Improving outcomes in high-grade goblet cell adenocarcinomas: The interplay of complete cytoreduction, HIPEC and fibrosis.

Abstract

e16379 Background: High-grade goblet cell adenocarcinomas (GCA), including signet-ring cell type (SRC) and poorly differentiated, behave more aggressively compared to typical GCA and are associated with poor prognosis. Due to GCA’s rarity, the treatment aligns with colon cancer guidelines, including surgery, chemotherapy and/or cytoreductive surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for peritoneal carcinomatosis (PC). In our case series, we assessed the outcome of patients with high grade GCA tumors and PC, who underwent either CRS with HIPEC or tumor debulking. Methods: A prospectively maintained database of patients treated at the Division of Surgical Oncology for Peritoneal Carcinomatosis (PC) from 2007 to 2022 was reviewed retrospectively. Patient selection was based on the primary tumor’s original pathology report and scheduling to undergo CRS/HIPEC for PC. We calculated median overall survival from the time of diagnosed peritoneal carcinomatosis, with focus on the attainment of complete cytoreduction (CC) and HIPEC administration. Results: 385 records were screened and 21 cases of GCA were identified. Thirteen (13) patients had a diagnosis of high-grade GCA with PC. Complete cytoreduction (CC0/CC1) with HIPEC was achieved in 7/13 patients, and 6/13 patients underwent tumor debulking. The median overall survival after diagnosing peritoneal carcinomatosis was 53 months for the patients who underwent CC/HIPEC and 20 months for the patients who received debulking. Of note, in the debulking group, 5/6 patients had a poorly differentiated GCA and exhibited intraoperatively tumor characteristics of infiltration, thickening and fibrosis, confirmed by the pathology report, which rendered CC unsuccessful. In contrast, within the CC/HIPEC group, pathology reported localized fibrosis as a chemotherapy response in only 2/7 patients, which did not impede the achievement of CC. Preoperative 5-FU based chemotherapy was administered to 4/7 patients in the CC/HIPEC group and to 5/6 patients in the debulking group. Conclusions: Our results demonstrate that CC with HIPEC may improve overall survival in patients with high grade GCA with PC. Notably, poorly differentiated GCA and the presence of fibrotic tissue, stemming from the tumor and/or preoperative chemotherapy, influences CC success. Considering the potential impact of fibrosis on surgical outcomes, pathological assessment of fibrosis preoperatively and/or use of fibrosis-specific biomarkers could guide cytoreduction strategies and treatment choices in patients diagnosed with high-grade GCA.