Assessment of response to preoperative therapy

Abstract

Assessment of response to preoperative therapy in borderline and locally advanced pancreatic cancer is a prerequisite for patient selection, surgical decision-making, clinical trial conduct, analysis, and comparison. Despite multiple studies on neoadjuvant treatment, universally accepted response measures are lacking as are clear definitions, standardized diagnostic work-up, and harmonization of classifications. Multiple different outcome measures have been proposed for response assessment including radiological criteria, pathologic response measures, surgical resection rates, and survival parameters. Unfortunately, studies have revealed marked differences between these endpoints preventing meaningful interpretation of data. In addition, inherent properties of pancreatic cancer like a pronounced desmoplastic stroma reaction impede response evaluation similar to the other solid tumors. All response measures proposed so far are prone to bias as long as patient selection, diagnostic evaluation, treatment regimes, restaging time points, pathologic work-up, and clinical follow-up are non-standardized. Therefore, standardized trials are needed to rigorously evaluate clinical and prognostic-relevant response endpoints. Furthermore, as neoadjuvant treatment regimes can lead to disease progression, toxicity, and clinical deterioration, a set of measures are needed to fully elucidate the radiologic, pathologic, and clinical response to neoadjuvant treatment. Given the current lack of evidence-based response measures, all borderline resectable pancreatic cancer patients are recommended to undergo surgical exploration at a specialized center following neoadjuvant therapy. For locally advanced unresectable patients, a specialized multidisciplinary team should define those patients in whom surgical exploration and resectability seems promising.