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Table of Contents
ORIGINAL ARTICLE: REAL WORLD DATA
Year : 2021  |  Volume : 4  |  Issue : 4  |  Page : 647-655

Neoadjuvant chemoradiotherapy followed by surgery for operable carcinoma esophagus: Ground reality in a tertiary care center of rural India - A retrospective audit


1 Department of Radiation Oncology, Homi Bhabha Cancer Hospital, Sangrur, Punjab, India
2 Department of Surgical Oncology, Rajiv Gandhi Super Specialty Hospital, Delhi, India
3 Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, India
4 Department of Medical Oncology, Homi Bhabha Cancer Hospital, Sangrur, Punjab, India
5 Department of Surgical Oncology, Homi Bhabha Cancer Hospital, Sangrur, Punjab, India
6 Department of OncoPathology, Homi Bhabha Cancer Hospital, Sangrur, Punjab, India
7 Department of Medical Physics, Homi Bhabha Cancer Hospital, Sangrur, Punjab, India

Date of Submission21-Jun-2021
Date of Decision29-Jul-2021
Date of Acceptance24-Oct-2021
Date of Web Publication29-Dec-2021

Correspondence Address:
Tapas Kumar Dora
Department of Radiation Oncology, Homi Bhabha Cancer Hospital, Civil Hospital Campus, Sangrur - 148 001, Punjab
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/crst.crst_147_21

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  Abstract 


Background: Carcinoma of the esophagus and gastroesophageal junction is an aggressive disease with limited survival. Standard management consists of multimodality therapy, incorporating chemotherapy, radiation, and surgery.
Objectives: We aimed to understand the obstacles in treating patients with resectable esophageal cancer with neoadjuvant chemoradiotherapy followed by surgery. We also assessed the disease outcomes in the patients who completed surgery.
Materials and Methods: We included patients with resectable esophageal carcinoma who received neoadjuvant chemoradiation between March 2017 and August 2019 at the Homi Bhabha Cancer Hospital in Sangrur, Punjab, a tertiary care center in rural India. As surgery for esophageal cancer was not performed at our center, patients had to be referred to a higher center for this. Patients were divided into two groups, based on the therapy they received following neoadjuvant chemoradiation: those who completed surgery (Group A) and those who did not (Group B). The pathologic response rates were noted. The disease-free survival (DFS) and overall survival (OS) were compared between the two groups.
Results: A total of 55 patients (32 in Group A and 23 in Group B) were included the study. In Group A, complete pathologic responses were noted in 19 (59.4%), partial responses in 11 (34.4%) and poor responses in 2 (6.2%) patients. The major reasons for not undergoing surgery were patient refusal as they were feeling better after chemoradiation (8, 34.8%) and the presence of advanced inoperable (5, 21.7%) or metastatic disease (3, 13%) on imaging after chemoradiation. The median DFS in Group A and Group B was 8 months (range, 0–38 months) and 14 months (range, 0–29 months), respectively, and the 2-year DFS was 57.8% and 73.3%, respectively (P = 0.28). Median OS in Group A and Group B was 17 months (range, 3–43 months) and 17 months (range, 2–31 months), respectively, and the 2-year OS was 52.6% and 53.5%, respectively (P = 0.70).
Conclusions: Implementing neoadjuvant chemoradiation followed by surgery for resectable esophageal cancer in a center where esophageal cancer surgery cannot be performed is challenging. Among patients who undergo surgery following neoadjuvant chemoradiation, complete pathologic responses occur in 59.4% patients, and clinical outcomes appear to be similar to those reported in the literature.

Keywords: Chemoradiotherapy, esophagus, induction, neoadjuvant, surgery, trimodality


How to cite this article:
Dora TK, Aeron T, Chatterjee A, Deshmukh J, Goel A, Bose S, Chaudhary D, Sharma R, Khandelwal S, Sancheti S, Pahwa S, Singh A, Saini A, Laskar SG, Agarwal JP, Shrivastava SK, Kapoor R. Neoadjuvant chemoradiotherapy followed by surgery for operable carcinoma esophagus: Ground reality in a tertiary care center of rural India - A retrospective audit. Cancer Res Stat Treat 2021;4:647-55

How to cite this URL:
Dora TK, Aeron T, Chatterjee A, Deshmukh J, Goel A, Bose S, Chaudhary D, Sharma R, Khandelwal S, Sancheti S, Pahwa S, Singh A, Saini A, Laskar SG, Agarwal JP, Shrivastava SK, Kapoor R. Neoadjuvant chemoradiotherapy followed by surgery for operable carcinoma esophagus: Ground reality in a tertiary care center of rural India - A retrospective audit. Cancer Res Stat Treat [serial online] 2021 [cited 2022 Jan 20];4:647-55. Available from: https://www.crstonline.com/text.asp?2021/4/4/647/334173




  Introduction Top


Carcinoma of the esophagus and gastroesophageal junction is an aggressive disease with a poor 5-year overall survival (OS).[1],[2] Data from both the National Cancer Database and the Taiwan Cancer Registry have shown that neoadjuvant chemoradiotherapy plus surgery is associated with a better survival rate compared to definitive chemoradiation.[3],[4]

To increase the rate of complete curative resection with no cancer cells seen microscopically at the margins (R0 resection rate) and improve the pathologic complete response (pCR), neoadjuvant chemotherapy or chemoradiotherapy have been explored. It has been shown that neoadjuvant chemoradiotherapy improved the survival compared to all other treatment modalities including neoadjuvant chemotherapy, neoadjuvant radiotherapy, or surgery alone, but at the cost of increased postoperative mortality.[5],[6] The meta-analysis by Gebski et al. showed a significant survival advantage of neoadjuvant chemoradiotherapy in both squamous cell carcinoma and adenocarcinoma of the esophagus, but neoadjuvant chemotherapy was found to be beneficial only in adenocarcinoma of the esophagus.[7] However, a clear advantage of neoadjuvant chemoradiotherapy over neoadjuvant chemotherapy has not been established yet. The meta-analysis by Deng et al. suggested that neoadjuvant chemoradiotherapy should be the standard preoperative treatment for patients with squamous cell carcinoma of the esophagus, but for patients with adenocarcinoma of the esophagus, neoadjuvant chemotherapy alone may be an appropriate strategy to avoid the side-effects of radiotherapy. It was also shown that the pCR rate, R0 resection rate, and 3-year survival rate were higher in patients who received neoadjuvant chemoradiotherapy than in those who received neoadjuvant chemotherapy alone.[8] A meta-analysis by Zhao et al. showed a significant 3-year and 5-year survival advantage with neoadjuvant chemoradiotherapy over neoadjuvant chemotherapy along with higher pCR and R0 resection rate for both squamous cell and adenocarcinoma of the esophagus.[9]

Cancers of the esophagus constitute 8% of the total annual caseload at our center. Our hospital has fully functional radiation oncology, medical oncology, and surgical oncology facilities, but does not cater to thoracic oncology surgery yet. However, considering that carcinoma of the esophagus is highly prevalent in the region, we embarked on using the ChemoRadiotherapy for esophageal Cancer followed by Surgery Study (CROSS) protocol after extensive counseling of patients, impressing upon them the need for surgery (which would have to be done at a higher center) to complete the treatment. Despite initial reservations, we initiated the treatment of patients using neoadjuvant chemoradiotherapy in 2017. We aimed to analyze the outcomes of patients who were treated using this protocol over the past 3 years.


  Materials and Methods Top


General study details

This retrospective audit of the standard treatment offered to patients with resectable cancer of the esophagus registered between March 2017 and August 2019 was conducted at the Homi Bhabha Cancer Hospital Sangrur, Punjab, which is a unit of the Tata Memorial Center, Mumbai, under the Department of Atomic Energy, Government of India. Patients were treated according to the standard operating procedure (SOP) of the institute after a discussion of each case in the tumor board. Routine consent to deliver radiotherapy was obtained from the patients. No written informed consent was obtained for participation with this study owing to its retrospective nature. As the patients were treated according to the institutional SOP, ethical approval was not sought for this analysis. No funding was utilized for this study. The study was not registered in any public clinical trials registry. 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 consecutive patients with resectable esophageal carcinoma who were found suitable for neoadjuvant chemoradiation based on the radiologic review and the decision of the multidisciplinary tumor board were included in the study. Patients who were unfit for surgery and/or concurrent chemoradiation were excluded.

Variables

The primary endpoints were the pathologic response rate in patients who underwent surgery, and the OS and disease-free survival (DFS) of the entire cohort. The secondary objective was to evaluate for any prognostic factors including age, sex, endoscopic length, thickness on computed tomography (CT) scan, grade, primary tumor extent (T-stage), nodal status (N-stage), the tumor-node-metastasis stage group, radiation duration, number of cycles of concurrent chemotherapy, gross tumor volume length, planning target volume (PTV) and PTV length.

Study methodology

After the decision for neoadjuvant chemoradiotherapy was made in the tumor board, patients were sent to the Rajiv Gandhi Super Specialty Hospital, New Delhi, under the Ministry of Health and Family Welfare, Government of India for the positron emission tomography (PET) scan and to be assessed by a surgeon regarding the resectability and operability of the tumor. The patients were also explained that they would need to undergo surgery at another center. The planned radiotherapy dose was 41.4 Gy in 23 fractions, delivered using volumetric arc therapy at our center. Concurrent chemotherapy comprised weekly paclitaxel (50 mg/m2) and carboplatin (area under the free carboplatin plasma concentration versus time curve 2). Four weeks after concurrent chemoradiotherapy, the patients were advised to visit the surgeon at the center at which the esophageal resection was going to take place. A repeat CT scan was performed before surgery to check the disease status. For patients who were found suitable for surgery, surgery was scheduled approximately 6 weeks post neoadjuvant chemoradiotherapy.

Post-surgery, the patients were advised to report back with the histopathology report along with the slides and paraffin blocks, and the pathologic response was reviewed at our hospital.

Patients who defaulted on their follow-up were regularly contacted telephonically to check whether they had undergone surgery and were repeatedly counseled to undergo surgery as per the plan. For patients who did not undergo surgery, we enquired about the reasons for defaulting and broadly categorized the responses as unwillingness for surgery, disease progression (advanced inoperable or metastatic), poor general condition, unfit for surgery, fear of surgery, and death. An attempt was made, wherever possible, to deliver further radiation up to the radical dose for those who reported back to our hospital without undergoing surgery.

Patients were followed up every 3 months for the first 2 years and every 6 months thereafter. Asymptomatic patients were asked about any history of dysphagia and a physical examination was performed to check for clinical evidence of disease progression. CT scan and upper gastrointestinal endoscopy were performed whenever the patient developed symptoms, or annually, in patients who were asymptomatic. Follow-up data were captured for disease recurrence and survival until October 2020. All clinical data were collected from the hospital's server-based electronic medical records. Radiation-treatment-related data were obtained from the Radiation Oncology Information System software. Radiation dosimetric data of different organs were collected from the treatment planning system (MONACO TPS, version no 5.51.01) of the linear accelerator (Elekta Versa-HD, Elekta Instrument AB Stockholm) used for delivering radiotherapy.

Definitions

OS was calculated in months from the date of diagnosis to the date of death or last follow-up. DFS was calculated in months from the date of completion of surgery (Group A) or chemoradiotherapy (Group B) to the date of tumor recurrence (locoregional/metastasis) or death or last follow-up. R0 resection was defined as a microscopically radial tumor-free resection margin of at least 1 mm. The pathologic response score was measured based on the response criteria proposed by Donahue et al. and Meredith et al. after discussion with our institution's pathologist.[10],[11] Complete pathologic response (pCR) was defined as microscopic absence of any tumor cells in the resected specimen. Partial pathologic response was defined as the presence of microscopic foci of tumor cells at the primary site and/or positive lymph nodes. Poor or no response was defined as the presence of macroscopic residual tumor at the primary site and/or lymph nodes.

Statistics

As this was a retrospective audit, all consecutive patients fitting the eligibility criteria within the time frame of the study were included and no sample size calculation was performed. The data were analyzed using the Statistical Package for the Social Sciences (IBM Corp. Released 2015. IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY, USA: IBM Corp.). The Kaplan–Meier method was used to estimate the OS and DFS.[12] Log-rank test was used to compare the estimates in the univariate analysis and the Cox proportional hazard model was used in the multivariate analysis to evaluate if any of the tested prognostic factors affected the DFS and OS in the two groups.[13],[14] P < 0.05 was considered statistically significant.


  Results Top


A total of 60 consecutive patients were screened, out of which 55 (32 in Group A and 23 in Group B) were included in this analysis [Figure 1]. Patients' disease characteristics at presentation are described in [Table 1].
Figure 1: Patient recruitment flowchart

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Table 1: Patient demographics and disease-related parameters

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The radiation dose delivered was 41.4 Gy in 53 patients and 45 Gy in 2 patients. The median number of concurrent chemotherapy cycles was 5 (range, 3–6) in Group A and 5 (range, 2–7) in Group B. The median duration of radiation was 35 days (range, 30–44) in Group A and 40 days (range, 30–126) in Group B. Post radiation, grade 2 pharyngoesophagitis was observed in <5% cases in both groups. No grade 3/4 toxicity was observed.

Out of 32 patients in Group A, 30 were operated at the Rajiv Gandhi Super Specialty Hospital, New Delhi, and 2 underwent resection at the Dayanand Medical College, Ludhiana, Punjab. The most common surgical procedure was video-assisted thoracoscopic surgery with two-field lymphadenectomy in 23 (72%) patients. The resection was R0 in all 32 patients, i.e., all margins were free of disease. Surgical pathologic details of the patients in Group A are described in [Table 2]. On histopathological examination, complete response (no microscopic viable cancer) was observed in 19 (59.4%) patients, partial response (microscopic residual cancer) in 11 (34.4%), and poor response (extensive macroscopic residual disease) in 2 (6.2%). Postoperative mortality occurred in 5 (29.41%) patients. The first patient died 2 months after surgery due to the development of a tracheoesophageal fistula; the second died in the hospital 11 days after surgery due to postoperative pneumonia; the third patient died in the hospital 3 weeks after surgery, requiring ventilator support during the last week due to postoperative complications; the fourth died 3 weeks post-surgery; the fifth died in the hospital 2 weeks post-surgery due to aspiration. One patient died during surgery.
Table 2: Surgical pathologic details of the patients who underwent surgery

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Out of 32 patients in Group A, at a median follow-up of 12 months (range, 0–38),15 (46.9%) patients were alive and 17 (53.1%) were dead. Recurrence was noted in 10 (31.2%) patients and in 16 (50%), the disease was clinically controlled without any recurrence. Six patients (18.8%) were lost to follow-up; hence the recurrence status was unknown. Out of 23 patients in Group B, at a median follow-up of 15 months (range, 0–29), 11 (47.8%) patients were alive, 10 (43.5%) were dead and the status of 2 (8.7%) was unknown. Residual disease was documented in only 4 (17.4%) patients; 16 patients (69.6%) were lost to follow-up after defaulting on surgery, and hence their recurrence status was unknown. The remaining three patients who reported to the hospital were given a radiation boost up to a radical dose of 63 Gy, out of which only 2 (8.7%) patients showed clinically controlled disease and 1 (4.3%) had persistent local residual disease even after the radiation boost. The reasons for defaulting on surgery with the final treatment outcomes for the patients who developed recurrent disease are shown in [Table 3].
Table 3: Treatment details for recurrent disease and their outcomes

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The median OS in Group A and Group B was 17 months (range, 3–43) and 17 months (range, 2–31), respectively. The 1-year and 2-year OS rates were 62.5% and 64.3%, and 52.6% and 53.5%, respectively (P = 0.70) [Figure 2]. The median DFS in Group A and Group B was 8 months (range, 0–38) and 14 months (range, 0–29), respectively, and the 2-year DFS was 57.8% and 73.3%, respectively (P = 0.28) [Figure 3].
Figure 2: Kaplan–Meier analysis of overall survival

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Figure 3: Kaplan–Meier analysis of disease-free survival

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The effect of various prognostic factors on DFS and OS in the two groups was assessed, but none were found to be significantly associated [Supplementary Table 1]. In Group A, factors such as the response score (complete/partial), proximal margin (</>5 cm), distal margin (</>5 cm), radial margin (</>0.5 cm), post-neoadjuvant post-surgical tumor status, i.e., ypT (present vs. absent) and post-neoadjuvant post-surgical nodal status, i.e., ypN (present/absent) also did not show any significant association with the DFS and OS [Supplementary Table 2]. The doses received by the different organs at risk are shown in [Supplementary Table 3].




  Discussion Top


In our study on the feasibility of implementing the CROSS trial protocol, i.e., neoadjuvant chemoradiotherapy followed by surgery at a regional cancer center in which surgery for esophageal cancer was not performed, we found that 58% of the patients were able to complete the entire multimodality therapy. Even though our study comprised only a small number of patients, we found that only 4 patients (12.5%) developed regional failures and 6 patients (18.8%) failed distantly out of the 32 who completed the trimodality treatment. On histopathological examination, all 32 patients underwent an R0 resection, with complete pathologic responses seen in 59.4% and partial responses in 34.4% of patients which was encouraging and comparable to the findings of major key randomized trials in the literature on patients with squamous cell carcinoma of the esophagus.[15]

Van Hagen et al. in the CROSS study on 366 patients with resectable esophageal or gastroesophageal junction cancers, reported a significant OS benefit from neoadjuvant chemoradiotherapy compared to surgery alone, a pCR rate of 29% in the neoadjuvant chemoradiotherapy arm and an R0 resection of 92%.[16] Shapiro et al. showed that the addition of neoadjuvant chemoradiotherapy to surgery led to a significant OS and progression-free survival (PFS) benefit for both squamous cell carcinoma and adenocarcinoma of the esophagus or gastroesophageal junction.[17] In our study, we observed a 100% R0 resection rate, and a pCR rate of 59.4%. In the CROSS trial, the median OS in patients who received neoadjuvant chemoradiotherapy followed by surgery was 48 months (81 months for squamous cell carcinoma and 43 months for adenocarcinoma). The median PFS was 38 months (75 months for squamous cell carcinoma and 30 months for adenocarcinoma). The 1-and 2-year OS and PFS were 81% and 58%, and 71% and 60%, respectively. Similarly, the 2-year OS and DFS in our study for patients who completed surgery were 52.6% and 57.8%, respectively. However, the median OS in our study was only 17 months, which was very low as compared to that reported in the CROSS study; this could be because the follow-up period in our study was short (84 months follow-up in the CROSS study, compared to 14 months in our study). In our study, among patients in Group B, the 2-year OS rate was 53.5% and DFS rate was 73.3%; however, these numbers may not be accurate as most of the patients in Group B (16/23, 69.6%) did not report for the assessment of residual or recurrent disease. The recent report by Eyck et al. on the 10-year outcome of the CROSS trial has further proven that the benefit of neoadjuvant chemoradiotherapy persisted for at least 10 years.[18] In a separate study, Eyck et al. summarized the key randomized trials and found a definite advantage of neoadjuvant chemoradiotherapy compared to surgery alone in terms of the pCR rate (25%–40%), R0 resection rate (80%–100%), and 3-year OS rate (32%–66%). The postoperative mortality was in the range of 4%–11% in these trials, but it was quite high in our study with 6 deaths (1 intra-operative and 5 postoperative) (18.8%) in Group A, which was a limitation of our study.[15]

The lack of a thoracic surgical facility at our center is a major limitation; having this facility at our center may have increased the patients' compliance towards surgery. A recent study by Depypere et al. have shown that 1 in 6 patients (16.7%) starting neoadjuvant treatment for esophageal cancer never made it to esophagectomy. The reasons for defaulting on surgery were disease progression (43.9%), poor general condition (22.8%), unresectability (12.3%), patient's decision (13.2%) and death (7.9%). A clinical complete response was seen in 20.2% of the patients, with a median OS of 10.5 months. Surprisingly, the majority of the patients refusing surgery (73.3%) had a complete clinical response with a median OS of 33.2 months compared to 12.9 months for those with poor general condition, 9.9 months for those with disease progression, 8.5 months for those with unresectable disease, and 3.8 months for those who died during neoadjuvant therapy.[19] Similarly, it is possible that in our series, the patients who refused surgery because they were feeling well could have been clinical complete responders. In the study by Depypere et al., defaulting on surgery was more common among patients with squamous cell carcinoma than adenocarcinoma especially for non-oncological reasons like medical inoperability and patients' own decision. Over time, medical inoperability became the more common reason, as more patients started neoadjuvant therapy without proper assessment of medical fitness, thus missing the upfront medically inoperable patients. Our results were similar to those of another observational study from India by Krishnamurthy et al. In this study, out of 50 patients, only 32 (64%) could undergo surgery after chemoradiation and 18 could not, for reasons such as unresectability on imaging (7, 38.9%), intraoperative unresectability (7, 38.9%), unfit for surgery (2, 11.1%), and default (2, 11.1%). pCR was seen in 19 out of 32 (59.4%) operated cases.[20] In the randomized NEOCRTEC5010 study, Yang et al. clearly illustrated the poor compliance towards neoadjuvant chemoradiotherapy, as only 83% of patients completed the therapy. Reasons for not undergoing surgery in 38 (17%) patients were refusal (29, 76.3%), progressive disease (2, 5.3%), poor performance status (2, 5.3%), cerebral infarction (1, 2.6%), death due to pneumonia (1, 2.6%), esophagus hemorrhage (2,5.3%), and car accident (1, 2.6%).[21] The compliance rate was reported to be much better in the corporate sector with educated patients (76.6% patients completed surgery) as shown in a retrospective study by Goel et al., with the pCR rate being 37.2% and 2-year OS being 62.8%.[22] The impact of patient selection and disease progression on delivering trimodality therapy in esophageal cancer has been clearly highlighted by Gilbert et al. in their retrospective study, where 22.9% of patients failed to undergo surgery after neoadjuvant chemoradiation, which was mainly due to disease progression (12.5%), treatment-related mortality (4.2%), unresectable tumor (2.1%), or death (4.2%), with 89% out of those who had surgery after neoadjuvant chemoradiotherapy achieving an R0 resection.[23]

Surprisingly, in our study, 11 of the 23 (47.8%) patients who did not undergo surgery were alive without disease at a median follow-up of 14 months (range, 0–38). This suggests that a significant number of patients may achieve a clinical complete response after neoadjuvant chemoradiotherapy, out of which the majority of patients may not recur even without surgery; for such patients, a morbid surgery could definitely compromise their quality of life. This observation raises the next research question: Are these patients potential candidates for deferral or even omission of surgery? There is an urgent need for a strong clinical response evaluation protocol to detect residual disease after chemoradiation to identify patients who would definitely require surgery and those with a clinical complete response who may be kept on active surveillance. In the past few years, the concept of active surveillance as an organ-sparing approach for the treatment of esophageal cancer has been suggested in multiple studies.[24],[25],[26],[27] Castoro et al. in a retrospective analysis of 77 patients (38 declined surgery and 39 underwent surgery) with clinical complete responses after propensity score matching showed no difference in the 5-year OS (57% vs. 50%, P = 0.65) and DFS (34.6% vs. 55.5%, P = 0.15).[28] However, as of now, there is no level 1 evidence to support active surveillance. The standard of care in patients with esophageal cancer following neoadjuvant chemoradiotherapy still remains surgery. Taketa et al. in a study using propensity-based matching concluded that trimodality therapy should be encouraged for all eligible patients with esophageal cancer until highly reliable predictive models are developed for esophageal preservation.[29]

De Gouw et al. in their systematic review have shown that the current imaging modalities such as CT, PET CT, and endoscopic ultrasonography are not sufficiently accurate at identifying complete responders, and hence, the results should be carefully interpreted before deciding on active surveillance.[30] Borggreve et al. in their PRIDE protocol proposed a multimodal prediction model integrating magnetic resonance imaging (W-MRI and DCE MRI) and PET CT to predict the probability of pCR prior to and after neoadjuvant chemoradiotherapy.[31] Noordman et al. have shown in the preSANO study that endoscopic ultrasonography with bite-on-bite biopsies reduced the chance of missing residual tumor with tumor regression grade (TRG) 3 or 4 in the deeper submucosal layer of the esophagus by regular endoscopic guided biopsy from 31% to 10%.[32] Another trial by Zhang et al., preSINO, is also currently underway to assess the accuracy of response evaluations after neoadjuvant chemoradiotherapy based on the preSANO trial.[33] The success of the preSANO trial design[34] in reliably predicting TRG3 and TRG4 residual tumors has given way to the concept of “surgery as needed” in the presently ongoing non-inferiority randomized trials, SANO,[35] comparing OS, and ESOTRATE,[36] comparing DFS, between neoadjuvant chemoradiotherapy plus surgery versus surgery as needed through active surveillance, which may result in an organ-preserving treatment strategy in future for esophageal cancer.

Hurdles in the delivery of trimodality therapy in rural India include the lack of education to understand the disease biology and recommended management, high cost of treatment, lack of social and financial support, lack of government facility in the vicinity, and long waiting period for both radiotherapy and surgery at government facilities. In our study, both centers being government facilities, finances were not a major hurdle, but not having a thoracic surgery facility at the primary hospital was definitely a factor that contributed to non-compliance to surgery. Moreover, the majority of the patients coming from a rural setup with a lack of education further contributed to the non-compliance.

The limitation of our study was that it was not a randomized study like the above trials. It was only a retrospective observational study and because of the lost-to-follow-up cases, we were unable to prove by deeper biopsies whether those who were doing well without undergoing surgery were actually complete responders to neoadjuvant chemoradiation. In addition, the follow-up period was short and endoscopic ultrasonography was not done routinely for initial staging.


  Conclusions Top


Implementing multimodality therapy for patients with locally advanced resectable esophageal cancer, consisting of neoadjuvant chemoradiotherapy followed by surgery at a center where esophageal cancer surgery cannot be performed is challenging. In our study, among the patients who underwent surgery following neoadjuvant chemoradiotherapy, complete pathologic responses were noted in almost 60% cases with 2-year OS and DFS rates of 52.6% and 57.8%, respectively. Thus, in patients who are able to complete trimodality therapy, the outcomes may be comparable to those reported in the literature.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

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This article has been cited by
1 At crossroads with CROSS: Implementing the CROSS protocol in a resource-limited setting
SenthilJ Rajappa
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[Pubmed] | [DOI]



 

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