Session Item

In locally advanced cervical cancer (LACC), the addition of concurrent chemotherapy (ChT) to RT is associated with a 6% 5yOS benefit (10% in stage IB/IIA; 7%, IIB; 3%, IVA). In primary CRT, the 7.5% OS benefit is with an 11.5% increase in grade ≥3 toxicity. Per the NCCN guidelines, the standard agent is cisplatin; the preferred alternative is carboplatin. For cisplatin-intolerant patients, who are underrepresented in trials, the increased toxicity risk due to advanced age, comorbidity or frailty, could offset the survival benefit. We synthesized evidence on treatment outcomes with definitive RT alone or with ChT in these patients.

We performed a systematic search on PubMed, EBSCOHost, and EuropePMC, and screened relevant studies that reported on patients treated from 1990 onwards. We extracted data on response, survival, compliance, and toxicity, and performed meta-analyses of outcome rates and risk ratios. Sensitivity, subgroup,  and meta-regression analyses were performed to elucidate heterogeneity. (PROSPERO Reg. No. CRD42022314067)

The 20 eligible studies (RCT, 1: single-arm trial, 1; prospective cohort, 3; retrospective cohort, 15) from the Asia-Pacific (13), South America (3), North America (2), Europe (1), and Oceania (1), included cases treated from 1992 to 2016. Twelve were elderly cohorts, one, a renal failure cohort, and seven, with mixed contraindications (age, renal failure, poor PS, comorbidity, etc). Five interventions were represented: standard CRT (weekly cisplatin)(4); modified CRT (standard RT with ChT other than weekly cisplatin)(11); standard RT alone (11); modified RT (1); and standard ChT with modified RT (1). Nodal boost (NB) was used in 5 studies.

Pooled complete response (85%) and 5yOS (62%) rates are comparable to those published for LACC patients without contraindications. Subgroup analyses showed that 5yOS is better with ChT than none (73% vs 58%), and with NB than none (71% vs 56%), and lowest for carboplatin CRT (44%) despite better ChT compliance (86%). ChT compliance is better in renal failure than elderly cohorts (89% vs 67%). RT compliance is lower with ChT than none (90% vs 96%), and higher with NB than none (96% vs 93%). When ChT is given, NB is associated with lower RT compliance than no NB.

Meta-regression analyses confirm ChT and NB to be significant positive factors for survival, and NB, for RT compliance, partly due to its association with the use of advanced RT (3DCRT, IMRT) techniques.

In LACC patients with relative contraindications, concurrent cisplatin is effective and well-tolerated. In those with absolute contraindications, carboplatin is well-tolerated but with unclear effectiveness. NB is effective but may lower compliance when given with concurrent ChT.

References

Datta NR, et al. Gynecol Oncol. 2017 May;145(2):374-385

Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration. J Clin Oncol. 2008. 26(35), 5802–5812