Preoperative or postoperative radiotherapy reduces the risk of local recurrence in patients with operable rectal cancer. However, improvements in surgery and histopathological assessment mean that the role of radiotherapy needs to be reassessed. We compared short-course preoperative radiotherapy versus initial surgery with selective postoperative chemoradiotherapy. We undertook a randomised trial in 80 centres in four countries. 1350 patients with operable adenocarcinoma of the rectum were randomly assigned, by a minimisation procedure, to short-course preoperative radiotherapy (25 Gy in five fractions; n=674) or to initial surgery with selective postoperative chemoradiotherapy (45 Gy in 25 fractions with concurrent 5-fluorouracil) restricted to patients with involvement of the circumferential resection margin (n=676). The primary outcome measure was local recurrence. Analysis was by intention to treat. This study is registered, number ISRCTN 28785842. At the time of analysis, which included all participants, 330 patients had died (157 preoperative radiotherapy group vs 173 selective postoperative chemoradiotherapy), and median follow-up of surviving patients was 4 years. 99 patients had developed local recurrence (27 preoperative radiotherapy vs 72 selective postoperative chemoradiotherapy). We noted a reduction of 61% in the relative risk of local recurrence for patients receiving preoperative radiotherapy (hazard ratio [HR] 0.39, 95% CI 0.27-0.58, p<0.0001), and an absolute difference at 3 years of 6.2% (95% CI 5.3-7.1) (4.4% preoperative radiotherapy vs 10.6% selective postoperative chemoradiotherapy). We recorded a relative improvement in disease-free survival of 24% for patients receiving preoperative radiotherapy (HR 0.76, 95% CI 0.62-0.94, p=0.013), and an absolute difference at 3 years of 6.0% (95% CI 5.3-6.8) (77.5%vs 71.5%). Overall survival did not differ between the groups (HR 0.91, 95% CI 0.73-1.13, p=0.40). Taken with results from other randomised trials, our findings provide convincing and consistent evidence that short-course preoperative radiotherapy is an effective treatment for patients with operable rectal cancer.

Local recurrence rates in operable rectal cancer are improved by radiotherapy (with or without chemotherapy) and surgical techniques such as total mesorectal excision. However, the contributions of surgery and radiotherapy to outcomes are unclear. We assessed the effect of the involvement of the circumferential resection margin and the plane of surgery achieved. In this prospective study, the plane of surgery achieved and the involvement of the circumferential resection margin were assessed by local pathologists, using a standard pathological protocol in 1156 patients with operable rectal cancer from the CR07 and NCIC-CTG CO16 trial, which compared short-course (5 days) preoperative radiotherapy and selective postoperative chemoradiotherapy, between March, 1998, and August, 2005. All analyses were by intention to treat. This trial is registered, number ISRCTN 28785842. 128 patients (11%) had involvement of the circumferential resection margin, and the plane of surgery achieved was classified as good (mesorectal) in 604 (52%), intermediate (intramesorectal) in 398 (34%), and poor (muscularis propria plane) in 154 (13%). We found that both a negative circumferential resection margin and a superior plane of surgery achieved were associated with low local recurrence rates. Hazard ratio (HR) was 0.32 (95% CI 0.16-0.63, p=0.0011) with 3-year local recurrence rates of 6% (5-8%) and 17% (10-26%) for patients who were negative and positive for circumferential resection margin, respectively. For plane of surgery achieved, HRs for mesorectal and intramesorectal groups compared with the muscularis propria group were 0.32 (0.16-0.64) and 0.48 (0.25-0.93), respectively. At 3 years, the estimated local recurrence rates were 4% (3-6%) for mesorectal, 7% (5-11%) for intramesorectal, and 13% (8-21%) for muscularis propria groups. The benefit of short-course preoperative radiotherapy did not differ in the three plane of surgery groups (p=0.30 for trend). Patients in the short-course preoperative radiotherapy group who had a resection in the mesorectal plane had a 3-year local recurrence rate of only 1%. In rectal cancer, the plane of surgery achieved is an important prognostic factor for local recurrence. Short-course preoperative radiotherapy reduced the rate of local recurrence for all three plane of surgery groups, almost abolishing local recurrence in short-course preoperative radiotherapy patients who had a resection in the mesorectal plane. The plane of surgery achieved should therefore be assessed and reported routinely.

Purpose: To assess magnetic resonance imaging (MRI) and pathologic staging after neoadjuvant therapy for rectal cancer in a prospectively enrolled, multicenter study. Methods: In a prospective cohort study, 111 patients who had rectal cancer treated by neoadjuvant therapy were assessed for response by MRI and pathology staging by T, N and circumferential resection margin (CRM) status. Tumor regression grade (TRG) was also assessed by MRI. Overall survival (OS) was estimated by using the Kaplan-Meier product-limit method, and Cox proportional hazards models were used to determine associations between staging of good and poor responders on MRI or pathology and survival outcomes after controlling for patient characteristics. Results: On multivariate analysis, the MRI-assessed TRG (mrTRG) hazard ratios (HRs) were independently significant for survival (HR, 4.40; 95% CI, 1.65 to 11.7) and disease-free survival (DFS; HR, 3.28; 95% CI, 1.22 to 8.80). Five-year survival for poor mrTRG was 27% versus 72% (P = .001), and DFS for poor mrTRG was 31% versus 64% (P = .007). Preoperative MRI-predicted CRM independently predicted local recurrence (LR; HR, 4.25; 95% CI, 1.45 to 12.51). Five-year survival for poor post-treatment pathologic T stage (ypT) was 39% versus 76% (P = .001); DFS for the same was 38% versus 84% (P = .001); and LR for the same was 27% versus 6% (P = .018). The 5-year survival for involved pCRM was 30% versus 59% (P = .001); DFS, 28 versus 62% (P = .02); and LR, 56% versus 10% (P = .001). Pathology node status did not predict outcomes. Conclusion: MRI assessment of TRG and CRM are imaging markers that predict survival outcomes for good and poor responders and provide an opportunity for the multidisciplinary team to offer additional treatment options before planning definitive surgery. Postoperative histopathology assessment of ypT and CRM but not post-treatment N status were important postsurgical predictors of outcome.

Purpose: The prognostic relevance of preoperative high-resolution magnetic resonance imaging (MRI) assessment of circumferential resection margin (CRM) involvement is unknown. This follow-up study of 374 patients with rectal cancer reports the relationship between preoperative MRI assessment of CRM staging, American Joint Committee on Cancer (AJCC) TNM stage, and clinical variables with overall survival (OS), disease-free survival (DFS), and time to local recurrence (LR). Patients and Methods: Patients underwent protocol high-resolution pelvic MRI. Tumor distance to the mesorectal fascia of ≤ 1 mm was recorded as an MRI-involved CRM. A Cox proportional hazards model was used in multivariate analysis to determine the relationship of MRI assessment of CRM to survivorship after adjusting for preoperative covariates. Results: Surviving patients were followed for a median of 62 months. The 5-year OS was 62.2% in patients with MRI-clear CRM compared with 42.2% in patients with MRI-involved CRM with a hazard ratio (HR) of 1.97 (95% CI, 1.27 to 3.04; P < .01). The 5-year DFS was 67.2% (95% CI, 61.4% to 73%) for MRI-clear CRM compared with 47.3% (95% CI, 33.7% to 60.9%) for MRI-involved CRM with an HR of 1.65 (95% CI, 1.01 to 2.69; P < .05). Local recurrence HR for MRI-involved CRM was 3.50 (95% CI, 1.53 to 8.00; P < .05). MRI-involved CRM was the only preoperative staging parameter that remained significant for OS, DFS, and LR on multivariate analysis. Conclusion: High-resolution MRI preoperative assessment of CRM status is superior to AJCC TNM–based criteria for assessing risk of LR, DFS, and OS. Furthermore, MRI CRM involvement is significantly associated with distant metastatic disease; therefore, colorectal cancer teams could intensify treatment and follow-up accordingly to improve survival outcomes.

To assess local recurrence, disease-free survival, and overall survival in magnetic resonance imaging (MRI)–predicted good prognosis tumors treated by surgery alone. The MERCURY study reported that high-resolution MRI can accurately stage rectal cancer. The routine policy in most centers involved in the MERCURY study was primary surgery alone in MRI-predicted stage II or less and in MRI “good prognosis” stage III with selective avoidance of neoadjuvant therapy. Data were collected prospectively on all patients included in the MERCURY study who were staged as MRI-defined “good” prognosis tumors. “Good” prognosis included MRI-predicted safe circumferential resection margins, with MRI-predicted T2/T3a/T3b (less than 5 mm spread from muscularis propria), regardless of MRI N stage. None received preoperative or postoperative radiotherapy. Overall survival, disease-free survival, and local recurrence were calculated. Of 374 patients followed up in the MERCURY study, 122 (33%) were defined as “good prognosis” stage III or less on MRI. Overall and disease-free survival for all patients with MRI “good prognosis” stage I, II and III disease at 5 years was 68% and 85%, respectively. The local recurrence rate for this series of patients predicted to have a good prognosis tumor on MRI was 3%. The preoperative identification of good prognosis tumors using MRI will allow stratification of patients and better targeting of preoperative therapy. This study confirms the ability of MRI to select patients who are likely to have a good outcome with primary surgery alone.