Histological regression of gastrointestinal peritoneal metastases after systemic chemotherapy

Abstract

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.

Response Evaluation in Patients with Peritoneal Metastasis Treated with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC)

“…Another phase II trial on different primary tumors showed a decrease in the median CA-125, CA 19-9, and CEA after the second and third PIPAC in those patients who had a radiological response to treatment [ 18 ]. Serum tumor markers were also measured in other PIPAC studies, but were not specifically correlated to the PRGS score [ 19 , 20 , 21 ]. Interestingly, a recent international survey on PIPAC revealed that only half of the surveyed (expert) centers used tumor markers for assessment, whereas all centers performed a detailed radiological evaluation [ 3 ].…”

Outcome of patients with peritoneal metastasis from ovarian cancer treated with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC)

“…Of note, it is difficult to deduce the impact and clinical consequences of the biopsy strategy in the PARROT trial where biopsies were taken after administration of chemotherapy [ 20 ]. Most centres recommend biopsies before administration of chemotherapy [ 22 , 35 ]. Data on the prognostic impact of PRGS are still dubious, and some studies have considered response to PIPAC as any decrease in PRGS during treatment [ 21 ].…”

Peritoneal regression grading score (PRGS): first evidence for independent predictive and prognostic significance

“…Taken together with our data, the evidence available strongly suggests that PRGS obtained from PM delivers crucial predictive information to distinguish between chemo-sensitive and-resistant tumors. This predictive information might be instrumental for improving therapeutic algorithms in patients with PM, in particular for selecting patients potentially benefitting from major peritoneal surgery [ 39 ].…”