Neoadjuvant and Adjuvant Chemotherapy for Variant Histology Bladder Cancers: A Systematic Review and Meta-Analysis

Abstract

ContextTo improve the prognosis of variant histology (VH) bladder cancers, clinicians have used neoadjuvant chemotherapy (NAC) or adjuvant chemotherapy (AC) on the basis of radical cystectomy (RC). Despite some new data, the evidence remains mixed on their efficacy.ObjectiveTo update the current evidence on the role of NAC and AC for VH bladder cancers.Evidence AcquisitionWe searched for all studies investigating NAC or AC for bladder cancer patients with variant histology in PubMed, Embase, and the Cochrane Central Register of Controlled Trials up to December 2021. The primary end points were recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS).Evidence SynthesisWe identified 18 reports comprising a total of 10,192 patients in the NAC studies. In patients with VH, the use of NAC did improve CSS (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.55–0.99, p = 0.044), and OS (HR 0.74, 95% CI 0.66–0.84, p = 0.000), but not RFS (HR 1.15, 95% CI 0.56–2.33, p = 0.706). Subgroup analyses demonstrated that receiving NAC was associated with better OS in sarcomatoid VH (HR 0.67, 95% CI 0.54–0.83, p = 0.000) and neuroendocrine VH (HR 0.54, 95% CI 0.43–0.68, p = 0.000). For AC, we identified eight reports comprising a total of 3254 patients. There was a benefit in CSS (HR 0.61, 95% CI 0.43–0.87, p = 0.006) and OS (HR 0.76, 95% CI 0.60–0.98, p = 0.032). Subgroup analyses demonstrated that only neuroendocrine VH had better CSS (HR 0.29, 95% CI 0.13–0.67, p = 0.174) when receiving AC.ConclusionsNAC or AC for VH bladder cancers confers an OS and CSS benefit compared with RC alone. For NAC, the benefit was independently observed in the sarcomatoid and neuroendocrine subgroups. As for AC, only neuroendocrine subgroups improved CSS.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021289487.

Neoadjuvant Cisplatin, Gemcitabine, and Docetaxel in Sarcomatoid Bladder Cancer: Clinical Activity and Whole Transcriptome Analysis

“…While the benefit of NAC in SBC has been inconsistent in prior small, singular retrospective studies, a recent examination of SEER population-based data suggests patients with metastatic SBC who receive chemotherapy derive OS benefit [8][9][10][11]36]. Furthermore, in a meta-analysis assessing the role of NAC or adjuvant chemotherapy in patients with bladder cancer with histologic subtypes, an OS benefit was observed in patients with SBC treated with NAC, but not adjuvant chemotherapy [14]. Similar to the patients with SBC treated with NAC in our cohort, the majority of patients in prior studies had clinical T2-T3 stage tumors [3,4,10].…”

“…Retrospective analyses suggest an improvement in overall survival (OS) in SBC patients treated with neoadjuvant chemotherapy (NAC) prior to RC compared to RC alone [8][9][10][11][12][13]. A metaanalysis has demonstrated a statistically significant 33% improvement in OS among patients with SBC who received NAC [14]. Similarly, a systemic review of NAC in patients with UC histological subtypes concluded that NAC may be beneficial to patients with SBC [15].…”

Small cell bladder carcinoma treated with nivolumab as adjuvant maintenance therapy

“…Pathological findings showed tumour degeneration, so additional adjuvant chemotherapy was performed. Zhu et al reported that only patients with neuroendocrine variant bladder cancer histology who received adjuvant chemotherapy showed a treatment benefit compared with patients who underwent surgery alone 7. Treatment algorithms have been extrapolated from the treatment of small cell cancer arising in the lung and often involved chemotherapy regimens using a platinum agent.…”

“…Most commonly, treatment approaches are surgical resection together with strategies that appear to have the best outcomes, including NAC followed by radical cystectomy 5. The efficacy of the programmed death-1 immune checkpoint inhibitor (ICI) antibody, nivolumab, as adjuvant therapy, has been reported in patients with muscle-invasive urothelial carcinoma following radical surgery; however, the efficacy of adjuvant maintenance therapy for variant histology bladder cancer remains uncertain 67. We report a unique case of a patient with advanced SCBC treated with nivolumab as adjuvant maintenance therapy.…”