgical oncologist, radiation oncologist, and medical oncologist before initiating the treatment.

Results

One hundred and fifty-seven patients were started on NACRT. The demographic details were captured for all patients (Table 1). The details of radiation therapy, chemotherapy, and surgery were documented (Table 2). An effort was made to find the causes of default after neoadjuvant therapy through either telephonic contact with the patient or personal home visit by the hospital representative. The treatment-related toxicities and survival were captured (Tables 34).

Discussion

The intention of this retrospective audit was to check the feasibility of NACRT followed by surgery in resectable carcinoma of the esophagus in a rural cancer center in western India. We neither aim to prove the efficacy of this approach nor do we question the efficacy of this approach in the rural setting. We want to highlight the practical problems that we faced in the implementation of this approach and the reasons for noncompliance to the treatment.

NACRT was tolerated well by all the patients with acceptable toxicity profile. The surgical complication rates were acceptable and less than reported in the literature.2

The practice at our institute till 2013 was upfront surgical resection, followed by adjuvant treatment for resectable carcinoma of the esophagus. The landmark randomized trial published in 2012 showed a significant OS benefit of 49.4 months in trimodality treatment versus 24 months in surgery alone arm.2 The “Evidence-Based Medicine Conference” conducted annually by the Tata Memorial Center, Mumbai, which discussed the guidelines for esophageal cancers in 2013 gave us the confidence to change our practice. We discussed the new strategy in our Institutional Review Board and started the new protocol from March 2013. Here, we present the retrospective audit of the patients afflicted with resectable carcinoma of the esophagus, and with curative intent, consecutively treated using NACRT. Fifty-six percent of the patients had carcinoma of the lower third of the esophagus; the most common histology was squamous cell carcinoma, in 87% of the patients, indicating squamous cell carcinoma is common histology even in the lower-third esophagus in our population. More than two-third of the patients were treated under one of the applicable government-sanctioned schemes, without any financial burden of the treatment on the patient or the family, but with certain limitations. The dose of radiotherapy for neoadjuvant setting in carcinoma of the esophagus varies in different randomized clinical trials. The range varies from 18.5 Gy to 50.4 Gy with different fractionation schedules.345678910 We implemented conventional fractionation schedules at doses of 41.4 Gy to 45 Gy with either 3DCRT or IMRT planning. The concomitant chemotherapy administered along with radiotherapy in neoadjuvant setting varies in different studies. The most commonly used drugs are cisplatin, 5 fluorouracil (5FU), paclitaxel, mitomycin, and etoposide.

Based on the CROSS trial results, we offered paclitaxel plus carboplatin regiment. However, due to financial reasons, this regimen was accepted by 72% of the patients. The rest received cisplatin or cisplatin with 5FU or capecitabine regimen. Sixteen patients received only neoadjuvant radiotherapy without concomitant chemotherapy, as they were unfit for chemotherapy. All the surgical specimens were reviewed by the single oncopathologist. There was no case with close or positive surgical cut margin in our group of patients. The pathological complete response rate was 40%, which is comparable with the published literature.345678910

The OS of patients who underwent the trimodality treatment and those who defaulted for surgery after neoadjuvant treatment was 18.5 months and 8 months, respectively, showing the obvious benefit of the completion surgery (Fig. 1).

Close

Fig. 1: Kaplan–Meier plot of overall survival. Green = patient receiving trimodality treatment; blue = patients defaulted after neoadjuvant chemoradiotherapy (NACRT). p = 0.025 (log-rank test).

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Out of 89 patients who did not complete the intended treatment, 45 patients could have completed their intended treatment, provided necessary intervening measures would have been taken such as financial support and social support. The treating oncologist tried to contact all these patients through telephonic conversations or home visit by the representative. In spite of the treatment being partly or fully covered under government scheme, the priority of their daily wages prevented these patients from completing their treatment.

The next common reason for noncompliance was symptomatic relief due to neoadjuvant treatment in nine patients. Although the efforts were taken to stress the importance of surgery in spite of complete clinical benefit after neoadjuvant therapy, these patients never turned up for surgery.

Of the 20 patients who progressed after NACRT, 10 patients progressed at a distant site, while 10 patients progressed locally. These patients were advised palliative treatment or best supportive care.

This study gave us an insight into careful selection and counseling of the patients beforehand, ensuring lasting financial and social support through the course of the treatment in the rural setting in India. Interestingly, we found that the patients who underwent surgery within 60 days of completion of neoadjuvant treatment had a median overall survival of 20 months versus 17 months for those who came for surgery after 60 days. Majority of the delays in surgery was due to finances and logistics for surgery. This highlights the importance of adherence to the treatment schedule, especially after NACRT.

Conclusion

Our results for patients who completed the trimodality treatment are similar to those in the literature. However, the dropout rate after NACRT was a matter of concern. This study gave us insight into the fact that trimodality treatment is feasible in rural India, provided the strategic selection of the patients and continuous socioeconomic support through the course of the treatment is ensured.