Prognostic and Predictive Role of SPOP Mutations in Prostate Cancer: A Systematic Review and Meta-analysis

Martino Pedrani; Giuseppe Salfi; Sara Merler; Irene Testi; Massimiliano Cani; Fabio Turco; Elena Trevisi; Luigi Tortola; Giorgio Treglia; Gian Luca Di Tanna; Ursula Vogl; Silke Gillessen; Jean-Philippe Theurillat; Ricardo Pereira Mestre

doi:10.1016/j.euo.2024.04.011

Prognostic and Predictive Role of SPOP Mutations in Prostate Cancer: A Systematic Review and Meta-analysis

Eur Urol Oncol. 2024 May 3:S2588-9311(24)00103-2. doi: 10.1016/j.euo.2024.04.011. Online ahead of print.

Authors

Affiliations

¹ Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland; Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy.
² Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland; Institute of Oncology Research (IOR), Bellinzona, Switzerland.
³ Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland; Institute of Oncology Research (IOR), Bellinzona, Switzerland; Section of Innovation Biomedicine - Oncology Area, Department of Engineering for Innovation Medicine, University of Verona and Verona University Hospital Trust, Verona, Italy; Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.
⁴ Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland; Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
⁵ Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland; Oncology Unit, Department of Oncology, University of Turin, S. Luigi Gonzaga Hospital, Orbassano, Italy.
⁶ Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland.
⁷ Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland; Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland; Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
⁸ Department of Business Economics, Health and Social Care, University of Applied Sciences and Arts of Southern Switzerland, Manno, Switzerland.
⁹ Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland; Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.
¹⁰ Institute of Oncology Research (IOR), Bellinzona, Switzerland; Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.
¹¹ Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland; Institute of Oncology Research (IOR), Bellinzona, Switzerland; Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland; Clinical Research Unit, myDoctorAngel Sagl, Bioggio, Switzerland. Electronic address: ricardo.pereiramestre@eoc.ch.

PMID: 38704358
DOI: 10.1016/j.euo.2024.04.011

Abstract

Context: Mutations in the speckle-type POZ (SPOP) gene are frequently identified in prostate cancer (PC); yet, prognostic implications for affected patients remain unclear. Limited consensus exists regarding tailored treatments for SPOP-mutant (SPOPmut) PC.

Objective: To elucidate the prognostic and predictive significance of SPOP mutations across distinct PC stages and treatments.

Evidence acquisition: A systematic literature search of PubMed, Embase, and Scopus was conducted up to January 29, 2024. The meta-analysis included studies comparing survival outcomes between SPOPmut and SPOP wild-type (SPOPwt) PC.

Evidence synthesis: From 669 records, 26 studies (including five abstracts) were analyzed. A meta-analysis of metastasis-free survival in localized (hazard ratio [HR]: 0.72, 95% confidence interval [CI]: 0.59-0.88; p < 0.01) and overall survival (OS) in metastatic PC (HR: 0.64, 95% CI: 0.53-0.76; p < 0.01) showed a favorable prognosis for patients with SPOPmut PC. In metastatic settings, SPOP mutations correlated with improved progression-free survival (PFS) and OS in patients undergoing androgen deprivation therapy ± androgen receptor signaling inhibitor (HR: 0.51, 95% CI: 0.35-0.76, p < 0.01, and HR: 0.60, 95% CI:0.46-0.79, p < 0.01, respectively). In metastatic castration-resistant PC, only abiraterone provided improved PFS and OS to patients with SPOP mutations compared with patients with SPOPwt, but data were limited. SPOP mutations did not correlate with improved PFS (p = 0.80) or OS (p = 0.27) for docetaxel.

Conclusions: Patients with SPOPmut PC seem to exhibit superior oncological outcomes compared with patients with SPOPwt. Tailored risk stratification and treatment approaches should be explored in such patients.

Patient summary: Speckle-type POZ (SPOP) mutations could be a favorable prognostic factor in patients with prostate cancer (PC) and may also predict better progression-free and overall survival than treatment with hormonal agents. Therefore, less intensified treatments omitting chemotherapy for patients with SPOP-mutant PC should be explored in clinical trials.

Keywords: Abiraterone; Androgen deprivation treatment; Docetaxel; Meta-analysis; Predictive; Prostate cancer; Speckle-type POZ; Survival; Systematic review.

Publication types

Review