Key result
Administration of cisplatin with definitive radiotherapy in women aged ≥65 years was associated with a significant reduction in 5-year cancer-specific mortality compared to radiotherapy alone (31% vs 39%; adjusted HR 0.72).
Why the study?
Older women are underrepresented in cervical cancer clinical trials, leading to uncertainty regarding the benefit of adding cisplatin to definitive radiotherapy in women aged ≥65 years.
Does cisplatin added to definitive radiotherapy reduce cancer-specific mortality in women aged ≥65 years with nonmetastatic cervical cancer?
Cohort (n=826)
Yes
Does cisplatin added to definitive radiotherapy reduce cancer-specific mortality in women aged ≥65 years with nonmetastatic cervical cancer?
Hazard Ratio: 0.72 (95% CI 0.54–0.96)
Absolute Event Rate: 31% vs 39%
Absolute Risk Reduction: 8%
p-value: p=0.02
Administration of cisplatin with definitive radiotherapy in women aged ≥65 years with cervical cancer is associated with a significant reduction in cancer-specific mortality, provided at least 5 cycles are received.
May support adding cisplatin to RT in fit older patients; leaves open need for randomized confirmation.
BACKGROUND: Cisplatin with definitive radiotherapy (RT) is considered the standard of care for cervical cancer; however, older women are frequently undertreated and have worse outcomes compared with younger patients. Because women aged ≥65 years have been disproportionately underrepresented in clinical trials, uncertainties exist regarding how much they benefit from the addition of cisplatin to RT. PATIENTS AND METHODS: Women aged ≥65 years with nonmetastatic cervical cancer treated with definitive external-beam RT and brachytherapy were identified in the SEER-Medicare database. Death attributable to cervical cancer (cancer-specific mortality [CSM]) was evaluated against competing risks of death using Gray's test. Propensity score analysis and the Fine-Gray multivariable regression model were used to adjust for baseline differences, including comorbidity. RESULTS: The total cohort comprised 826 patients, of whom 531 (64%) received cisplatin, 233 (28%) were FIGO stage I, 374 (45%) were stage II, and 219 (27%) were stage III-IVA. Older age and chronic kidney disease significantly predicted omission of cisplatin. Virtually all cisplatin dosing was weekly, with a median of 5 cycles. Death from cervical cancer was significantly lower with cisplatin than without (5-year CSM, 31% vs 39%; P=.02; adjusted hazard ratio, 0.72; P=.02), which persisted in propensity score analysis. Receiving ≥5 cycles was required for benefit, as no difference in CSM was seen in patients receiving 1 to 4 cycles versus no cisplatin. Subgroup analyses revealed that the benefit of cisplatin persisted in women aged ≥75 years and those with early-stage disease. Incidence of cytopenia, nausea/vomiting, and hypovolemia increased in patients treated with cisplatin. CONCLUSIONS: Administration of cisplatin with definitive RT in women aged ≥65 years was associated with a significant benefit in the incidence of death attributable to cervical cancer, despite competing risks for mortality in an older population. Receiving at least 5 cycles of weekly cisplatin was required for benefit.
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Xiang et al. (2019) conducted a cohort in Nonmetastatic cervical cancer (n=826). Cisplatin with definitive radiotherapy vs. Definitive radiotherapy without cisplatin was evaluated on Death attributable to cervical cancer (cancer-specific mortality) (adjusted HR 0.72, 95% CI 0.54-0.96, p=0.02). Administration of cisplatin with definitive radiotherapy in women aged ≥65 years was associated with a significant reduction in 5-year cancer-specific mortality compared to radiotherapy alone (31% vs 39%; adjusted HR 0.72).
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