Evidence-informed management of metastatic castration-sensitive prostate cancer

This summary was generated by artificial intelligence and edited by humans for clarity.

A recent Urology Times Clinical Forum moderated by Eric Giesler, MD, of Urology Austin, brought together urologists and multidisciplinary clinicians to discuss contemporary approaches to advanced and metastatic prostate cancer, with a particular focus on metastatic castration-sensitive prostate cancer (mCSPC) and early castration-resistant disease. The discussion highlighted how rapid advances in imaging, expanding systemic therapy options, and evolving clinical trial data have reshaped treatment paradigms, placing increased emphasis on individualized, patient-centered decision-making.

Refining diagnosis and risk stratification

Participants emphasized the growing role of advanced imaging, including prostate-specific membrane antigen (PSMA)-PET, in identifying metastatic disease earlier and more accurately than conventional modalities. Many clinicians reported that PSMA-PET frequently upstages patients who would previously have been considered to have localized or biochemically recurrent disease. This earlier identification of metastatic involvement has important implications for therapy selection, as it often prompts consideration of systemic intensification strategies at an earlier point in the disease course.

Risk stratification remains central to treatment planning. Clinicians routinely consider disease volume, presence of visceral metastases, pace of progression, symptom burden, and performance status. Although traditional definitions of high- and low-volume disease still guide many decisions, participants acknowledged that these categories may evolve as imaging sensitivity improves and new biomarkers become incorporated into clinical practice.

ADT as the therapeutic foundation

There was broad agreement that androgen deprivation therapy (ADT) continues to serve as the backbone of treatment for metastatic prostate cancer. However, ADT alone is increasingly viewed as insufficient for most patients with mCSPC. Instead, combination strategies incorporating additional systemic agents have become standard for appropriate candidates.

Clinicians described a shift away from monotherapy toward early treatment intensification, reflecting accumulating evidence that combination approaches improve disease control and delay progression. The challenge now lies in selecting the most appropriate partners for ADT based on individual patient characteristics.

Role of androgen receptor pathway inhibitors

Androgen receptor pathway inhibitors (ARPIs) were discussed extensively as a cornerstone of modern therapy. Agents such as abiraterone acetate (Zytiga), enzalutamide (Xtandi), apalutamide (Erleada), and darolutamide (Nubeqa) were all recognized as effective options when combined with ADT in mCSPC.

Rather than favoring a single agent, participants emphasized that these therapies share broadly comparable efficacy in appropriate patient populations. Differences in adverse-event profiles, drug–drug interactions, monitoring requirements, and patient comorbidities often drive selection. For example, cardiovascular history, hepatic function, risk of fatigue or falls, and baseline cognitive concerns may influence choice among ARPIs.

Clinicians also highlighted the convenience of oral administration and the feasibility of long-term use in community practice. Ongoing monitoring for hypertension, metabolic changes, and fatigue was considered essential, and participants stressed the importance of setting expectations with patients about chronic therapy.

Chemotherapy and triplet approaches

Docetaxel chemotherapy remains an important option, particularly for patients with high-volume or aggressive disease. Some participants described continued use of ADT plus docetaxel as a reasonable strategy for selected patients, especially those who may not be ideal candidates for ARPIs due to comorbidities or access issues.

The concept of triplet therapy—combining ADT, an ARPI, and docetaxel—was discussed as an emerging approach for fit patients with high-risk features. Clinicians noted that although triplet therapy may offer deeper initial disease control, it also introduces greater complexity and potential toxicity. As a result, careful patient selection and shared decision-making are critical.

Sequencing vs upfront intensification

A recurring theme was the debate between upfront combination therapy and sequential escalation. Some clinicians favor early intensification for most patients, citing the potential to maximize disease control while patients are healthiest. Others prefer a stepwise approach, particularly for patients with lower-volume disease or significant comorbidities.

PSA kinetics were frequently mentioned as a practical tool to help guide sequencing decisions. Rapid and deep PSA responses to initial therapy may support continued observation, whereas suboptimal declines can prompt earlier escalation. Participants emphasized, however, that PSA trends should be interpreted alongside imaging findings and clinical symptoms.

Managing treatment-related toxicities

As patients remain on systemic therapy for longer periods, management of cumulative toxicity has become increasingly important. Common concerns include fatigue, hot flashes, sexual dysfunction, bone loss, metabolic changes, and cardiovascular risk.

Clinicians discussed proactive strategies to mitigate these effects, including lifestyle counseling, bone-protective agents when indicated, and close coordination with primary care providers. The involvement of advanced practice providers and nursing staff was viewed as essential for monitoring, education, and adherence support.

Multidisciplinary collaboration

The forum underscored the value of multidisciplinary care in advanced prostate cancer. Early involvement of medical oncology, radiation oncology, and supportive care specialists can help ensure comprehensive treatment planning.

Radiation therapy to the primary tumor or selected metastatic sites was discussed as part of a multimodal approach in certain patients, particularly those with low-volume metastatic disease. Although optimal patient selection continues to evolve, participants agreed that local and metastasis-directed therapies may complement systemic treatment in carefully chosen cases.

Transition to castration-resistant disease

Clinicians also addressed the eventual transition from castration-sensitive to castration-resistant prostate cancer. Recognizing this shift early allows timely modification of therapy and consideration of additional options, including alternative ARPIs, chemotherapy, targeted therapies, and clinical trial enrollment.

Participants stressed the importance of maintaining longitudinal treatment plans that anticipate future lines of therapy while preserving quality of life.

Conclusion

The Austin Clinical Forum highlighted a rapidly evolving landscape in advanced prostate cancer management. Combination systemic therapy has become the norm for most patients with metastatic disease, with multiple effective options available. Rather than a one-size-fits-all approach, clinicians emphasized individualized treatment selection based on disease characteristics, patient comorbidities, and personal preferences. Ongoing advances in imaging, systemic therapy, and supportive care will continue to shape practice, underscoring the importance of multidisciplinary collaboration and patient-centered decision-making.