Post-Neoadjuvant Surveillance and Surgery as Needed Compared with Post-Neoadjuvant Surgery on Principle in Multimodal Treatment for Esophageal Cancer: A Scoping Review.

Abstract

Simple SummaryA substantial fraction of patients with esophageal cancer show post-neoadjuvant pathological complete response (pCR). Principal esophagectomy after neoadjuvant treatment is the standard of care for all patients, including those with pCR. Surveillance and surgery as needed may be a treatment alternative for these patients. We performed a scoping review and described all relevant clinical studies addressing these two treatment approaches. We identified three completed randomized controlled trials (RCTs) including 468 participants, three planned/ongoing RCTs with a planned sample size of 752 participants, one non-randomized controlled study with 53 participants, ten retrospective cohort studies (2228 participants) and one survey on patients’ preferences (100 participants). The current scoping review reveals that although surveillance and surgery as needed has been investigated within different study designs, the available study pool show methodological limitations and clinical results are heterogeneous. A thoroughly planned RCT considering these limitations will be of great importance to provide these patients with the best treatment.Background: A substantial fraction of patients with esophageal cancer show post-neoadjuvant pathological complete response (pCR). Principal esophagectomy after neoadjuvant treatment is the standard of care for all patients, although surveillance and surgery as needed in case of local recurrence may be a treatment alternative for patients with complete response (CR). Methods: We performed a scoping review to describe key characteristics of relevant clinical studies including adults with non-metastatic esophageal cancer receiving multimodal treatment. Until September 2020, relevant studies were identified through systematic searches in the bibliographic databases Medline, Web of Science, Cochrane Library, Science Direct, ClinicalTrials, the German study register, and the WHO registry platform. Results: In total, three completed randomized controlled trials (RCTs, with 468 participants), three planned/ongoing RCTs (with a planned sample size of 752 participants), one non-randomized controlled study (NRS, with 53 participants), ten retrospective cohort studies (with 2228 participants), and one survey on patients’ preferences (with 100 participants) were identified. All studies applied neoadjuvant chemoradiation protocols. None of the studies examined neoadjuvant chemotherapeutic protocols. Studies investigated patient populations with esophageal squamous cell carcinoma, adenocarcinoma, and mixed cohorts. Important outcomes reported were overall, disease-free and local recurrence-free survival. Limitations of the currently available study pool include heterogeneous chemoradiation protocols, a lack of modern neoadjuvant treatment protocols in RCTs, short follow-up times, the use of heterogeneous diagnostic methods, and different definitions of clinical CR. Conclusion: Although post-neoadjuvant surveillance and surgery as needed compared with post-neoadjuvant surgery on principle has been investigated within different study designs, the currently available results are based on a wide variation of diagnostic tools to identify patients with pCR, short follow-up times, small sample sizes, and variations in therapeutic procedures. A thoroughly planned RCT considering the limitations in the currently available literature will be of great importance to provide patients with CR with the best and less harmful treatment.