Tumor Excision as a Metastatic Russian Roulette: Perioperative Interventions to Improve Long-Term Survival of Cancer Patients

Uncertainty regarding the development of postoperative metastatic disease is highly prevalent. Here we assert that numerous processes that occur during the immediate perioperative period (IPP) markedly affect the probability of postoperative metastatic disease and that these processes can be manipulated to improve cancer survival. Specifically, tumor excision facilitates both prometastatic and antimetastatic processes, which, within each domain, are often synergistic and self-propagating. Consequently, minor perioperative dominance of either prometastatic or antimetastatic processes can trigger a 'snowball-like effect' leading to either accelerated progression of minimal residual disease (MRD) or its dormancy/elimination, establishing the 'surgical metastatic roulette'. Thus, the IPP should become a significant antimetastatic therapeutic arena, exploiting feasible approaches including immunotherapies and manipulations/modifications of inflammatory-stress responses, surgical procedures, and hormonal status.