Clinical Forum: Addressing prostate cancer treatment gaps

A recent Urology Times Clinical Forum brought together leading clinicians and researchers in Puerto Rico to discuss evolving strategies in prostate cancer management, with a particular focus on castrate-sensitive and castrate-resistant disease. Emphasizing the integration of emerging clinical evidence with real-world practice, the forum highlighted the growing importance of personalized treatment, regional health care considerations, and the evolving role of novel androgen receptor signaling inhibitors like darolutamide (Nubeqa) in improving patient outcomes. The forum was moderated by Gilberto Ruiz Deya, MD, FACS.

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

The conversation began with an acknowledgment of the rapidly evolving landscape of prostate cancer treatment, highlighting the significance of recent developments and the need to adapt clinical practice accordingly. A key theme throughout the discussion was the importance of personalized treatment strategies based on patient-specific factors, including disease volume, comorbidities, and regional health care constraints.

A notable focus was placed on the stratification of patients upon diagnosis, especially regarding metastatic castrate-sensitive prostate cancer. The clinicians discussed the significance of distinguishing between high-volume and low-volume disease, referencing the criteria of organ metastases in organs like the liver or soft tissue, or having more than 4 bone metastases or lesions outside the axial skeleton. The primary goal, as expressed by multiple participants, is to establish realistic expectations with patients early in the treatment process. This includes discussing survival outcomes, potential adverse events, and treatment options to ensure that patients are well-informed and aligned with their care plan. The importance of communication between urologists and oncologists is underlined to prevent a fragmented approach that could lead to patient loss to follow-up or suboptimal care delivery.

Treatment strategies discussed include combining androgen deprivation therapy (ADT) with newer androgen receptor signaling inhibitors (ARSi) and chemotherapeutic agents like docetaxel. The clinicians observed that, historically, drugs such as enzalutamide (Xtandi) and more recent agents like apalutamide (Erleada) and darolutamide are influencing the treatment algorithms, and regional factors such as insurance coverage and drug tier status often dictate the choice in practice. It was remarked that in Puerto Rico, where insurance considerations significantly affect drug selection, enzalutamide was historically the preferred agent because of its Tier 1 status, despite some patients having contraindications like a history of seizure disorders.

The discussion of darolutamide highlighted its distinct pharmacological profile and its role in the management of prostate cancer, particularly in the context of metastatic castrate-sensitive and non-metastatic disease. The clinicians noted that, unlike other androgen receptor signaling inhibitors such as apalutamide and enzalutamide, darolutamide possesses unique properties that influence both its efficacy and safety profile.

One of the key advantages of darolutamide, as emphasized in the discussion, is its limited ability to cross the blood-brain barrier, which reduces central nervous system (CNS) adverse events such as fatigue, cognitive disturbances, and neurological events. This contrasts with other AR inhibitors, which can cause such adverse events due to CNS penetration. The participants discussed a paper that demonstrated darolutamide's efficacy in achieving and maintaining low prostate-specific antigen (PSA) levels; for example, they mention that approximately 70% of patients on darolutamide had PSA levels below 0.2 ng/mL after treatment, suggesting a potent anti-tumor activity. These low PSA levels are correlated with better clinical outcomes, including prolonged progression-free survival and delayed progression to castration-resistant disease.

Further, the clinicians discussed data indicating that darolutamide offers a significant delay in radiological disease progression and metastasis development. Specific studies referenced show that, at 2 years, a higher proportion of patients treated with darolutamide remained free of disease progression compared twith placebo, with a notable difference in the time to progression and resistance. The evidence suggests that darolutamide effectively extends the time before disease progression and resistance occurs, even when combined with ADT in different patient populations, including those with high-risk or sensitive disease.

Another aspect addressed was darolutamide’s safety profile, especially relevant given the often comorbid elderly patients in Puerto Rico who may have cardiovascular or metabolic issues. The participants highlighted that the adverse events associated with darolutamide are comparable to placebo in many respects, with minimal CNS or systemic adverse events. They mentioned a clinical trial where adverse events rates were essentially the same between darolutamide and placebo, underscoring its tolerability. This reduces concerns about drug interactions, sedation, or CNS-related toxicity that are more common with other AR inhibitors.

The clinicians also process regional treatment considerations and barriers. They pointed out that in Puerto Rico, access to medications can be limited by insurance tier positioning, and this influences drug selection. Given its favorable safety profile, darolutamide could be particularly advantageous in populations with multiple comorbidities, such as cardiovascular disease or metabolic syndrome, which are prevalent in their practice setting. The possibility of minimizing adverse events makes darolutamide especially appealing in community settings where patients might be more vulnerable to drug-related toxicity.

The discussion also touched on the ongoing research with darolutamide and its stratification of patients in clinical trials. For example, a recent pivotal trial stratified patients based on performance status, visceral metastasis, and prior intervention, revealing that patients treated with darolutamide plus ADT had a significantly higher rate of being free of disease progression at 2 years compared with placebo plus ADT. These findings reinforce the importance of PSA levels, specifically achieving ultra-low PSA (<0.2) as a harbinger of favorable prognosis with darolutamide, similar to other AR inhibitors.

In the context of castrate-resistant disease, the discussion shifted to how recent trials and emerging evidence are shaping practice. The group reflected on the impact of clinical trial data in identifying which patient populations benefit most from specific therapies. The clinicians acknowledged that some practitioners are slow to adopt new therapies, often due to skepticism about the evidence, the need for patient-specific considerations, or simply inertia in clinical practice. There was a recognition that the evidence from recent studies supports the use of ARSi in newly diagnosed metastatic castrate-sensitive disease, and that combination approaches tend to improve outcomes compared with ADT alone.

The role of metastasis burden—whether high or low volume—was a recurrent theme. Participants emphasized that high-volume disease often warrants a more aggressive approach, combining ADT with chemotherapy, such as docetaxel, to optimize survival. Conversely, low-volume disease allows for more conservative management, although the trend is moving toward previously reserved strategies for broader patient groups.

Several clinicians shared their individual approaches, with some noting that in Puerto Rico, treatment decisions are heavily influenced by insurance policies. For instance, historically, the choice was dictated by what drugs were accessible via tiers in the insurance formulary. This sometimes led to suboptimal therapeutic choices or the use of more toxic options, such as chemotherapy, in situations where newer oral ARSi might be better tolerated. This regional context influences not only drug selection but also the timing of interventions and criteria for starting treatments like docetaxel.

Discussing patient management, the clinicians rotated through example scenarios to illustrate practical decision-making. One example involved a patient presenting with symptomatic metastases; in such cases, the consensus was to initiate systemic therapy promptly, often combining ADT with an ARSi, and consider adding chemotherapy if the disease burden is high or symptoms are severe. The importance of patient education and expectation management was underlined, with clinicians emphasizing the necessity of aligning treatment goals with patient preferences and understanding their overall health status, especially given the prevalence of comorbidities such as cardiovascular disease.

The clinicians also explored the potential future of prostate cancer management, contemplating whether combinations involving androgen receptor agents will become the standard of care for all stages of metastatic disease. There was a shared belief that the integration of ARSi with existing therapies, including chemotherapy, could serve as a default approach in the near future, provided that patient-specific factors like frailty and comorbidities are carefully considered.

Another aspect discussed was the recognition that androgen deprivation alone is insufficient for optimal disease control in metastatic contexts, especially with evidence showing that monotherapy yields inferior survival benefits compared to combination strategies. The clinicians highlighted that ADT alone is increasingly viewed as inadequate once metastasis is established, reinforcing the trend toward multi-modality systemic therapy.

Significant attention was paid to regional challenges affecting treatment implementation. Participants acknowledged disparities in health care access, drug availability, and insurance coverage as barriers to optimal care. For instance, the high incidence of metabolic syndrome and cardiovascular disease in Puerto Rican patients complicates systemic therapy choices, prompting calls for greater collaboration with cardiologists and internists to manage comorbidities and optimize overall health during cancer treatment. These considerations influence decisions, especially regarding the tolerability of certain ARSi, which may have cardiovascular adverse events.

The conversation concluded with reflections on the importance of ongoing clinical trials and research translating into practice changes. The clinicians underscored the need for continued adaptation of treatment protocols based on emerging data and regional practicalities. They expressed optimism that future research into the genetic and epigenetic landscape of their patient population, including DNA repair mechanisms, may yield more tailored therapies. The discussion emphasized that regional variations, such as those seen in Puerto Rico, must be acknowledged and addressed to ensure equitable and effective prostate cancer care. The clinicians agreed that ongoing dialogue, regional research, and sharing of practical experiences will support the evolution toward more precise, patient-centered therapies in this complex disease landscape.