Prof. Dingwei Ye: From Molecular Testing to Precision Treatment — Advancing Personalized Prostate Cancer Care

Advances in molecular testing and innovative therapies are reshaping the management of prostate cancer. Clinical decision-making is increasingly moving beyond disease stage and treatment sequence toward a more personalized approach informed by molecular characteristics and individual patient needs.

In metastatic castration-resistant prostate cancer (mCRPC), growing evidence supporting the combination of PARP inhibitors and androgen receptor pathway inhibitors (ARPIs) is expanding treatment options for patients with specific molecular profiles.

The 2026 edition of the Chinese Society of Clinical Oncology (CSCO) Guidelines for Prostate Cancer, developed to guide clinical practice in China, reflects these advances in precision diagnosis, molecular stratification, and individualized treatment.

Professor Dingwei Ye of Fudan University Shanghai Cancer Center and Shanghai GoBroad Cancer Hospital, GoBroad Healthcare Group, shares his perspectives on evolving prostate cancer management, the clinical implications of PARP inhibitor combination therapy, and the role of molecular biomarkers such as BRCA in guiding treatment decisions.

1. From Precision Diagnosis to Molecular Stratification: How Is Prostate Cancer Care Evolving?

Prof. Dingwei Ye:

Prostate cancer management has undergone significant changes in recent years. Imaging, molecular profiling, and personalized treatment strategies are playing increasingly important roles in clinical decision-making.

The updated Chinese guidelines highlight three key developments.

First, greater diagnostic precision through multimodal assessment.

The 2026 guidelines upgrade the recommendation level for combining MRI with PSA density from Level III to Level II. They also introduce micro-ultrasound and incorporate artificial intelligence-assisted image interpretation.

These updates reflect a broader shift toward integrating imaging, clinical parameters, and emerging technologies to improve diagnostic accuracy and risk assessment.

Second, an expanding role for molecular testing in treatment decisions.

The guidelines strengthen recommendations for testing genes associated with prostate cancer prognosis and treatment, including TP53, RB1, and PTEN. Homologous recombination repair (HRR) testing is also designated a Level I recommendation in the mCRPC setting.

Among these biomarkers, BRCA1/2 alterations have particular clinical relevance, helping identify patients who may benefit from targeted therapies such as PARP inhibitors.

Molecular testing is therefore becoming more than a tool for understanding tumor biology; it is increasingly influencing treatment selection.

Third, a shift from treatment-line-based to biomarker-guided therapy.

Evidence from Phase III trials investigating PARP inhibitor–ARPI combinations has demonstrated that treatment benefits may vary across molecular subgroups.

As a result, treatment decisions should consider not only disease stage and prior therapies but also molecular characteristics, disease burden, and the patient's overall clinical condition.

The ultimate goal of precision medicine is to deliver the most appropriate evidence-based treatment to the right patient at the right time.

2. PARP Inhibitor Combination Therapy: What Have We Learned from the PROpel Trial?

Prof. Dingwei Ye:

Phase III trials such as PROpel, MAGNITUDE, and TALAPRO-2 have contributed to the evolving first-line treatment landscape for mCRPC.

Among them, PROpel has provided important clinical evidence supporting the combination of olaparib and abiraterone.

PROpel was a randomized, double-blind, placebo-controlled Phase III trial involving 796 patients with mCRPC who had not received prior treatment for mCRPC.

In the intention-to-treat (ITT) population, olaparib plus abiraterone significantly improved radiographic progression-free survival (rPFS) compared with abiraterone plus placebo.

Median rPFS was 24.8 months versus 16.6 months, representing a 34% reduction in the risk of radiographic progression or death (HR 0.66; 95% CI 0.54–0.81; P<0.001).

In the final overall survival (OS) analysis, median OS was 42.1 months in the combination group versus 34.7 months in the control group (HR 0.81). Although the combination demonstrated a numerical OS improvement, the difference did not reach statistical significance in the overall ITT population.

No new safety signals were identified, and health-related quality of life was generally maintained.

Importantly, patients with BRCA mutations demonstrated particularly pronounced benefits.

In the BRCA-mutated subgroup, median OS had not been reached with olaparib plus abiraterone, compared with 23.0 months in the control group (HR 0.29).

Similarly, median rPFS had not been reached in the combination group, compared with 8.4 months in the control group (HR 0.23).

These findings highlight BRCA mutation status as an important biomarker for identifying patients who may derive substantial benefit from this treatment approach.

Reflecting the available evidence, the 2026 Chinese CSCO guidelines assign a Level I recommendation, supported by Category 1A evidence, to olaparib plus abiraterone for patients with BRCA-mutated mCRPC who have not previously received novel hormonal therapy.

Beyond establishing the efficacy of a combination regimen, PROpel reinforces the importance of biomarker-guided treatment selection.

However, precision medicine does not mean that every patient should receive the same combination therapy. Molecular characteristics, prior treatment exposure, disease status, and individual tolerability must all be considered when developing a personalized treatment plan.

3. From Molecular Testing to Clinical Decisions: How Can Precision Treatment Be Optimized?

Prof. Dingwei Ye:

Molecular testing is essential to precision oncology, but its value extends beyond obtaining a genetic report. The real challenge is translating molecular findings into meaningful treatment decisions.

Several priorities deserve particular attention.

First, integrate molecular testing earlier into treatment planning.

For biomarkers with established therapeutic relevance, particularly BRCA1/2, timely testing can help clinicians identify appropriate treatment options.

In patients entering the mCRPC stage, HRR testing should be considered early enough to inform first-line treatment decisions.

Second, standardize testing and interpretation.

BRCA1/2 alterations can be assessed using next-generation sequencing (NGS) of tumor tissue or blood-based samples.

Liquid biopsy provides an important alternative when tissue is unavailable or insufficient. However, a negative liquid biopsy result should be interpreted cautiously, taking into account sample quality, tumor burden, and other clinical factors. Additional testing may be appropriate when clinical suspicion remains high.

Patients who meet criteria for germline testing, particularly those with relevant family histories or potentially hereditary pathogenic variants identified through tumor testing, should receive appropriate germline assessment and genetic counseling.

Third, distinguish between different HRR gene alterations.

Not all HRR-related mutations have the same biological implications or predict equivalent responses to PARP inhibitors.

Treatment decisions should therefore consider the specific gene involved, the type of alteration, and the strength of the supporting clinical evidence.

The substantial benefits observed in BRCA-mutated patients in PROpel underscore the importance of identifying molecular subgroups most likely to respond to targeted treatment.

Fourth, integrate molecular information throughout the disease course.

Prostate cancer evolves over time, and disease status, treatment response, and resistance patterns may change.

Clinical management should therefore combine molecular findings with imaging, disease progression assessments, and treatment response to support ongoing therapeutic decisions.

Ultimately, precision prostate cancer care requires a continuous process of testing, stratification, treatment, assessment, and reassessment.

Expert Perspective: Translating Molecular Insights into Better Patient Care

From multimodal imaging to molecular profiling and targeted combination therapies, prostate cancer care is becoming increasingly personalized.

According to Professor Ye, further progress will depend not only on new treatments and stronger clinical evidence but also on the effective integration of molecular testing, patient selection, and evidence-based treatment into routine practice.

The clinical value of precision oncology lies in translating molecular insights into treatment decisions that better reflect each patient's disease characteristics and individual needs.