Long-term efficacy of perioperative chemoradiotherapy on esophageal squamous cell carcinoma

Jin, LJ; Cao, Xiu Feng; Zhu, Bin; Ji, Luo; Tao, Lei; Wang, Dong Dong

doi:10.3748/wjg.v16.i13.1649

Cited by 142 publications

(170 citation statements)

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We thank Palma et al for bringing to our attention the 3-arm randomized controlled trial (RCT) from China by Lv et al 1 We agree with many of the limitations of any Surveillance, Epidemiology, and End Results (SEER) study that they point out. Specifically, confounding because of unmeasured covariates is always a potential source of error in observational studies.

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confidence: 65%

Reply to When randomized trials and observational data disagree: The case of preoperative versus postoperative chemoradiotherapy for esophageal cancer

Wojcieszynski

Mitra

Apisarnthanarax

2013

Cancer

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We thank Palma et al for bringing to our attention the 3-arm randomized controlled trial (RCT) from China by Lv et al. 1 We agree with many of the limitations of any Surveillance, Epidemiology, and End Results (SEER) study that they point out. Specifically, confounding because of unmeasured covariates is always a potential source of error in observational studies. However, in our study, we conducted a thorough sensitivity analysis to assess the effects of unmeasured variables, such as clinical tumor staging. 2 A similar sensitivity analysis demonstrated that, even if the preoperative patients were half as likely to have comorbid disease as postoperative patients, our statistically significant results would hold.Palma et al suggest that some of the postoperative patients may have received radiotherapy for palliation of early recurrence after surgery, confounding the results. This is unlikely, because SEER data only capture first course of treatment information within 4 months of the cancer diagnosis, and the likelihood of patients developing recurrence within the first few months after surgery is less than 5% according to recent randomized data. 3 More important, the RCT by Lv et al warrants deeper exploration of the results beyond reading the results and conclusions of the abstract. The lack of difference in outcomes between preoperative and postoperative patients was noted for the entire cohort of patients, which also included patients receiving a "palliative resection or esophageal bypass." When looking at the overall survival data pertaining only to patients who underwent curative, radical resection (see Lv et al, Fig. 1D), it is clear that there is a trend toward improved overall survival with preoperative treatment. The authors also acknowledge these findings in their discussion section. Therefore, we believe that the data as reported in this RCT, if anything, may lean in favor of preoperative therapy, particularly when considering the lower local recurrence rate with preoperative treatment.Given the limitations of this RCT and our own observational study, we acknowledge that, without a well designed and sufficiently large RCT comparing preoperative versus postoperative treatment, the question of the optimal sequencing of perioperative treatment cannot be definitively answered. We applaud the investigators who are actively studying this topic in the ongoing Quality of Life in Neoadjuvant Versus Adjuvant Therapy of Esophageal Cancer Treatment Trial (QUINTETT) RCT and eagerly await their results.

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confidence: 65%

Reply to When randomized trials and observational data disagree: The case of preoperative versus postoperative chemoradiotherapy for esophageal cancer

Wojcieszynski

Mitra

Apisarnthanarax

2013

Cancer

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“…Ten countries, including China, Australia, Japan, Korea, Thailand, United States of America, France, The Netherlands, Ireland and Norway, were included in the RCTs. Of the 22 studies, 20 (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) reported OSR1y, 19 (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(24)(25)(26)(27) reported OSR3y and 15 (8,(11)(12)(13)(15)(16)(17)(24)(25)(26)(27) reported information...…”

Section: Summary Of Included Studiesmentioning

confidence: 99%

“…As regards pathological type, 5 RCTs (10,15,24,26,27) on adenocarcinoma and 12 studies (7)(8)(9)11,13,14,16,21,23,24,26) on squamous cell carcinoma investigated OSR1y, OSR3y and OSR5y after CRTS or SA for resectable esophageal carcinoma.…”

Section: Summary Of Included Studiesmentioning

confidence: 99%

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Traditional and cumulative meta‑analysis: Chemoradiotherapy followed by surgery versus surgery alone for resectable esophageal carcinoma

et al. 2017

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Abstract. The role of neoadjuvant chemoradiotherapy followed by surgery (CRTS) compared with surgery alone (SA) for resectable esophageal carcinoma has been established by several randomized controlled trials (RCTs). The present study aimed to investigate the difference in survival between the two treatments by a review of meta-analyses. Related research indicators were extracted from RCTs investigating CRTS or SA for resectable esophageal carcinoma by searching electronic databases for eligible articles. Outcomes were synthesized by adopting a fixed-or random-effects model with 95% confidence interval (CI). A total of 22 RCTs including 3,419 patients were selected. The odds ratio (OR) (95% CI, P-value), expressed as CRTS vs. SA, was 1.06 (0.94-1.19, P=0.348) for 1-year overall survival rate (OSR1y), 1.38 (1.20-1.58, P<0.001) for 3-year overall survival rate (OSR3y), and 1.42 (1.22-1.66, P<0.001) for 5-year overall survival rate (OSR5y). The R0 resection rate increased in patients treated by CRTS (OR=2.76, 95% CI: 2.15-3.53, P<0.001). CRTS lowered the locoregional cancer recurrence (OR=0.49, 95% CI: 0.36-6.65, P<0.001) and distant metastasis rate (OR=0.76, 95% CI: 0.60-0.97, P=0.02). However, the incidence of postoperative mortality was similar between the two groups (OR=0.97, 95% CI: 0.72-1.32, P=0.87). The subgroup analysis revealed that OSR3y and OSR5y for Asian, European and American populations were significantly higher in the CRTS group compared with those in the SA group (P<0.05). When comparing the OSR1y between the two groups for patients in all three continents, there was no significant difference (P>0.05). Histological subgroup analysis indicated that patients with esophageal adenocarcinoma may benefit from CRTS in terms of OSR1y (OR=1.55, 95% CI: 1.09-2.20, P=0.01), OSR3y (OR=1.77, 95% CI: 1.34-2.36, P<0.0001) and OSR5y (OR=1.92, 95% CI: 1.34-2.75, P=0.0004). The pooled OR of squamous cell carcinoma in terms of OSR3y and OSR5y between the two groups was 1.57 (95% CI: 1.21-2.04, P=0.0006) and 1.69 (95% CI: 1.32-2.16, P<0.0001), respectively, but there was no statistical difference in terms of OSR1y (OR=1.13, 95% CI: 0.88-1.45, P=0.35). Thus, neoadjuvant CRT followed by surgery may improve long-term survival and surgical parameters, and reduce locoregional cancer recurrence and distant metastasis.

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“…Unfortunately, very limited trials ever compared adjuvant chemoradiation to neoadjuvant chemoradiation, which is the current standard of care in esophageal cancer. Lv et al did the randomized trial comparing preoperative chemoradiation, postoperative chemoradiation and surgery alone in patients with clinical stage II and III esophageal squamous cell carcinoma (8). Although significant differences in the 5-year OS (43.5% vs. 42.3% vs. 33.8%, P=0.018) and progression-free survival (PFS; 37.5% vs. 37.2% vs. 25.9%, P=0.015) were detected among the three arms, there were no significant differences in OS and PFS between the preoperative and postoperative chemoradiation arms (P>0.05).…”

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confidence: 99%

Do we have enough evidence for adjuvant postoperative chemoradiation in esophageal cancer?

Hsu

2017

J. Thorac. Dis.

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Long-term efficacy of perioperative chemoradiotherapy on esophageal squamous cell carcinoma

Abstract: Rational application of preoperative or postoperative CRT can provide a benefit in PFS and OS in patients with locally advanced ESCC.

Cited by 142 publications

References 19 publications

Reply to When randomized trials and observational data disagree: The case of preoperative versus postoperative chemoradiotherapy for esophageal cancer

Reply to When randomized trials and observational data disagree: The case of preoperative versus postoperative chemoradiotherapy for esophageal cancer

Traditional and cumulative meta‑analysis: Chemoradiotherapy followed by surgery versus surgery alone for resectable esophageal carcinoma

Do we have enough evidence for adjuvant postoperative chemoradiation in esophageal cancer?

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