14 Chapter 1 Treatment options Only a selection of physically fit patients with limited colorectal PM (based on a low peritoneal cancer index (PCI) score) are considered eligible for current available treatment options 33. The most common applied treatment is the surgical removal of all visible tumor deposits which is called cytoreductive surgery (CRS), followed by the application of heated chemotherapy in the abdominal cavity, known as hyperthermic intraperitoneal chemotherapy (HIPEC). Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is also increasingly investigated as a palliative treatment option for patients 40. Nonetheless, the exposure of tumor cells to the cytostatic drug remains restricted in both HIPEC and PIPAC, diminishing the therapeutic effectiveness 41. Subsequently, minimally invasive alternatives that are applicable to a larger selection of patients with prolonged exposure of the cytostatic to the cancer cells are currently investigated. Recently, new research has been done to develop such a new minimally invasive treatment for PM, namely intraperitoneal administration of a cytostatic-loaded supramolecular hydrogel 41-43. These previous investigations demonstrated enhanced survival among animals subjected to mitomycin C (MMC)-loaded hydrogels in a PM model. Given the promising nature of these findings, there arises not only potential interest in employing this approach as a therapeutic intervention but also in considering its application as a prophylactic intervention during primary surgery to mitigate the likelihood of metachronous PM in at-risk patients. It is therefore important to further investigate this hydrogel in colorectal surgery setting. Risk factors and prevention Given that the prospects for preventing metachronous peritoneal metastases (PM) are more encouraging than for synchronous PM, previous research on risk factors for metachronous PM is more comprehensive 33. Various studies indicate that independent risk factors for metachronous PM include advanced tumor stages, infiltration of the radial margin, elevated preoperative tumor markers, emergency surgery, a primary tumor in the colon rather than the rectum, and the presence of free intraperitoneal cancer cells both before and/or after the resection of the primary tumor 33, 44, 45. Currently, these clinical risk factors do not function as a landmark to apply certain prophylactic treatments. In recent years, there has been a growing recognition of the potential role of biomarkers in disease course prediction and not only offering a promising avenue for early detection, but also for potential preventive interventions 46. The role of biomarkers may play an interesting role in the prevention of metachronous colorectal PM. If specific biomarkers, based on DNA/RNA alterations identified in the primary colorectal tumor during curative surgery, could characterize colorectal PM patients that have a higher risk of developing metachronous PM, these patients may benefit from preventive treatments regimes.
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