Quantifying the absolute benefit of neoadjuvant chemotherapy followed by definitive therapy in patients with muscle-invasive bladder cancer: A systematic review and meta-analysis.

Authors

null

Waleed Ikram

Mayo Clinic, Phoenix, AZ

Waleed Ikram , Syed Arsalan Ahmed Naqvi , Ammad Raina , Ezza Fatima , Rabbia Siddiqi , Mahnoor Islam , Noureen Asghar , Kaneez Zahra Rubab Khakwani , Ahsan Masood Khan , Syed A. Hussain , Alan Haruo Bryce , Irbaz Bin Riaz , Parminder Singh

Organizations

Mayo Clinic, Phoenix, AZ, Midwestern University, Sierra Vista, AZ, UPMC Mckeesport, Mckeesport, PA, Dow University of Health Sciences, Karachi, Pakistan, University of Arizona, Tucson, AZ, The University of Arizona, Tucson, AZ, University of Michigan, Detroit, MI, University of Sheffield and Sheffield Teaching Hospitals, Sheffield, United Kingdom, Mayo Clinic Arizona, Phoenix, AZ, Department of Oncology, Mayo Clinic, Phoenix, AZ

Research Funding

No funding received

Background: Cisplatin based neoadjuvant chemotherapy (NAC) followed by definitive therapy improves survival in patients with muscle invasive bladder cancer (MIBC). However, the clinical benefit of NAC might vary with the choice of definitive therapy. Therefore, we assessed the absolute benefit of NAC followed by radical cystectomy or radical radiotherapy separately using the totality of evidence. Methods: MEDLINE and EMBASE were systematically searched to identify randomized trials assessing cisplatin based neoadjuvant chemotherapy followed by either radical cystectomy or definitive radiotherapy in patients with MIBC. Outcomes of interest included overall survival (OS) and disease-free survival (DFS). Treatment effects were expressed as hazard ratios (HR) with 95% confidence interval (CI). Incidence rate ratios were calculated to estimate time to event outcomes for trials not reporting HR. A random-effects DerSimonian-Laird meta-analysis was conducted. Absolute effects were then obtained using baseline risks from the control arm of RCTs. Results: Of 4887 studies identified, 13 trials with 2529 patients were included in this meta-analysis. Most trials included patients with T2-4 and N0 patients and only 3 trials included patients with node positive disease. Total of 180 (47%) DFS events were observed with NAC+RC compared to 213 (56%) events in RC alone (HR: 0.72; 95% CI: 0.59-0.89) and 346 (58%) OS events were observed with NAC+ RC compared to 385 (52%) events in RC alone (HR: 0.80; 95% CI: 0.69-0.92). Total of 186 (70%) DFS events were observed with NAC + radiotherapy compared to 205 (71%) events in radiotherapy alone (HR: 0.91; 95% CI: 0.74-1.12) and 263 (58%) OS events were observed with NAC+ radiotherapy compared to 294 (61%) events in radiotherapy alone (HR:0.93; 95% CI: 0.79-1.08). Conclusions: The choice of definitive therapy after cisplatin-based NAC impacts survival in patients with MIBC. RC after NAC improved DFS (114 fewer events per 1000 events) and OS (76 fewer per 1000 events) whereas radiotherapy after NAC showed no survival benefit.

Outcome
Studies (Participants)
Relative effect
Anticipated absolute effects
Risk with Radical cystectomy
Risk difference with Neoadjuvant Chemotherapy
OS
8 (1511)
HR 0.80 (0.69 to 0.92)
528 per 1,000
76 fewer per 1,000 (from 124 fewer to 28 fewer)
DFS
5 (765)
HR 0.72 (0.59 to 0.87)
563 per 1,000
114 fewer per 1,000 (from 177 fewer to 50 fewer)
Risk with Radical radiotherapy
Risk difference with Neoadjuvant Chemotherapy
OS
6 (1018)
HR 0.93 (0.79 to 1.08)
632 per 1,000
27 fewer per 1,000 (from 86 fewer to 28 more)
DFS
2 (520)
HR 0.91 (0.74 to 1.12)
734 per 1,000
66 fewer per 1,000 (from 191 fewer to 88 more)

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Abstract Details

Meeting

2022 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Genitourinary Cancer—Kidney and Bladder

Track

Genitourinary Cancer—Kidney and Bladder

Sub Track

Urothelial Cancer - Local-Regional Disease

Citation

J Clin Oncol 40, 2022 (suppl 16; abstr 4594)

DOI

10.1200/JCO.2022.40.16_suppl.4594

Abstract #

4594

Poster Bd #

85

Abstract Disclosures