Outcomes with definitive radiotherapy among patients with locally advanced cervical cancer with relative or absolute contraindications to cisplatin: A systematic review and meta-analysis

Background. The standard treatment for locally advanced cervical cancer (LACC) is chemoradiation (CRT) with cisplatin, followed by brachytherapy, but is less defined for cisplatin-intolerant patients. We synthesized evidence on treatment outcomes with definitive radiotherapy (RT) with or without chemotherapy (ChT) in these patients.Methods. We performed a systematic search and included 20 relevant studies. We extracted data on response, survival, compliance, and toxicity, and performed meta-analyses of outcome rates and risk ratios. Sensitivity and subgroup analyses were performed to explore sources of heterogeneity. Meta-regression was performed to examine the effects of other variables.Results. Due to lack of comparative data, most comparisons were indirect and derived from the proportional meta-analyses. Complete response (85%) and survival (62% 5yOS) rates are comparable to those published for LACC without contraindications to cisplatin. Survival rate is better with CRT than RT alone (5yOS, 73% vs 58%), and with nodal boost (NB) than without (5yOS, 71% vs 56%). Carboplatin CRT is associated with lower 5yOS (44%) but better ChT compliance (86%) when compared to other interventions. ChT compliance is better in renal failure than elderly cohorts (89% vs 67%). RT compliance is lower with CRT than RT alone (90% vs 96%), and higher with NB than none (96% vs 93%). NB is associated with lower RT compliance than no NB, when ChT is given. Meta-regression results affirm ChT and NB to be significant positive factors for survival, and NB, which is associated with greater use of advanced RT techniques, for RT compliance. Conclusion. For those with relative contraindications, cisplatin CRT is effective and well-tolerated. For those with absolute contraindications, carboplatin is well-tolerated but with unclear effectiveness. Nodal boost is effective and well-tolerated, but is less tolerated when concurrent ChT is given.(c) 2022 Elsevier Inc. All rights reserved.

Automated summary

This study synthesized evidence on treatment outcomes with radiotherapy (RT) with or without chemotherapy (ChT) in locally advanced cervical cancer (LACC) patients who are intolerant to cisplatin. The results showed that the complete response rate and survival rate in these patients were comparable to those without contraindications to cisplatin. Chemoradiation therapy (CRT) had a better survival rate than RT alone, and nodal boost (NB) improved survival rate compared to no NB. Carboplatin CRT had lower survival rate but better ChT compliance compared to other interventions. ChT compliance was better in renal failure patients than elderly cohorts. RT compliance was lower with CRT than RT alone, and higher with NB than no NB. Meta-regression analysis indicated that ChT and NB were significant positive factors for survival, and NB was associated with better RT compliance.