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

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.

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.

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).

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.