Reproducibility of the peritoneal regression grading score for assessment of response to therapy in peritoneal metastasis

Abstract

Aims The four‐tiered peritoneal regression grading score (PRGS) assesses the response to chemotherapy in peritoneal metastasis (PM). The PRGS is used, for example, to assess the response to pressurised intraperitoneal aerosol chemotherapy (PIPAC). However, the reproducibility of the PRGS is currently unknown. We aimed to evaluate the inter‐ and intraobserver variability of the PRGS. Methods and results Thirty‐three patients who underwent at least three PIPAC treatments as part of the PIPAC‐OPC1 or PIPAC‐OPC2 clinical trials at Odense University Hospital, Denmark, were included. Prior to each therapy cycle, peritoneal quadrant biopsies were obtained and three haematoxylin and eosin (H&E)‐stained step sections were scanned and uploaded to a pseudonymised web library. For determining interobserver variability, eight pathologists assessed the PRGS for each quadrant biopsy, and Krippendorff's alpha and intraclass correlation coefficients (ICCs) were calculated. For determining intraobserver variability, three pathologists repeated their own assessments and Cohen's kappa and ICCs were calculated. A total of 331 peritoneal biopsies were analysed. Interobserver variability for PRGS of each biopsy and for the mean and maximum PRGS per biopsy set was moderate to good/substantial. The intraobserver variability for PRGS of each biopsy and for the mean and maximum PRGS per biopsy set was good to excellent/almost perfect. Conclusions Our data support the PRGS as a reproducible and useful tool to assess response to intraperitoneal chemotherapy in PM. Future studies should evaluate the prognostic and predictive role of the PRGS.

MESOTIP: Phase II multicenter randomized trial evaluating the association of PIPAC and systemic chemotherapy vs. systemic chemotherapy alone as 1st-line treatment of malignant peritoneal mesothelioma

“…Indeed, no other ongoing front line trial in MPM is currently listed on clinical-trials.gov [25]. The RENAPE network will facilitate the implementation of the trial, and thus patient recruitment, in France [26].…”

“…Patients will be considered resectable if the preservation of at least 1.5 meters of small bowel and of at least 2 meters of lower gastrointestinal tube is possible in case of complete cytoreduction. The histological response to treatment will be assessed comparing the peritoneal regression grading score (PRGS) score [25,26] of the samples at the last laparoscopic evaluation in the standard arm or the last PIPAC in the experimental arm compared to the initial histologic aspect. Last, quality of life will be assessed using the EORTC QLQ-C30 questionnaire.…”

Pressurized IntraPeritoneal Aerosol Chemotherapy with one minute of electrostatic precipitation (ePIPAC) is feasible, but the histological tumor response in peritoneal metastasis is insufficient

“…The clinical and prognostic impact of the PRGS evaluation has not been validated so far. Still, the intra-and interobserver variability of the PRGS is good [23] and at the moment PRGS seems to be the only validated tool for histological tumor response evaluation. The study populations of both the present study and the PIPAC-OPC1 "control group" were heterogeneous, since patients had different primary tumors and had received different lines and types of chemotherapy before inclusion.…”

Overcoming Drug Resistance by Taking Advantage of Physical Principles: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC)

“…Over the years, in addition to the aerosolization of a drug, we found it useful to add two further components, namely steering the operating environment (pressure, temperature, electrostatic charges, etc.) and objective assessment of tumor response (by comparing biopsies between repeated applications) [55,56]. All three components are now part of PIPAC [57].…”