Low blood levels of LRG1 before radical prostatectomy identify patients with high risk of progression to castration-resistant prostate cancer

Ingrid Jenny Guldvik, Peder Rustøen Braadland, Shivanthe Sivanesan, Håkon Ramberg, Gitte Kristensen, Pierre Tennstedt, Andreas Røder, Thorsten Schlomm, Viktor Berge, Lars Magne Eri, Wolfgang Lilleby, Ian G. Mills, Kristin Austlid Taskén

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Abstract

Background
After radical prostatectomy (RP), depending on stage, up to 40% of patients with prostate cancer (PCa) will experience biochemical failure (BF). Despite salvage therapy, approximately one-third of these patients will need permanent hormone therapy (pHT) and are at risk of progression to castration-resistant PCa (CRPC). Prognostic markers herald the need for neoadjuvant, adjuvant, or multimodal treatment.

Objective
To evaluate the added value of blood LRG1 in predicting treatment failure in patients who have undergone radical prostatectomy (RP).

Design, setting, and participants
We quantified LRG1 in serum or plasma sampled before radical prostatectomy from patients from the Martini-Klinik (Martini; n = 423), the Danish CuPCa cohort (CuPCa; n = 182), and Oslo University Hospital (OUH; n = 145).

Outcome measurements and statistical analysis
The endpoints were BF, pHT, and CRPC. The association between LRG1 and survival outcomes was evaluated using Kaplan-Meier estimation and Cox proportional-hazards modeling. The added predictive value of LRG1 in nested models was estimated using the concordance index, time-dependent area under the receiver operating characteristic curve, and decision curve analysis.

Results and limitations

In multivariable Cox models using preoperative characteristics, LRG1 was associated with an estimated lower risk of BF in the Martini cohort (adjusted hazard ratio [aHR] 0.68, 95% confidence interval [CI] 0.52–0.90) and in the CuPCa cohort (aHR 0.47, 95% CI 0.30–0.73). Using preoperative prognostic variables, our data showed that doubling of LRG1 was also associated with a lower risk of pHT receipt in the CuPCa cohort (aHR 0.43, 95% CI 0.20–0.93) and of CRPC development in the OUH cohort (aHR 0.32, 95% CI 0.15–0.69). Similar aHR values were observed using either preoperative or postoperative variables for all endpoints.

Conclusions
PCa patients with high blood LRG1 are at lower risk of BF, pHT receipt, and progression to CRPC. Since LRG1 adds value to established prognostic models, new prognostic factor combinations including LRG1 should be considered in future studies.

Patient summary
We measured concentrations of the blood-based protein LRG1 before surgery for prostate cancer. Patients with high LRG1 levels had better disease-free survival, suggesting that LRG1 can help in predicting prognosis.
Original languageEnglish
Pages (from-to)68-75
Number of pages8
JournalEuropean Urology Open Science
Volume45
Early online date04 Oct 2022
DOIs
Publication statusPublished - Nov 2022
Externally publishedYes

Keywords

  • Biomarkers
  • Castration resistance
  • Hormone treatment
  • Noninvasive
  • LRG1
  • Prostate cancer
  • Radical prostatectomy
  • Surgery
  • Treatment resistance

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