Preoperative chemoradiotherapy associated with reduced recurrence rates of esophageal cancer

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1. Compared to patients receiving surgery alone, patients undergoing chemoradiotherapy (CRT) prior to resection experience reduced local recurrence, peritoneal carcinomatosis and hematogenous spread.

2. Local recurrence was particularly reduced within radiation target volumes.

Evidence rating level: 2 (Good)

Study Rundown: Though patients with esophageal cancer commonly present with distant metastasis and thus have poor prognosis, surgery offers a potential cure for patients with resectable disease. However, incomplete resection and locoregional recurrence are associated with poor survival and investigations of the role of preoperative chemoradiotherapy (CRT) to prevent this outcome are ongoing. The CROSS (Chemoradiotherapy for Oesophageal Cancer followed by Surgery Study) trial is a RCT demonstrated improved overall 5-year survival with CRT prior to surgery compared to surgery alone. The authors of this study retrospectively analyzed the results from this trial in order to better understand effects of preoperative CRT.

In this retrospective analysis, the authors found that CRT prior to surgery was associated with reduced locoregional recurrent, peritoneal carcinomatosis, and hematogenous dissemination as compared to surgery alone. Furthermore, they found recurrences of only 5% within the radiation target area. Based on these results, the authors concluded that CRT can reduce locoregional recurrence of esophageal cancer, as well as more distant metastasis. These findings are supported by the rigorous randomized, controlled multi-center design of the original CROSS trials. The use of both Phase II and III trials of the CROSS study also improved the statistical power of this analysis. However, it should be noted that this was a retrospective review of the secondary outcomes of a previous trial.

Click to read the article in JCO

Relevant reading: Preoperative chemoradiotherapy for esophageal or junctional cancer

In-Depth [retrospective analysis]: For this retrospective analysis, the study authors collected data from patients enrolled in Phase II and III CROSS trials, all of whom had histologically proven and resectable squamous cell carcinoma or adenocarcinoma of the esophagus. These patients were randomly assigned to either surgery or surgery preceded by CRT. A total of 418 patients from both trials were eligible for analysis. Multivariable and univariable regression models were used to analyze the relationship between treatment arm and local and distant recurrence.

The authors found that the overall recurrence rate was 58% versus 35% in the surgery and CRT + surgery arms, respectively, with a median follow-up of 45 months. Preoperative CRT was associated with reduced local recurrent from 34% to 14% (P < 0.001). Peritoneal carcinomatosis was reduced from 14% to 4% (P < 0.001). Furthermore, hematogenous dissemination was also significantly reduced from 35% to 29% (P = 0.025). On further analysis of the location of local recurrence, the authors found that locoregional occurrence occurred in 5% within the target radiotherapy volume, in 2% on the margins, and in 6% outside the target area.

By Monica Parks and Andrew Bishara

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