Modern strategies shape the care of mCSPC

In a recent Urology Times Clinical Forum held in Wayne, Pennsylvania, moderators Benjamin H. Lowentritt, MD, FACS, and Gregory C. McMahon, DO, led a discussion among urologists focused on practical strategies for managing metastatic castration-sensitive prostate cancer (mCSPC). The conversation reflected how rapidly the therapeutic landscape has evolved, with systemic intensification now considered standard for most patients.

Evolving beyond ADT monotherapy

Participants agreed that the days of treating metastatic disease with androgen deprivation therapy (ADT) alone are largely past. The growing body of evidence demonstrating improved survival with treatment intensification has reshaped initial management strategies. Most clinicians now employ either an

androgen receptor pathway inhibitor (ARPI) or chemotherapy in combination with ADT, reserving monotherapy for select older or frail patients.

This shift, they noted, requires greater familiarity with systemic regimens traditionally managed in medical oncology. Urologists have become increasingly comfortable overseeing ARPI therapy, incorporating it into routine practice as experience and comfort with monitoring grow.

Refining treatment selection

Panelists emphasized that the decision between doublet and triplet therapy must be individualized. Disease volume, timing of metastasis, and patient comorbidity remain major determinants of treatment choice. In community practice, the logistical and toxicity burdens of chemotherapy have limited its use, prompting many clinicians to favor oral agents for systemic intensification.

The discussion highlighted how genomic and imaging data now contribute to earlier identification of patients most likely to benefit from aggressive therapy. Molecular testing for DNA repair mutations and other actionable markers is increasingly routine, helping to guide sequencing and long-term planning.

Darolutamide’s expanding role

Much of the discussion focused on the growing real-world adoption of darolutamide (Nubeqa). Data from the ARASENS trial confirmed that combining darolutamide with ADT and docetaxel improves overall survival without adding substantial toxicity. For many clinicians, the agent’s distinct pharmacologic properties—limited central nervous system penetration and fewer drug–drug interactions—translate into a favorable tolerability profile in practice.

Participants shared that darolutamide is often selected when aiming for intensification without compromising quality of life. Compared with other ARPIs, its lower rates of fatigue, cognitive changes, and falls were seen as key advantages, particularly for older adults or those with existing comorbidities.

In community settings, many physicians have moved toward darolutamide-based doublet therapy—ADT plus darolutamide—as a practical, well-tolerated approach for patients who are not candidates for chemotherapy yet still warrant systemic escalation. The consensus was that real-world adherence has been strong, likely driven by its tolerability and ease of integration.

Balancing doublet and triplet approaches

A recurring theme was how to balance the survival advantage of triplet therapy against its additional complexity. Several participants noted that although triplet regimens remain an option for fit patients with high-volume disease, most community practices lean toward doublets due to feasibility and patient comfort. The role of darolutamide within both frameworks continues to expand as clinicians gain confidence in its safety and efficacy.

Shared decision-making was described as critical. Patients who understand the rationale for therapy escalation and the trade-offs between efficacy and adverse events are more likely to commit to long-term adherence. The panel also emphasized the importance of coordination between urology and medical oncology to streamline care, especially for patients transitioning between local and tertiary settings.

Tolerability and quality of life considerations

Participants underscored that although survival benefit is the foundation of intensification, quality of life ultimately determines success. With darolutamide, physicians reported fewer discontinuations for fatigue or cognitive concerns, allowing patients to maintain daily activity levels and independence. These factors have made it easier to sustain therapy across long treatment courses and may contribute to better long-term outcomes.

Clinicians also discussed strategies for managing metabolic and cardiovascular risks associated with chronic ADT, including regular screening and coordination with primary care. Maintaining bone health and addressing sexual function were identified as ongoing priorities.

Looking ahead

The conversation concluded with reflections on future directions in mCSPC management. Genomic testing, evolving imaging techniques, and new targeted agents are expected to further refine treatment sequencing. Participants noted that the next phase of progress will likely focus on identifying which patients can benefit from therapy de-escalation once deep responses are achieved.

Despite the increasing complexity of systemic therapy, panelists expressed optimism about the durability of current options. The growing role of darolutamide exemplifies how newer agents can deliver survival benefit while preserving tolerability—an outcome that aligns closely with the goals of both clinicians and patients.

Conclusion

The Wayne, Pennsylvania discussion reflected the current state of prostate cancer care: data-driven, multidisciplinary, and increasingly personalized. Urologists continue to play a central role in guiding systemic therapy, emphasizing thoughtful patient selection and proactive management of side effects. As new evidence emerges, therapies such as darolutamide have strengthened clinicians’ ability to intensify treatment without sacrificing quality of life, helping define the modern standard for men with mCSPC.