Ki67 does not predict recurrence for low-grade appendiceal mucinous neoplasms with peritoneal dissemination after cytoreductive surgery and HIPEC

Abstract

Low-grade appendiceal mucinous neoplasms (LAMN) can disseminate to become low-grade mucinous carcinoma peritonei (LGMCP), which is optimally treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Approximately half of the patients with LGMCP recur despite complete cytoreduction, and risk factors for recurrence are poorly understood. We sought to evaluate if Ki67 predicts progression of LGMCP after CRS/HIPEC. A retrospective review of a prospectively maintained database was performed to identify patients treated with complete CRS/HIPEC for LGMCP from 2008 to 2019 with Ki67 assessed. Patient characteristics, histologic data, average and focally high "hotspot") Ki67 index, progression-free survival (PFS), and overall survival (OS) were analyzed. Ki-67 immunostain was performed on the histologic section with the highest cellularity and architectural complexity. Forty-four patients with LGMCP (55% male, median age 61) were identified. The median Ki67 score and hotspot Ki67 score was 15% (1-70) and 50% (1-90), respectively. On univariate analysis, average Ki67 and hotspot Ki67 were not predictive of PFS when analyzed as continuous normalized values (HR 1.0, p=0.79 and HR 1.1, p=0.38, respectively) or as categorical values when stratified by the median (HR 0.9, p=0.67 and HR 1.0, p=0.93). This remained true on multivariate analysis when stratified for peritoneal cancer index, CEA, and completeness of cytoreduction score for both normalized Ki67 and hotspot Ki67 (HR 0.9 [95% CI 0.8-1.3], p=0.94 and HR 1.04 [95% CI 0.8-1.3], p=0.73, respectively). Ki67 failed to predict disease recurrence for patients with LGMCP in this cohort.