Pre-operative radiotherapy and curative surgery for the management of localized rectal carcinoma

Abstract

Preoperative radiotherapy (PRT) has become part of standard practice offered to improve treatment outcomes in patients with rectal cancer. To determine if PRT improves outcome for patients with localized resectable rectal cancer and how it compared with other adjuvant or neoadjuvant strategies. A computerized search was performed December 2006 on MEDLINE (from 1966 to December 2006) and the Cochrane Central Register of Controlled Trials (CENTRAL), conference proceedings, using MeSH and textwords where appropriate to identify randomized trials in PRT and rectal cancer. In addition, MetaRegister of Clinical Trials was searched for ongoing trials. Randomized trials with a PRT arm versus surgery alone, or other neoadjuvant or adjuvant (NA/A) strategies, targeted patients with localized rectal cancer planned for radical surgery were included. Trials were selected, data extracted and quality assessed by 2 authors. Quality was assessed using a 14 point checklist. Summary statistics included Hazard ratios and variances (for the outcomes: overall (OA) mortality, cause specific (CS) mortality, any recurrence and local recurrences (LR)) and Odds Ratio (OR) for other outcomes. Potential sources of heterogeneity hypothesized a priori included study quality, biological effective dose (BED), radiotherapy RT technique, and total mesorectal excision (TME) surgery. Nineteen trials compared PRT versus surgery alone. Overall (OA) mortality was marginally improved HR 0.93 [95% CI -0.87-1](absolute difference is 2% if the expected survival rate is 60%). Local recurrence (LR) was improved but the magnitude of benefit was heterogeneous across trials. Sensitivity analyses suggested greater benefits in patients treated with BED>30Gy(10) and multiple field RT techniques. There was significantly more pelvic or perineal wound infection, late rectal and sexual dysfunction. Nine trials compared PRT vs. other NA/A. Available evidence did not support an OA mortality or sphincter preserving benefit with the use of combined chemoradiotherapy (CRT) or selective postoperative RT. CRT provides incremental benefit for local control compared with PRT, which was independent of the timing of the CT. There was no significant difference in outcome for different intervals between RT and surgery (2 vs. 8 wk). Dose escalation with endocavitary boost showed significant effect on sphincter preservation. Optimal PRT improves LR, OA mortality, but no increase in sphincter sparing procedure. CRT further increases local control. If the objective is to increase the incidence of sphincter sparing surgery, endocavitary boost showed the most promise. Strategies with the potential to improve outcomes, especially OAS and sphincter sparing while reducing acute and late toxicities (rectal and sexual function) are needed to guide future strategy designs.