Median follow-up was 5.7 years. Lethal toxicity was less than 1%, with grade 3 to 4 hematologic toxicity in 55% and 49% of patients in the two bolus arms, respectively (i.e., arms 1 and 3) versus 4% of patients in the continuous-infusion arm. No DFS, OS, or locoregional failure (LRF) difference was detected (across all arms: 3-year DFS, 67% to 69%; 3-year OS, 81% to 83%; LRF, 4.6% to 8%).[Level of evidence: 1iiA]
Addition of radiation therapy
Although the above data demonstrate a benefit with postoperative radiation therapy and 5-FU chemotherapy for patients with stage II and III rectal cancer, a follow-up study to the NSABP-R-01 trial, the NSABP-R-02 study, addressed whether the addition of radiation therapy to chemotherapy would enhance the survival advantage reported in R-01.[Level of evidence: 1iiA] The addition of radiation, while significantly reducing local recurrence at 5 years (8% for chemotherapy and radiation vs. 13% for chemotherapy alone, P = .02), demonstrated no significant benefit in terms of survival. The interpretation of the interaction of radiation therapy with prognostic factors, however, was challenging. Radiation appeared to improve survival among patients younger than 60 years, as well as among patients who received abdominoperineal resection. This trial has initiated discussion in the oncologic community as to the proper role of postoperative radiation therapy. Omission of radiation therapy seems premature, since locoregional recurrence remains a clinically relevant problem.
Using current surgical techniques, including TME, it may be possible to identify subsets of patients whose chance of pelvic failure is low enough to omit postoperative radiation. A trial conducted by the Dutch Colorectal Cancer Group (CKVO-9504 ) randomly assigned patients with resectable rectal cancers (stages I-IV) to a short course of radiation (5 Gy × 5 days) followed by TME compared to TME alone and demonstrated no difference in OS at 2 years (82% for both arms).[Level of evidence: 1iiA] Local recurrence rates were significantly reduced in the radiation therapy plus TME arm (2.4%) as compared to the TME only arm (8.2%, P < .001).
At present, acceptable postoperative therapy for patients with stage II or III rectal cancer not enrolled in clinical trials includes continuous-infusion 5-FU during 45 Gy to 55 Gy pelvic radiation and four cycles of adjuvant maintenance chemotherapy with bolus 5-FU with or without modulation with leucovorin.
An analysis of patients treated with postoperative chemotherapy and radiation therapy suggests that these patients may have more chronic bowel dysfunction compared to those who undergo surgical resection alone. Improved radiation planning and techniques can be used to minimize treatment-related complications. These techniques include the use of multiple pelvic fields, prone positioning, customized bowel immobilization molds (belly boards), bladder distention, visualization of the small bowel through oral contrast, and the incorporation of three-dimensional or comparative treatment planning.[30,31]