Professor Jingjing Wang Provides an In-Depth Analysis of Precision Strategies and PARP Inhibitor–Based Combinations in Prostate Cancer

Highlights from the 15th Shanghai Urologic Oncology Academic Conference

Editor’s Note: In 2025, the 15th Shanghai Urologic Oncology Academic Conference was grandly held in Pudong, Shanghai. The meeting convened leading experts in urologic oncology from across China to discuss cutting-edge diagnostic and therapeutic strategies for genitourinary malignancies, including prostate cancer, renal cell carcinoma, and bladder cancer. During the conference, Professor Jingjing Wang, representing the field of medical oncology, delivered an outstanding presentation grounded in the latest evidence-based data, focusing on precision treatment strategies for metastatic castration-resistant prostate cancer (mCRPC), with particular emphasis on combination regimens involving PARP inhibitors. Based on Professor Wang’s presentation, this article systematically reviews the therapeutic challenges of mCRPC, genetic screening strategies, and the clinical benefits of emerging combination approaches, with the aim of providing practical insights for clinicians.

Challenges and Opportunities in the Era of Precision Treatment for mCRPC

Metastatic castration-resistant prostate cancer (mCRPC) represents the terminal stage of prostate cancer progression and is often associated with a poor prognosis. Professor Wang noted that although prostate cancer generally has favorable outcomes, once the disease progresses to the mCRPC stage, therapeutic options become increasingly limited. In real-world practice, many patients endure a prolonged disease course managed primarily by surgical teams, exhausting nearly all available novel hormonal therapies before being referred to medical oncology for end-stage management.

Historical data indicate that first-line monotherapy for mCRPC typically yields a progression-free survival (PFS) of less than six months, while multi-line treatment rarely extends PFS beyond 20 months. Median overall survival (OS) remains under three years. Such outcomes clearly fall short of patient needs, underscoring the limitations of monotherapy approaches.

From a mechanistic perspective, the poor prognosis and marked heterogeneity of mCRPC are driven by complex molecular alterations. Beyond aberrations in the androgen receptor (AR) signaling pathway, dysregulation of the Wnt, PI3K, and cell-cycle pathways—as well as the increasingly recognized DNA damage repair (DDR) pathway—collectively contribute to the aggressive and treatment-refractory nature of the disease.

Encouragingly, the advent of precision oncology has opened new avenues. Targeting defects in the homologous recombination repair (HRR) pathway has emerged as a promising strategy. Since 2020, the prostate cancer treatment landscape has witnessed a rapid expansion of PARP inhibitors, including olaparib, niraparib, and talazoparib, offering novel therapeutic options for patients with mCRPC.

Identifying High-Risk Populations: Precision Screening for BRCA Mutations and HRR Deficiency

Within a precision treatment framework, identifying patients most likely to benefit is critical to improving outcomes. The prospective CAPTURE study demonstrated that patients harboring BRCA mutations have significantly worse prognoses than those without such mutations. Specifically, median PFS was 7.1 months in BRCA-mutated patients versus 10.3 months in non-mutated patients, while median OS was 19.4 months compared with 27.9 months, respectively. These striking survival differences highlight the urgent need for early identification and targeted intervention in this high-risk population.

Professor Wang emphasized that recognizing high-risk clinical features is essential to improving the yield of genetic testing. Evidence from cross-sectional studies and recommendations from the Chinese Society of Clinical Oncology (CSCO) guidelines consistently indicate that the following characteristics are associated with a high likelihood of HRR deficiency:

A positive family history of cancer
Younger age at diagnosis (BRCA mutation carriers are diagnosed at an average age of 69 years, approximately five years earlier than non-carriers)
Rapid disease progression during prior treatment (e.g., PSA progression, radiographic progression, or clinical deterioration within one year of systemic therapy)
High Gleason score (≥8) or poor ECOG performance status

For patients meeting these criteria, CSCO guidelines explicitly recommend HRR-related gene testing, with 60 years of age serving as an important screening threshold. Through precise molecular screening, clinicians can more effectively identify patients likely to benefit from PARP inhibitor therapy and develop individualized treatment plans.

A Three-Pillar Landscape: Key Phase III Trials of PARP Inhibitor–Based Combination Therapy

In the first-line treatment of mCRPC, three landmark phase III trials have established the role of combining PARP inhibitors with novel hormonal therapies (NHTs):

MAGNITUDE (niraparib plus abiraterone)
PROpel (olaparib plus abiraterone)
TALAPRO-2 (talazoparib plus enzalutamide)

Professor Wang conducted a detailed comparative analysis of the eligibility criteria across these trials.

Although all three studies evaluated first-line therapy, their patient selection criteria differed substantially:

MAGNITUDE featured the broadest inclusion criteria, allowing prior exposure to AR inhibitors or docetaxel chemotherapy and permitting up to four months of abiraterone use in the mCRPC setting. As a result, its study population more closely reflects the complexity of real-world clinical practice.
PROpel and TALAPRO-2 applied more stringent criteria. PROpel excluded patients previously treated with novel hormonal agents, while TALAPRO-2 required that patients be treatment-naïve in the mCRPC stage.

These differences in trial design have important implications for real-world clinical decision-making.

Optimizing Treatment Decisions: Clinical Scenarios and Evidence-Based Benefits

Building on these data, Professor Wang discussed how PARP inhibitor–based combination strategies can be optimally applied across different clinical scenarios:

Treatment Selection After Progression on Prior NHT

Real-world data indicate that approximately 62% of patients with mCRPC receive novel hormonal therapy as first-line treatment. Retrospective studies have shown that re-challenging enzalutamide after progression yields limited benefit, with only 25% of patients achieving a PSA decline greater than 50% and a median PFS of just three months. In this context, the unique design of the MAGNITUDE trial provides evidence-based support for combining a PARP inhibitor with abiraterone in patients previously treated with NHT, offering meaningful survival benefits.

Symptom Control and Quality-of-Life Improvement

Beyond survival extension, improving quality of life is a central goal in advanced cancer care. NHT combined with PARP inhibitors has been shown to significantly delay disease progression and postpone the initiation of cytotoxic chemotherapy. Importantly, these regimens have also demonstrated statistically significant improvements in pain scores, pain interference, and worst pain intensity, translating into a better overall patient experience.

Safety Profiles and Adverse Event Management

Different combinations of PARP inhibitors and NHTs exhibit distinct safety profiles. Professor Wang noted that although PARP inhibitors share similar mechanisms of action, the incidence of adverse events such as hypertension, venous thromboembolism, and pulmonary embolism varies among regimens. Careful evaluation of toxicity profiles is therefore essential to tailor individualized treatment strategies.

Simplifying Complexity: Fixed-Dose Combinations, Adherence, and Future Directions

In routine mCRPC management, patients often have multiple comorbidities—such as hypertension and diabetes—and may take six to eleven medications daily. For many elderly patients, “a bowl of pills a day” has become a stark reality, severely compromising treatment adherence.

Professor Wang highlighted that fixed-dose combination formulations of NHTs and PARP inhibitors, administered once daily, represent a major advance. Compared with flexible combination regimens, these formulations significantly improve adherence, reduce hospitalization rates, and enhance convenience, while maintaining therapeutic efficacy.

Conclusions and Outlook

As one of the most challenging entities in prostate cancer treatment, mCRPC is undergoing a profound shift from traditional monotherapy to precision-based combination strategies. Professor Wang concluded that by identifying high-risk features such as BRCA mutations and implementing combinations of novel hormonal agents with PARP inhibitors, even patients with extremely poor prognoses can achieve meaningful survival extension and improved quality of life.

Looking ahead, as genetic testing becomes more widely adopted and fixed-dose combinations gain broader clinical use, prostate cancer care will continue to move toward greater precision and simplicity. These advances not only offer renewed hope for patients with mCRPC in China but also signal the arrival of a new era in urologic oncology—one defined by reduced treatment burden and enhanced therapeutic efficiency.

Professor Jingjing Wang

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