Top Poster Takeaways for Prostate Cancer From 2026 ESMO Congress

Posters presented at the 2026 European Society for Medical Oncology (ESMO) Congress in Madrid examined how genomic testing can guide treatment for patients with metastatic prostate cancer. One study validated a tissue-based next-generation sequencing (NGS) assay to identify patients with BRCA1/2 mutations who may benefit from niraparib (Zejula) plus abiraterone acetate (Zytiga) and prednisone (AAP). A French multicenter analysis assessed whether genomic alterations predict benefit with lutetium Lu 177 vipivotide tetraxetan (Pluvicto). Additionally, a UK cohort study evaluated differences in genomic alterations by ethnicity and how well tissue and circulating tumor DNA (ctDNA) testing agree in metastatic castration-resistant prostate cancer (CRPC).

Refining Patient Selection for PARP- and PSMA-Directed Therapy

2278P: Clinical Validation of a Tissue-Based Next-Generation Sequencing Kit for Identifying Patients with BRCA1/2-Mutated Prostate Cancer for Niraparib + Abiraterone Acetate and Prednisone Therapy

The HRD Complete tissue-based NGS assay showed high concordance with the clinical trial assays used to enroll patients in the phase 3 MAGNITUDE study (NCT03748641) of niraparib plus AAP in metastatic prostate cancer. Patients identified as BRCA1/2 positive by the assay also showed clinical benefit similar to that seen in the trial.¹

The companion diagnostic validation study, presented by Dingwei Ye, MD, of Fudan University Shanghai Cancer Center, retrospectively tested residual tissue DNA from patients in the MAGNITUDE BRCA subgroup. It also tested samples from the PREVALENCE study (NCT03871816) that were negative for homologous recombination repair gene mutations by the same clinical trial assays.

Of 121 MAGNITUDE samples that were BRCA1/2 positive by the clinical trial assays, 100 were positive by HRD Complete. Of 87 negative PREVALENCE samples, 86 were negative by HRD Complete. Agreement with the clinical trial assays was:

• Positive percent agreement: 82.6% (95% CI, 74.7%-88.9%)
• Negative percent agreement: 98.9% (95% CI, 93.8%-100%)
• Overall percent agreement: 89.4% (95% CI, 84.4%-93.3%)

Concordance with the tissue-based clinical trial assay alone was higher, with positive, negative, and overall agreement of 91.7% (95% CI, 84.8%-96.1%), 99.0% (95% CI, 94.4%-100%), and 95.1% (95% CI, 91.2%-97.6%), respectively.

Among patients who were BRCA1/2 positive by HRD Complete, niraparib plus AAP (n = 43) reduced the risk of radiographic progression or death by 45% compared with placebo plus AAP (n = 54). The hazard ratio (HR) was 0.549 (95% CI, 0.297-1.017; P = .0534), and the median radiographic progression-free survival (rPFS) by central review was 18.43 months (95% CI, 11.10-not estimable [NE]) vs 11.17 months (95% CI, 8.08-13.93). That benefit was comparable to the result in the full MAGNITUDE BRCA subgroup (HR, 0.533; 95% CI, 0.361-0.789; P = .0014). The authors concluded that the assay may identify patients with BRCA1/2 mutations who may benefit from niraparib plus AAP.

2226P: Impact of DNA repair gene alterations, PTEN Loss, AR alteration, ARPI efficacy, time to castration resistance and metastatic sites on 177LuPSMA-617 efficacy

In a multicenter retrospective cohort, alterations in DNA damage repair (DDR) genes, BRCA1/2, PTEN, and the androgen receptor (AR) were not associated with outcomes after treatment with lutetium Lu 177 vipivotide tetraxetan for metastatic CRPC. Longer prior benefit from hormonal therapy, however, was associated with longer rPFS.²

The GETUG-endorsed study, presented by Anthime Flaus, MD, of Hospices Civils de Lyon, included 222 patients with PSMA-positive mCRPC from 7 French centers. All patients received at least 1 cycle of lutetium Lu 177 vipivotide tetraxetan as third-line or later therapy between March 2019 and January 2025. The population was heavily pretreated, with a median of 4 previous systemic treatment lines (IQR, 3-5). Prior treatment included an androgen receptor pathway inhibitor (ARPI) in 98.6% of patients, docetaxel in 82.0%, and cabazitaxel in 60.4%. Molecular profiling used ctDNA alone in 59.0% of patients, tissue alone in 32.9%, and both in 7.7%.

In the overall cohort, the median rPFS was 7.7 months (95% CI, 6.4-8.6), and the 12- and 18-month rPFS rates were 25.4% and 10.5%. The PSA50 response rate was 47.3%. The median overall survival (OS) was 13.8 months (95% CI, 11.8-16.1), with 12- and 18-month OS rates of 56.2% and 32.7%.

Genomic alterations included DDR alterations in 28.8% of patients, AR alterations in 23.2%, BRCA1/2 alterations in 12.6%, PTEN loss in 11.8%, and ATM alterations in 9.5%. None of these alterations were significantly associated with rPFS, PSA50 response, or OS. The median rPFS in patients with vs without each alteration was:

• DDR alterations: 8.8 vs 7.3 months (P = .613)
• BRCA1/2: 7.6 vs 7.7 months (P = .578)
• PTEN loss: 6.9 vs 7.6 months (P = .887)
• AR alterations: 5.5 vs 7.3 months (P = .640)

Two clinical factors were associated with longer rPFS. Patients whose prior ARPI had worked for more than 1 year had a median rPFS of 8.1 months (95% CI, 7.6-9.9), compared with 4.9 months (95% CI, 4.2-8.1) for those whose ARPI had worked for 1 year or less (P = .020). Patients whose time to castration resistance was at least 1 year had a median rPFS of 8.4 months (95% CI, 7.4-9.5), compared with 4.8 months (95% CI, 4.0-7.5) for those who progressed sooner (P = .002).

Metastatic site was not significantly associated with rPFS. The median rPFS was 13.6 vs 7.6 months for node-only disease (P = .206) and 5.1 vs 7.8 months for liver metastases (P = .402). The investigators said prospective validation is warranted.

Genomic Profiling Across Diverse Populations

2223P: Actionable Genomic Alterations (AGAs), Tumour Mutational Burden (TMB), circulating tumour DNA (ctDNA) Fraction by Ethnicity and Tissue–ctDNA Concordance in Metastatic Castration-Resistant Prostate Cancer (mCRPC)

In a single-center cohort of patients with metastatic CRPC, actionable genomic alterations, tumor mutational burden (TMB), and ctDNA fraction did not differ significantly by ethnicity. Tissue and ctDNA testing agreed closely for BRCA1/2 alterations but not for PTEN alterations.³

The retrospective study, presented by Virginia Yuk-Chun Lam, MD, of Guy’s and St Thomas’ NHS Foundation Trust in London, included 349 men with metastatic CRPC that progressed after at least 1 ARPI. Their tissue and/or ctDNA underwent NGS between 2017 and 2025, generating 553 reports. Overall, 67% of patients were White, 19% were Black, and 14% were of other or unspecified ethnicity. Tissue testing failed in 22.6% of cases and ctDNA testing in 5.3%.

TP53 was the most common alteration across all groups, followed by PTEN. Black patients had numerically more BRCA1/2 alterations, but the difference was not statistically significant. Aggressive variant prostate cancer molecular profiles (P = .243) and PTEN alterations (P = .527) also did not differ significantly by ethnicity. Median TMB was 5.0 mut/Mb in Black patients vs 3.0 mut/Mb in White patients (P = .29). A ctDNA fraction of at least 1% did not vary significantly by ethnicity (OR, 1.92; 95% CI, 0.97-5.76; P = .19).

Among 101 patients with paired tissue and ctDNA samples, the 2 methods agreed for 93.07% of BRCA1/2 results (κ = 0.63) and 95.05% of aggressive variant profiles (κ = 0.64). PTEN results showed significant discordance (κ = 0.12; McNemar P = .003), with most alterations detected by ctDNA. The investigators suggested that tissue-only testing may miss PTEN alterations and that combining tissue and ctDNA profiling maximizes detection.

Some rare but actionable alterations were found only in White patients: microsatellite instability–high disease (3.2%), TP53 Y220C mutations (0.5%), and NTRK1 amplification (0.29%). The authors said the numerically higher rates of BRCA1/2 alterations and ctDNA positivity in Black patients should be confirmed in larger, adequately powered multiethnic cohorts.

Disclosures

2278P: Ye, Xu, Zadorozhny, Singh, Zhuo, Farrington, Chen, Wu, Luo, Yang, Bell, Lyu, Liu, Fei Shen, Zhou, and Berisha are employees of Johnson & Johnson and may hold stock or stock options in Johnson & Johnson. Zhang and Zheng are employees of AmoyDx and may own stock or shares in AmoyDx. Lu and Ye reported no competing interests. The study was sponsored by Johnson & Johnson.

2226P: Flaus reported no conflicts of interest. The study was funded by Micro-crédit HCL.

2223P: The presenting author declared no conflict of interest for this work.

References

1. Lu X, Ye D, Ye X, et al. Clinical validation of a tissue-based next-generation sequencing kit for identifying patients with BRCA1/2-mutated prostate cancer for niraparib + abiraterone acetate and prednisone therapy. Presented at: 2026 European Society for Medical Oncology Congress; October 23-27, 2026; Madrid, Spain. Abstract 2278P.
2. Flaus A, Thouvenin J, Subtil F, et al. Impact of DNA repair gene alterations, PTEN loss, AR alteration, ARPI efficacy, time to castration resistance and metastatic sites on 177LuPSMA-617 efficacy. Presented at: 2026 European Society for Medical Oncology Congress; October 23-27, 2026; Madrid, Spain. Abstract 2226P.
3. Lam VYC, Konstantinidou E, So A, et al. Actionable genomic alterations (AGAs), tumour mutational burden (TMB), circulating tumour DNA (ctDNA) fraction by ethnicity and tissue–ctDNA concordance in metastatic castration-resistant prostate cancer (mCRPC). Presented at: 2026 European Society for Medical Oncology Congress; October 23-27, 2026; Madrid, Spain. Abstract 2223P.