Real-world insights into treating metastatic castration-sensitive prostate cancer

A group of urologists from across the Dallas region convened for a recent Urology Times Clinical Forum moderated by Matthew L. Wilner, MD, of Urology Clinics of North Texas to discuss evolving approaches to managing metastatic castration-sensitive prostate cancer (mCSPC). The discussion focused on treatment selection, sequencing of therapies, and real-world factors affecting adoption of combination systemic therapy. Special attention was given to the integration of darolutamide (Nubeqa) into treatment paradigms and how clinicians weigh efficacy, tolerability, and patient characteristics when personalizing care. What follows is a summary of this discussion.

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

Treatment intensification and the shifting role of the urologist

Participants opened with a review of the modern treatment landscape, emphasizing how quickly the management of mCSPC has changed over the past decade. Although androgen deprivation therapy (ADT) remains foundational, it was widely agreed that ADT monotherapy is no longer sufficient for most patients. The discussion centered on how the evidence base supporting treatment intensification—through the addition of androgen receptor pathway inhibitors (ARPIs) or chemotherapy—has transformed expectations for outcomes and survival.

Clinicians acknowledged that these developments have expanded the role of urologists in the early treatment phase. Historically, many patients were referred to medical oncology immediately after diagnosis, but the current data support early combination therapy initiated by urologists. The panel discussed strategies for improving coordination with oncology colleagues and ensuring that patients are not under-treated due to care fragmentation or delayed access to advanced therapies.

Several panelists noted that, despite strong evidence supporting treatment intensification, real-world adoption remains inconsistent. Barriers include patient comorbidities, cost, insurance coverage, and variations in familiarity with newer agents. Participants emphasized that proactive patient education—particularly at the time of diagnosis—can improve adherence and treatment satisfaction, while also setting expectations for adverse events and disease trajectory.

Choosing among ARPIs

A major portion of the discussion focused on selecting among ARPIs for use with ADT in the mCSPC setting. Available agents—including enzalutamide (Xtandi), apalutamide (Erleada), abiraterone acetate (Zytiga), and darolutamide—were evaluated based on efficacy, safety, and practical considerations. Panelists noted that all agents have demonstrated survival benefits when used early in the disease course, but differences in tolerability and drug interactions frequently influence choice.

Several clinicians pointed to darolutamide as a particularly attractive option for patients in whom cognitive preservation and daily functioning are priorities. Its limited penetration across the blood–brain barrier was cited as a key differentiator that may translate into fewer central nervous system–related adverse events such as fatigue or cognitive impairment. The panel observed that this feature makes darolutamide especially suitable for older patients, those with pre-existing neurologic conditions, or individuals still working or maintaining active lifestyles.

In addition, participants referenced findings from the ARASENS trial and related studies that established the combination of darolutamide, ADT, and docetaxel as a standard-of-care regimen for appropriate patients with mCSPC. The discussion highlighted that the triplet regimen can improve overall survival while maintaining a favorable tolerability profile compared with other combination approaches. However, some clinicians noted that not all patients are suitable candidates for chemotherapy, and for those individuals, a doublet regimen of ADT plus darolutamide remains a viable and effective alternative.

Managing adverse events and patient quality of life

Panelists exchanged experiences regarding adverse event management and the balance between treatment efficacy and quality of life. Fatigue, hypertension, liver function abnormalities, and cardiovascular risks were cited as key concerns with various ARPIs. Urologists emphasized the importance of coordinating care with primary physicians and cardiologists to optimize comorbidity management before and during systemic therapy.

Darolutamide was viewed as having a comparatively favorable adverse event profile, allowing patients to maintain activity levels and cognitive clarity. Several clinicians described this as an important advantage in maintaining adherence and minimizing the need for dose interruptions. The panel noted that in real-world practice, minimizing cognitive and cardiovascular toxicity can help sustain patient engagement with long-term therapy, especially in older or medically complex individuals.

The conversation also touched on how monitoring strategies differ among agents. Regular assessment of prostate-specific antigen (PSA) response, testosterone suppression, and tolerability was considered essential, with several clinicians noting that rapid PSA decline can serve as an early indicator of therapeutic success. Some participants expressed interest in using intermittent ADT schedules or adjusting treatment duration based on response, though these strategies remain individualized and guided by ongoing trial data.

Economic and access considerations

Economic and logistical challenges emerged as consistent themes. Participants noted that although newer ARPIs have transformed outcomes, their high cost and insurance-related hurdles remain significant obstacles for patients. Co-pays, formulary restrictions, and prior authorization delays were described as major pain points that can affect timely initiation of therapy. Some clinicians reported collaborating with specialty pharmacies and patient assistance programs to facilitate access, whereas others emphasized the need for greater institutional support in navigating reimbursement processes.

Regional differences were also discussed, including variation in which agents are more readily covered by insurers. Although all ARPIs have strong clinical evidence, some participants shared that they are often required to select therapies based on formulary status rather than solely on clinical preference. The group agreed that these barriers underscore the need for continued advocacy to ensure equitable access to evidence-based therapies.

Sequencing and future directions

The latter portion of the discussion focused on how to sequence therapies in patients who progress on initial treatment. Urologists agreed that, despite substantial progress, optimal sequencing strategies remain an evolving area. Many panelists prefer to start with ADT plus an ARPI rather than triplet therapy unless the patient has high-volume disease and can tolerate chemotherapy. Others emphasized that sequencing decisions often hinge on comorbidity profiles, prior exposure, and patient preference.

Panelists also discussed the emerging importance of genomic profiling in guiding therapy selection. Identifying DNA repair mutations and other actionable alterations was recognized as increasingly relevant, particularly as more targeted agents enter clinical use. The panel noted that integrating molecular testing earlier in the disease course may help personalize therapy and identify candidates for PARP inhibitors or clinical trials.

Key takeaways

In summary, the Dallas Clinical Forum emphasized that treatment for mCSPC has entered a new era of precision and personalization. Darolutamide was highlighted as a well-tolerated and versatile option that can be used effectively as part of both doublet and triplet therapy regimens. Its safety profile, particularly the limited central nervous system penetration, was considered a meaningful advantage in many real-world settings.

Despite strong evidence supporting treatment intensification, clinicians acknowledged ongoing challenges in implementation—ranging from cost barriers to multidisciplinary coordination. Urologists agreed that maintaining active involvement in systemic therapy selection is critical to optimizing patient outcomes. As more agents and data continue to shape the therapeutic landscape, collaboration between urologists, oncologists, and support staff remains essential to delivering comprehensive and patient-centered care.

Ultimately, the panel concluded that modern mCSPC management requires balancing evidence-based intensification with individualized consideration of patient characteristics, comorbidities, and preferences. Agents like darolutamide continue to reinforce that effective, tolerable systemic therapy is achievable for a wide range of patients—supporting longer survival and improved quality of life.