By Benjamin Lowentritt, MD
Dr. Benjamin Lowentritt is Director of Prostate Cancer Services at United Urology Group, Director of the Comprehensive Prostate Cancer Care Program and Director of Minimally Invasive Surgery and Robotics at Chesapeake Urology.
When a patient learns they have metastatic castration-sensitive prostate cancer (mCSPC), it often marks the beginning of a long and uncertain journey. The first conversations that follow can shape how that patient feels about their treatment and their role in it. In those early moments, how we respond matters. We can either move quickly to decisions, or we can take the time to engage patients as partners in their care. Because, in my experience, patients who feel well-informed are more likely to stay engaged with their treatment over time.
Balance urgency with optimism
Prostate cancer is the most common cancer in US men, excluding skin cancers, with approximately 1 in 8 men diagnosed during their lifetime.1,2 Despite advancements in treatment, disease recurrence currently remains substantial; up to 50% of patients within 10 years of treatment experience recurrence and carry a significant risk of disease progression.3 mCSPC represents about 15% of annual prostate cancer incidence in the United States.4 From my perspective, shared clinical decision-making is essential from the beginning across all types of prostate cancer.
But those early conversations require a difficult balancing act. And here’s where timing becomes critical. In my experience, patients may not always be symptomatic when they’re diagnosed with mCSPC. We often detect prostate cancer initially through a blood test, including prostate-specific antigen (PSA) screenings. But to confirm metastatic disease, we need additional imaging, like positron emission tomography (PET) scans, computed tomography (CT) scans, or magnetic resonance imaging (MRI), and a bone scan to determine the extent and location of metastasis.5,6
That diagnostic window, while we’re waiting for imaging and testing results, is when we must build a trusted relationship with the patient.
Patients need to process both the weight of the diagnosis as well as their role in the treatment journey ahead. You can't do that through a one-way conversation. You need dialogue.
Make room for the patient’s real world
Shared clinical decision-making isn’t about giving up medical expertise. It’s about expanding the conversation to include what’s really happening in that patient’s life.
Consider something that may seem like a small detail but absolutely determines whether a patient will adhere to their medication timeline for the next 3, 4, or 5 plus years. A patient tells you they have trouble swallowing larger pills. Now you have critical information.
ERLEADA® (apalutamide) is an androgen receptor inhibitor (ARPI) indicated for treatment of patients with mCSPC and non-metastatic castration prostate cancer (nmCRPC).7 It is the first and only next-generation ARPI offering a once-daily, single-tablet oral treatment option.7,8,9 It can be dispersed in noncarbonated water, orange juice, or applesauce, or administered through a feeding tube. For detailed instructions on administration, please see the full Prescribing Information for ERLEADA®.
That flexibility matters for patients committed to sustained, long-term use.
But we don’t always ask patients whether they take their medications once or twice a day. We don’t ask whether they need to take them with food. We don’t always understand their baseline mobility or cognitive status. We don’t always bring caregivers into conversations even though they may be the ones managing their medications.
These questions are critical because they help determine whether someone will adhere to their doctor’s orders, and consistently. And medication adherence is a critical factor influencing overall survival.
That’s where shared clinical decision-making becomes essential. But there’s a misconception about what it means.
Use evidence your patients can trust
From what I hear in the field, some physicians worry that it means handing over the reins to a patient, even when a decision is not in their best interest. That’s not what this is.
Shared clinical decision-making means both sides have the opportunity to learn and adjust their thinking. There has to be real dialogue where your expertise can influence the patient, and the patient’s circumstances can influence you. This is an example of when real-world evidence (RWE) may become valuable, and not just for understanding underrepresented populations but for gaining broader insights into how medications perform and are used in everyday clinical practice. Traditional randomized clinical trials (RCTs) provide rigorous efficacy data but often involve highly controlled populations that may not reflect the diversity of patients clinicians actually treat. For example, African American and Caribbean men of African ancestry have a higher risk of developing prostate cancer2 but aren’t always represented in RCTs.10
While RCTs are foundational, they may not always capture the diverse circumstances we see in everyday clinical practice.11 RWE offers valuable, rigorous insights that complement clinical trial data and inform everyday treatment decisions.12,13 Real-world data can play a key role in complementing clinical trial data by helping us understand a medicine’s impact and safety on a larger scale,14-16 especially those from underrepresented populations. It also allows healthcare providers to make treatment discussions more personalized, supporting shared decision-making.
I have a lot of Black patients. When they tell me they know there aren’t many Black men on these trials, I can now point to RWE showing strong outcomes in a population that actually reflects the US population. That’s very powerful. It answers questions that clinical trials often can’t. And when patients have that confidence, they’re more likely to actually take their medication consistently over years. That’s how we practice shared clinical decision-making, with data that actually reflect the patients sitting in our exam rooms.
Building trust by being a partner
When patients feel heard, they engage differently when they know they influenced the treatment plan. They become active participants. They stay with treatment. They trust that you’re working with them, not just telling them what to do.
I try to frame every decision this way: What would I want if I were the patient? I’d like my expertise in the room, sure, but I'd also want to be heard. I want my concerns to be taken seriously. I want to feel like a partner in my own care, not just a body receiving instructions. To me, that matters more than any clinical guideline. It matters especially now as mCSPC treatment options have expanded. When patients have choices between different treatment pathways, shared clinical decision-making helps them take ownership of their treatment plan.
Partnership begins the moment you give the diagnosis. It begins when you, as the clinician, recognize that your medical background is most powerful when combined with the patients lived experience and their own preferences.
It starts with understanding each individual patient and meeting them where they are.
INDICATIONS
ERLEADA® (apalutamide) is an androgen receptor inhibitor indicated for the treatment of patients with:
• Metastatic castration-sensitive prostate cancer (mCSPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Cerebrovascular and Ischemic Cardiovascular Events, including events leading to death, occurred in patients receiving ERLEADA. Monitor for signs and symptoms of ischemic heart disease and cerebrovascular disorders. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Consider discontinuation of ERLEADA for Grade 3 and 4 events.
In a randomized study (SPARTAN) of patients with nmCRPC, ischemic cardiovascular events occurred in 3.7% of patients treated with ERLEADA and 2% of patients treated with placebo. In a randomized study (TITAN) in patients with mCSPC, ischemic cardiovascular events occurred in 4.4% of patients treated with ERLEADA and 1.5% of patients treated with placebo. Across the SPARTAN and TITAN studies, 4 patients (0.3%) treated with ERLEADA and 2 patients (0.2%) treated with placebo died from an ischemic cardiovascular event. Patients with history of unstable angina, myocardial infarction, congestive heart failure, stroke, or transient ischemic attack within 6 months of randomization were excluded from the SPARTAN and TITAN studies.
In the SPARTAN study, cerebrovascular events occurred in 2.5% of patients treated with ERLEADA and 1% of patients treated with placebo. In the TITAN study, cerebrovascular events occurred in 1.9% of patients treated with ERLEADA and 2.1% of patients treated with placebo. Across the SPARTAN and TITAN studies, 3 patients (0.2%) treated with ERLEADA and 2 patients (0.2%) treated with placebo died from a cerebrovascular event.
Fractures occurred in patients receiving ERLEADA. Evaluate patients for fracture risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents.
In a randomized study (SPARTAN) of patients with nmCRPC, fractures occurred in 12% of patients treated with ERLEADA and in 7% of patients treated with placebo. In a randomized study (TITAN) of patients with mCSPC, fractures occurred in 9% of patients treated with ERLEADA and in 6% of patients treated with placebo.
Falls occurred in patients receiving ERLEADA with increased frequency in the elderly. Evaluate patients for fall risk.
In a randomized study (SPARTAN), falls occurred in 16% of patients treated with ERLEADA compared with 9% of patients treated with placebo. Falls were not associated with loss of consciousness or seizure.
Seizure occurred in patients receiving ERLEADA. Permanently discontinue ERLEADA in patients who develop a seizure during treatment. It is unknown whether anti-epileptic medications will prevent seizures with ERLEADA. Advise patients of the risk of developing a seizure while receiving ERLEADA and of engaging in any activity where sudden loss of consciousness could cause harm to themselves or others.
In two randomized studies (SPARTAN and TITAN), five patients (0.4%) treated with ERLEADA and one patient treated with placebo (0.1%) experienced a seizure. Seizure occurred from 159 to 650 days after initiation of ERLEADA. Patients with a history of seizure or, predisposing factors for seizure, or receiving drugs known to decrease the seizure threshold or to induce seizure were excluded. There is no clinical experience in re-administering ERLEADA to patients who experienced a seizure.
Severe Cutaneous Adverse Reactions — Fatal and life-threatening cases of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) occurred in patients receiving ERLEADA.
Monitor patients for the development of SCARs. Advise patients of the signs and symptoms of SCARs (eg, a prodrome of fever, flu-like symptoms, mucosal lesions, progressive skin rash, or lymphadenopathy). If a SCAR is suspected, interrupt ERLEADA until the etiology of the reaction has been determined. Consultation with a dermatologist is recommended. If a SCAR is confirmed, or for other Grade 4 skin reactions, permanently discontinue ERLEADA [see Dosage and Administration (2.2)].
Interstitial Lung Disease (ILD)/Pneumonitis — Fatal and life-threatening interstitial lung disease (ILD) or pneumonitis can occur in patients treated with ERLEADA.
Post-marketing cases of ILD/pneumonitis, including fatal cases, occurred in patients treated with ERLEADA. Across clinical trials (TITAN and SPARTAN, n=1327), 0.8% of patients treated with ERLEADA experienced ILD/pneumonitis, including 0.2% who experienced Grade 3 events [see Adverse Reactions (6.1, 6.2)].
Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever). Immediately withhold ERLEADA if ILD/pneumonitis is suspected. Permanently discontinue ERLEADA in patients with severe ILD/pneumonitis or if no other potential causes of ILD/pneumonitis are identified [see Dosage and Administration (2.2)].
Embryo-Fetal Toxicity — The safety and efficacy of ERLEADA have not been established in females. Based on findings from animals and its mechanism of action, ERLEADA can cause fetal harm and loss of pregnancy when administered to a pregnant female. Advise males with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of ERLEADA [see Use in Specific Populations (8.1, 8.3)].
Interference with Immunoassay Measurement of Digoxin
ERLEADA can interfere with certain digoxin immunoassays (e.g., Chemiluminescent Microparticle Immunoassays), resulting in falsely elevated digoxin plasma concentration results. Notify the laboratory conducting the digoxin plasma concentration assay to use an appropriate method in patients receiving ERLEADA and digoxin [see Drug Interactions (7.3)].
ADVERSE REACTIONS
The most common adverse reactions (≥10%) that occurred more frequently in the ERLEADA-treated patients (≥2% over placebo) from the randomized placebo-controlled clinical trials (TITAN and SPARTAN) were fatigue, arthralgia, rash, decreased appetite, fall, weight decreased, hypertension, hot flush, diarrhea, and fracture.
Laboratory Abnormalities — All Grades (Grade 3-4)
- Hematology — In the TITAN study: white blood cell decreased ERLEADA 27% (0.4%), placebo 19% (0.6%). In the SPARTAN study: anemia ERLEADA 70% (0.4%), placebo 64% (0.5%); leukopenia ERLEADA 47% (0.3%), placebo 29% (0%); lymphopenia ERLEADA 41% (1.8%), placebo 21% (1.6%)
- Chemistry — In the TITAN study: hypertriglyceridemia ERLEADA 17% (2.5%), placebo 12% (2.3%). In the SPARTAN study: hypercholesterolemia ERLEADA 76% (0.1%), placebo 46% (0%); hyperglycemia ERLEADA 70% (2%), placebo 59% (1.0%); hypertriglyceridemia ERLEADA 67% (1.6%), placebo 49% (0.8%); hyperkalemia ERLEADA 32% (1.9%), placebo 22% (0.5%)
Rash — In 2 randomized studies (SPARTAN and TITAN), rash was most commonly described as macular or maculopapular. Adverse reactions of rash were 26% with ERLEADA vs 8% with placebo. Grade 3 rashes (defined as covering >30% body surface area [BSA]) were reported with ERLEADA treatment (6%) vs placebo (0.5%).
The onset of rash occurred at a median of 83 days. Rash resolved in 78% of patients within a median of 78 days from onset of rash. Rash was commonly managed with oral antihistamines and topical corticosteroids, and 19% of patients received systemic corticosteroids. Dose reduction or dose interruption occurred in 14% and 28% of patients, respectively. Of the patients who had dose interruption, 59% experienced recurrence of rash upon reintroduction of ERLEADA.
Hypothyroidism — In 2 randomized studies (SPARTAN and TITAN), hypothyroidism was reported for 8% of patients treated with ERLEADA and 1.5% of patients treated with placebo based on assessments of thyroid-stimulating hormone (TSH) every 4 months. Elevated TSH occurred in 25% of patients treated with ERLEADA and 7% of patients treated with placebo. The median onset was at the first scheduled assessment. There were no Grade 3 or 4 adverse reactions. Thyroid replacement therapy, when clinically indicated, should be initiated or dose adjusted.
DRUG INTERACTIONS
Effect of Other Drugs on ERLEADA
ERLEADA Strong CYP2C8 or CYP3A4 Inhibitors
Reduce the ERLEADA dose as recommended for adverse reactions [see Dosage and Administration (2.2)]. Co-administration of a strong CYP2C8 or CYP3A4 inhibitor is predicted to increase the steady-state exposure of the active moieties (sum of unbound apalutamide plus the potency-adjusted unbound N-desmethyl-apalutamide).
Effect of ERLEADA on Other Drugs
Substrates of CYP3A4, CYP2C9, CYP2C19, P-gp, BCRP, or OATP1B1
Refer to the Prescribing Information for these substrates. Consider alternative agents when possible or evaluate for loss of activity of the substrate if concomitant use cannot be avoided.
Apalutamide is a strong inducer of CYP3A4 and CYP2C19, a weak inducer of CYP2C9, and an inducer of P-gp, BCRP, and OATP1B1. Apalutamide decreases exposure of substrates of CYP3A4, CYP2C19, CYP2C9, P-gp, BCRP, or OATP1B1, which may decrease the effectiveness of these substrates.
USE IN SPECIFIC POPULATIONS
The recommended ERLEADA dosage in patients with severe hepatic impairment (Child-Pugh C) is lower than the recommended dosage in patients with normal hepatic function. No dosage modification is recommended for patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment.
Please see full Prescribing Information for ERLEADA.
cp-50507v11
References
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https://www.cancer.org/cancer/types/prostate-cancer/about/key-statistics.html
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