Precision Oncology in Surgery: Patient Selection for Operable Pancreatic Cancer.

Area of Science:

• Oncology
• Surgical Oncology
• Molecular Diagnostics

Background:

• Pancreatic ductal adenocarcinoma (PDAC) surgery offers the only chance for long-term survival, yet 80% of patients succumb to the disease.
• Current surgical oncology lacks molecular patient selection, unlike systemic therapies, despite its critical importance.
• High mortality rates post-surgery underscore the need for improved patient selection strategies.

Purpose of the Study:

• To define preoperative clinical and molecular characteristics for enhanced patient selection in pancreatic cancer operative resection.
• To investigate the prognostic value of S100A2 and S100A4 protein expression in PDAC.
• To develop and validate a predictive nomogram for surgical outcomes in PDAC.

Main Methods:

• Analysis of 3 independent PDAC cohorts (n=1184) assessing the relationship between S100A2/S100A4 expression and survival.
• Construction of a preoperative nomogram integrating clinical variables and S100A2/S100A4 expression.
• Validation of findings in training (n=518) and independent patient cohorts (n=198, n=468).

Main Results:

• High S100A2 or S100A4 expression identified as independent poor prognostic factors in PDAC.
• Aberrant biomarker expression stratified patients into three distinct prognostic groups.
• A preoperative nomogram incorporating S100A2/S100A4 expression demonstrated predictive survival capabilities, validated against postoperative data.

Conclusions:

• Preoperative nomogram scores can identify patients with poor prognosis, with ~50% mortality within a year for those with low scores.
• Nomograms integrating molecular markers like S100A2/S100A4 can optimize surgical candidate selection.
• These tools may help avoid unnecessary surgery in aggressive PDAC and justify extensive resections in favorable cases.