Do I discontinue leuprolide acetate (leuprolide) after 36 months for metastatic prostate cancer?

Management of Leuprolide Acetate in Metastatic Prostate Cancer

For metastatic prostate cancer, leuprolide acetate therapy should be continued indefinitely rather than discontinued after 36 months, as long as the patient continues to derive clinical benefit from the treatment. 1

Understanding Androgen Deprivation Therapy (ADT) Duration

• The Prostate Cancer Clinical Trials Working Group 3 (PCWG3) guidelines recommend continuing ADT therapy (such as leuprolide) until the patient is "no longer clinically benefiting" (NLCB) from the treatment, rather than discontinuing at a predetermined timepoint 1
• Continuation of therapy is advised even if there is progression by PSA or isolated disease sites, as long as the patient is otherwise tolerating the treatment and experiencing overall disease control 1
• The decision to discontinue therapy should be based on comprehensive assessment of the patient's clinical status rather than an arbitrary time limit 1

Clinical Decision-Making Framework

Continue Leuprolide When:

• Patient maintains testosterone suppression (≤50 ng/dL) 2, 3
• Disease remains responsive in the majority of metastatic sites 1
• Disease-related symptoms remain controlled 1
• PSA progression is slow or isolated 1
• Patient is tolerating the therapy without significant adverse effects 2

Consider Discontinuation Only When:

• Patient experiences clinical deterioration directly related to disease progression 1
• Multiple sites of disease show progression requiring change in systemic therapy 1
• Intolerable adverse effects develop that outweigh clinical benefits 4
• Patient develops castration resistance requiring therapy modification 1

Evidence Supporting Continued Therapy

• Leuprolide acetate 22.5mg administered subcutaneously every 3 months has demonstrated effective testosterone suppression to castration levels (≤50 ng/dL) in 100% of patients by day 35 of treatment, with 94% achieving levels ≤20 ng/dL by study completion 2
• Continuous ADT remains the backbone of treatment for metastatic prostate cancer, even when additional agents (such as abiraterone, enzalutamide, apalutamide, or darolutamide) are added for treatment intensification 1
• The PCWG3 guidelines specifically note that therapy may be continued if progression is slow and disease-related symptoms remain controlled 1

Monitoring During Continued Therapy

• Regular assessment of serum testosterone levels to ensure continued suppression to castration levels (≤50 ng/dL) 2, 3
• Periodic PSA measurements to evaluate biochemical response 2
• Imaging studies as clinically indicated to assess disease status 1
• Evaluation of treatment-related adverse effects, particularly hot flashes, which occur in approximately 57% of patients (mild in most cases) 2
• Assessment of bone health and consideration of supportive measures to prevent skeletal-related events 1

Common Pitfalls to Avoid

• Discontinuing leuprolide based solely on PSA progression without considering overall clinical benefit 1
• Stopping therapy at an arbitrary timepoint (such as 36 months) without evaluating continued clinical benefit 1
• Failing to distinguish between isolated progression in limited disease sites versus global disease progression 1
• Not recognizing that withdrawal of ADT in metastatic disease may lead to rapid clinical deterioration and symptomatic progression 5
• Overlooking the need for continued testosterone suppression even when adding other systemic therapies 1

In summary, for metastatic prostate cancer, leuprolide acetate therapy should be maintained indefinitely as long as the patient continues to derive clinical benefit, with the decision to discontinue based on comprehensive assessment of disease status rather than a predetermined treatment duration 1.