Preoperative therapy for pancreatic adenocarcinoma—precision beyond anatomy

Abstract

Despite recent advances in the systemic treatment of gastrointestinal tumors, pancreatic adenocarcinoma (PDAC) remains a challenging disease, with 5‐year survival just over 10%. Pancreatectomy in patients meeting defined anatomic criteria can result in cure; however, perioperative morbidity and mortality, as well as high rates of both local and distant recurrence even after “potentially curative” resection, have limited survival. Although perioperative chemotherapy has been shown to improve patients' longevity and chance for cure, debate continues about whether the preoperative or adjuvant approach is most effective in treatment of localized PDAC. Large, randomized multicenter trials in patients with resectable and borderline resectable PDAC have evaluated an evolving therapeutic landscape with mixed results. Importantly, these landmark studies share the fundamentally flawed assumption that tumor anatomical characteristics are an indicator of behavior and natural history. Concurrent biologic and translational research has revealed that rather than a single disease, PDAC represents a phenotypically variable group of malignancies arising in physiologically diverse patients. Ongoing novel trials have begun to capture this heterogeneity both in patient selection as well as the measurement of response by using genomic, transcriptional and radiomic markers. By moving away from classic anatomic descriptors to a more nuanced landscape of biomarkers predictive of tumor behavior and response, we can further refine the questions asked in preoperative trials and translate the answers to clinically meaningful precision therapy in localized PDAC.

Body mass index and pancreatic adenocarcinoma: A nationwide registry-based cohort study

“…7 The disease is often diagnosed late rendering a high mortality. Although use of chemotherapy and centralization of pancreatic surgery has improved prognosis, [8][9][10] 1-year overall survival and 5-year relative survival in Norway are still reported to be 30% and 15%, respectively. 8,11 Several observational studies and meta-analyses indicate a positive relationship between excess weight and pancreatic cancer.…”

Improved Clinical Staging System for Localized Pancreatic Cancer Using the ABC Factors: A TAPS Consortium Study

“…Future studies should search for additional biomarkers reflecting tumor behavior, such as circulating tumor DNA, to further improve staging. 21,22 Moreover, a decrease in standardized uptake value of PDAC on positron emission tomography scans after neoadjuvant treatment is a promising prognostic factor, especially in patients who are nonsecretors of CA 19-9. [23][24][25][26] Several smaller studies found that a poor performance status of ≥2 was a poor prognostic factor for OS for patients with PDAC.…”

Causes of Death Among Patients With Initially Inoperable Pancreas Cancer After Induction Chemotherapy and Ablative 5-fraction Stereotactic Magnetic Resonance Image Guided Adaptive Radiation Therapy

“…If such an association between radiation dose, LRC, and OS is eventually confirmed, then patient selection for radiation dose escalation would become paramount, although biomarkers to identify appropriate patients are currently limited. 19 …”