Neoadjuvant Chemoradiotherapy Using Cisplatin and 5-Fluorouracil (PF) Versus Carboplatin and Paclitaxel (CROSS Regimen) for Esophageal Squamous Cell Carcinoma (ESCC)

Abstract

Objective: This study compared the efficacy of PF-based and CROSS-based neoadjuvant chemoradiotherapy for ESCC. Background: PF-based regimen has been a standard regimen for ESCC, but it has been replaced by the CROSS regimen in the past few years, despite no prospective head-to-head comparative study has been performed. Methods: This is a single center retrospective study. Records of all ESCC patients who have received neoadjuvant PF with 40 Gy radiotherapy in 20 daily fractions (PFRT Group) or CROSS with 41.4 Gy radiotherapy in 23 daily fractions (CROSS Group) during the period 2002 to 2019 were retrieved. Propensity score matching (1:1) was performed to minimize baseline differences. The primary and secondary endpoints were overall survival and clinicopathological response. Subgroup analysis (“CROSS Eligibility”) was performed based on tumor length, cT-stage, cM-stage, age, and performance status. Results: One hundred (out of 109) patients (CROSS group) and propensity score matched 100 (out of 210) patients (PFRT group) were included. Esophagectomy rates in CROSS and PFRT group were 69% and 76%, respectively (P = 0.268). R0 resection rates were 85.5% and 81.6% (P = 0.525) and the pathological complete remission rates were 24.6% and 35.5% (P = 0.154). By intention-to-treat, the median survival was 16.7 and 32.7 months (P = 0.083). For “CROSS Eligible subgroup,” the median survival of the CROSS and PFRT group was 21.6 versus 44.9 months (P = 0.093). Conclusions: There is no statistically difference in survival or clinicopathological outcome between both groups, but the trend favors PFRT. Prospective head-to-head comparison and novel strategies to improve the outcomes in resectable ESCC are warranted.

Neoadjuvant Carboplatin/Paclitaxel versus 5-Fluorouracil/Cisplatin in Combination with Radiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma: A Multicenter Comparative Study

“…This difference may be attributed to a higher number of patients with advanced disease in our cohort (cN+ rate: 96.6% versus 65% in the original CROSS trial) as well as to different EC biology, suggesting the ethnicity may have an impact on pCR rates. Interestingly, a similar pCR rate after CROSS (24.5%) was reported in a recent study conducted in Hong Kong [ 13 ]. Although pCR rates were consistent with our current results, this study showed an unfavorable trend for CROSS compared to PF (MST 32.7 versus 16.7 months, respectively, p = 0.083).…”

“…This practice is different from that implemented in Western countries, where all locally advanced resectable tumors (cT1N1-3M0/cT2-4aN0-3M0) are treated with nCRT prior to surgery [ 16 , 17 , 18 ]. To our knowledge, no prospective study in Asia has addressed the effectiveness of CROSS, and retrospective studies in the field have been inconclusive [ 13 ].…”

“…The relatively low toxicity profile of the CROSS regimen compared to PF while maintaining the same efficacy has made CROSS widely popular as nCRT in Western regions, mainly in response to esophageal adenocarcinoma [ 10 , 11 , 12 ]. While the subset of patients with ESCC in the CROSS trial showed promising findings (i.e., pathologically complete response [pCR] rate = 49%; median survival = 81.6 months), replication of these findings in Asia has not been successful [ 13 , 14 , 15 ].…”

“…Furthermore, neoadjuvant treatment is reserved to patients with more advanced malignancies (cT3-4aN1-3M0) in Asia [ 18 ]. The efficacy of CROSS in advanced stages of ESCC has recently been called into question by a study from Hong Kong—which showed an unfavorable survival trend for patients who received CROSS versus those who had been treated with PF [ 13 ]. In addition, traditional PF schemes with 41.4–50.4 Gy of RT are still extensively used for nCRT in Asian patients with EC [ 3 ].…”

Neoadjuvant Therapy for Locally Advanced Esophageal Cancers

“…However, no prospective head-to-head comparative study was conducted. A propensity score-matched study, comparing the efficacy of the cisplatin/fluorouracil regimen versus the CROSS regimen in patients with locally advanced ESCC, recently reported that there were no differences in the pathological or survival outcome between the two regimens but the study showed a trend in favor of the cisplatin/fluorouracil regimen ( 44 ). For adenocarcinoma, one retrospective study (adenocarcinoma: 86%) showed that the CF regimen could increase the pCR rate ( P =0.032), improve the recurrence-free survival (HR 0.39, 95%CI 0.21–0.73, P =0.003) and OS (HR 0.46, 95%CI 0.24–0.87, P =0.016) ( 45 ).…”