Is tailoring treatment of rectal cancer the only true benefit of long-course neoadjuvant chemoradiation? Another view.

Diseases of the Colon & ReCtum Volume 56: 2 (2013) it would seem that in the shortto medium-term radiotherapy is best delivered preoperatively rather than postoperatively; compliance is better, efficacy is greater, and the side effects are considerably less. Preoperative radiotherapy reduces local failure after total mesorectal excision (tme) surgery, even when the surgical technique is considered optimal. in the mRC CR07 study, nonirradiated patients with grade 3 tme (mesorectal fascia intact) and R0 resection experienced local failure rates of 6% at 3 years. the addition of short-course preoperative radiotherapy (sCPRt) reduced this figure to 1%. Radiotherapy was of most benefit in high-risk cases, notably those with advanced disease or a poor quality of surgery. Prevention of 1 local recurrence by using sCPRt required treatment of 79 stage i, 21 stage ii, or 13 stage iii cases. mid and lower third tumors were associated with the highest recurrence rates; nonetheless, sCPRt was effective in all parts of the rectum. short-course preoperative radiotherapy did not compensate for a positive histopathological circumferential resection margin (CRm), because 13.8% of cases developed local recurrence at 3 years. however, the alternative strategy of selective postoperative chemoradiation therapy (CRt) for microscopically involved margins (tumor ≤1 mm from mesorectal fascia) fared worse with 20.7% local recurrence. long-term follow-up suggests that, in some cases, preoperative treatment merely postpones, rather than prevents, pelvic recurrence. Consequently, the efficacy of preoperative radiotherapy is less marked over time in both the Dutch and German studies. the recent German update with a median follow-up of 11 years indicates the convergence of local recurrence rates for preand postoperative CRt: 5% versus 9.7% at 5 years in comparison with 7% versus 10.1% at 10 years. they had earlier reported figures of 6% versus 13% at 5 years, estimates derived from a median follow-up of 4 years. it should be pointed out that underlying methodological anomalies account for this reduction in efficacy over time. one-third of patients randomly assigned to postoperative CRt did not receive it, in general, owing to finding unexpected stage i or iV disease at surgery. this cohort of nonirradiated patients contributed half of all recurrences attributed to the “postoperative” group. events preceded those in irradiated subjects, leading to a false impression of enhanced efficacy for “preop” at earlier time points. another confounding subtlety, this time in favor of postoperative treatment, was the delivery of an additional 5.4-Gy boost to the tumor bed. two studies have directly compared sCPRt with preoperative CRt. the Polish study was powered to determine whether CRt improved sphincter preservation rates; it did not. in addition, there was no difference in local recurrence rates at 5 years, 9% for sCPRt versus 14% for CRt (p = 0.17). the most striking result was a much greater rate of acute severe toxicity with CRt in comparison with sCPRt, 18% versus 3%, whereas long-term toxicity profiles were similar. the German and Dutch studies yielded comparable acute toxicity data. Chemoradiation therapy was associated with reduced rates of CRm positivity in comparison with sCPRt, but no improvements in either local control or overall survival followed. the transtasman Radiation oncology Group also reported no difference in local recurrence rates between sCPRt and CRt at 3 years, 7.5% for sCPRt versus 4.4% for CRt (p = 0.24). one caveat is that neither study was powered to detect small differences in either local recurrence or survival. John R. t. monson, m.D., Section Editor