St. James's Hospital, Dublin, Ireland
Jessie A Elliott , Sheraz Markar , Fredrik Klevebro , Asif Johar , Lucas Goense , Maeve Aine Lowery , Pernilla Lagergren , Giovanni Zaninotto , Richard van Hillegersberg , Magnus Nilsson , George Hanna , John V. Reynolds
Background: Although established and emerging therapies for recurrent esophageal cancer (EC) may impact on survival and health related quality of life (HRQL), surveillance protocols after the primary curative treatment of EC are varied and inconsistent, reflecting a limited evidence-base to guide an optimum approach. Specifically, whether advantages exist for an intensive surveillance protocol is unknown and was the focus of this study. Methods: European iNvestigation of SUrveillance after Resection for Esophageal cancer (ENSURE) is an international multicenter retrospective observational study of consecutive patients undergoing surgery with curative intent for esophageal and gastroesophageal junction cancers (2009 – 2015) across 20 European and North American cancer centers (NCT03461341). Intensive surveillance (IS) was defined as routine annual CT/PET-CT along with clinical assessment during the first three postoperative years, and compared with standard surveillance (SS) with investigation as clinically indicated. The primary outcome measure was overall survival (OS), secondary outcomes included treatment administered, disease-specific survival (DSS), disease-free survival (DFS), recurrence pattern, and HRQL. Multivariable linear, logistic and Cox proportional hazards regression analyses were performed to determine the independent impact of surveillance on oncologic outcomes and HRQL. Results: 4,682 patients were studied (72.6% adenocarcinoma, 69.1% neoadjuvant therapy). 45.5% underwent IS. At a median follow-up of 60 months, 47.5% developed disease recurrence. Oligometastatic recurrence occurred in 39% of cases, with 31% receiving best supportive care, 60% chemotherapy and/or radiation, and 8% surgical resection. IS was associated with reduced symptomatic recurrence (odds ratio [OR] 0.17 [0.12–0.25]), increased tumor-directed therapy (OR 2.09 [1.58–2.77]), and improved OS (HR 0.90 [0.82–0.98], 5-year OS 47.9±1.2% versus 43.2±1.1%). After adjusting for confounders, significantly improved overall survival with IS was maintained for patients who underwent surgery alone as initial therapy (HR 0.60 [0.47–0.78]) and in those with lower pathological (y)pT stages (Tis-2, HR 0.72 [0.58–0.89]). IS was associated with greater anxiety (P= 0.016), but similar overall HRQL. Conclusions: These data suggest that IS may improve oncologic outcomes, particularly in patients with early stage disease at presentation or with a favorable pathological stage post induction therapy. This may be relevant to guideline development and provide a framework and rationale for RCTs. It may also inform shared decision-making with patients at a time where therapeutic options for recurrence are expanding.
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