Potential impact of invasive surgical procedures on primary tumor growth and metastasis

Abstract

Surgical procedures such as tumor resection and biopsy are still the gold standard for diagnosis and (determination of) treatment of solid tumors, and are prognostically beneficial for patients. However, growing evidence suggests that even a minor surgical trauma can influence several (patho) physiological processes that might promote postoperative metastatic spread and tumor recurrence. Local effects include tumor seeding and a wound healing response that can promote tumor cell migration, proliferation, differentiation, extracellular matrix remodeling, angiogenesis and extravasation. In addition, local and systemic immunosuppression impairs antitumor immunity and contributes to tumor cell survival. Surgical manipulation of the tumor can result in cancer cell release into the circulation, thus increasing the chance of tumor cell dissemination. To prevent these undesired effects of surgical interventions, therapeutic strategies targeting immune response exacerbation or alteration have been proposed. This review summarizes the current literature regarding these local, systemic and secondary site effects of surgical interventions on tumor progression and dissemination, and discusses studies that aimed to identify potential therapeutic approaches to prevent these effects in order to further increase the clinical benefit from surgical procedures.

Keywords: Biopsy; Immune suppression; Metastasis; Tumor cell behavior; Tumor resection; Wound healing.

Fig. 1

Evidence of tumor seeding after needle biopsy of a glioblastoma. Six weeks after a needle biopsy of a glioblastoma (blue arrow), MR-imaging shows evidence of tumor seeding along the needle track (red arrow). (Color figure online)

Fig. 2

Surgical procedure impact on tumor cell progression and metastatic spread and prevention strategies. Surgical trauma induced immune-suppression, acute inflammation, pro-angiogenic factors release, and tumor architecture rupture contribute to tumor cell proliferation, migration, EMT; release and survival in circulation; adhesion to the endothelial wall and extravasation; escape of immune surveillance and angiogenic switch. Several therapeutic approaches show potential benefit to prevent these undesired effects: immune and neuroendocrine modulators, mediators of acute inflammation resolution and anti-angiogenic treatments. IL-2 interleukin 2, IFNα interferon alpha, TNFα tumor necrosis factor alpha, MΦ macrophages, Treg regulatory T cell, MDSC myeloid-derived suppressor cell, NK natural killer, COX-2 cyclooxygenase 2, CxCL2 chemokine (C–X–C motif) ligand 2, CCL3 chemokine (C–C motif) ligand 3, IL-1 interleukin 1, VEGF vascular endothelial growth factor, EMT epithelial–mesenchymal transition, CTC circulating tumor cell, HPA hypothalamic–pituitary–adrenal