Timing of surgery following preoperative therapy in rectal cancer: the need for a prospective randomized trial?

Abstract

In rectal cancer, the standard of care after the completion of radiotherapy is surgery at 6 to 8 weeks. However, there is variation regarding the timing of surgery. This investigation aimed to audit the timing of surgery following radiotherapy and to compare perioperative morbidity and tumor downstaging in patients operated on, before and after the 6- to 8-week window. A retrospective review of rectal cancers treated preoperatively in our cancer network over a 27-month period. The effect of "time till surgery" of 6 to 8 weeks, <6 weeks, and >8 weeks on T downstaging and nodal downstaging was calculated by univariate and multivariate logistic regression analyses. This study was conducted in an oncology tertiary referral center in the Southwest London Cancer Network. Patients receiving preoperative radiotherapy for primary locally advanced rectal cancer undergoing subsequent surgical resection were eligible. The primary outcome measurement was time to surgery following the completion of (chemo) radiotherapy. Thirty-day perioperative morbidity and mortality and tumor and nodal downstaging were examined according to the timing of surgery. This study was limited by its nonrandomized retrospective design and the lack of standardization of preoperative chemotherapy. Thirty-two (34%) patients underwent surgery at 6 to 8 weeks, 45 (47%) at >8 weeks, and 18 (19%) at <6 weeks after radiotherapy. Delay was attributed to scheduling in 87% of cases and to comorbidities in the remainder. T downstaging occurred in 6 (33.3%) patients in the <6 weeks group, in 12 (37.5%) in the 6 to 8 weeks group, and in 28 (62.2%) in >8 weeks group with no significant differences in perioperative morbidity. On multivariate analysis, T downstaging was significantly greater for the >8 weeks group (OR, 3.79; 95% CI: 1.11-12.99; P = .03). More patients were staged ypT0-T2, 19 of 45 (42%) in the >8 weeks group vs other groups, 14 of 50 (28%, P < .05). Following radiotherapy, surgery frequently occurs at >8 weeks and is associated with increased downstaging. The consequences on survival and perioperative morbidity warrant further investigation.