Effect of timing of surgery on survival after preoperative hyperfractionated accelerated radiotherapy (HART) for locally advanced rectal cancer (LARC): Is it a matter of days?

We intend to analyse retrospectively whether the time interval (‘‘gap duration’’ /GD) between preoperative radiotherapy and surgery in locally advanced rectal cancer (LARC) has an impact on overall survival (OS), cancer specific survival (CSS), disease free survival (DFS) and local control (LC). Two hundred seventy nine patients with LARC were entered in Trial 93-01 (hyperfractionated accelerated radiotherapy 41.6 Gy/26 Fx BID) shortly followed by surgery. From these 250 patients are fully assessable. The median GD of 5 days was used as a discriminator. The median follow-up for all patients was 39 months. GD � /5 days was a significant discriminator for actuarial 5-years OS (69% vs 47%, p /0.002), CSS (82% vs 57%, p /0.0007), DFS (62% vs 41%, p /0.0003) but not for LC (93% vs 90%, p /non-significant). In multivariate analysis, the following factors independently predict outcome; for OS: age, GD, circumferential margin (CM) and nodal stage (ypN); for CSS: GD, ypN and vascular invasion (VI); for DFS: CEA, distance to anal verge, GD, ypN and VI; for LC: CM only. Gap duration predicts survival outcome but not local control. The patients submitted to surgery after a median delay of more than 5 days had a significantly better outcome. Surgery is the mainstay of treatment in rectal cancer [19]. The incidence of local recurrence should be well below 15% provided surgery is performed according to the now well accepted surgical standard, which is a total (TME) or a partial mesorectal excision with sharp dissection. Nevertheless, preoperative radiotherapy yields a significant better local control and in some trials a positive impact on survival [1015]. In the randomized trials, in which a clear benefit in favour of 5 times 5 Gy has been reported, the interval between the end of radiotherapy and surgery is very short. In the Swedish rectal cancer trial (SRCT) the patients are submitted to surgery immediately after the weekend [15]. In the Dutch ColoRectal Cancer Group trial (DCRCG), the overall treatment time between the start of the radiotherapy and the surgery has to be within 10 days [13]. Therefore, in these trials the analysis of the impact of the timing of surgery after the end of radiotherapy is difficult to perform. In Trial 93-01, a prospective non-randomized phase II trial on hyperfractionated accelerated radiotherapy (HART) in locally advanced resectable rectal cancer (LARC), there is a variation of the GD. Therefore, we are able to analyze the importance of the GD on patient’s outcome.