Surgery Timing Linked To Oesophageal Cancer pCR Rate

Delaying surgery after neoadjuvant chemoradiotherapy may help oesophageal cancer patients achieve a complete pathological response but shows no impact on survival

medwireNews: Timing of surgery after completion of neoadjuvant chemoradiotherapy (CRT) may influence the likelihood of a complete pathological response (pCR) in patients with oesophageal cancer, researchers say.

The study included 234 patients treated at a single centre in the USA between 2000 and 2015 for cancers of the mid or distal oesophagus. The patients, who were mostly White, male and diagnosed with adenocarcinoma, all completed a course of neoadjuvant radiation plus a chemotherapy regimen based on carboplatin plus paclitaxel, cisplatin plus fluorouracil or another combination.

Compared with those who underwent resection within 42 days, patients whose surgery was carried out 85–98 days after their last CRT dose were a significant 5.46 times more likely to achieve a pCR, after adjusting for clinical stage, demographical information and the CRT regimen received.

This compared with nonsignificant odds ratios of 2.23, 2.10 and 1.70 for patients whose surgery was performed on days 43– 56, 57–70 and 71–84, respectively, and an odds ratio of 3.55 for those whose procedure happened on day 99 or later, report James Dolan, from Oregon Health and Science University in Portland, USA, and co-workers.

They hypothesize that CRT-induced cell death may provoke an immune response to the tumour lasting several months, potentially stretching beyond the traditional 6–8 week timing for surgery after neoadjuvant therapy.

“By proceeding with esophagectomy within the currently recommended time frame, we may be redirecting the immune system’s capability toward recovering from a major operation rather than continuing in its tumoricidal role”, the researchers suggest. “Thus, we may be limiting its potential anticancer capacity.”

However, the team also reports in JAMA Surgery that, although median patient survival was significantly longer in patients who achieved a pCR on final pathology, at 8.7 versus 2.0 years, the increased likelihood of pCR with surgery on days 85–98 did not lead to a significant improvement in survival.

Indeed, the risk of mortality did not significantly differ by timing of operation or the presence or absence of residual tumour at time of surgery after adjusting for patient age, gender, clinical stage and CRT type, they say.

Describing the lack of a mortality benefit with improved pCR as “perhaps surprising”, the team suggests it may be linked to the higher rate of comorbidity in patients whose surgery occurred on days 85–98 compared with at other time points.

“This may reflect the fact that the later resection groups were not there because of preference or chance but because of the need to optimize medical comorbidities or recover from complications of CRT, which may have put them at an inherent disadvantage in terms of survival”, the researchers hypothesize.

They therefore conclude: “Validation of our observations in similar cohorts, ideally through a multi-institutional, prospective, randomized evaluation, is warranted to address the issues of bias.”

Marco Patti, from the University of North Carolina at Chapel Hill, USA, cites conflicting trial results showing no benefit from delayed surgery in a comment accompanying the study.

“Based on these data—and until a multi-institution, prospective, and randomized trial is performed—it is reasonable to operate on patients fit for surgical procedures after the traditional 4- to 8-week interval, postponing the operation only in patients who have not fully recovered after CRT”, he says.

References

Haisley KR, Laird AE, Nabavizadeh N, et al. Association of intervals between neoadjuvant chemoradiation and surgical resection with pathologic complete response and survival in patients with esophageal cancer. JAMA Surg 2016; Advance online publication 14 September. doi:10.1001/jamasurg.2016.2743

Patti MG. Esophageal resection for cancer after neoadjuvant chemoradiation. To wait or not to wait? JAMA Surg 2016; Advance online publication 14 September. doi:10.1001/jamasurg.2016.2750

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