Radiotherapy boost to the primary tumour in locally advanced rectal cancer: Systematic review of practices and meta-analysis

Abstract

Introduction

In locally advanced rectal cancer (LARC), increasing the complete response (CR) rate after total neo-adjuvant treatment may increase the patient eligibility for non-operative management (“watch and wait”, W&W). Although a radiotherapy (RT) boost to the primary tumour may enhance CR rates, clear guidelines are currently lacking. This systematic review and meta-analysis investigate the technical parameters used for rectal boost RT and assess their impact on oncological outcomes.

Methods

Following PRISMA guidelines, the terms “rectum,” “radiotherapy,” and “boost” were searched in PubMed and EMBASE (PROSPERO: CRD42023444685). Studies reporting on external beam RT boost to the primary tumour in LARC and meeting quality criteria were included. Descriptive analyses extracted data on RT technique, preparation, boost delineation, dose, chemotherapy, and follow-up. A mixed-effects meta-analysis model evaluated the impact of selected parameters on CR and local recurrence rate (LRR). Studies were analysed separately based on treatment intent: planned surgery or W&W.

Results

Out of 3904 references, 83 were included in the descriptive analysis and 78 in the meta-analysis. Substantial variability in RT parameters was observed across studies. Pathologic CR rates were significantly higher with intensity-modulated/volumetric-modulated arc RT (IMRT/VMAT, p = 0.007), simultaneous boost (p = 0.020), dose escalation (Biological equivalent dose > 74 Gy, p = 0.035), and the combination of induction and consolidation chemotherapy (p = 0.023). No significant associations were found for clinical CR or LRR.

Conclusion

While rectal RT boost is already part of real-world practices, the wide heterogeneity in techniques highlights the urgent need for standardisation. Our meta-analysis suggests that IMRT/VMAT, simultaneous boost, and dose escalation are associated with higher pathological CR rates and should be considered in future rectal boost guidelines. These findings, however, warrant careful interpretation due to the absence of adjustments for clinical, tumoral, or patient-related parameters that may also influence response rate and oncological outcomes.