Dr Wang on Evolving Challenges in the Management of CRPC

“This is a moving target, [especially when] patients move from castration sensitive to castration resistant. They have already experienced a lot of treatment.”

Jue Wang, MD, a professor in the Department of Internal Medicine at UT Southwestern Medical Center, discussed the evolving challenges in the management of castration-resistant prostate cancer (CRPC). He emphasized that as patients progress from castration-sensitive disease to CRPC, prior therapies both suppress tumor growth and drive resistance mechanisms, making CRPC a “moving target.”

Historically, treatment has been guided by sequencing strategies, whereby clinicians moved stepwise through available agents. However, with the expansion of life-prolonging therapies—including androgen receptor pathway inhibitors, chemotherapy, PARP inhibitors, radioligand therapy, and immunotherapy—treatment selection has become increasingly complex, Wang said. He noted that cancer care delivery in 2025 can no longer be reduced to replicating clinical trial protocols in a rigid order. Instead, the application of evidence in practice requires careful reinterpretation and reinvention to optimize real-world outcomes.

According to Wang, advances in molecular testing and imaging over the past decade have enabled the development of precise, patient-centered algorithms, rather than a one-size-fits-all approach. For example, molecular profiling can identify patients with DNA repair deficiencies who may benefit from PARP inhibitors, while novel imaging modalities provide improved staging and therapeutic guidance. These tools support the design of individualized strategies that go beyond sequencing to integrate clinical, biologic, and patient-specific factors, he said.

Wang stressed that having a broad menu of therapeutic options does not automatically translate to better patient outcomes. Rather, the effectiveness of treatment depends on aligning therapies with disease biology, treatment history, performance status, and patient preferences. He cautioned against delaying use of active agents until patients are too ill to benefit, underscoring the importance of timely integration of therapies within a precision medicine framework.

Ultimately, Wang concluded that the future of CRPC management lies in combining real-world lessons with precision oncology. While randomized clinical trials establish the foundation of evidence, clinical practice requires flexibility, adaptation, and patient-centered decision-making. The challenge for oncologists is to move beyond rigid sequencing and instead deliver individualized strategies that maximize the benefit of available therapies in this heterogeneous and evolving disease.