Considerations for integrating systemic therapies in metastatic prostate cancer

A recent Urology Times Clinical Forum moderated by Murilo De Almeida Luz, MD, brought together urologists and multidisciplinary clinicians to examine contemporary management strategies for advanced prostate cancer, with a primary focus on metastatic castration-sensitive prostate cancer (mCSPC). The discussion reflected the rapidly evolving treatment landscape and emphasized practical decision-making, patient selection, and coordination of care as systemic options continue to expand.

Evolving diagnosis and risk stratification

Participants highlighted how advances in imaging, particularly prostate-specific membrane antigen (PSMA)-PET scanning, are reshaping disease staging. Many clinicians noted that patients once classified as having localized disease are now being identified with metastatic involvement, altering both prognosis and treatment planning. This shift has increased collaboration between urology and medical oncology, as earlier detection of metastatic disease necessitates more comprehensive systemic approaches.

Risk stratification remained a central theme, with clinicians weighing disease volume, metastatic burden, symptomatology, and performance status when determining therapy. Conventional definitions of high- vs low-volume disease continue to inform treatment selection, although the growing use of PSMA-PET imaging is prompting reassessment of these criteria. Participants acknowledged that imaging modality and insurance coverage can influence staging pathways, underscoring real-world constraints that affect care delivery.

Foundation of therapy and treatment intensification

Androgen deprivation therapy (ADT) was consistently described as the foundation of treatment for metastatic disease. However, there was strong consensus that ADT alone is no longer sufficient for most patients with mCSPC. Instead, combination strategies incorporating androgen receptor pathway inhibitors (ARPIs) or chemotherapy have become standard for appropriate patients.

Clinicians discussed the expanding role of ARPIs, including abiraterone acetate (Zytiga), enzalutamide (Xtandi), apalutamide (Erleada), and darolutamide (Nubeqa), each of which has demonstrated benefits when added to ADT. Importantly, the discussion emphasized that no single agent was viewed as universally superior. Rather, treatment selection was individualized based on patient characteristics, comorbidities, tolerability, and logistical considerations such as drug interactions and monitoring requirements.

Docetaxel chemotherapy was recognized as an important option, particularly for patients with high-volume or aggressive disease. Some clinicians favored triplet therapy—combining ADT, an ARPI, and docetaxel—in selected patients who are fit and motivated for intensive treatment. Others noted that doublet therapy may be appropriate initially, with escalation reserved for patients who show suboptimal response.

Sequencing vs upfront combination strategies

A recurring point of discussion centered on whether to intensify treatment upfront or adopt a more sequential approach. Participants acknowledged growing interest in tailoring therapy escalation based on early treatment response, particularly prostate-specific antigen (PSA) dynamics. Achieving deep PSA responses was frequently cited as a marker of favorable disease control, although clinicians emphasized that PSA trends must be interpreted in the broader clinical context.

The group explored whether early intensification with combination therapy improves long-term outcomes compared with stepwise escalation. Although upfront combination approaches were often favored for younger patients with high disease burden, there was recognition that sequential strategies may be appropriate for patients with lower-volume disease, significant comorbidities, or concerns about cumulative toxicity.

Quality of life and patient-centered decision-making

Quality of life emerged as a critical driver of treatment decisions. Participants emphasized that patients with metastatic prostate cancer often prioritize maintaining function and minimizing treatment-related adverse events over maximal survival gains. Fatigue, hot flashes, sexual dysfunction, gynecomastia, and metabolic effects were commonly cited concerns across systemic therapies.

Clinicians discussed strategies to mitigate these effects, including supportive care measures, lifestyle interventions such as exercise, and pharmacologic management when needed. The role of advanced practice providers in monitoring chronic therapy, managing adverse events, and supporting adherence was highlighted as increasingly important in busy clinical practices.

Role of multidisciplinary care

The forum underscored the importance of multidisciplinary collaboration in managing advanced prostate cancer. Medical oncologists, urologists, radiation oncologists, and allied health professionals each play a role in delivering comprehensive care. Participants described evolving referral patterns, with greater involvement of medical oncology earlier in the disease course, particularly for patients receiving systemic combination therapies.

Radiation therapy was also discussed as part of a multimodal approach, especially for patients with low-volume metastatic disease or oligometastatic presentations. Treating the primary tumor and selected metastatic sites was viewed as an emerging strategy in carefully selected patients, although optimal patient selection and treatment duration remain areas of ongoing evaluation.

Emerging therapies and future directions

Looking ahead, clinicians acknowledged that the treatment landscape for advanced prostate cancer is becoming increasingly complex. Novel triplet regimens, incorporation of targeted therapies such as PARP inhibitors in molecularly selected patients, and the potential role of radioligand therapies were noted as developments that will further challenge treatment algorithms.

Participants emphasized the need for continued education and adaptability as new data emerge. Shared decision-making, grounded in evidence but tailored to individual patient goals and circumstances, was viewed as essential in navigating this complexity.

Conclusion

The Clinical Forum highlighted the dynamic and nuanced nature of advanced prostate cancer management. Although ADT remains the cornerstone of therapy, combination approaches using ARPIs and chemotherapy have become integral to improving outcomes. The discussion reflected a balanced view of available treatment options, emphasizing individualized care, quality of life considerations, and multidisciplinary collaboration. As diagnostic tools and therapeutic options continue to evolve, clinicians must remain flexible and patient-centered in their approach to managing metastatic prostate cancer.