Early failure following pelvic exenteration: Who are the bad actors?

Abstract

Background: Pelvic exenteration for locally advanced (LARC) or recurrent rectal cancer (LRRC) is technically challenging with considerable morbidity for the patient. Though surgery can confer long-term survival in selected patients, early failure, defined as recurrence with one year, represents a major issue as both survival and quality of life are severely impacted. This study aims to highlight the "bad actors" associated with early failure.

Methods: A retrospective study of patients who underwent exenteration for LARC & LRRC in a quaternary referral unit was performed. Specifically, characteristics of patients with early recurrence were identified and compared to those who recurred after one year.

Results: 159 and 85 patients underwent pelvic exenteration for LARC and LRRC, respectively. Of these, there were 61 (38.3 %) recurrences in the LARC and 74 (87.1 %) LRRC cohorts. For LARC, 18 patients had an early failure. Expectantly, these patients had a higher proportion of positive margins (R1) (50 % vs. 21 % in the remaining 141 patients, ∗p = 0.04). Interestingly, early failure was also associated with more genetic mutations (33 % vs. 22 %), extramural venous invasion (32 % vs. 24 %), lymphovascular invasion (38 % vs. 22 %), and other adverse histopathological features including poor-differentiation, signet-ring and/or mucinous disease (38 % vs. 21 %). Median and 3-year overall survival (OS) in the early failure group compared to the rest of the cohort was 96 months versus 30 months and 35 % versus 73 %, respectively (∗p = 0.003). There were 18 early failures in the LRRC cohort. Similarly, there were more patients with positive margins in the early failure group (55 % versus 39 %, ∗p = 0.02). The early failure group was also associated with extramural venous invasion (38 % versus 23 %) and adverse histopathological features (55 % versus 28 %). Median and 3-year overall survival (OS) in the early failure group compared to the non-early-failure group was 15 versus 0 months and 17 % versus 68 % respectively (∗p=<0.001).

Conclusion: Tailoring treatment strategies according to tumour characteristics is increasingly important in the management of advanced rectal cancer. Multicentre data is needed to validate these findings and would have a profound impact to patient counselling and outcome expectations.