Should ADT Be Continued in Progressing mCRPC?
Yes, androgen deprivation therapy (ADT) with an LHRH agonist or antagonist must be continued indefinitely in patients with metastatic castration-resistant prostate cancer (mCRPC), even as the disease progresses, to maintain castrate serum testosterone levels (<50 ng/dL). 1
Rationale for Continuing ADT
The continuation of ADT in CRPC is a fundamental principle based on the understanding that:
Castration-resistant disease does not mean androgen-independent disease. Despite progression, prostate cancer cells remain dependent on residual androgen signaling from non-gonadal sources, including intratumoral androgen synthesis and adrenal production. 1, 2
All novel therapies for mCRPC are studied and approved with concurrent ADT as the backbone. The survival benefits demonstrated by abiraterone, enzalutamide, darolutamide, docetaxel, cabazitaxel, sipuleucel-T, and radium-223 were all achieved while maintaining castrate testosterone levels. 1
Discontinuing ADT risks testosterone recovery, which can accelerate disease progression and compromise the efficacy of subsequent therapies. 3
Clinical Implementation
Verification of Castrate Status
- Before diagnosing CRPC, confirm serum testosterone is <50 ng/dL (<1.7 nmol/L) through laboratory testing. 1
- If testosterone is not adequately suppressed, optimize ADT delivery or switch LHRH agents before adding additional therapies. 1
Treatment Sequencing While Maintaining ADT
When mCRPC progresses, the following therapies are added on top of continued ADT, not as replacements:
- Secondary hormone therapies: Abiraterone + prednisone, enzalutamide, or other androgen receptor pathway inhibitors 1, 4
- Chemotherapy: Docetaxel or cabazitaxel 1, 4
- Immunotherapy: Sipuleucel-T 1
- Radiopharmaceuticals: Radium-223 for bone metastases 1
- Targeted therapies: PARP inhibitors for HRR mutations, 177Lu-PSMA-617 for PSMA-positive disease 1, 4
Monitoring Requirements
- Monitor testosterone levels periodically to ensure maintenance of castrate levels throughout treatment. 1, 5
- Continue ADT even when PSA becomes undetectable, as radiographic progression can still occur. 1
- Maintain ADT through all lines of therapy until end-of-life care. 1
Evidence Strength
This recommendation has the highest level of evidence support:
The 2023 NCCN Guidelines explicitly state: "ADT is continued in patients with mCRPC while additional therapies, including secondary hormone therapies, chemotherapies, immunotherapies, radiopharmaceuticals, and/or targeted therapies, are sequentially applied." 1
The 2014 ASCO/Cancer Care Ontario guideline recommends: "Continue androgen deprivation (pharmaceutical or surgical) indefinitely regardless of additional therapies" with moderate benefit and moderate recommendation strength. 1
Multiple guidelines from 2013-2023 consistently emphasize this principle without exception. 1
Common Pitfalls to Avoid
Never discontinue ADT when adding novel agents for mCRPC, as this compromises treatment efficacy and survival outcomes. 4
Do not assume "castration-resistant" means "hormone-independent." The terminology is misleading—these cancers remain hormone-sensitive through alternative androgen pathways. 1, 2
Avoid testosterone escape by ensuring consistent ADT delivery, particularly with depot formulations that require timely re-administration. 6, 5
Do not stop ADT based on PSA response alone to subsequent therapies, as maintaining castrate testosterone is essential regardless of biochemical markers. 1