Metastatic castration-resistant prostate cancer (mCRPC) has become one of the major settings where precision oncology directly influences treatment decisions. The emergence of PARP inhibitors has provided a targeted therapeutic option for patients harboring homologous recombination repair alterations, particularly BRCA1/2 mutations. However, while clinical trials established the efficacy of olaparib, less is known about how genomic testing and PARP inhibitor treatment are implemented in routine clinical practice.
Published on May 9, 2026, in Drugs – Real World Outcomes, the study evaluated real-world genomic testing patterns, olaparib utilization, and outcomes in patients with BRCA-mutated metastatic castration-resistant prostate cancer using data from the Dutch CAPRI-3 registry.
Title: From Genomic Testing to Olaparib Treatment: Real-World Utilization and Outcomes in BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer
Authors: Dianne Bosch, Kim J. M. van der Velden, Aart Beeker, Hendrik P. van den Berg, André M. Bergman, Maarten J. van der Doelen, Alfons J. M. van den Eertwegh, Mathijs P. Hendriks, Thomas M. A. Kerkhofs, Addy C. M. van de Luijtgaarden, Niven Mehra, Reindert J. A. van Moorselaar, Metin Tascilar, Walter L. Vervenne, Nir I. Weijl, Carin A. Uyl-de Groot, Peter F. A. Mulders, Malou C. P. Kuppen, and Inge M. van Oort.
Why This Study Matters
Olaparib became the first approved PARP inhibitor for mCRPC after the PROfound trial demonstrated improved radiographic progression-free survival and overall survival in the BRCA-mutated subgroup compared with physician’s choice of a second androgen receptor pathway inhibitor.
Still, randomized trials often enroll highly selected patient populations. Real-world practice can differ substantially because of variations in genomic testing access, patient selection, comorbidities, and treatment sequencing. The authors therefore aimed to investigate how genomic testing is being applied in clinical practice across the Netherlands and how patients treated with olaparib perform outside of clinical trials.
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How the Analysis Was Conducted
This retrospective analysis used data from the CAPRI-3 registry, which includes patients diagnosed with metastatic castration-resistant prostate cancer between 2016 and 2021 across ten Dutch hospitals. Follow-up continued until death or database cut-off on January 7, 2024.
Patients receiving olaparib as part of routine clinical care after national approval in November 2020 were eligible for analysis. Patients treated through compassionate use programs or clinical trials were excluded. The investigators evaluated genomic testing prevalence, frequency of HRR alterations, and clinical outcomes with olaparib. The primary endpoint was overall survival, while secondary endpoints included progression-free survival, radiographic progression-free survival, PSA response, and occurrence of progressive disease.
Patients treated with olaparib were divided into two groups: those who received olaparib before taxane chemotherapy and those treated after taxane exposure.
Key Real-World Findings
The registry included 1,996 patients with metastatic castration-resistant prostate cancer. Genomic testing was performed in only 467 patients, representing 23.4% of the overall cohort. Importantly, testing rates differed markedly between hospitals, ranging from 3.8% to 63.2%, with a single university medical center accounting for the majority of tested patients.
Patients who underwent genomic testing were generally younger, had fewer comorbidities, and more frequently received intensified treatment earlier in the disease course. Among the 467 tested patients, HRR alterations were identified in 22.9% (107 patients), while BRCA mutations were found in 53 patients — roughly 11% of those tested. Most BRCA alterations involved BRCA2.
Overall, 81 patients had received olaparib since 2018, with follow-up continuing until death or the database cut-off on January 7, 2024. After excluding patients treated through clinical trials or compassionate use, 27 patients with BRCA-mutated mCRPC who received standard-of-care olaparib after national approval on November 1, 2020 remained eligible for the efficacy analysis. Notably, of the 35 BRCAm patients alive at the time of national approval, 27 (77.1%) received olaparib, indicating that most identified eligible patients received olaparib after national approval.
Median overall survival in the olaparib-treated cohort was 13.4 months. Outcomes differed substantially according to prior taxane exposure: patients who received olaparib before taxane chemotherapy had a median overall survival of 28.7 months, compared with 10.5 months in post-taxane patients. Median progression-free survival was 8.0 months overall, reaching 21.1 months in taxane-naïve patients versus 4.6 months in post-taxane patients. Median radiographic progression-free survival was 12.7 months overall. Median duration of olaparib treatment was 8.8 months, with four patients remaining on treatment at the time of database cutoff.
PSA responses also favored the earlier treatment setting, with a PSA50 response observed in 75% of taxane-naïve patients compared with 21.1% of post-taxane patients. The authors additionally noted poorer survival outcomes in patients who had previously received platinum-based chemotherapy, with a median overall survival of 7.3 months in that group versus 20.1 months in those without prior platinum exposure.
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What the Findings Suggest
One of the most important findings of the study was the substantial variability in genomic testing implementation across centers. Although international guidelines increasingly support germline and somatic testing in metastatic prostate cancer, testing remained relatively limited in this real-world cohort.
The results also suggest that earlier integration of PARP inhibition may be associated with improved outcomes. The authors point to supporting evidence from trials such as PROfound, TRITON-3, and the AMPLITUDE trial, which have evaluated PARP inhibitors in earlier disease settings. Notably, however, neither PROfound nor TRITON-3 demonstrated a significant overall survival benefit, underscoring the importance of appropriate control arms and study endpoints when interpreting these results.
The investigators emphasized that the present findings should be interpreted cautiously. The study was retrospective, subgroup sizes were small, and important baseline differences existed between taxane-naïve and post-taxane patients — meaning the apparent survival advantage with earlier treatment is likely influenced by confounding factors rather than representing a clean treatment effect.
Clinical Takeaway
This Dutch real-world analysis demonstrated that genomic testing in metastatic castration-resistant prostate cancer remains inconsistent across medical centers, despite increasing availability of targeted therapies.
Among patients with BRCA-mutated disease who were eligible for treatment, most received olaparib after approval, and outcomes appeared more favorable when olaparib was introduced before taxane chemotherapy. The findings support broader implementation of genomic testing and continued investigation of earlier PARP inhibitor use in metastatic prostate cancer.
The full article is available on Drugs – Real World Outcomes.