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
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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