David Olmos, MD, PhD, a medical oncologist, group leader, and distinguished investigator, Genetic, Genomics & Therapeutics in Prostate Cancer, at Instituto de Investigación Hospital 12 de Octubre in Madrid. 

Dr Olmos on Evaluating HRR Alterations in mHSPC

“We found that the frequency of breakout two alteration and HRR, defined by 11 genes in the study, was almost the same the mCRPC.”

David Olmos, MD, PhD, head of the Prostate Cancer Clinical Research Unit at CNIO and a medical oncologist at Hospital Universitario 12 de Octubre, discussed findings from the prospective, multi-cohort CAPTURE study evaluating homologous recombination repair (HRR) alterations in patients with metastatic hormone-sensitive prostate cancer (mHSPC).

Data were collected from 4 multicenter, observational studies: PROREPAIR-B (NCT03075735), PROSENZA (NCT02922218), PROSTAC (NCT02362620) and PROSABI (NCT02787837).

The study examined the prevalence of HRR mutations across 11 genes and their association with clinical outcomes, including radiographic progression-free survival (rPFS), time to castration resistance, and overall survival (OS).

During the analysis, investigators found that the frequency of 

 and other HRR alterations in mHSPC was comparable with what has been observed in metastatic castration-resistant prostate cancer (mCRPC), Olmos said. This suggests that many of these genomic changes are present early in the disease course rather than being acquired during progression. The proportion of germline vs somatic mutations was also similar to mCRPC, although there was a slightly higher rate of germline 

 alterations in the patients with mHSPC. This observation is consistent with prior reports linking germline 

 mutations to an increased risk of metastatic spread at presentation, he noted.

From an efficacy perspective, the study reinforced the prognostic effect of

alterations, Olmos explained. Patients with either germline or somatic mutations in these genes demonstrated worse outcomes compared with patients without such alterations. Specifically, these patients had shorter rPFS durations, a reduced time to castration resistance, and poorer OS, with 

emerging as a particularly strong adverse prognostic biomarker.

Olmos emphasized that these results highlight the importance of early molecular profiling in metastatic disease. Identifying patients with 

 or other HRR mutations at the time of diagnosis could enable earlier risk stratification and potentially inform treatment strategies beyond conventional androgen receptor–targeted therapy. The findings also support the rationale for integrating genetic testing in the hormone-sensitive setting, as the prevalence and effect of HRR mutations appear consistent across the disease continuum from mHSPC to mCRPC, he added.

He concluded that the CAPTURE study underscores the poor prognostic implications of 

 mutations in prostate cancer and reinforces the role of HRR testing at diagnosis of metastatic disease to guide clinical decision-making and trial design.

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David Olmos, MD, PhD, discusses the evaluation of homologous recombination repair alterations in metastatic hormone-sensitive prostate cancer.

Dr Olmos on the Prognostic Implications of Data From the CAPTURE Study for BRCA-Mutant mHSPC

"We have to monitor these patients more closely and maybe cannot rely solely on PSA [levels] because these patients tend to progress much earlier, even with lower PSA values. That is very important."

David Olmos, MD, PhD, medical oncologist, group leader, and distinguished investigator, Genetic, Genomics & Therapeutics in Prostate Cancer, at Instituto de Investigación Hospital 12 de Octubre in Madrid, discussed how findings from the prospective, multi-cohort CAPTURE study could inform future approaches to risk stratification and management strategies in metastatic hormone-sensitive prostate cancer (mHSPC).

The CAPTURE study revealed that patients with mHSPC harboring 

 mutations experienced significantly poorer outcomes vs those who did not. Data presented at the 

 showed that their median radiographic progression-free survival (rPFS) was 13.6 months, notably shorter than the 30.4 months observed in those without 

 < .001). Similarly, median overall survival (OS) was 26.2 months for 

-mutated patients vs 55.1 months for the wild-type group (HR, 2.7; 95% CI, 2.0-3.6; 

Olmos emphasized that despite potential responses to standard options, patients with homologous recombination repair (HRR) mutations like 

 still face a poor prognosis, even with treatment intensification. A crucial insight is the much shorter interval from biochemical to radiographic progression and overall survival in 

-mutated patients, he noted. This necessitates closer monitoring, as relying solely on prostate-specific antigen (PSA) levels may be insufficient due to earlier progression even with lower PSA values, Olmos said.

Furthermore, the biology associated with HRR alterations, such as 

 mutations, is more critical than simply counting metastases, Olmos asserted. These patients inherently have a poor prognosis, independent of other factors, underscoring the need to implement this knowledge in treatment decisions and research, he added. Olmos concluded that treatment intensification is essential for these patients, even when PARP inhibitors are unavailable.

David Olmos, MD, PhD, discusses the implications of data from the CAPTURE study for risk stratification in mHSPC harboring BRCA mutations.

David Olmos, MD, PhD

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Dr Olmos on Evaluating HRR Alterations in mHSPC

Dr Olmos on the Prognostic Implications of Data From the CAPTURE Study for BRCA-Mutant mHSPC