Histological regression of gastrointestinal peritoneal metastases after systemic chemotherapy.

Objectives: Peritoneal metastases (PM) are relatively resistant to systemic chemotherapy, and data on histological response to therapy is rare. The aim of this study was to quantify the treatment response of PM after systemic chemotherapy.

Methods: Retrospective monocentric cohort study of 47 consecutive patients with PM from gastrointestinal origin undergoing surgery (cytoreduction: CRS + Hyperthermic IntraPEritoneal Chemotherapy [HIPEC] or Pressurized IntraPeritoneal Aerosol Chemotherapy [PIPAC]) after prior systemic chemotherapy from 1.2015 to 3.2019. Tumor response was assessed using the 4-scale Peritoneal Regression Grading System (PRGS) (4: vital tumor to 1: complete response).

Results: Patients had a median of 2 (range: 1-7) lines and 10 (3-39) cycles of prior systemic chemotherapy. A median of four biopsies (range: 3-8) was taken with a total of 196 analyzed specimens. Twenty-four biopsies (12%) showed no histological regression (PRGS4), while PRGS 3, two and one were diagnosed in 37 (19%), 39 (20%), and 69 (49%) specimens, respectively. A significant heterogeneity was found between peritoneal biopsies in 51% patients. PRGS correlated strongly with peritoneal spread (PCI, p<0.0001), and was improved in patients with more than nine cycles of systemic chemotherapy (p=0.04). Median survival was higher in patients with PRGS < 1.8 (Quartiles one and 2) than higher (Q3 and Q4), but the difference did not reach significance in this small cohort.

Conclusions: PRGS is an objective too to describe histological response of PM of GI origin after systemic chemotherapy. This response differs significantly between patients, allowing to distinguish between chemosensitive and chemoresistant tumors.