Sequencing vs upfront intensification in metastatic prostate cancer

A recent Urology Times Clinical Forum moderated by David S. Yee, MD, MPH, convened practicing urologists to discuss current approaches to the management of metastatic castration-sensitive prostate cancer, with particular attention to treatment intensification, selection among systemic therapies, and real-world considerations that influence clinical decision-making. The discussion reflected the continued evolution of care in an era where multiple effective therapeutic options are available, and treatment strategies are increasingly individualized.

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

The conversation began with recognition that the management of metastatic prostate cancer has shifted substantially over the past decade. Participants agreed that androgen deprivation therapy (ADT) alone is no longer sufficient for most patients and that combination approaches have become central to improving disease control and survival. As a result, clinicians must now integrate disease characteristics, patient health status, and practical considerations into increasingly nuanced treatment plans.

A key theme throughout the forum was the importance of assessing disease volume and clinical presentation at diagnosis. Participants discussed how high-volume disease often prompts earlier treatment intensification, particularly in patients who are fit for combination therapy. However, clinicians also noted that patients with low-volume disease may still benefit from additional systemic therapy beyond ADT alone, depending on comorbidities, life expectancy, and patient preferences. The group emphasized that disease volume should inform—but not dictate—treatment decisions.

Androgen receptor pathway inhibitors; namely, enzalutamide (Xtandi), apalutamide (Erleada), abiraterone acetate (Zytiga), and darolutamide (Nubeqa), were discussed as foundational components of contemporary management across metastatic disease states. Participants noted that these agents have reshaped treatment algorithms by providing effective disease control while allowing many patients to delay or avoid chemotherapy. Rather than viewing these therapies as interchangeable, clinicians emphasized thoughtful selection based on individual patient factors, tolerability considerations, and anticipated long-term use.

The discussion addressed how clinicians choose among available androgen receptor pathway inhibitors in routine practice. Participants emphasized that efficacy across agents appears broadly comparable, making safety profiles, drug interactions, and patient-specific risks key differentiators. Factors such as cardiovascular history, cognitive concerns, baseline fatigue, fall risk, and seizure history were commonly cited as influencing therapy selection. Clinicians described tailoring treatment choices to minimize adverse events while maintaining disease control.

Participants also discussed the importance of monitoring and managing treatment-related adverse events across all androgen receptor pathway inhibitors. Fatigue, hypertension, metabolic changes, and effects on cognition or mood were highlighted as issues that may emerge over time and require proactive management. The group emphasized that early recognition and intervention can help patients remain on therapy longer and preserve quality of life.

Chemotherapy was discussed as an important option for select patients, particularly those with high-volume, symptomatic, or rapidly progressive disease. Participants described using docetaxel in combination with ADT in patients who are fit and motivated for aggressive therapy, while recognizing that chemotherapy may not be appropriate for all individuals. The group emphasized that chemotherapy should be considered within the broader context of patient goals, comorbidities, and anticipated tolerability rather than applied uniformly.

Another major area of discussion was treatment sequencing over the disease course. Clinicians acknowledged that although evidence supports early intensification, real-world patients often require adjustments as disease biology and patient circumstances evolve. Participants described reassessing treatment strategies at each stage of disease progression, balancing the benefits of additional therapy against cumulative toxicity and patient priorities. The lack of definitive guidance on optimal sequencing was noted, reinforcing the need for individualized decision-making.

The management of older patients and those with significant comorbidities was also addressed. Participants agreed that age alone should not exclude patients from intensified therapy, but functional status and physiologic reserve must be carefully evaluated. Oral androgen receptor pathway inhibitors were discussed as attractive options for some patients who may not tolerate chemotherapy, provided that clinicians remain attentive to adverse events and drug interactions.

Patient communication and shared decision-making were emphasized as critical elements of care. Participants stressed the importance of discussing the chronic nature of metastatic prostate cancer, the likelihood of long-term therapy, and the need for ongoing monitoring and adjustments. Clinicians noted that aligning treatment strategies with patient goals—whether focused on longevity, symptom control, or maintaining independence—helps improve adherence and satisfaction with care.

Coordination of care among urologists, medical oncologists, and other specialists was identified as increasingly important as treatment pathways become more complex. Participants highlighted the value of multidisciplinary collaboration in managing adverse events, addressing comorbid conditions, and ensuring continuity across different phases of treatment. Clear communication among providers was viewed as essential to avoiding fragmentation of care.

The forum also touched on the influence of real-world factors such as insurance coverage, formulary restrictions, and access to medications. Participants acknowledged that these considerations often affect therapy selection and timing, sometimes necessitating adjustments that differ from idealized treatment pathways. The group emphasized the importance of advocating for patients while remaining flexible in adapting treatment plans to practical constraints.

In closing, participants reflected on the ongoing evolution of metastatic prostate cancer management. While acknowledging that unanswered questions remain regarding optimal sequencing and combination strategies, the group expressed confidence that earlier use of effective systemic therapies has improved outcomes for many patients. The discussion reinforced the view that successful management now depends on personalized treatment planning, proactive toxicity management, and continuous reassessment as new evidence emerges.

Overall, the Clinical Forum highlighted a balanced, patient-centered approach to metastatic prostate cancer care. By integrating androgen receptor pathway inhibitors, ADT, and chemotherapy when appropriate—and tailoring therapy to individual patient needs—clinicians aim to optimize both disease control and quality of life in this complex and evolving disease setting.