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.