Prognostic significance of signet ring cell predominance in peritoneal metastases from appendix cancer undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND

Signet ring cells (SRC) are a known poor prognostic factor in appendix cancer (AC), but their significance in peritoneal metastases (PM) remains unclear. Given the frequent advanced presentation, we hypothesized that SRC predominance in PM confers additional prognostic value.

METHODS

We conducted a single-center retrospective study of patients with high-grade mucinous carcinoma peritonei ± SRC (HGMCP ± S) undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) (2004-2025). Based on specimen slide evaluation, each case was categorized as: >50% SRC (≥1 metastatic site with SRC predominance), <50% SRC (SRCs present without predominance), and No SRC (control). Cox regression compared progression-free (PFS) and overall survival (OS).

RESULTS

Among 198 patients, 155 had No SRC, 25 had <50% SRC, and 18 had >50% SRC. Groups were balanced by age, sex, and peritoneal cancer index (PCI). Incomplete cytoreduction (CC-2/3) occurred in 29.7% of No SRC, 44.0% of <50% SRC, and 50.0% of >50% SRC (p = 0.107). Median OS was 53, 15, and 13 months, and median PFS was 43, 19 and 12 months for No SRC, <50%, and >50%, respectively. In CC-0/1 patients, >50% SRC was associated with worse OS (HR: 4.27, p < 0.001). After adjusting for age, PCI, and CC-2/3 (OS only), both <50% SRC (HR: 2.34, p = 0.001) and >50% SRC (HR: 3.68, p < 0.001) predicted worse OS, while only >50% SRCs predicted worse PFS (HR: 2.81, p = 0.007).

CONCLUSION

SRC predominance in PM from AC is independently associated with worse survival. These findings support incorporating SRC quantification into pathology reporting and warrant further studies refining SRC-associated prognostication.