Yes, Lupron (or another form of ADT) must be continued with Erleada in stage 4 prostate cancer.
Apalutamide (Erleada) is FDA-approved and guideline-recommended specifically for use in combination with androgen deprivation therapy (ADT), not as monotherapy. Discontinuing Lupron while on Erleada would be off-label and contradict the evidence base that established its efficacy.
Why ADT Must Continue
The FDA label for Erleada explicitly states that patients should "start or continue a gonadotropin-releasing hormone (GnRH) analog therapy during your treatment with ERLEADA unless you have had a surgery to lower the amount of testosterone in your body (surgical castration)" 1. This requirement applies to both metastatic hormone-sensitive prostate cancer (mHSPC) and non-metastatic castration-resistant prostate cancer (nmCRPC).
The pivotal trials that established Erleada's efficacy—TITAN (for metastatic disease) and SPARTAN (for non-metastatic castration-resistant disease)—both required concurrent ADT in all patients. 2 The ASCO guidelines specifically recommend "apalutamide (240 mg per day) with ADT" as the evidence-based regimen 2. The combination therapy showed:
- Significantly longer radiographic progression-free survival (rPFS) and overall survival (OS) compared to ADT plus placebo
- Consistent benefits across disease volume subgroups
- Manageable safety profile when used together 2
The Mechanism Requires Both
Even in castration-resistant prostate cancer (CRPC), maintaining castrate testosterone levels (<50 ng/dL) remains essential. The NCCN guidelines explicitly state: "For patients who develop CRPC, ADT with orchiectomy or a luteinizing hormone-releasing hormone agonist or antagonist should be continued to maintain castrate serum levels of testosterone" 3.
Apalutamide works by blocking androgen receptor signaling, but it does not suppress testosterone production. Without concurrent ADT, testosterone levels would rise, overwhelming the androgen receptor blockade and allowing disease progression. The two therapies work synergistically—ADT suppresses testosterone production while apalutamide blocks residual androgen receptor activity.
Real-World Evidence Confirms This Approach
Multiple real-world studies demonstrate that apalutamide is used with continuous ADT in clinical practice 4, 5, 6. The ARON-3 real-world study of 531 patients with metastatic castration-sensitive prostate cancer treated with apalutamide showed excellent outcomes (87% achieved PSA90 response, 69% achieved PSA ≤0.2 ng/ml) when used with ADT 5.
The Only Exception
The sole exception to continuing ADT is if the patient has undergone bilateral orchiectomy (surgical castration), which permanently maintains castrate testosterone levels without medication 1. In this case, no additional ADT medication is needed, but castrate testosterone levels are still maintained surgically.
Bottom Line
Continue Lupron (or switch to another GnRH agonist/antagonist if preferred) throughout the entire duration of Erleada therapy. Stopping ADT would eliminate the foundation upon which Erleada's efficacy depends and would represent a deviation from FDA-approved use and evidence-based guidelines. Monitor testosterone levels periodically to confirm castrate levels (<50 ng/dL) are maintained 3.