Abstract

Background: Multimodal therapeutic strategies have improved the outcome of peritoneal metastases (PM). However, objective assessment of therapy response remains difficult in PM, since radiological studies have a poor accuracy for low-volumetric disease. There is an obvious need for a histological gold standard allowing assessment of tumor response to treatment in PM. Content: We propose to perform peritoneal punch biopsies with a diameter of 3 to 5 mm in all four abdominal quadrants. We propose a four-tier Peritoneal Regression Grading Score (PRGS), defined as Grade 1: complete response (absence of tumor cells), Grade 2: major response (major regression features, few residual tumor cells), Grade 3: minor response (some regressive features but predominance of residual tumor cells), Grade 4: no response (tumor cells without any regressive features). Acellular mucin and infarct-like necrosis should be regarded as regression features. We recommend reporting the mean and the worst value of the regression grades obtained. When complete tumor response is suspected intraoperatively, a peritoneal cytology should be sampled. Summary: A generic, unique score for the assessment of histological tumor response to chemotherapy in PM makes sense because of the clinical impact of histological response to therapy and because the organ of metastasis (peritoneum) is the same. By adopting PRGS, different centers will be able to use a uniform terminology and grading that will allow meaningful comparison of their results. Outlook: PRGS has now to be validated in several gastrointestinal and gynecological cancer types and may be useful both in clinical and research settings.

Highlights

  • Tumor regression grading (TRG) scores are widely used in the neoadjuvant setting for primary tumors

  • Previous published studies in the field are limited to histological response evaluation of initially unresectable colorectal liver metastases (CRLM)

  • There is an urgent need for a gold standard for therapy assessment in peritoneal metastases (PM)

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Summary

Introduction

Tumor regression grading (TRG) scores are widely used in the neoadjuvant setting for primary tumors. First data on tumor response of PM after PIPAC reported large areas of devitalized tumor with mucin pools in a patient with diffuse carcinomatosis from an appendiceal signet ring cell carcinoma [15] These first results have been reproduced in three retrospective studies evaluating histological tumor response after PIPAC in ovarian [10], colorectal [16], and gastric cancer [17]. One of the studies just mentioned was a regulatory phase-2 study on the efficacy of PIPAC with low-dose cisplatin and doxorubicin in platin-resistant, recurrent ovarian cancer [10] Taken together, these data support the need for a histological gold standard allowing assessment of tumor response to chemotherapy in PM. We propose standard operating procedures for peritoneal sampling and introduce a novel Peritoneal Regression Grading Score (PRGS) for reporting the regressive changes in the obtained biopsies and/or surgical specimens

Recommendations for peritoneal sampling
Recommendations for fixation and staining
Interpretation of the Peritoneal Regression Grading Score
Findings
Summary
Full Text
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