Preoperative short-course radiotherapy (5 × 5 Gy) with delayed surgery versus preoperative long-course radiotherapy for locally resectable rectal cancer: a meta-analysis

PURPOSE: Preoperative short-course radiotherapy (PSRT) and preoperative long-course radiotherapy (PLRT) are standard treatment regimens for locally advanced rectal cancer. However, whether the efficacy and safety of PSRT with delayed surgery (more than 4 weeks) are superior to those of PLRT remains unresolved and was explored in this meta-analysis.

METHODS: Studies published in PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov databases were systematically searched. RevMan 5.3 was used to calculate pooled hazard ratios (HR) and relative risk (RR).

RESULTS: Seven studies including 4973 patients were identified in the meta-analysis. Pooled statistics showed that there was no statistically significant difference in overall survival (HR = 1.30, 95% CI 0.58-2.89, P = 0.52) or disease-free survival (HR = 1.10, 95% CI 0.73-1.66, P = 0.64) between the preoperative short-course and long-course radiotherapy groups. Moreover, pathological complete remission, early postoperative complications, treatment-related grade 3/4 toxicity, local recurrence, and distant metastasis were similar between the two groups. Interestingly, a subgroup analysis revealed that preoperative short-course radiotherapy without adjuvant chemotherapy not only resulted in lower treatment-related grade 3/4 toxicity than the long-course radiotherapy group (RR = 0.19, 95% CI 0.08-0.48, P < 0.01) but also resulted in significantly lower overall survival and pathological complete remission (P = 0.02, P < 0.01, respectively). Disappointingly, pooled statistics observed few advantages over long-course radiotherapy in short-course radiotherapy with the adjuvant chemotherapy subgroup.

CONCLUSIONS: PSRT with delayed surgery was as effective as PLRT for the management of locally resectable rectal cancer. However, not adding additional chemotherapy to PSRT not only significantly decreased grade 3/4 toxicity but also decreased pathological complete remission and overall survival.

TRIAL REGISTRATION: The protocol for this meta-analysis was prospectively registered with PROSPERO (CRD42019133641).