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Cancer Genomics and Diagnostics / Bladder and Urothelial Cancer Treatments · Journal article
JAMA Network Open · September 8, 2026
Well-designed and adequately powered for the question it asks.
This systematic review and meta-analysis of 38 phase 3 randomized trials comprising 31,721 patients demonstrates that immune checkpoint inhibitors significantly improve overall survival (HR 0.83) and disease-free survival (HR 0.73) in curative-intent solid tumor treatment without statistically significant sex-based differences, although females are substantially underrepresented. Neoadjuvant or perioperative ICI administration showed superior outcomes compared to adjuvant-only use, supporting broader adoption of earlier treatment timing.
Systematic review and meta-analysis of randomized phase 3 clinical trials. Randomized phase 3 clinical trials investigating ICI treatment in non–sex-specific solid cancer types in curative settings, including surgery and radiotherapy or chemoradiotherapy as local therapies.. Intervention: Immune checkpoint inhibitors (ICIs) administered in curative-intent settings; timing analyzed as neoadjuvant/perioperative or adjuvant-only. Compared with: Standard of care or active control arms in included randomized trials. n = 31,721.
ICIs improved OS overall with HR 0.83 (95% CI, 0.79–0.89; P <.001) and combined disease-free/event-free/progression-free/recurrence-free endpoints with HR 0.73 (95% CI, 0.68–0.77; P <.001) No statistically significant OS difference by sex: females HR 0.76 (95% CI, 0.67–0.86) vs. males HR 0.78 (95% CI, 0.72–0.85) No statistically significant combined endpoint difference by sex: females HR 0.74 (95% CI, 0.69–0.79) vs. males HR 0.73 (95% CI, 0.67–0.78)
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
Clinicians should recognize that ICIs provide substantial OS and disease-free survival benefits in curative solid tumor treatment without sex-based differences in efficacy. The superiority of neoadjuvant or perioperative timing over adjuvant-only administration supports consideration of earlier ICI integration into treatment protocols. The significant underrepresentation of female patients (29.7%) warrants caution in generalizing findings to women and highlights a need for more balanced recruitment in future trials.
Large, rigorous meta-analysis of 38 randomized phase 3 trials with 31,721 patients showing statistically significant OS and disease-free survival benefits from ICIs in curative solid tumors, with no sex difference detected, though female underrepresentation limits generalizability.
As stated by the source record.
Quoted from the source exactly as published.
Clinicians should recognize that ICIs provide substantial OS and disease-free survival benefits in curative solid tumor treatment without sex-based differences in efficacy. The superiority of neoadjuvant or perioperative timing over adjuvant-only administration supports consideration of earlier ICI integration into treatment protocols. The significant underrepresentation of female patients (29.7%) warrants caution in generalizing findings to women and highlights a need for more balanced recruitment in future trials.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Importance The impact of sex on the efficacy of immune checkpoint inhibitors (ICIs) in curative treatments of solid tumors remains insufficiently explored. Optimal timing of ICIs is clinically relevant, with practice shifting toward broader adoption of neoadjuvant approaches. Objective To assess the association of patient sex and treatment timing with outcomes of ICI administration in curative treatments for solid tumors. Data Sources In this systematic review and meta-analysis, MEDLINE, Embase, the Cochrane Library, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform were systematically searched from January 1, 2010, to June 23, 2025, using controlled vocabulary combined with free-text search terms. A manual search in PubMed was conducted through August 10, 2025. Study Selection Reports of randomized phase 3 clinical trials investigating ICI treatment in non–sex-specific solid cancer types in curative settings, including surgery and radiotherapy or chemoradiotherapy as local therapies, were included. Data Extraction and Synthesis Three authors were involved in data abstraction; data from each record were extracted independently by 2 of these 3 authors. Hazard ratios (HRs) and corresponding 95% CIs were calculated using random-effects meta-analysis. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Main Outcomes and Measures Pooled HRs for overall survival (OS) and for time to the combined end point of disease-free, event-free, progression-free, and recurrence-free survival were analyzed overall, by sex, and by treatment timing relative to surgery. Results A total of 62 reports of 38 trials comprising 31 721 patients (29.7% female and 70.3% male) were analyzed. ICIs were associated with improvement in OS (HR, 0.83; 95% CI, 0.79-0.89; P <.001) and the combined end points (HR, 0.73; 95% CI, 0.68-0.77; P <.001). No statistically significant sex-specific differences were observed for OS (females: HR, 0.76 [95% CI, 0.67-0.86]; males: HR, 0.78 [95% CI, 0.72-0.85]) or the combined end points (females: HR, 0.74 [95% CI, 0.69-0.79]; males: HR, 0.73 [95% CI, 0.67-0.78]). Neoadjuvant or perioperative ICIs were associated with better OS (HR, 0.77 [95% CI, 0.69-0.86]) and combined end point outcomes (HR, 0.64 [95% CI, 0.57-0.73]) compared with adjuvant-only use (OS: HR, 0.84 [95% CI, 0.78-0.91]; combined end points: HR, 0.74 [95% CI, 0.68-0.81]). Conclusions and Relevance This systematic review and meta-analysis detected no statistically significant difference in survival outcomes associated with ICIs by patient sex, although female patients were underrepresented. In exploratory analyses, neoadjuvant or perioperative ICIs were associated with superior survival outcomes compared with strictly adjuvant administration, a finding that supports increased adoption of neoadjuvant ICI therapy approaches.
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