Best Timing of Chemo in Rectal Cancer Unclear
Best Timing of Chemo in Rectal Cancer Unclear
Bosset JF, Calais, G, Mineur L, et al
Lancet Oncol. 2014;15:184-190
The investigators provide a long-term follow-up report of EORTC 22921, which examined the addition of preoperative or postoperative chemotherapy to preoperative radiation therapy in patients with rectal cancer. There were 2 randomizations. Patients with clinical stage T3 or T4 resectable rectal cancer were randomly assigned to receive radiotherapy without concomitant chemotherapy (fluorouracil plus leucovorin for 2 cycles, given at weeks 1 and 5 of the radiotherapy) before surgery. After surgery, patients were randomly assigned to surveillance or adjuvant chemotherapy (fluorouracil plus leucovorin for 4 cycles, given every 3 weeks).
The primary endpoint was overall survival. Of 1011 patients, 252 were randomly assigned to receive preoperative radiotherapy and 253 were assigned to each of the other 3 groups. After a median follow-up of 10.4 years, 10-year overall survival was 49.4% (95% CI, 44.6-54.1) for the preoperative radiotherapy group and 50.7% (95% CI, 45.9-55.2) for the preoperative chemoradiation group (HR, 0.99; 95% CI, 0.83-1.18; P = .91). The 10-year overall survival for the group receiving postoperative chemotherapy was 51.8% (95% CI, 47.0-56.4) and 48.4% (43.6-53.0) for the surveillance group (HR, 0.91; 95% CI, 0.77-1.09; P = .32). Incidence of local relapse at 1 year was 22.4% (95% CI, 17.1-27.6) for those patients receiving radiation therapy alone, 11.8% (95% CI, 7.8-15.8) for those receiving preoperative chemoradiation, 14.5% (95% CI, 10.1-18.9) for those receiving preoperative radiation and postoperative chemotherapy, and 11.7% (95% CI, 7.7-15.6) for those receiving both preoperative and postoperative chemotherapy (P = .0017). There was no significant difference in toxicity profile between the various arms.
Current oncologic practice is to recommend both preoperative and postoperative systemic chemotherapy in patients with locally advanced rectal cancer. This study underscores the lack of clear benefit with this approach. Strengths of the study include the large sample size and long-term follow-up. The study confirms that adding chemotherapy improves local control, which is of major clinical benefit to patients. However, there was no significant difference in local control rates with chemotherapy given as part of the preoperative regimen (which is current standard of care) or as part of the postoperative treatment. Therefore, there are no clear data supporting postoperative chemotherapy, although we can continue to extrapolate from the colon cancer literature. Limitations of the study include the notable fact that only 43% of patients received full-dose postoperative treatment; in fact, 25% received none. This speaks to the difficulty of maintaining patients on postoperative therapy, and perhaps the best time to receive treatment may be upfront in this setting (as in esophageal cancer patients). Ongoing trials are addressing this approach.
Abstract
Fluorouracil-Based Adjuvant Chemotherapy After Preoperative Chemoradiotherapy in Rectal Cancer: Long-term Results of the EORTC 22921 Randomised Study
Bosset JF, Calais, G, Mineur L, et al
Lancet Oncol. 2014;15:184-190
Study Summary
The investigators provide a long-term follow-up report of EORTC 22921, which examined the addition of preoperative or postoperative chemotherapy to preoperative radiation therapy in patients with rectal cancer. There were 2 randomizations. Patients with clinical stage T3 or T4 resectable rectal cancer were randomly assigned to receive radiotherapy without concomitant chemotherapy (fluorouracil plus leucovorin for 2 cycles, given at weeks 1 and 5 of the radiotherapy) before surgery. After surgery, patients were randomly assigned to surveillance or adjuvant chemotherapy (fluorouracil plus leucovorin for 4 cycles, given every 3 weeks).
The primary endpoint was overall survival. Of 1011 patients, 252 were randomly assigned to receive preoperative radiotherapy and 253 were assigned to each of the other 3 groups. After a median follow-up of 10.4 years, 10-year overall survival was 49.4% (95% CI, 44.6-54.1) for the preoperative radiotherapy group and 50.7% (95% CI, 45.9-55.2) for the preoperative chemoradiation group (HR, 0.99; 95% CI, 0.83-1.18; P = .91). The 10-year overall survival for the group receiving postoperative chemotherapy was 51.8% (95% CI, 47.0-56.4) and 48.4% (43.6-53.0) for the surveillance group (HR, 0.91; 95% CI, 0.77-1.09; P = .32). Incidence of local relapse at 1 year was 22.4% (95% CI, 17.1-27.6) for those patients receiving radiation therapy alone, 11.8% (95% CI, 7.8-15.8) for those receiving preoperative chemoradiation, 14.5% (95% CI, 10.1-18.9) for those receiving preoperative radiation and postoperative chemotherapy, and 11.7% (95% CI, 7.7-15.6) for those receiving both preoperative and postoperative chemotherapy (P = .0017). There was no significant difference in toxicity profile between the various arms.
Viewpoint
Current oncologic practice is to recommend both preoperative and postoperative systemic chemotherapy in patients with locally advanced rectal cancer. This study underscores the lack of clear benefit with this approach. Strengths of the study include the large sample size and long-term follow-up. The study confirms that adding chemotherapy improves local control, which is of major clinical benefit to patients. However, there was no significant difference in local control rates with chemotherapy given as part of the preoperative regimen (which is current standard of care) or as part of the postoperative treatment. Therefore, there are no clear data supporting postoperative chemotherapy, although we can continue to extrapolate from the colon cancer literature. Limitations of the study include the notable fact that only 43% of patients received full-dose postoperative treatment; in fact, 25% received none. This speaks to the difficulty of maintaining patients on postoperative therapy, and perhaps the best time to receive treatment may be upfront in this setting (as in esophageal cancer patients). Ongoing trials are addressing this approach.
Abstract
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