Pre‐operative radiotherapy and curative surgery for the management of localized rectal carcinoma
Abstract
Background
Preoperative radiotherapy (PRT) has become part of standard practice offered to improve treatment outcomes in patients with rectal cancer.
Objectives
To determine if PRT improves outcome for patients with localized resectable rectal cancer and how it compared with other adjuvant or neoadjuvant strategies.
Search methods
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.
Selection criteria
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.
Data collection and analysis
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.
Main results
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>30Gy10 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.
Authors' conclusions
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 spincter sparing while reducing acute and late toxicities (rectal and sexual function) are needed to guide future strategy designs.
PICOs
Plain language summary
Pre‐operative radiotherapy and curative surgery for the management of localized rectal carcinoma
Optimal preoperative radiotherapi for localized rectal cancer provide a modest improvement in overall survival, definite improvement in local recurrences, modest increase in the proportion of patients undergoing curative surgery, but is also accompanied by an increase in acute and late rectal and sexual function compared with surgery alone. A combination chemoradiotherapy provides further improvement in local recurrence.
Surgery (i.e. mesorectal excision) is the mainstay of therapy for resectable rectal cancers. This review examines the value of preoperative radiotherapy, and include nineteen randomized trials comparing preoperative radiotherapy with surgery alone.
Preoperative radiotherapy is effective in improving local control. It provides only a marginal benefit in cure rate, and does not improve the likelihood of avoiding a permanent colostomy. It is associated with an increase risk of wound infections following surgery, and long term effect on rectal and sexual function.
Nine trials compared preoperative radiotherapy with other strategies. The addition of chemotherapy to radiotherapy provides even better local control but did not increase the likelihood of cure or the ability to avoiding a permanent colostomy.
