The emergence of pressurized intraperitoneal aerosol chemotherapy as a palliative treatment option for patients with diffuse peritoneal metastases: a narrative review

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an emerging palliative treatment for patients with unresectable peritoneal metastases. Potential advantages of PIPAC over current treatment options are a homogeneous intraperitoneal distribution, low local and systemic toxicity, and enhanced tumour penetration. Given these possible benefits, PIPAC is increasingly implemented in many centres worldwide. Scientific research into PIPAC is currently available from in vitro/in vivo/in animal studies, retrospective cohorts in humans, and phase I and II studies in humans. There are no results from randomised trials comparing PI PAC with conventional treatment, such as palliative systemic therapy. This narrative review aimed to provide an overview of the currently available literature on PIPAC. In general, repetitive PIPAC was feasible and safe for patients and operating room personnel. Primary and secondary non-access rates varied from 0-17% and 0-15%, respectively. Iatrogenic bowel injury was observed in 0-3% of PIPAC procedures. CTCAE grade 1-2 complications were common, mostly consisting of abdominal pain, nausea, vomiting, and fatigue. CTCAE grade 3-4 complications were uncommon, occurring on 0-15% of PIPAC procedures. Post-operative mortality rates of 0-2% were reported. The risk of occupational exposure to cytotoxic drugs was very low when strict safety guidelines were followed. Clinical heterogeneity was high in most studies, since, in general, patients with unresectable peritoneal metastases from a variety of primary tumours were included. Also, patients received either PIPAC monotherapy or PIPAC combined with concomitant systemic therapy, and were able to receive PIPAC in any line of palliative treatment. Since the results were generally not stratified for these three important factors, this severely complicates the interpretation of results. Based on the current literature, PIPAC may be regarded as a promising palliative treatment option in patients with diffuse peritoneal metastases. Initial results show that it is feasible and safe. However, well designed and (ideally) randomized controlled trials are urgently needed to determine the additional value of PIPAC in this setting. Until then, PIPAC should preferably be performed in the setting of clinical trials.