Intensification of Systemic Therapy in Addition to Definitive Local Treatment in Nonmetastatic Unfavourable Prostate Cancer: A Systematic Review and Meta-analysis
Language English Country Switzerland Media print-electronic
Document type Journal Article, Meta-Analysis, Review, Systematic Review, Research Support, Non-U.S. Gov't
PubMed
35465985
DOI
10.1016/j.eururo.2022.03.031
PII: S0302-2838(22)01802-4
Knihovny.cz E-resources
- Keywords
- Abiraterone, Chemotherapy, Docetaxel, Enzalutamide, Prostate cancer, Radiation therapy, Radical prostatectomy,
- MeSH
- Androgen Antagonists adverse effects MeSH
- Docetaxel therapeutic use MeSH
- Humans MeSH
- Prostatic Neoplasms * drug therapy pathology MeSH
- Prospective Studies MeSH
- Antineoplastic Agents * therapeutic use MeSH
- Antineoplastic Combined Chemotherapy Protocols therapeutic use MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Meta-Analysis MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Systematic Review MeSH
- Names of Substances
- Androgen Antagonists MeSH
- Docetaxel MeSH
- Antineoplastic Agents * MeSH
CONTEXT: Several recent randomised trials have evaluated the role of combination systemic treatment using androgen deprivation therapy (ADT) plus chemotherapy or an androgen receptor signaling inhibitor (ARSI) in patients with high-risk and/or unfavourable nonmetastatic prostate cancer (nmPC). OBJECTIVE: To assess the outcomes associated with adding combination systemic treatment to primary definitive local therapy in patients with high-risk and/or unfavourable nmPC. EVIDENCE ACQUISITION: We queried the PubMed, Web of Science, and Scopus databases and conference abstracts to identify prospective randomised trials examining the value of adding chemotherapy or an ARSI to ADT and primary local therapy with curative intent for nmPC. The primary endpoints were overall survival (OS), cancer-specific survival (CSS), metastasis-free survival (MFS), and failure-free survival (FFS). Secondary endpoints included adverse events (AEs) and pathologic outcomes. EVIDENCE SYNTHESIS: We identified 15 randomised studies, of which nine evaluated chemohormonal and six investigated ARSI-based treatment strategies. In both radical prostatectomy (RP) and radiation therapy (RT) settings, addition of docetaxel to ADT was associated with significantly better CSS (pooled hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.49-0.95; p = 0.025), MFS (pooled HR 0.82, 95% CI 0.71-0.95; p = 0.008), and FFS (pooled HR 0.70, 95% CI 0.62-0.79; p < 0.001); the difference did not meet the conventional level of statistical significance for OS (pooled HR 0.86, 95% CI 0.73-1.01; p = 0.072). For patients treated with RT alone, docetaxel-based combination treatment did not meet the significance threshold set for OS (p = 0.3), CSS (p = 0.072), or MFS (p = 0.079), but the difference for FFS was statistically significant (pooled HR 0.72, 95% CI 0.63-0.84; p < 0.001). On network meta-analyses including RT studies, ARSI + ADT outperformed docetaxel + ADT for survival endpoints and had a more favourable AE profile. CONCLUSIONS: Intensification of systemic therapy with docetaxel or an ARSI in addition to ADT improves oncologic endpoints in high-risk and/or unfavourable nmPC treated with local definitive therapy. The highest efficacy was achieved with ARSI + ADT, specifically in patients treated with RT. PATIENT SUMMARY: Our findings highlight that selected patients with high-risk nonmetastatic prostate cancer benefit from intensification of systemic therapy beyond hormonal treatment.
Department of Medical Oncology Institut Bergonié Bordeaux France
Department of Pathology Hôpital Tenon Sorbonne University Paris 6 Paris France
Department of Urology La Croix du Sud Hospital Quint Fonsegrives France
Department of Urology Medical University of Silesia Zabrze Poland
Department of Urology Medical University of Vienna Vienna Austria
Department of Urology St Antonius Hospital Nieuwegein the Netherlands
Department of Urology University Hospital Schleswig Holstein Lübeck Germany
Department of Urology University Hospitals Leuven Leuven Belgium
Department of Urology Yale School of Medicine New Haven CT USA
Unit of Urology Division of Oncology IRCCS San Raffaele San Raffaele Hospital Milan Italy
References provided by Crossref.org
Prostate cancer risk, screening and management in patients with germline BRCA1/2 mutations
